ABSTRACT BackgroundA magnetic resonance imaging (MRI) compatible robotic system for focused ultrasound was developed for small animal like mice or rats that fits into a 9.4T MRI scanner (Bruker Biospec 9420, Bruker Biospin, Ettlingen, Germany). The robotic system includes two computer‐controlled linear stages.Materials and MethodsThe robotic system was evaluated in a mouse‐shaped, real‐size agar‐based mimicking material, which has similar acoustical properties as soft tissues. The agar content was...
Mon Sep 14, 2020 14:44
Abstract BackgroundMagnetic technologies have been introduced to reduce invasiveness of surgical procedures. This study was aimed to analyze the performance of a novel combined magnetic‐robotic controller as an enhanced accessory to the Magnetic Surgical System in laparoscopic cholecystectomy.MethodsThis was a prospective study of 10 consecutive patients undergoing laparoscopic cholecystectomy with this novel surgical system.ResultsTen patients were included, 9 were female. The mean age was 30.3...
Mon Sep 14, 2020 13:32
Concomitant Proton Pump Inhibitor Use and Survival in Urothelial Carcinoma Treated with Atezolizumab
Purpose:Emerging evidence indicates that gut microbiota dysbiosis can reduce the effectiveness of immune checkpoint inhibitors (ICI). Proton pump inhibitors (PPI) are known to induce gut microbiota changes. However, little is known on the effects of PPIs on outcomes with ICI therapy, and it has not been explored in urothelial cancer treatment.Experimental Design:Individual–participant data from the advanced urothelial cancer trials, IMvigor210 (single-arm atezolizumab trial, n = 429) and IMvigor211...
10:05
Purpose: Biliary tract cancers (BTC) are a rare heterogeneous disease with dismal prognosis often associated with inflammation. We assessed the prognostic value of IL-6 and YKL-40 compared to CA19-9 before and during palliative chemotherapy. We also investigated in mice if IL-6R inhibition in combination with gemcitabine could prolong chemosensitivity. Experimental Design: 452 Danish participants with advanced (locally advanced and metastatic) BTC were included from six clinical trials (February...
10:05
Purpose: Using next-generation sequencing (NGS), we recently documented T-cell oligoclonality in treatment-naïve chronic lymphocytic leukemia (CLL), with evidence indicating T-cell selection by restricted antigens. Experimental Design: Here, we sought to comprehensively assess T-cell repertoire changes during treatment in relation to (i) treatment type [fludarabine-cyclophosphamide-rituximab (FCR) versus ibrutinib (IB) versus rituximab-idelalisib (R-ID)], and (ii) clinical response, by...
10:05
Purpose: Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms. Experimental Design: We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated...
10:05
Purpose: Advances in prostate cancer lag behind other tumor types partly due to the paucity of models reflecting key milestones in prostate cancer progression. Therefore, we develop clinically relevant prostate cancer models. Experimental Design: Since 1996, we have generated clinically annotated patient-derived xenografts (PDXs; the MDA PCa PDX series) linked to specific phenotypes reflecting all aspects of clinical prostate cancer. Results: We studied two cell line–derived xenografts...
10:05
Purpose: The tumor immune microenvironment (TIME) has an important impact on response to cancer immunotherapy using immune checkpoint inhibitors. Specifically, an "infiltrated-excluded"/"cold" TIME is predictive of poor response. The antidiabetic agent metformin may influence anticancer immunity in esophageal squamous cell carcinoma (ESCC). Experimental Design: We analyzed matched pre- and posttreatment ESCC specimens in a phase II clinical trial of low-dose metformin treatment (250 mg/day)...
10:05
Purpose: We evaluated the prognostic and predictive value of circulating tumor cells (CTCs) hormone receptor–positive (HR+) metastatic breast cancer (MBC) patients randomized to letrozole alone or letrozole plus bevacizumab in the first-line setting (CALGB 40503). Experimental Design: Blood samples were collected at pretreatment and three additional time points during therapy. The presence of ≥5 CTCs per 7.5 mL of blood was considered CTC positive. Association of CTCs with progression-free...
10:05
Purpose: To determine the impact of basal-like and classical subtypes in advanced pancreatic ductal adenocarcinoma (PDAC) and to explore GATA6 expression as a surrogate biomarker. Experimental Design: Within the COMPASS trial, patients proceeding to chemotherapy for advanced PDAC undergo tumor biopsy for RNA-sequencing (RNA-seq). Overall response rate (ORR) and overall survival (OS) were stratified by subtypes and according to chemotherapy received. Correlation of GATA6 with the subtypes...
10:05
Purpose: Metastatic castration-resistant prostate cancer (mCRPC) is a lethal, heterogeneous disease with few therapeutic strategies that significantly prolong survival. Innovative therapies for mCRPC are needed; however, the development of new therapies relies on accurate imaging to assess metastasis and monitor response. Standard imaging modalities for prostate cancer require improvement and there remains a need for selective and sensitive imaging probes that can be widely used in patients with...
10:05
Purpose: Plasma genotyping may identify mutations in potentially "actionable" cancer genes, such as BRCA1/2, but their clinical significance is not well-defined. We evaluated the characteristics of somatically acquired BRCA1/2 mutations in patients with metastatic breast cancer (MBC). Experimental Design: Patients with MBC undergoing routine cell-free DNA (cfDNA) next-generation sequencing (73-gene panel) before starting a new therapy were included. Somatic BRCA1/2 mutations were classified...
10:05
Purpose: Tumor mutational burden (TMB) has emerged as a potential predictive biomarker for clinical response to ICI therapy, but whether TMB also predicts toxicity remains unknown. We investigated the relationship between TMB, objective response rate (ORR), overall survival (OS), and toxicity for ICI therapy across multiple cancer types. Experimental Design: We searched MEDLINE, PubMed, and ASCO/ESMO/AACR meetings for clinical trials of anti-PD(L)1, CTLA-4, or combination in 29 cancer types....
