bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers predictive of response to pembrolizumab in head and neck cancer
Authors: Pfister David G. , Haddad Robert I. , Worden Francis P. , Weiss Jared , Mehra Ranee , Chow Laura Q. M. , Liu Stephen V. , Kang Hyunseok , Saba Nabil F. , Wirth Lori J. , Sukari Ammar , Massarelli Erminia , Ayers Mark , Albright Andrew , Webber Andrea L. , Mogg Robin , Lunceford Jared , Huang Lingkang , Cristescu Razvan , Cheng Jonathan , Seiwert Tanguy Y. , Bauml Joshua M. 
Published: December 2022

AbstractBackgroundWe performed an integrated biomarker evaluation in pembrolizumab‐treated patients with R/M HNSCC enrolled in KEYNOTE‐012 or KEYNOTE‐055. The relationship between biomarkers and HPV status was explored.MethodsWe evaluated PD‐L1 (combined positive score [CPS]), TMB, T‐cell‐inflamed gene expression profile (TcellinfGEP), and HPV status. Associations between biomarkers were evaluated by logistic regression (ORR) and Cox regression (PFS, OS).ResultsTwo hundred and fifty‐seven patients (KEYNOTE‐012, n = 106; KEYNOTE‐055, n = 151) had TMB data available; of these, 254 had PD‐L1 and 236 had TcellinfGEP. TMB, PD‐L1, and TcellinfGEP were each significantly associated with ORR (p < 0.01). Kaplan–Meier curves at prespecified cutoffs generally showed PFS and OS separation in the anticipated direction for these biomarkers, except for OS and TMB. TMB did not correlate with PD‐L1 or TcellinfGEP (Spearman ρ = −0.03 and ρ = −0.13, respectively); PD‐L1 and TcellinfGEP were moderately correlated (Spearman ρ = 0.47). In multivariate models, TMB, PD‐L1, and TcellinfGEP were each independently predictive for ORR (p < 0.001). ORR was higher in patients with high versus low levels of biomarkers when dichotomized using prespecified cutoffs; patients with higher versus lower levels of TMB and PD‐L1 or TMB and TcellinfGEP had the highest ORRs. Within HPV subgroups, higher versus lower distributions of biomarkers (PD‐L1, TMB, and TcellinfGEP) were associated with response. HPV detection by p16‐immunohistochemistry and WES showed good concordance (81%); results were generally similar by HPV status, regardless of the detection method.ConclusionsTMB and the inflammatory biomarkers PD‐L1 and TcellinfGEP, assessed alone or together, may be useful for characterizing clinical response to pembrolizumab in R/M HNSCC.
Potential targets of severe acute respiratory syndrome coronavirus 2 of clinical drug fluvoxamine: Docking and molecular dynamics studies to elucidate viral action
Authors: Panda Saroj Kumar , Gupta Parth Sarthi Sen , Rana Malay Kumar 
Published: December 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has continued evolving for survival and adaptation by mutating itself into different variants of concern, including omicron. Several studies and clinical trials found fluvoxamine, an Food and Drug Administration‐approved antidepressant drug, to be effective at preventing mild coronavirus disease 2019 (COVID‐19) from progressing to severe diseases. However, the mechanism of fluvoxamine's direct antiviral action against COVID‐19 is still unknown. Fluvoxamine was docked with 11 SARS‐CoV‐2 targets and subjected to stability, conformational changes, and binding free energy analyses to explore its mode of action. Of the targets, nonstructural protein 14 (NSP14), main protease (Mpro), and papain‐like protease (PLpro) had the best docking scores with fluvoxamine. Consistent with the docking results, it was confirmed by molecular dynamics simulations that the NSP14 N7‐MTase ((N7‐guanine)‐methyltransferase)–fluvoxamine, Mpro–fluvoxamine, and PLpro–fluvoxamine complexes are stable, with the lowest binding free energies of −105.1, −82.7, and − 38.5 kJ/mol, respectively. A number of hotspot residues involved in the interaction were also identified. These include Glu166, Asp187, His41, and Cys145 in Mpro, Gly163 and Arg166 in PLpro, and Glu302, Gly333, and Phe426 in NSP14, which could aid in the development of better antivirals against SARS‐CoV‐2.
Inorganic Drugs as a Tool for Protein Structure Solving and Studies on Conformational Changes
Authors: Tolbatov Iogann , Marrone Alessandro , Shepard William , Chiaverini Lorenzo , Upadhyay Kahaly Mousumi , La Mendola Diego , Marzo Tiziano , Ciccone Lidia 
Published: December 2022

