bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifocal Organoid Capturing of Colon Cancer Reveals Pervasive Intratumoral Heterogenous Drug Responses
Authors: Kim Soon‐Chan , Park Ji Won , Seo Ha‐Young , Kim Minjung , Park Jae‐Hyeon , Kim Ga‐Hye , Lee Ja Oh , Shin Young‐Kyoung , Bae Jeong Mo , Koo Bon‐Kyoung , Jeong Seung‐Yong , Ku Ja‐Lok 
Published: December 2021

AbstractIntratumor heterogeneity (ITH) stands as one of the main difficulties in the treatment of colorectal cancer (CRC) as it causes the development of resistant clones and leads to heterogeneous drug responses. Here, 12 sets of patient‐derived organoids (PDOs) and cell lines (PDCs) isolated from multiple regions of single tumors from 12 patients, capturing ITH by multiregion sampling of individual tumors, are presented. Whole‐exome sequencing and RNA sequencing of the 12 sets are performed. The PDOs and PDCs of the 12 sets are also analyzed with a clinically relevant 24‐compound library to assess their drug responses. The results reveal unexpectedly widespread subregional heterogeneity among PDOs and PDCs isolated from a single tumor, which is manifested by genetic and transcriptional heterogeneity and strong variance in drug responses, while each PDO still recapitulates the major histologic, genomic, and transcriptomic characteristics of the primary tumor. The data suggest an imminent drawback of single biopsy‐originated PDO‐based clinical diagnosis in evaluating CRC patient responses. Instead, the results indicate the importance of targeting common somatic driver mutations positioned in the trunk of all tumor subregional clones in parallel with a comprehensive understanding of the molecular ITH of each tumor.
Validity evidence for an instrument for cognitive load for virtual didactic sessions
Authors: Hickam Grace , Jordan Jaime , Haas Mary R C , Wagner Jason , Manthey David , John Cico Stephen , Wolff Margaret , Santen Sally A 
Published: December 2021

AbstractBackgroundCOVID necessitated the shift to virtual resident instruction. The challenge of learning via virtual modalities has the potential to increase cognitive load. It is important for educators to reduce cognitive load to optimize learning, yet there are few available tools to measure cognitive load. The objective of this study is to identify and provide validity evidence following Messicks’ framework for an instrument to evaluate cognitive load in virtual emergency medicine didactic sessions.MethodsThis study followed Messicks’ framework for validity including content, response process, internal structure, and relationship to other variables. Content validity evidence included: (1) engagement of reference librarian and literature review of existing instruments; (2) engagement of experts in cognitive load, and relevant stakeholders to review the literature and choose an instrument appropriate to measure cognitive load in EM didactic presentations. Response process validity was gathered using the format and anchors of instruments with previous validity evidence and piloting amongst the author group. A lecture was provided by one faculty to four residency programs via ZoomTM. Afterwards, residents completed the cognitive load instrument. Descriptive statistics were collected; Cronbach's alpha assessed internal consistency of the instrument; and correlation for relationship to other variables (quality of lecture).ResultsThe 10‐item Leppink Cognitive Load instrument was selected with attention to content and response process validity evidence. Internal structure of the instrument was good (Cronbach's alpha = 0.80). Subscales performed well‐intrinsic load (α = 0.96, excellent), extrinsic load (α = 0.89, good), and germane load (α = 0.97, excellent). Five of the items were correlated with overall quality of lecture (p < 0.05).ConclusionsThe 10‐item Cognitive Load instrument demonstrated good validity evidence to measure cognitive load and the subdomains of intrinsic, extraneous, and germane load. This instrument can be used to provide feedback to presenters to improve the cognitive load of their presentations.
Prevalence and factors contributing to primary sarcopenia in relatively healthy older Indians attending the outpatient department in a tertiary care hospital: A cross‐sectional study
Authors: Rahman Rishal , Wilson Benny Paul , Paul Thomas Vizhalil , Yadav Bijesh , Kango Gopal Gopinath , Viggeswarpu Surekha 
Published: December 2021