10:05
Purpose: Duration of first remission is important for the survival of patients with multiple myeloma. Experimental Design: From the CoMMpass study (NCT01454297), 926 patients with newly diagnosed multiple myeloma, characterized by next-generation sequencing, were analyzed to evaluate those who experienced early progressive disease (PD; time to progression, TTP ≤18 months). Results: After a median follow-up of 39 months, early PD was detected in 191/926 (20.6%) patients, 228/926 (24.6%) patients...
10:05
Purpose: Quantitative relationships between treatment-induced changes in tumor size and circulating tumor cell (CTC) counts, and their links to overall survival (OS), are lacking. We present a population modeling framework identifying and quantifying such relationships, based on longitudinal data collected in patients with metastatic colorectal cancer (mCRC) to evaluate the value of tumor size and CTC counts as predictors of OS. Experimental Design: A pharmacometric approach (i.e., population...
10:05
Purpose: One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel). Experimental Design: Serum cytokine and catecholamine levels were measured...
10:05
Purpose: Assess safety and efficacy of nivolumab plus nab-paclitaxel and gemcitabine in patients with locally advanced/metastatic pancreatic cancer in a two-part, open-label, phase I trial. Patients and Methods: Fifty chemotherapy-naive patients received nab-paclitaxel 125 mg/m2 plus gemcitabine 1,000 mg/m2 (days 1, 8, and 15) and nivolumab 3 mg/kg (days 1 and 15) in 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs; part 1) and grade 3/4 treatment-emergent adverse...
10:05
Purpose: Drug-induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. Patients and Methods: A total of 2,499 consecutive patients with advanced cancer on phase I clinical trials were included. DILD was identified by a dedicated radiologist and investigators, categorized per internationally recognized radiological patterns, and graded per Common Terminology Criteria...
10:05
Purpose: The phase III CELESTIAL study demonstrated improved overall survival (OS) and progression-free survival (PFS) with cabozantinib versus placebo in patients with previously treated, advanced hepatocellular carcinoma (HCC). We analyzed outcomes by baseline alpha-fetoprotein (AFP) and on-treatment AFP changes. Patients and Methods: Serum AFP was measured every 8 weeks by blinded, centralized testing. Outcomes were analyzed by baseline AFP bifurcated at 400 ng/mL and by on-treatment...
10:05
Purpose: Taletrectinib (DS-6051b/AB-106) is an oral, tyrosine kinase inhibitor of ROS1 and NTRK with potent preclinical activity against ROS1 G2032R solvent-front mutation among others. We report the first-in-human U.S. phase I results of taletrectinib. Patients and Methods: Patients ≥18 years old with neuroendocrine tumors, with tumor-induced pain, or tumors harboring ROS1/NTRK rearrangements were eligible. Accelerated titration followed by modified continuous reassessment method and escalation...
10:05
Purpose: AT13148 is an oral AGC kinase inhibitor, which potently inhibits ROCK and AKT kinases. In preclinical models, AT13148 has been shown to have antimetastatic and antiproliferative activity. Patients and Methods: The trial followed a rolling six design during dose escalation. An intrapatient dose escalation arm to evaluate tolerability and a biopsy cohort to study pharmacodynamic effects were later added. AT13148 was administered orally three days a week (Mon–Wed–Fri) in 28-day cycles....
10:05
Purpose: Preclinical studies show that adavosertib, a WEE1 kinase inhibitor, sensitizes TP53-mutant cells to chemotherapy. We hypothesized that adavosertib, plus chemotherapy, would enhance efficacy versus placebo in TP53-mutated ovarian cancer. Patients and Methods: Following safety run-in, this double-blind phase II trial (NCT01357161) randomized women with TP53-mutated, platinum-sensitive ovarian cancer to oral adavosertib (225 mg twice daily for 2.5 days/21-day cycle) or placebo, plus...
10:05
Purpose: We examined cabazitaxel, a novel next-generation taxoid, in patients with metastatic gastric cancer in a multicenter phase II study. Patients and Methods: Patients who have progressed on one or more prior therapies for locally advanced, unresectable, or metastatic disease were eligible, and prior taxane therapy was allowed. Taxane-naïve and pretreated cohorts were analyzed independently for efficacy. The primary endpoint for both cohorts was progression-free survival (PFS) using...
10:05
Purpose: Ganetespib, a highly potent, small-molecule Heatshock protein 90 inhibitor, has potential efficacy in malignant pleural mesothelioma (MPM) via activity on critical survival pathways and known synergies with antifolates and platinum chemotherapy. We conducted a dose-escalation study to identify the maximum tolerated dose (MTD) of ganetespib in patients with chemotherapy-naïve MPM. Patients and Methods: MESO-02 (ClinicalTrials.gov: NCT01590160) was a nonrandomized, multicenter, phase...
10:05
The 2019 Accelerating Anticancer Agent Development Workshop assembled a panel of experts for an in-depth discussion session to present "novel therapeutic interventions early in the disease trajectory." The panel reviewed the limitations of evaluating investigational cancer therapeutics solely in advanced metastatic and relapsed/refractory disease settings, and recommended strategies for drug evaluation earlier in the disease course, including in the first line in combination with standard chemotherapy,...
10:05
The COVID-19 global pandemic has drastically impacted cancer care, posing challenges in treatment and diagnosis. There is increasing evidence that cancer patients, particularly those who have advanced age, significant comorbidities, metastatic disease, and/or are receiving active immunosuppressive therapy may be at higher risk of COVID-19 severe complications. Controlling viral spread from asymptomatic carriers in cancer centers is paramount, and appropriate screening methods need to be established....