AbstractInorganic drugs are capable of tight interactions with proteins through coordination towards aminoacidic residues, and this feature is recognized as a key aspect for their pharmacological action. However, the “protein metalation process” is exploitable for solving the phase problem and structural resolution. In fact, the use of inorganic drugs bearing specific metal centers and ligands capable to drive the binding towards the desired portions of the protein target could represent a very intriguing and fruitful strategy. In this context, a theoretical approach may further contribute to solve protein structures and their refinement. Here, we delineate the main features of a reliable experimental‐theoretical integrated approach, based on the use of metallodrugs, for protein structure solving.
CRISPR/Cas‐Based MicroRNA Biosensors
Authors: Zhang Qian , Zhang Xinyi , Zou Xiaoran , Ma Fei , Zhang Chun‐Yang 
Published: December 2022

AbstractAs important post‐transcriptional regulators, microRNAs (miRNAs) play irreplaceable roles in diverse cellular functions. Dysregulated miRNA expression is implicated in various diseases including cancers, and thus miRNAs have become the valuable biomarkers for disease monitoring. Recently, clustered regularly interspaced short palindromic repeats/CRISPR‐associated (CRISPR/Cas) system has shown great promise for the development of next‐generation biosensors because of its precise localization capability, good fidelity, and high cleavage activity. Herein, we review recent advance in development of CRISPR/Cas‐based biosensors for miRNA detection. We summarize the principles, features, and performance of these miRNA biosensors, and further highlight the remaining challenges and future directions.
m‐Benziporphyrin(1.1.0.0)s as a Rare Example of Ring‐Contracted Carbaporphyrins with Metal‐Coordination Ability: Distorted Coordination Structures and Small HOMO‐LUMO Gaps
Authors: Liu Le , Zhang Fenni , Xu Ling , Zhou Mingbo , Yin Bangshao , Tanaka Takayuki , Osuka Atsuhiro , Song Jianxin 
Published: December 2022

Abstractm‐Benziporphyrin(1.1.0.0) and m‐pyreniporphyrin(1.1.0.0) were prepared as ring‐contracted carbaporphyrins. While m‐Benziporphyrin(1.1.0.0) was unstable, m‐pyreniporphyrin(1.1.0.0) was fairly stable. Both of their PdII complexes showed distorted coordination structures with extremely short Pd−C bonds. As compared with the reported m‐benziporphyrin PdII complexes, these PdII complexes showed considerably small HOMO‐LUMO gaps, despite their smaller molecular size. PdII metalation of the m‐pyreniporphyrin(1.1.0.0) dimer gave the corresponding PdII complex, which showed similar distorted coordination and a smaller HOMO‐LUMO gap. Finally, PdII metalation of a pyrene‐sharing formal p‐benziporphyrin(1.1.1.1) dimer gave a nonaromatic PdII dimer, which rearranged to an aromatic PdII complex upon treatment with alumina.
Precise modulation of embryonic development through optogenetics
Authors: Fan Huaxun , Barnes Collin , Hwang Hyojeong , Zhang Kai , Yang Jing 
Published: December 2022

SummaryThe past decade has witnessed enormous progress in optogenetics, which uses photo‐sensitive proteins to control signal transduction in live cells and animals. The ever‐increasing amount of optogenetic tools, however, could overwhelm the selection of appropriate optogenetic strategies. In this work, we summarize recent progress in this emerging field and highlight the application of opsin‐free optogenetics in studying embryonic development, focusing on new insights gained into optical induction of morphogenesis, cell polarity, cell fate determination, tissue differentiation, neuronal regeneration, synaptic plasticity, and removal of cells during development.
Repeated evolution of blanched coloration in a lizard across independent white‐sand habitats
Authors: Laurentino Telma G. , Dittmer Drew E. , Grundler Maggie R. , Pina‐Martins Francisco , Haddock Janey , Hibbitts Toby J. , Rosenblum Erica Bree 
Published: December 2022

AbstractThe White Sands lizards of New Mexico are a rare and classic example of convergent evolution where three species have evolved blanched coloration on the white gypsum dunes. Until now, no geological replicate of the pattern had been described. However, one of the White Sands species, the lesser earless lizard (Holbrookia maculata), has been discovered to also inhabit the Salt Basin Dunes of Texas, where it has also evolved a blanched morph. We here present a first phenotypic and genetic description of the Salt Basin Dunes population of H. maculata. Phylogenetic inference based on a housekeeping gene (ND4) and a classic candidate gene in the melanin‐synthesis pathway (Melanocortin 1 Receptor; Mc1r) shows the newly discovered population as an independent lineage, with no evidence of genetic parallelism in the coding region of Mc1r. Initial morphological data suggest that while this population displays convergent evolution in blanched coloration, there are divergent patterns in limb length and habitat use behavior between the gypsum environments. Our findings present the White Sands/Salt Basin Dunes as an exceptionally promising comparative model for studies of adaptation and convergent evolution.
“Process‐based similarity” revealed by discharge‐dependent relative submergence dynamics of thousands of large bed elements
Authors: Wiener Jason , Pasternack Gregory 
Published: December 2022