AbstractBackgroundLiterature is scarce on primary sarcopenia among Indian older adults. This study was aimed to estimate the prevalence of primary sarcopenia among older persons in India using the European Working Group on Sarcopenia in the Older People 2010 (EWGSOP) diagnostic criteria and to elucidate the factors leading to its development.MethodologyTwo hundred twenty‐seven subjects over 60 years of age attending the geriatric outpatient clinic were recruited for the study. Sarcopenia was diagnosed based on set criteria for gait speed, handgrip, and skeletal muscle mass assessment by dual‐energy x‐ray absorptiometry.ResultThe prevalence of primary sarcopenia in the study population was 39.2% (n = 89). Male patients were more sarcopenic than women, 47% (n = 72) vs 23% (n = 17). Obese subjects (body mass index > 25 kg/m2) had a lower prevalence of sarcopenia (odds ratio = 0.10; 95% confidence interval = 0.05–0.19). There was no association between sarcopenia and other postulated risk factors like low vitamin D levels, dietary protein or carbohydrate intake, or sedentary lifestyle.ConclusionContrary to published data, primary sarcopenia appears to be higher among older Indians using presently available guidelines. Community studies with validated cutoffs suited for the Indian subcontinent may yield a lower prevalence of primary sarcopenia.
A homozygous missense variant in the MLC1 gene underlies megalencephalic leukoencephalopathy with subcortical cysts in large kindred: Heterozygous carriers show seizure and mild motor function deterioration
Authors: Ain ul Batool Syeda , Almatrafi Ahmad , Fadhli Fatima , Alluqmani Majed , Sadia  , Ali Ghazanfar , Basit Sulman 
Published: December 2021

AbstractMegalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy characterized by epileptic seizures, macrocephaly, and vacuolization of myelin and astrocyte. The magnetic resonance imaging of the brain of MLC patients shows diffuse white‐matter anomalies and the occurrence of subcortical cysts. MLC features have been observed in individuals having mutations in the MLC1 or HEPACAM genes. In this study, we recruited a six generation large kindred with five affected individuals manifesting clinical features of epileptic seizures, macrocephaly, ataxia, and spasticity. In order to identify the underlying genetic cause of the clinical features, we performed whole‐genome genotyping using Illumina microarray followed by detection of loss of heterozygosity (LOHs) regions. One affected individual was exome sequenced as well. Homozygosity mapping detected several LOH regions due to extensive consanguinity. An unbiased and hypothesis‐free exome data analysis identified a homozygous missense variant (NM_015166.3:c.278C>T) in the exon 4 of the MLC1 gene. The variant is present in the LOH region on chromosome 22q (50 Mb) and segregates perfectly with the disorder within the family in an autosomal recessive manner. The variant is present in a highly conserved first cytoplasmic domain of the MLC1 protein (NM_015166.3:p.(Ser93Leu)). Interestingly, heterozygous individuals show seizure and mild motor function deterioration. We propose that the heterozygous variant in MLC1 might disrupt the functional interaction of MLC1 with GlialCAM resulting in mild clinical features in carriers of the variant.
Paleodemography: From archaeology and skeletal age estimation to life in the past
Authors: Boldsen Jesper L. , Milner George R. , Ousley Stephen D. 
Published: December 2021

AbstractMuch of paleodemography, an interdisciplinary field with strong ties to archaeology, among other disciplines, is oriented toward clarifying the life experiences of past people and why they changed over time. We focus on how human skeletons contribute to our understanding of preindustrial demographic regimes, including when changes took place that led to the world as we know it today. Problems with existing paleodemographic practices are highlighted, as are promising directions for future work. The latter requires both better age estimates and innovative methods to handle data appropriately. Age‐at‐death estimates for adult skeletons are a particular problem, especially for adults over 50 years that undoubtedly are mistakenly underrepresented in published studies of archaeological skeletons. Better age estimates for the entirety of the lifespan are essential to generate realistic distributions of age at death. There are currently encouraging signs that after about a half‐century of intensive, and sometimes contentious, research, paleodemography is poised to contribute much to understandings of evolutionary processes, the structure of past populations, and human‐disease interaction, among other topics.
Oral corticosteroid use and the risk of developing avascular necrosis: A large retrospective review
Authors: Grond Sarah E , Little Ryan E , Campbell David A , Loehrl Todd A , Poetker David M 
Published: December 2021