10:05
Newer technical improvements in radiation oncology have been rapidly implemented in recent decades, allowing an improved therapeutic ratio. The development of strategies using local and systemic treatments concurrently, mainly targeted therapies, has however plateaued. Targeted molecular compounds and immunotherapy are increasingly being incorporated as the new standard of care for a wide array of cancers. A better understanding of possible prior methodology issues is therefore required and should...
10:05
The FDA has approved three androgen receptor inhibitors—enzalutamide, apalutamide, and darolutamide—for the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). These approvals were all based on randomized, double blind, placebo-controlled trials demonstrating large improvements in metastasis-free survival (MFS) and internally consistent evidence of benefit seen across secondary endpoints. In this article, we summarize the FDA regulatory history of MFS and we describe...
10:05
Pancreatic cancer patients are in desperate need of effective therapy virtually from the moment of their diagnosis. As we acquire more therapies, how best to deploy them, in what order and to which patients is emerging as an important clinical question. Pancreatic cancer subtypes, identifiable with common lab diagnostics in diagnostic biopsy samples, may be helpful in guiding therapy selection. See related article by O'Kane et al., p. 4901
10:05
Purpose: In the S-TRAC trial, adjuvant sunitinib improved disease-free survival (DFS) compared with placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence. This post hoc exploratory analysis investigated the neutrophil-to-lymphocyte ratio (NLR) for predictive and prognostic significance in the RCC adjuvant setting. Experimental Design: Kaplan–Meier estimates and Cox proportional analyses were performed on baseline NLR and change from baseline at week...
10:05
Purpose: The ATM (ataxia telangiectasia mutated) gene is mutated in a subset of prostate cancers, and ATM mutation may confer specific therapeutic vulnerabilities, although ATM-deficient prostate cancers have not been well-characterized. Experimental Design: We genetically validated a clinical grade IHC assay to detect ATM protein loss and examined the frequency of ATM loss among tumors with pathogenic germline ATM mutations and genetically unselected primary prostate carcinomas using tissue...
10:05
Abstract Colorectal cancer (CRC) is besides breast, prostate, lung and skin cancers the most common cancers worldwide, and CRC is suitable for screening. The incidence of CRC varies considerably in different parts of the world; in well‐developed countries, the incidence is between 30 and 70 per 100 000 inhabitants. In less developed countries such as Sub‐Saharan Africa, the incidence is 10–20/100 000. Women have a lower incidence of CRC, and usually they have a 1/3 lower incidence....
Mon Sep 14, 2020 20:51
Abstract Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. There are over 15 types of systemic amyloidosis, each caused by a different precursor protein which promotes amyloid formation and tissue deposition. Amyloidosis can be acquired or hereditary and can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin and soft tissues. Symptoms are usually insidious and...
Mon Sep 14, 2020 15:35
Abstract By reducing the cerebral blood flow and thereby increasing the resting deoxyhemoglobin concentration, many human studies have shown that caffeine has a beneficial effect on enhancing the magnitude of blood‐oxygenation‐level‐dependent (BOLD) responses. However, the effect of caffeine on BOLD responses in animals under anesthesia has not been demonstrated. In this study, we aimed to determine the effect of systemic caffeine administration on BOLD responses in rats under alpha‐chloralose....
Mon Sep 14, 2020 20:49
Using oxygen permeable membranes (OPMs) to upgrade low‐purity hydrogen is a promising concept for high‐purity H 2 production. At high temperatures, water dissociates into hydrogen and oxygen. The oxygen permeates through OPM and oxidizes hydrogen in a waste stream on the other side of membrane. Pure hydrogen can be obtained on the water splitting side after condensation. However, the existing Co‐ and Fe‐based OPMs are chemically unstable due to the over‐reduction of Co and Fe ions under reducing...
Mon Sep 14, 2020 22:34
Iron(IV)‐oxo intermediates in nature contain two unpaired electrons in the Fe–O antibonding orbitals, which are thought to contribute to their high reactivity. To challenge this hypothesis, we designed and synthesized closed‐shell singlet iron(IV)‐oxo complex [(quinisox)Fe(O)] + ( 1 + ; quinisox‐H = ( N ‐(2‐(2‐isoxazoline‐3‐yl)phenyl)quinoline‐8‐carboxamide). We identified the quinisox ligand by DFT computational screening out of over 450 candidates. Following the ligand synthesis, we detected...
Mon Sep 14, 2020 22:00
Oligosilanes as Silyl Radical Precursors through Oxidative Si−Si Bond Cleavage using Redox Catalysis
Oligosilanes are of great interest in the fields of organic photonics and electronics. In this communication, a highly efficient visible‐light‐mediated hydrosilylation of electron‐deficient alkenes through cleavage of a trimethylsilyl‐polysilanyl Si−Si bond is explored. These reactions smoothly occur on readily available organo(tristrimethylsilyl)silanes and other oligosilanes in the presence of an Ir III ‐based photo‐redox catalyst under visible light irradiation. Silyl radicals are generated...
Mon Sep 14, 2020 21:43
We report the Pd‐catalyzed C–N coupling of hydrazine with (hetero)aryl chlorides and bromides to form aryl hydrazines with catalyst loadings as low as 100 ppm of Pd and KOH. Mechanistic studies revealed two catalyst resting states: an arylpalladium(II) hydroxide and arylpalladium(II) chloride. These compounds are present in two interconnected catalytic cycles and react with hydrazine and base or hydrazine alone to give the product. The selectivity of the hydroxide complex with hydrazine to form aryl...