AbstractRelative submergence of macroroughness elements such as boulders and bedrock outcrops, or large bed elements (LBEs), collectively, is a primary control on hydraulics and morphodynamics in steep, coarse‐bedded rivers. However, in practice, the property is typically represented by singular, often reach‐ or cross‐section‐averaged values that mask bed‐surface heterogeneity and joint distributions of local flow depths. By coupling sub‐meter resolution two‐dimensional (2D) hydrodynamic modeling with spatially explicit mapping of LBEs from a 13.2 km segment of a boulder‐bedded mountain river, we present complete distributions of LBE relative submergences at multiple spatial scales and explore their dynamism across discharges. Through distribution fitting and statistical analysis of resultant discharge‐dependent LBE relative submergence datasets, it was confirmed that segment‐ and reach‐scale datasets exhibited similar statistical properties and were able to be drawn from the same type of distribution. Further, the rate at which statistical and parametric properties changed between discharge‐dependent datasets were statistically equivalent between spatial domains, which we term “process‐based similarity”. Commonality in distribution type and the uniform between discharge–scaling relationships suggest mutual self‐organizing processes associated with the size‐frequency distribution, spatial arrangement, and submergence of LBEs were present between most domains.
Morphological diversity of indigenous wild pomegranate (Punica granatum L. var. spinosa) accessions from northeast of Iran
Authors: Ashrafi Seyed Hasan , Bodaghi Hojatollah , Rezaei Mehdi 
Published: December 2022

AbstractWild pomegranate is a valuable edible species in the plant ecosystem of the Hyrcanian forests and the northern plains of the Caspian coast in Iran. The genetic diversity of these wild pomegranates can be effective in pomegranate breeding programs and germplasm conservation. In the present study, morphological diversity in 103 wild pomegranates (Punica granatum L. var. spinosa) in the northeastern area of Iran was studied using 46 traits related to trees, flowers, and fruits. The results showed that the fruit weight ranged from 17.93 to 99.9 g with an average of 48.92 g, the total aril weight ranged from 0.54 g to 64.78 g with an average of 24.25 g, and the weight of 100 arils was between 4.89 and 46.21 with an average of 13.79. The fruit cracking percent, crown shape, aril juiciness, calyx, and corolla colors show a high coefficient of variation (CV > 70%). Based on PCA results, fruit weight and total aril weight, peel weight, and fruit length and diameter were important on determining differences among accessions. In biplot analysis, genotype distribution was determined by two main factors. In cluster analysis, the studied accessions were divided into two different major clusters and two subclusters in each one. The results showed a high diversity of important pomological traits in wild pomegranates such as fruit weight, fruit cracking percent, crown shape, total aril weight, aril juiciness corolla, and calyx color that can be used in breeding programs to improve pomegranate juice quality and marketability.
Association between simple test assessing hand dexterity and mild cognitive impairment in independent older adults
Authors: Miyano Ichiro , Bae Seongryu , Lee Sangyoon , Shimada Hiroyuki , Kitaoka Hiroaki 
Published: December 2022

AbstractObjectivesThis study aimed to clarify the association between hand function, including grip strength and hand dexterity, assessed using snap fasteners, and mild cognitive impairment (MCI) in older adults with normal global cognitive function.MethodsA total of 228 functionally independent older adults (mean age 77.7 ± 6.1 years) participated in this study. None of the participants had a history of dementia diagnosis, and all the participants had a Mini‐Mental State Examination score of ≥24. Participants were evaluated for hand function using grip strength and snap fastener tests, and for cognitive function using the National Center for Geriatrics and Gerontology‐Functional Assessment Tool.ResultsA total of 72 participants (31.6%) were diagnosed with MCI. The slow snap fastener test group had a higher proportion of participants with MCI (p < 0.001) and impairments in memory (p = 0.010), attention (p = 0.043), executive function (p < 0.001), and processing speed (p = 0.044) compared to the fast snap fastener test group. The slow speed of fastening snap fasteners was significantly associated with MCI and impairment in memory, attention, executive function, and processing speed (MCI: adjusted odds ratio (AOR) = 3.88, 95% confidence interval (CI) = 1.64–9.19; memory: AOR = 5.73, 95% CI = 1.58–20.82; attention: AOR = 3.95, 95% CI = 1.10–14.11; executive function: AOR = 7.22, 95% CI = 1.78–29.24; processing speed: AOR = 7.52, 95% CI = 1.19–47.66) according to the multiple logistic regression analysis. Grip strength was not significantly associated with cognitive impairment.ConclusionsThus, hand dexterity assessed using the snap fastener test was associated with MCI in older adults with normal global cognitive function. Hand dexterity assessment using the snap fastener test is useful for detecting MCI in apparently healthy older adults.
Diverse functional genes harboured in extracellular vesicles from environmental and human microbiota
Authors: Zhu Li‐Ting , Huang Hai‐Ning , Avellán‐Llaguno Ricardo David , Qin Yifei , An Xin‐Li , Su Jian‐Qiang , Huang Qiansheng , Zhu Yong‐Guan 
Published: December 2022