AbstractIntroductionThe risk of adverse events, specifically avascular necrosis (AVN), associated with corticosteroid use is not well reported. The aim of this study was to evaluate the prevalence of AVN among patients with prior oral corticosteroid administration.MethodsAn institutional database query recognized 113,734 adult patients with oral corticosteroid administration between January 2006 and May 2017. A temporal query performed on this cohort determined that 789 had a diagnosis of AVN following oral corticosteroids. A retrospective review was performed on this cohort. Data collected included demographics, comorbidities, date of initial oral corticosteroid exposure, and time to diagnosis of AVN. Records without radiographic confirmation of AVN were excluded from analysis. Patients with cumulative lifetime dosages greater than 10,000 mg prednisone were excluded from analysis.ResultsA total of 789 patients with oral corticosteroid use prior to diagnosis of AVN were identified. Five hundred and seventy‐two patients were excluded due to insufficient documentation of oral corticosteroid dosage, no radiographic evidence supporting the diagnosis of AVN, insufficient data confirming the temporal relationship between oral corticosteroids and AVN, and/or a cumulative dosing of >10,000 mg prednisone. This left 217 patients included in the analysis. The mean duration of use prior to diagnosis of AVN was 219 (± 374) days, and mean cumulative dose was 3314 (± 2908) mg prednisone equivalents. Mean time between diagnosis of AVN and onset of pathologic fracture was 379 (± 1046) days.ConclusionFor patients receiving low cumulative doses of oral corticosteroids, corticosteroids pose a small risk of development of AVN. More studies are required to better characterize risk.
A Symmetric All‐Organic Proton Battery in Mild Electrolyte
Authors: Tie Zhiwei , Deng Shenzhen , Cao Hongmei , Yao Minjie , Niu Zhiqiang , Chen Jun 
Published: December 2021

AbstractAll‐organic proton batteries are attracting extensive attention due to their sustainability merits and excellent rate capability. Generally, strong acids (e.g. H2SO4) have to be employed as the electrolytes to provide H+ for all‐organic proton batteries due to the high H+ intercalation energy barrier. Until now, the design of all‐organic proton batteries in mild electrolytes is still a challenge. Herein, a poly(2,9‐dihydroquinoxalino[2,3‐b]phenazine) (PO) molecule was designed and synthesized, where the adjacent C=N groups show two different chemical environments, resulting in two‐step redox reactions. Moreover, the two reactions possess considerable voltage difference because of the large LUMO energy gap between PO and its reduction product. More impressively, the C=N groups endow the π‐conjugated PO molecule with H+ uptake/removal in the ZnSO4 electrolyte. As a result, a symmetric all‐organic proton battery is achieved in a mild electrolyte for the first time, which exhibits enhanced electrochemical performance and also broadens the chemistry of proton‐based batteries.
Bulky Selenium Ligand Stabilized Trans‐Palladium Dichloride Complexes as Catalyst for Silver‐Free Decarboxylative Coupling of Coumarin‐3‐Carboxylic Acids
Authors: Meena Neha , Kumar Sunil , Shinde Vikki N. , Reddy S. Rajagopala , Himanshi  , Bhuvanesh Nattamai , Kumar Anil , Joshi Hemant 
Published: December 2021

AbstractThis report describes the syntheses of three new trans‐palladium dichloride complexes of bulky selenium ligands. These complexes possess a Cl−Pd−Cl rotor spoke attached to a Se−Pd−Se axle. The new ligands and palladium complexes (C1−C3) were characterized with the help of NMR, HRMS, UV‐Vis., IR, and elemental analysis. The single‐crystal structure of metal complex C2 confirmed a square planar geometry of complex with trans‐orientation. The X‐ray structure revealed intramolecular secondary interactions (SeCH—Cl) between chlorine of PdCl2 and CH2 proton of selenium ligand. Variable‐temperature NMR data shows coalescence of diastereotopic protons, which indicates pyramidal inversion of selenium atom at elevated temperature. The relaxed potential energy scan of C2 suggests a rotational barrier of ∼12.5 kcal/mol for rotation of chlorine atom through Cl−Pd−Cl rotor. The complex C3 possesses dual intramolecular secondary interactions (OCH2—Cl and SeCH2—Cl) with stator ligand. Molecular rotor C2 was found to be a most efficient catalyst for the decarboxylative Heck‐coupling under mild reaction conditions. The protocol is applicable to a broad range of substrates with large functional group tolerance and low catalyst loading (2.5 mol %). The mechanism of decarboxylative Heck‐coupling reaction was investigated through experimental and computational studies. Importantly the reaction works under silver‐free conditions which reduces the cost of overall protocol. Further, the catalyst also worked for decarboxylative arylation and decarboxylative Suzuki‐Miyaura coupling reactions with good yields of the coupled products.
An Artificial SEI Layer Based on an Inorganic Coordination Polymer with Self‐Healing Ability for Long‐Lived Rechargeable Lithium‐Metal Batteries
Authors: Beichel Witali , Skrotzki Julian , Klose Petra , Njel Christian , Butschke Burkhard , Burger Stephan , Liu Lili , Thomann Ralf , Thomann Yi , Biro Daniel , Thiele Simon , Krossing Ingo 
Published: December 2021