Mon Sep 14, 2020 21:42
Abstract: A general catalytic method using Mn‐porphyrin‐based catalytic system is discovered that enables two different reactions (click reaction and denitrogenative annulation) affording two different classes of nitrogen heterocycles, such as 1,5‐disubstituted 1,2,3‐triazoles (with a pyridyl motif) and 1,2,4‐triazolo‐pyridines. Mechanistic investigations suggest that while click reaction likely proceeds through an ionic mechanism, which is different from the traditional click reaction, denitrogenative...
Mon Sep 14, 2020 20:22
On‐surface synthesis of exceptionally stable and p‐conjugated carbon‐carbon (C‐C) bonded nanostructures requires metal surfaces. Albeit beneficial for characterization, metal surfaces are detrimental for electronic applications. To also facilitate C‐C coupling on inert surfaces, we devised a radical deposition source (RDS) for the direct deposition of aryl radicals onto arbitrary substrates. Its core piece is a heated reactive drift tube through which halogenated precursors are deposited and en route...
Mon Sep 14, 2020 20:03
We present an effective approach to favorably modify the electronic structure of PbSe using Ag doping coupled with SrSe or BaSe alloying. The Ag 4d states make a contribution to in the top of the heavy hole valence band and raise its energy. The Sr and Ba atoms diminish the contribution of Pb 6s 2 states and decrease the energy of the light hole valence band. This electronic structure modification increases the density‐of‐states effective mass, and strongly enhances the thermoelectric performance....
Mon Sep 14, 2020 19:41
Here we report the in situ generation of nucleophilic allylboranes from H 2 and allenes mediated by a pyridonate borane that displays frustrated Lewis Pair reactivity. Experimental and computational mechanistic investigations reveal that upon H 2 activation, the covalently bound pyridonate substituent becomes a datively bound pyridone ligand. Dissociation of the formed pyridone borane complex liberates Piers borane and enables a hydroboration of the allene. The allylboranes generated in this...
Mon Sep 14, 2020 19:41
Flexible metal‐organic frameworks (MOFs) show large structural flexibility as a function of temperature or (gas)pressure variation, a fascinating property of high technological and scientific relevance. The targeted design of flexible MOFs demands control over macroscopic thermodynamics as determined by microscopic chemical interactions and remains an open challenge. Here we apply high‐pressure powder X‐ray diffraction and molecular dynamics simulations to gain insight into the microscopic chemical...
Mon Sep 14, 2020 19:39
Sugar alcohols are of great importance to the food industry and are promising building blocks for bio‐based polymers. Industrially, they are produced by heterogeneous hydrogenation of sugars with H 2 , usually with none to low stereoselectivities . Now, we present a homogeneous system based on commercially available components (DTBM‐SEGPHOS and [RuCl 2 (benzene)] 2 ), which not just increases the overall yield (d.r. up to 31:1), but also allows a wide range of unprotected, densely functionalized...
Mon Sep 14, 2020 18:40
Previously, we and other laboratories have reported an unusual and strong Raman optical activity (ROA) induced in solvents by chiral dyes. Various theories of the phenomenon appeared, but they were not capable of explaining fully the observed ROA band signs and intensities. In this work, an analysis based both on the light scattering theory and dedicated experiments provides a more complete understanding. For example, double‐cell magnetic circular dichroism and magnetic ROA experiments with copper‐porphyrin...
Mon Sep 14, 2020 18:39
Crystal engineering based on σ ‐hole interactions is an emerging approach for realization of new materials with higher complexity. Neutral inorganic clusters derived from 1,2‐dicarba‐ closo ‐dodecaborane, substituted with –SeMe, –TeMe, and –I moieties on both skeletal carbon vertices are experimentally demonstrated here as outstanding chalcogen‐ and halogen‐bond donors. In particular, these new molecules strongly interact with halide anions in the solid‐state. The halide ions are coordinated...
Mon Sep 14, 2020 18:39
It is still a great challenge to achieve high selectivity of CH 4 in CO 2 electroreduction reactions (CO 2 RR) because of the similar reduction potentials of possible products and the sluggish kinetics for CO 2 activation. Stabilizing the key reaction intermediates by single type of active sites supported on porous conductive material is crucial to achieve high selectivity for single product such as CH 4 . Here, Cu 2 O(111) quantum dots with an average size of 3.5 nm are in situ synthesized...
Mon Sep 14, 2020 18:09
Hydrogen peroxide (H 2 O 2 ), as a green fuel and oxidant, has drawn increasing attention in the energy and environment field recently. Compared with the traditional anthraquinone process, electrochemical (EC) and photoelectrochemical (PEC) synthesis of H 2 O 2 , are cost‐effective and environmental‐friendly. In order to construct membrane‐less EC/PEC devices for full H 2 O 2 synthesis, anodic H 2 O 2 production by water oxidation which is less developed compared with cathodic H ...
Mon Sep 14, 2020 18:08
Ammonia is an industrial large volume chemical, with its main application in fertilizer production. It also attracts increasing attention as a green energy vector. Over the past century, ammonia production has been dominated by the Haber‐Bosch process, in which a mixture of nitrogen and hydrogen gas is converted to ammonia at high temperatures and pressures. Haber‐Bosch processes with natural gas as source of hydrogen are responsible for a significant share of the global CO2 emissions. Processes...
Mon Sep 14, 2020 18:04
Vortex flow field is widely used to manipulate objects at microscale in the microfluidics. Previous approaches to produce the vortex flow field mainly focused on inertia flows. It remains a challenge to create vortexes in Stokes flow regime. Here we reported an evaporation induced spontaneous vortex flow system in Stokes flow regime by engineering Marangoni flow in a micro‐structured microfluidic chip. The Marangoni flow is created by nonuniform evaporation of surfactant solution. Various vortexes...