AbstractExchange of mobile functional genes within microbiota benefits the microbial community. However, the status of the mobile gene pool in environment is still largely unclear, impeding the understanding on the process of gene transfer in natural microbial communities. The release of extracellular vesicles (EVs) by diverse organisms has been proposed to be a vital way in the complex networks of interactions between microbes and their habitats. In this study, we hypothesized that microbial EVs encapsulating functional DNA are widely distributed in the environmental matrix. The prevalence, source and DNA cargoes of EVs in three types of typical microbial habitats were studied. High abundance of EVs comparable to the bacterial concentration was found in human faeces, wastewater and soil. Metagenomic analysis showed the diverse and differential taxonomy of EVs‐associated DNA compared to source microbiome. An array of efficient EVs producing species was identified. A wide variety of mobile genes including glycoside hydrolase family 25 were enriched. Antibiotic resistance genes co‐localizing with mobile genetic elements were abundant in the EVs. This study provides novel insights into the prevalent EVs as a reservoir for the mobile functional genes in the natural environment.
Challenges in modeling microemulsion phase behavior
Authors: Batista Fernandes Bruno Ramon , Sepehrnoori Kamy , Delshad Mojdeh 
Published: December 2022

AbstractModeling the complex phase behavior of microemulsions has been the subject of research for decades for hydrocarbon oil and organic contaminant recoveries. The empirical Hand model has been the standard scheme for calculating phase behavior in reservoir simulators. On the other hand, the hydrophilic–lipophilic deviation (HLD) model in conjunction with the net curvature and average curvature models (HLD‐NAC) has provided some theoretical basis for modeling microemulsions. While the HLD‐NAC has been successful in describing salinity scans, only recently an HLD‐NAC approach was devised that could represent binodal curves with physical behavior, resulting in a succession of new microemulsion flash algorithms. While these new algorithms claimed to include the effects of cosolvent, there are only few works in the literature, which give an in‐depth description of the cosolvent modeling. Furthermore, to the best of our knowledge, no work has investigated the capability of HLD‐NAC models for predicting data for different cosolvent concentrations nor did any work present a comprehensive study of the application of HLD‐NAC against Hand model for formulations including cosolvents. This paper aims to contribute in filling such gap. We modify different versions of the new HLD‐NAC approach with physical binodal curves by providing more flexibility into controlling the binodal heights with the cosolvent concentration and investigate how well they can calibrate and predict data. Experimental data sets were considered here. The results suggest that some of the HLD‐NAC approaches produced negative solubilization ratios and the Hand model gave better predictions of the ternary diagram for extreme salinity values.
Development of two fully automated quick, easy, cheap, effective, rugged, and safe pretreatment methods for the extraction of psychotropic drugs from whole blood samples
Authors: Murakami Takaya , Ishimaru Reiko , Minami Eriko , Iwamuro Yoshiaki , Takamura Naoki , Torai Aya , Watanabe Tsutomu , Miki Akihiro , Katagi Munehiro , Kusano Maiko , Tsuchihashi Hitoshi , Zaitsu Kei , Chinaka Satoshi 
Published: December 2022