AbstractUpon immersion of a lithium (Li) anode into a diluted 0.05 to 0.20 M dimethoxyethane‐solution of the phosphoric acid derivative (CF3CH2O)2P(O)OH (HBFEP), an artificial solid electrolyte interphase (SEI) is generated on the Li‐metal surface. Hence, HBFEP reacts on the surface to the corresponding Li salt (LiBFEP), which is a Li‐ion conducting inorganic coordination polymer. This film exhibits – due to the reversibly breaking ionic bonds – self‐healing ability upon cycling‐induced volume expansion of Li. The presence of LiBFEP as the major component in the artificial SEI is proven by ATR‐IR and XPS measurements. SEM characterization of HBFEP‐treated Li samples reveals porous layers on top of the Li surface with at least 3 μm thickness. Li−Li symmetrical cells with HBFEP‐modified Li electrodes show a three‐ to almost fourfold cycle‐lifetime increase at 0.1 mA cm−2 in a demanding model electrolyte that facilitates fast battery failure (1 M LiOTf in TEGDME). Hence, the LiBFEP‐enriched layer apparently acts as a Li‐ion conducting protection barrier between Li and the electrolyte, enhancing the rechargeability of Li electrodes.
Molecular Design Strategy for Orange Red Thermally Activated Delayed Fluorescence Emitters in Organic Light‐Emitting Diodes (OLEDs)
Authors: Rayappa Naveen Kenkera , Prabhu CP Keshavananda , Braveenth Ramanaskanda , Hyuk Kwon Jang 
Published: December 2021

AbstractPure organic molecules based thermally activated delayed fluorescence (TADF) emitters have been successfully developed in recent years for their propitious application in highly efficient organic light emitting diodes (OLEDs). In the case of orange red emitters, the non‐radiative process is known to be a serious issue due to its lower lying singlet energy level. However, recent studies indicate that there are tremendous efforts put to develop efficient orange red TADF emitters. In addition, the external quantum efficiency (EQE) of heteroaromatic based orange red TADF OLEDs surpassed 30 %. Such heteroaromatic type emitters showed wide emission spectra; therefore, more attention is being paid to develop highly efficient orange red TADF emitters along with good color purity. Herein, the recent progress of orange red TADF emitters based on molecular structures, such as cyanobenzene, heteroaromatic, naphthalimide, and boron‐based acceptors, are reviewed. Further, our insight on these acceptors has been provided by their photophysical studies and device performances. Future perspectives of orange red TADF emitters for real practical applications are discussed.
Bright Luminescence by Combining Chiral [2.2]Paracyclophane with a Boron–Nitrogen‐Doped Polyaromatic Hydrocarbon Building Block
Authors: Rapp Mario R. , Leis Wolfgang , Zinna Francesco , Di Bari Lorenzo , Arnold Tamara , Speiser Bernd , Seitz Michael , Bettinger Holger F. 
Published: December 2021