Mon Sep 14, 2020 17:05
Two novel two‐dimensional metal‒organic frameworks (2D MOF), 2D‐M 2 TCPE (M = Co or Ni, TCPE = 1,1,2,2‐tetra(4‐carboxylphenyl)ethylene), which are composed of staggered (4,4)‐grid layers based on paddlewheel‐shaped dimers, serve as heterogeneous photocatalysts and achieve efficient reduction of CO 2 to CO. During the visible‐light‐driven catalysis, these structures undergo in‐situ exfoliation to form nanosheets, which exhibit excellent stability and improved catalytic activity. The exfoliated...
Mon Sep 14, 2020 16:37
There is an urgent demand for analytic approaches that enable quick, precise and representative quantification of transport of small biologically active chemical compounds across cellular membranes. In this study, we established a new means to monitor membrane permeation kinetics, using total internal reflection fluorescence (TIRF) microscopy strictly confined to a ~500 nm thick silica mesoporous substrate, positioned underneath a planar supported cell membrane mimic. This way, we demonstrate spatiotemporally...
Mon Sep 14, 2020 15:12
Different communication mechanisms can be switched within a copolymer by acting on the conformational composition of the components and their chirality. Thus, a Sergeant and Soldiers effect is produced in two diastereomeric copolymer series —poly[( S )‐ 1 r ‐ co ‐( S )‐ 2 ( 1‐r ) ] and poly[( R )‐ 1 r ‐ co ‐( S )‐ 2 ( 1‐r ) ]— due to the presence in chloroform of a preferred conformation in ( S )‐ 2 , and a conformational equilibrium in 1 , where a P helix is induced...
Mon Sep 14, 2020 13:33
The enzyme 3‐methylglutaconyl coenzyme A (CoA) decarboxylase (called AibA/AibB), catalyzes the decarboxylation of 3‐methylglutaconyl CoA to generate 3,3‐dimethylacrylyl‐CoA, which is an important step in the biosynthesis of isovaleryl‐coenzyme A in Myxococcus xanthus when the regular pathway is blocked. A novel mechanism has previously been proposed for this enzyme, involving a pericyclic transition state, which would make AibA/AibB unique among decarboxylases. Herein, we use density functional...
Fri Sep 11, 2020 22:00
Abstract The fundamental aim of this study is to determine the effects of prolonged usage of N95 respirators and surgical facemasks amid health care workers in our institution. Cross-sectional study. SRM medical college hospital, Kattankulathur. A self-constructed questionnaire containing 20 queries regarding the effects of prolonged use of face masks, after being analysed by the experts of our institution were handed over to 250 participants.. All participants wore either surgical...
03:00
Abstract Background Operable stage IV gingivobuccal complex cancer is classified as Stage IVA and IVB. Among patients with Stage IVA disease, different subgroups with likely different prognoses are combined. Patients with advanced nodal status tend to have a poorer prognosis. We divided these patients into four groups: group I (T4aN0), group II (T4aN1-2), group III (T1-3N2) constituting stage IVA category, and group IV (TanyN3) representing...
03:00
Objective: Hearing loss remains a significant morbidity for patients with vestibular schwannomas (VS). A growing number of reports suggest audibility with cochlear implantation following VS resection; however, there is little consensus on preferred timing and cochlear implant (CI) performance. Data Sources: A systematic literature search of the Ovid Medline, Embase, Scopus, and clinicaltrails.gov databases was performed on 9/7/2018. PRISMA reporting guidelines were followed. Study Selection:...
04:23
Objectives: To evaluate blood–labyrinth barrier permeability using delayed gadolinium enhanced three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) in patients with untreated sporadic vestibular schwannoma (VS) to interrogate the etiopathogenesis of progressive sensorineural hearing loss. Design: Prospective case series. Setting: Single institution tertiary care center. Participants: Patients with previously untreated small to medium-sized unilateral VS undergoing 3D-FLAIR...
04:23
Background: Tinnitus is a prevalent auditory disorder that frequently co-occurs with hearing loss. It is suggested that tinnitus might have negative impact on speech perception. However, studies thus far have not been able to disentangle tinnitus, hearing loss, and speech in noise intelligibility. We therefore investigated whether there is an association between tinnitus and speech understanding in noise, independent of hearing loss. Methods: Of 4,211 participants from the population-based...
04:23
Objective: To test the feasibility of image-guided Baha Attract implant surgery with mixed reality (MR) in the form of the HoloLens to visualize critical structures and facilitate precise Baha implant placement. Methods: A cadaveric case study of bilateral Baha Attract implant approaches was conducted using Star Atlas MR three-dimensional (3D) medical interaction system guidance at the Otolaryngology Department of PUMCH, Beijing, China. The accuracy of visual surface registration was determined...
04:23
Introduction: Endoscopic stapes surgery is a technically demanding procedure that is increasing in popularity. Surgical outcomes and complication rates have been demonstrated to be comparable to traditional microscopic techniques. The surgical outcomes for patients undergoing stapes surgery performed by the Sydney Endoscopic Ear Surgery Research Group are presented. Study Design: Retrospective review from prospectively gathered database. Setting: Tertiary referral centers. Patients:...
04:23
Objective: Patients with chronic, subjective tinnitus are often administered a battery of audiometric tests to characterize their tinnitus percept. Even a comprehensive battery, if applied just once, cannot capture fluctuations in tinnitus strength or quality over time. Moreover, subjects experience a learning curve when reporting the detailed characteristics of their tinnitus percept, such that a single assessment will reflect a lack of familiarity with test requirements. We addressed these challenges...
04:23
Objective: Although it is commonly held that otosclerosis has become increasingly uncommon over recent decades, no population-based data exist to characterize this trend. Moreover, because most large epidemiologic databases within the United States primarily include cancer data, even the modern incidence of otosclerosis is unknown. The chief objective of the current work was to characterize the trend in the incidence of otosclerosis over 70 years using the unique resources of the Rochester Epidemiology...