Quick, easy, cheap, effective, rugged, and safe extraction strategies are becoming increasingly adopted in various analytical fields to determine drugs in biological specimens. In the present study, we developed two fully automated quick, easy, cheap, effective, rugged, and safe extraction methods based on acetonitrile salting‐out assisted liquid‐liquid extraction (method 1) and acetonitrile salting‐out assisted liquid‐liquid extraction followed by dispersive solid‐phase extraction (method 2) using a commercially available automated liquid‐liquid extraction system. We applied these methods to the extraction of 14 psychotropic drugs (11 benzodiazepines and carbamazepine, quetiapine, and zolpidem) from whole blood samples. Both methods prior to liquid chromatography–tandem mass spectrometry analysis exhibited high linearity of calibration curves (correlation coefficients, > 0.9997), ppt level detection sensitivities, and satisfactory precisions (< 8.6% relative standard deviation), accuracies (within ± 16% relative error), and matrix effects (81–111%). Method 1 provided higher recovery rates (80–91%) than method 2 (72–86%), whereas method 2 provided higher detection sensitivities (limits of detection, 0.003–0.094 ng/mL) than method 1 (0.025–0.47 ng/mL) owing to the effectiveness of its dispersive solid‐phase extraction cleanup step. These fully automated extraction methods realize reliable, labor‐saving, user‐friendly, and hygienic extraction of target analytes from whole blood samples.
Role of Transabdominal Ultrasonography in the Evaluation of Pediatric Patients With Daytime Wetting
Authors: Oktay Cemil , Işık Güneş 
Published: December 2022

ObjectivesUrinary incontinence (UI) is a frequent cause of admission to pediatric nephrology outpatient clinics. The aim of this study was to determine whether anatomical changes in lower urinary tract structures (retrovesical angulation [RVA] and bladder neck position [BNP]) are associated with UI in pediatric patients with daytime‐wetting in comparison to healthy children.MethodsIn this prospective study, patients with daytime UI diagnosed using the Dysfunctional Voiding Symptom Score of the International Children's Continence Society and 3‐day‐voiding/bowel diary were compared with an age‐ and sex‐matched control group without incontinence. In addition to routine clinical evaluation, RVA and BNP were measured at rest using transabdominal ultrasound (TA‐US). Intra‐rater agreement was estimated.ResultsA total of 88 children were included in the study, with 44 children (22 boys, 22 girls) each in patient and control groups. RVA was significantly greater and BNP was significantly lower in the patient group versus control group (RVA: 134.30 ± 10.05 vs 127.94 ± 13.15, P = .013; BNP: 11.88 ± 4.53 vs 17.20 ± 5.55, P < .001, respectively). Irrespective of the presence of incontinence, girls had a significantly greater RVA than boys (P < .001). However, there was no difference between sexes in BNP values (P = .630). Intra‐rater agreement was very strong for RVA (P < .001, r = .897), and strong for BNP (P < .001, r = .774).ConclusionsTA‐US imaging is a non‐invasive and practical procedure routinely performed in pediatric patients presenting with UI complaints. Our study demonstrated anatomical changes in lower urinary tract structures in pediatric patients with UI. These changes should be considered in the diagnosis, follow‐up, and treatment of patients with UI.
Quantifying Neck Fibrosis: Establishing the Domain Structure of the Neck Fibrosis Scale
Authors: Saleem Ahmed , Noel Christopher W , Hueniken Katrina , Grewal Rajan , Kwinter Adam , Peralta Giselle , de Almeida John R , Goldstein David P 
Published: December 2022

ObjectiveWe recently described the development of the Neck Fibrosis Scale (NFS). In this submission, we confirm domain structure and validate a scoring system for the NFS.Study DesignProspective cross‐sectional study.MethodsBetween January 2020 and December 2021, 127 head and neck cancer patients with varying degrees of cutaneous neck fibrosis completed the original 15 item NFS. Exploratory factor analysis was used to identify optimal groupings with similar underlying factors. The association between the domains of the NFS and various measures of neck morbidity (i.e., construct validity) were assessed using gamma regression.ResultsExploratory factor analysis confirmed 13 of the 15 items from the NFS mapped onto two factors, which were labelled ‘physical’ and ‘emotional’ domains. Of the remaining two items, ‘energy’ did not load uniquely onto one factor and was removed. ‘Neck‐swelling’ did not load on either factor (loadings <0.3) but was retained within the physical domain based on clinical importance. This resulted in a revised 14‐item questionnaire. Internal consistency for these two domains was high (>0.8,p < 0.01). Both the physical and emotional domains of the revised NFS show strong correlation with the neck dissection impairment index and neck range of motion. The physical domain strongly correlated with neck elasticity (0.902 [95%CI 0.839–0.972],p < 0.01). Patients receiving multimodal therapy had physical domain scores that were 31.6% [95% 13.9–51.8] higher (worse) than unimodal therapy patients.ConclusionsA domain structure and scoring strategy have been developed for the NFS. Future efforts should be directed toward an evaluation of responsiveness.Level of EvidenceNALaryngoscope, 133:2198–2202, 2023