AbstractNovel BN‐doped compounds based on chiral, tetrasubstituted [2.2]paracyclophane and NBN‐benzo[f,g]tetracene were synthesized by Sonogashira–Hagihara coupling. Conjugated ethynyl linkers allow electronic communication between the π‐electron systems through‐bond, whereas through‐space interactions are provided by strong π–π overlap between the pairs of NBN‐building blocks. Excellent optical and chiroptical properties in racemic and enantiopure conditions were measured, with molar absorption coefficients up to ϵ=2.04×105 M−1 cm−1, fluorescence quantum yields up to ΦPL=0.70, and intense, mirror‐image electronic circular dichroism and circularly polarized luminescence signals of the magnitude of 10−3 for the absorption and luminescence dissymmetry factors. Computed glum,calcd. values match the experimental ones. Electroanalytical data show both oxidation and reduction of the ethynyl‐linked tetra‐NBN‐substituted paracyclophane, with an overlap of two redox processes for oxidation leading to a diradical dication.
The risk of rupture and abdominal aortic aneurysm morphology: A computational study
Authors: Živić Josip , Virag Lana , Horvat Nino , Smoljkić Marija , Karšaj Igor 
Published: December 2021

AbstractPrediction of rupture and optimal timing for abdominal aortic aneurysm (AAA) surgical intervention remain wanting even after decades of clinical, histological, and numerical research. Although studies estimating rupture from AAA geometrical features from CT imaging showed some promising results, they are still not being used in practice. Patient‐specific numerical stress analysis introduced too many assumptions about wall structure for the related rupture potential index (RPI) to be considered reliable. Growth and remodeling (G&R) numerical models eliminate some of these assumptions and thus might have the most potential to calculate mural stresses and RPI and increase our understanding of rupture. To recognize numerical models as trustworthy, it is necessary to validate the computed results with results derived from imaging. Elastin degradation function is one of the main factors that determine idealized aneurysm sac shape. Using a hundred different combinations of variables defining AAA geometry or influences AAA stability (elastin degradation function parameters, collagen mechanics, and initial healthy aortic diameters), we investigated the relationship between AAA morphology and RPI and compared numerical results with clinical findings. Good agreement of numerical results with clinical expectations from the literature gives us confidence in the validity of the numerical model. We show that aneurysm morphology significantly influences the stability of aneurysms. Additionally, we propose new parameters, geometrical rupture potential index (GRPI) and normalized aneurysm length (NAL), that might predict rupture of aneurysms without thrombus better than currently used criteria (i.e., maximum diameter and growth rate). These parameters can be computed quickly, without the tedious processing of CT images.
Translation system from Tunisian Dialect to Modern Standard Arabic
Authors: Torjmen Roua , Haddar Kais 
Published: December 2021

SummaryNowadays, Tunisian Dialect (TD) is widely used in social media such as Facebook and Twitter to communicate and express opinions. However, the absence of a TD translator prevents comprehension and communication for non‐Tunisian users. Thus, Tunisian translator becomes an important task to overcome these problems. In this article, our main objective is to create a translator from TD to Modern Standard Arabic (MSA). In this context, we are carrying out an in‐depth linguistic study in order to better choose the translation rules which are applicable on the TD sentences. This study guarantees the best quality to obtain MSA sentences. Indeed, our proposed method is based on a linguistic approach. In addition, the method consists of the elaboration of a set of dictionaries and the construction of inflectional, morphological, and syntactic grammars using finite‐state transducers. Then, our method is implemented and tested with new technologies provided by the NooJ linguistic platform. To evaluate our constructed tool, we apply it to two different test corpora containing more than 15,000 words. The obtained results are promising and do highlight our proposed method.
Homo‐ and Heterovalent Neoglycoproteins as Ligands for Bacterial Lectins
Authors: Goyard David , Roubinet Benoît , Vena Federica , Landemarre Ludovic , Renaudet Olivier 
Published: December 2021

AbstractClick chemistry gives access to unlimited set of multivalent glycoconjugates to explore carbohydrate‐protein interactions and discover high affinity ligands. In this study, we have created supramolecular systems based on a carrier protein that was grafted by Cu(I)‐catalyzed azide‐alkyne cycloaddition with tetravalent glycodendrons presenting αGal, βGal and/or αFuc. Binding studies of the homo‐ (4 a–c) and heterovalent (5) neoglycoproteins (neoGPs) with the LecA and LecB lectins from P. aeruginosa has first confirmed the interest of the multivalent presentation of glycodendrons by the carrier protein (IC50 up to 2.8 nM). Moreover, these studies have shown that the heterovalent display of glycans (5) allows the interaction with both lectins (IC50 of 10 nM) despite the presence of unspecific moieties, and even with similar efficiency for LecB. These results demonstrate the potential of multivalent and multispecific neoGPs as a promising strategy to fight against resistant pathogens.