04:23
Objectives: Brain volumetric declines may underlie the association between hearing loss and dementia. While much is known about the peripheral auditory function and brain volumetric declines, poorer central auditory speech processing may also be associated with decreases in brain volumes. Methods: Central auditory speech processing, measured by the speech recognition threshold (SRT) from the Digits-in-Noise task, and neuroimaging assessments (structural magnetic resonance imaging [MRI] and...
04:23
Background: Confirmation of permanent hearing loss in a newborn should be followed by a search for an underlying etiology because this may impact hearing loss management and counselling. Methods: Retrospective chart review of all newborns seen at a tertiary referral center after referral from newborn hearing screening over a 20-year period. The changes in the diagnostic protocol over the years are outlined and the most recent protocol includes targeted next-generation sequencing using a panel...
04:23
Objective: Intratympanic (IT) steroid injections are often used for the treatment of inner ear pathologies, including sudden sensorineural hearing loss. IT steroids are also commonly used in conjunction with or in case of systemic steroid therapy failure. They are viable options for patients who cannot endure side effects or are at high risk of complications from systemic therapy. The duration of treatment, strength, and type of steroid, and number of IT injections are important factors that impact...
04:23
Objective: A new active transcutaneous bone conduction hearing implant system that uses piezoelectric technology has been developed: an active osseointegrated steady-state implant system (OSI). This was the first clinical investigation undertaken to demonstrate clinical performance, safety, and benefit of the new implant system. Study Design and Setting: A multicenter prospective within-subject clinical investigation was conducted. Patients: Fifty-one adult subjects with mixed and conductive...
04:23
Objective: To determine the effects of cochlear implant (CI) hearing rehabilitation on quality of life in older patients (≥65 yr). Study design: Prospective observational study. Setting: Department of Oto-Rhino-Laryngology, Medical University Frankfurt/Main. Patients: Patients aged between 65 and 86 years who received unilateral CI therapy for the first time. Intervention: Unilateral cochlear implantation. Main Outcome Measures: In addition to audiological parameters,...
04:23
Objective: To examine the high frequency horizontal vestibular ocular-reflex (hVOR) during acute attacks of vertigo in Menière's disease (MD). Study Design: Retrospective case series and literature review. Setting: Tertiary academic medical center. Patients: Patients with clinical diagnosis of unilateral “definite MD.” Intervention: Review of medical records. Main Outcome Measures: Spontaneous nystagmus and the dynamic hVOR gain change at different stages of an acute episode...
04:23
Objective: A decrease in intracochlear electrocochleographic (ECochG) amplitude during cochlear implantation has been associated with poorer postoperative hearing preservation in several short-term studies. Here, we relate the stability of ECochG during surgery to hearing preservation at 3- and 12-months. Methods: Patients with hearing ≤80-dB HL at 500 Hz were implanted with a slim-straight electrode array. ECochG responses to short, high-intensity, 500-Hz pure tones of alternating polarity...
04:23
Objective: The aim of the study was to evaluate the predictive value regarding postoperative hearing benefit of electrically evoked auditory brainstem response audiometry in sporadic vestibular schwannoma patients undergoing simultaneous tumor resection and cochlear implantation. Design: Patients were included in a prospective study conducted between October 2016 and January 2019. Setting: The study was conducted at a tertiary care center. Participants: Subjects with unilateral...
04:23
Objectives: To investigate the intracochlear position of the latest Cochlear Nucleus 532 electrode array compared with the straight Nucleus 522 and the precurved 512 arrays and determine the effect of the electrode–modiolus distance on electrically evoked compound action potential, C-levels, electrically evoked stapedius reflex thresholds (ESRTs), and impedances. Methods: Postoperative high-resolution cone beam computational tomography images of 30 patients with Cochlear Nucleus 532, 522,...
04:23
Objective: Posterior external auditory canal (EAC) hypesthesia (Hitselberger's sign) has been previously described to occur in all vestibular schwannomas (1966) but has not been studied since. We hypothesized that sensory loss may be related to tumor size and sought to determine if this clinical sign could predict preoperative characteristics of vestibular schwannomas, intraoperative findings, and/or surgical outcomes. Study Design: Prospective observational study. Setting: Tertiary...
04:23
Objective: To investigate whether ultrasound is a reliable diagnostic tool to identify magnet dislocation in patients with cochlear implant. Design: Retrospective analysis. Setting: A tertiary referral medical center. Patients: Patients with cochlear implant who presented with the suspicion of magnet dislocation between January 1, 2009 and July 31, 2019. Interventions: Preinterventional ultrasound with subsequent surgical magnet repositioning. Main Outcome Measures: Accuracy...
04:23
Objective: Compare outcomes for patients who were seen via telemedicine visits after otology/neurotology surgical procedures with those who were seen in traditional office visits. Study Design: Retrospective case review. Setting: Tertiary care academic medical center. Patients: Inclusion criteria were patients who underwent otologic/neurotologic surgery and were seen in at least one telemedicine visit for postoperative care. Intervention (s): Telemedicine visit for postoperative...
04:23
Objective: To review our experience with cochlear implant infections over the past 5 years, the management strategy and to identify predictive factors that led to explantation. Study Design: Retrospective record-base case series of cochlear implant infections. Setting: Tertiary otology and implant center. Patients: All patients who had cochlear implantation over a period of 5 years. Intervention(s): None. Main Outcome Measure(s): To identify risk factors, rates and outcomes...
04:23
Hypothesis: The presence and distribution of ionized calcium binding adaptor 1 and CD68 macrophages in the human cochlea is altered in cochlear implantation (CI) compared with the normative or nonimplanted cochlea. Background: It has been hypothesized that CI induces an immunological response in macrophages leading to implant failure or reduced hearing. Macrophages are resident immune cells in human cochlea and have been shown to phagocytize implant material. In animal models, macrophage...
04:23
Objective: To assess the benefits of bimodal listening (i.e., addition of contralateral hearing aid) for cochlear implant (CI) users on real-world tasks involving high-talker variability speech materials, environmental sounds, and self-reported quality of life (quality of hearing) in listeners’ own best-aided conditions. Study Design: Cross-sectional study between groups. Setting: Outpatient hearing clinic. Patients: Fifty experienced adult CI users divided into groups based on...
04:23
Objective: Menière's disease (MD) is characterized by episodes of vertigo, tinnitus, and sensorineural hearing loss. In the setting of bilateral deafness due to MD alone or contralateral pathology, cochlear implantation (CI) improves hearing. Active MD is characterized by fluctuating auditory symptoms and vertigo; whereas remittance of vertiginous symptoms and severe, permanent sensorineural hearing loss characterizes the inactive disease state. This study evaluates outcomes for MD patients compared...
04:23
Objective: We sought to examine the intra- and interobserver variability in measuring the cochlear duct length (CDL) from magnetic resonance imaging (MRI) images versus computed tomography (CT) images using an otological surgical planning software that uses measurements of the basal turn diameter and cochlear width to estimate the CDL. Patients: Twenty-one adult cochlear implant patients with preoperative MRI and CT images. Intervention: Three fellowship-trained neurotologists served...
04:23
To celebrate the 250th anniversary of the birth of the great classical composer, Ludwig van Beethoven (1770–1827), we point out how his hearing loss affected him and how the primitive hearing aids at that time helped mitigate his hearing loss. From the age of 26, Beethoven began to suffer from a fluctuating, progressive hearing loss (“my hearing grew worse and worse”), This started in his left ear (“in my left ear, with which this illness of my ears had started”), where he had difficulty hearing...
04:23
Background: COVID-19 has become a global pandemic with a dramatic impact on healthcare systems. Concern for viral transmission necessitates the investigation of otologic procedures that use high-speed drilling instruments, including mastoidectomy, which we hypothesized to be an aerosol-generating procedure. Methods: Mastoidectomy with a high-speed drill was simulated using fresh-frozen cadaveric heads with fluorescein solution injected into the mastoid air cells. Specimens were drilled for...
04:23
Cerebrospinal fluid (CSF) gusher encountered during cochlear implantation are most commonly encountered in the setting of an inner ear abnormality. Repair of the gusher is essential to prevent CSF egress postoperatively and to decrease the risk of meningitis. Various methods to repair a CSF gusher have been described, including tight packing of the cochleostomy with fascia, lumbar drainage, and Eustachian tube packing with ear canal overclosure. We describe a novel and simple technique using a fascia...
04:23
Analysis of COX-2, PD-L1 and ARG1 expression in human pituitary adenoma. World Neurosurg. 2020 Sep 10;: Authors: Zhao G, Chen W, He J, Cui C, Zhao L, Zhao Y, Sun C, Nie D, Jin F, Kong L Abstract BACKGROUND: Cyclooxygenase-2(COX-2) is a key enzyme in the synthesis of prostaglandins. Recent studies have shown that overexpression of COX-2 can reduce the antitumor effect of the immune system by inhibiting the proliferation of B and T lymphocytes....
04:22
Intracranial Capillary Hemangiomas: A Peripartum Presentation and Review of the Literature. World Neurosurg. 2020 Sep 10;: Authors: Massman LJ, Conteh F, Cochran EJ, Zwagerman NT Abstract BACKGROUND: Intracranial capillary hemangiomas (ICHs) are rare vascular tumors comprised of a bed of many narrow thin-walled vessels. Within the confines of the skull, these tumors can lead to serious neurological deficits including cranial nerve dysfunction,...
04:22
Thin cervical spinal cord between ossifications of the ligamentum flavum and the posterior longitudinal ligament: a case report and literature review. World Neurosurg. 2020 Sep 10;: Authors: Ishikawa Y, Miyakoshi N, Hongo M, Kasukawa Y, Kudo D, Sato C, Shimada Y Abstract BACKGROUND: Cervical ossification of the ligamentum flavum (OLF) is a rare condition; however, the coexistence of OLF and ossification of the posterior longitudinal ligament...
04:22
Resection of an Isolated Pituitary Stalk Epidermoid Cyst through a Pretemporal Approach: Case Report and Review of the Literature. World Neurosurg. 2020 Sep 10;: Authors: Lee P, Krisht KM, Mukunyadzi P, Krisht AF PMID: 32920157 [PubMed - as supplied by publisher]
04:22
Cu(II) complexes with peptides from FomA protein containing -His-Xaa-Yaa-Zaa-His and -His-His-motifs. ROS generation and DNA degradation. J Inorg Biochem. 2020 Sep 06;212:111250 Authors: Lesiów MK, Bieńko A, Sobańska K, Kowalik-Jankowska T, Rolka K, Łęgowska A, Ptaszyńska N Abstract Mono- and dinuclear Cu(II) complexes with Ac-PTVHNEYH-NH2 (L1) and Ac-NHHTLND-NH2 (L2) peptides from FomA protein of Fusobacterium nucleatum were studied by potentiometry,...
04:10
Antibacterial activities and antiproliferative assays over a tumor cells panel of a silver complex with 4-aminobenzoic acid: Studies in vitro of sustained release using bacterial cellulose membranes as support. J Inorg Biochem. 2020 Sep 06;212:111247 Authors: Aquaroni NAS, Nakahata DH, Lazarini SC, Resende FA, Cândido ALP, da Silva Barud H, Claro AM, de Carvalho JE, Ribeiro CM, Pavan FR, Lustri BC, Ribeiro TRM, Moreira CG, Cândido TZ, Lima CSP, Ruiz ALTG, Corbi...
04:10
Anti-diabetic and anti-parasitic properties of a family of luminescent zinc coordination compounds based on the 7-amino-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine ligand. J Inorg Biochem. 2020 Aug 23;212:111235 Authors: Esteban-Parra GM, Sebastián ES, Cepeda J, Sánchez-González C, Rivas-García L, Llopis J, Aranda P, Sánchez-Moreno M, Quirós M, Rodríguez-Diéguez A Abstract We report on the formation of a triazolopyrimidine derivative ligand, 7-amino-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine...
04:10
Harnessing Peptides against lead pollution and poisoning: Achievements and prospects. J Inorg Biochem. 2020 Sep 04;212:111251 Authors: Sauser L, Shoshan MS Abstract Among the broad applicability of peptides in numerous aspects of life and technologies, their interactions with lead (Pb), one of the most harmful substances to the environment and health, are constantly explored. So far, peptides were developed for environmental remediation of...
04:10
An enhanced antibacterial nanoflowers AgPW@PDA@Nisin constructed from polyoxometalate and nisin. J Inorg Biochem. 2020 Aug 07;212:111212 Authors: Zhang C, Zhao M, Zou H, Zhang X, Sheng R, Zhang Y, Zhang B, Li C, Qi Y Abstract A new composite, AgPW@PDA@Nisin, with shell-core structure was successfully synthesized by a polydopamine (PDA) surfaced conjugated nisin (an antibacterial 34 amino acid polycyclic peptide) as shell and polyoxometalates...
04:10
Cognitive, adaptive, and behavioral effects of adjunctive rufinamide in Lennox-Gastaut syndrome: A prospective observational clinical study. Epilepsy Behav. 2020 Sep 10;112:107445 Authors: Operto FF, Verrotti A, Marrelli A, Ciuffini R, Coppola G, Pastorino GMG, Striano P, Sole M, Zucca C, Manfredi V, Città S, Elia M Abstract INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by multiple drug-resistant...
04:08
Evaluation of pediatric patients in new-onset seizure clinic (NOSc). Epilepsy Behav. 2020 Sep 10;112:107428 Authors: Kim S, DeGrauw T, Berg AT, Hass KB, Koh S Abstract AIM: We evaluated the clinical and demographic features of children presenting with unprovoked seizures at a regional new-onset seizure clinic (NOSc). METHODS: We retrospectively reviewed charts of 492 consecutive patients evaluated in the NOSc at the Childrne's Healthcare...
04:08
Access to healthcare and prevalence of anxiety and depression in persons with epilepsy during the COVID-19 pandemic: A multicountry online survey. Epilepsy Behav. 2020 Sep 10;112:107350 Authors: Van Hees S, Siewe Fodjo JN, Wijtvliet V, Van den Bergh R, Faria de Moura Villela E, da Silva CF, Weckhuysen S, Colebunders R Abstract OBJECTIVE: The objective of this study was to assess access to healthcare and to estimate the prevalence of depression...
04:08
Adipose-Derived Stem Cell transplantation improves learning and memory via releasing neurotrophins in rat model of temporal lobe epilepsy. Brain Res. 2020 Sep 10;:147121 Authors: Wang L, Zhao Y, Pan X, Zhang Y, Lin L, Wu Y, Huang Y, He H Abstract Epilepsy is a common neurological disease and its most common type is temporal lobe epilepsy (TLE). Novel therapeutics is needed as many TLE patients are resistant to treatments like anticonvulsants...
04:08
Analysis of Financial Risk Protection Indicators in Myanmar for Paediatric Surgery. World J Surg. 2020 Sep 12;: Authors: Nataraja RM, Yin Mar Oo, Andolfatto L, Moore EM, Watters D, Aye Aye, Htun Oo, Moe Moe Tin, Shrime M, McLeod E Abstract PURPOSE: To estimate proportion of Myanmar paediatric population at risk of impoverishment and catastrophic expenditure due to emergency surgical intervention. METHODS: Prospective data were collected...
03:51
ERRATUM FOR "Safety and Efficacy of Oral Octreotide in Acromegaly: Results of a Multicenter Phase III Trial". J Clin Endocrinol Metab. 2020 Sep 13;: Authors: PMID: 32920646 [PubMed - as supplied by publisher]
03:42
Exploring the epigenetic regulation of telomerase reverse transcriptase (TERT) in human cancer cell lines. Mol Oncol. 2020 Sep 13;: Authors: McKelvey BA, Zeiger MA, Umbricht CB Abstract Telomerase regulation, including TERT promoter methylation, has been of long-standing interest to cancer biologists. Rowland et al. have now vastly expanded their ongoing characterization of TERT promoter methylation in cancer cells, analyzing the methylation...
03:38
Lack of Knowledge, the main Stumbling Block of Fertility Preservation Promotion in China. J Cancer Educ. 2020 Sep 12;: Authors: Wang M, Zhu L, Xiong H, Wang J, Li Z, Yang L, Jin L, Xi Q Abstract The aim of this study is to evaluate fertility preservation (FP) popularization in China among female cancer patients in terms of awareness of fertility, knowledge about FP, and attitudes toward FP. A questionnaire-based survey was conducted among female...
03:38
Predicting adjuvant endocrine therapy initiation and adherence among older women with early-stage breast cancer. Breast Cancer Res Treat. 2020 Sep 12;: Authors: Meneveau MO, Keim-Malpass J, Camacho TF, Anderson RT, Showalter SL Abstract PURPOSE: The CALGB 9343 trial demonstrated that women age 70 or older with early-stage, estrogen receptor positive (ER +) breast cancer (BC) may safely forgo radiation therapy (RT) and be treated with breast...
03:38
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου