bluuebunny/crossref_metadata_2025_split huggingface dataset:
LEA motifs promote desiccation tolerancein vivo
Authors: Hibshman Jonathan D. , Goldstein Bob 
Published: February 2021

AbstractBackgroundCells and organisms typically cannot survive in the absence of water. However, there are some notable exceptions, including animals such as nematodes, tardigrades, rotifers, and some arthropods. One class of proteins known to play a role in desiccation resistance is the late embryogenesis abundant (LEA) proteins. These largely disordered proteins protect plants and animals from desiccation. A multitude of studies have characterized stress-protective capabilities of LEA proteinsin vitroand in heterologous systems. However, the extent to which LEA proteins exhibit such functionsin vivo, in their native contexts in animals, is unclear.Furthermore, little is known about the distribution of LEA proteins in multicellular organisms or tissue-specific requirements in conferring stress protection.ResultsTo study the endogenous function of an LEA protein in an animal, we created a true null mutant ofC. elegansLEA-1, as well as endogenous fluorescent reporters of the protein. We confirmed thatC. eleganslacking LEA-1 are sensitive to desiccation. LEA-1 mutant animals were also sensitive to heat and osmotic stress and were prone to protein aggregation. During desiccation, LEA-1 expression increased and became more widespread throughout the body. LEA-1 was required at high levels in body wall muscle for animals to survive desiccation and osmotic stress. We identified minimal motifs withinC. elegansLEA-1 that are sufficient to increase desiccation survival ofE. coli. To test whether such motifs are central to LEA-1’sin vivofunctions, we then replaced the sequence oflea-1with these minimal motifs and found thatC. eleganssurvived mild desiccation and osmotic stress at the same levels as worms with the full-length protein.ConclusionsOur results provide insights into the endogenous functions and expression dynamics of an LEA protein in a multicellular animal. The results show that LEA-1 buffers animals from a broad range of stresses. Our identification of LEA motifs that can function in both bacteria and in a multicellular organism suggests the possibility of engineering LEA-1-derived peptides for optimized desiccation protection.
Codon arrangement modulates MHC-I peptides presentation: implications for a SARS-CoV-2 peptide-based vaccine
Authors: Daouda Tariq , Dumont-Lagacé Maude , Feghaly Albert , Villani Alexandra-Chloé 
Published: February 2021

SummaryAmong various vaccination strategies, peptide-based vaccines appear as excellent candidates because they are cheap to produce, are highly stable and harbor low toxicity. However, predicting which MHC-I Associated Peptide (MAP) will ultimately reach cell surface remains challenging, due to high false discovery rates. Previously, we demonstrated that synonymous codon arrangement (usage and placement) is predictive of, and modulates MAP presentation. Here, we apply CAMAP (Codon Arrangement MAP Predictor), the artificial neural network we used to unveil the role of codon arrangement in MAP presentation, to predict SARS-CoV MAPs. We report that experimentally identified SARS-CoV-1 and SARS-CoV-2 MAPs are associated with significantly higher CAMAP scores. Based on CAMAP scores and binding affinity, we identified 48 non-overlapping MAP candidates for a peptide-based vaccine, ensuring coverage for a high proportion of HLA haplotypes in the US population (>78%) and SARS-CoV-2 strains (detected in >98% of SARS-CoV-2 strains present in the GISAID database). Finally, we built an interactive web portal (https://www.epitopes.world) where researchers can freely explore CAMAP predictions for SARS-CoV-1/2 viruses. Collectively, we present an analysis framework that can be generalizable to empower the rapid identification of virus-specific MAPs, including in the context of an emergent virus, to help accelerate target identification for peptide-based vaccine designs that could be critical in safely attaining group immunity in the context of a global pandemic.
A different outlook on othering
Authors: Marques Joan F. 
Published: February 2021

Purpose
To encourage those who feel victimized by the tendency of “othering” or being part of an “outgroup” in any organization, in perceiving this reality from a more constructive angle.

Design/methodology/approach
A reflective viewpoint, supported by observations, conversations, and readings.

Findings
Othering exists, but it is a perspective that we can choose as a source of oppression or growth.

Practical implications
Considering the five ideas in this article can assist readers in becoming more resilient and positive members of their work- and other environments.

Social implications
As more people decide to rethink othering, the ridiculousness of the entire tendency may get deposed, and othering may become an obsolete behavioral pattern.

Originality/value
Presenting five ideas pertaining to performance excellence, making a constructive difference, keeping a mindset of elevating rather than defeating perspectives, maintaining dignity, and moving to new horizons. Through these five ideas, the author proposes a constructive perspective to a trend that is usually considered discriminatory and subjugating.
Analysing the AAOIFI Sharīʿah standard on zakat
Authors: Raja Khurram Parvez 
Published: February 2021

Purpose
The Sharīʿah Standard No. (35) issued by the Accounting and Auditing Organization for Islamic Financial Institutions (AAOIFI) aims to identify the zakāt base for institutions (including Islamic insurance companies) as well as the subsidiary and the mother company of the institution (the company). By zakāt base, the standard means the items of financial statements that should or should not be included in the calculation of the zakāt base, and the liabilities or allocations that should or should not be deducted from zakatable assets. The standard also covers payable zakāt rates, disbursement of zakāt funds on the eight categories of zakāt recipients and the rulings pertaining to disbursement. The focus then is on companies or corporations. There is no indication in the aims as to who owns the wealth of the corporation, that is, whether it is the company itself or it is the shareholders and whether it is treated as a joint wealth of the shareholders or of a single individual in the form of the company. The author will rely on this issue as one factor on the basis of which the standard is to be judged.

Design/methodology/approach
Quran and hadith. Works of earlier jurists.

Findings
In this study, the author has summarized the provisions of zakāt according to the traditional law, but only those that are relevant for the financial institutions and the standard issued by the AAOIFI. After that, the author mentioned the major points that have been addressed by the standard. In the last section, the author has shown that the rulings of the Islamic Fiqh Academy and the AAOIFI on zakāt are totally confusing and merely a reproduction of the rulings of traditional law. The main reason for this confusion is that the nature and entity of a corporation have not been addressed and have been treated like a partnership, thus, jumbling up the entire issue of zakāt through banks.

Originality/value
The main purpose in undertaking this original work is to examine the AAOIFI Sharīʿah Standards from the perspective of traditional Islamic law, that is, the law of the senior schools as laid down in their authentic manuals. If there is an extensive deviation from this law, then this must be pointed out in the hope that it will be corrected by the concerned institution and the banks that adopt these standards. Neglecting such a corrective action for long will result in damage not only to these institutions in the long run but also to the law of Islam that has been so carefully crafted over centuries. The purpose is to show how far this standard deviates from traditional Islamic law and claims to be called the authentic view on a particular subject. Nevertheless, it is not the purpose of this work to explain and elaborate on the meaning and utility of these standards.
Knowledge Production and Britain's Expansion in China: Constructing the Narrative of the Cruelty of Chinese Punishment in the Nineteenth Century
Authors: YU QIONG 
Published: February 2021

AbstractThis article looks into Britain's knowledge production about China and the Chinese in the nineteenth century, through a case study of how a narrative of the cruelty of Chinese punishment was constructed by publications and activities of two closely connected institutions, the Royal Asiatic Society and the British Consular Service. Concentrating on the period between the end of the First Opium War and the end of the Second Opium War, and looking into the post‐factum criticism, eye‐witness accounts and personal experience of the two institutions, it examines how ideas around the cruelty of Chinese punishment was constructed in relation to Britain's expansion in China, the change of sentiment towards judicial torture in Europe, and the social disorder in South China. Approaching Sino‐British encounters in the nineteenth century from a cultural perspective, this article provides a more comprehensive understanding of British knowledge production of China and the Chinese, and reveals a more complicated picture of Britain's expansion in China, shedding some light on Sino‐British encounters at that time.
Stillbirth: are we making more progress than we think? A retrospective cohort study
Authors: Selvaratnam RJ , Rolnik DL , Davey M‐A , Wallace EM 
Published: February 2021

ObjectiveTo quantify how the changing stillbirth risk profile of women is affecting the interpretation of the stillbirth rate.DesignA retrospective, population‐based cohort study from 1983 to 2018.SettingVictoria, Australia.PopulationA total of 2 419 923 births at ≥28 weeks of gestation.MethodsChanges in maternal characteristics over time were assessed. A multivariable logistic regression model was developed for stillbirth, based on maternal characteristics in 1983–1987, and used to calculate individual predictive probabilities of stillbirth from the regression equation. The number of expected stillbirths per year as a result of the change in maternal demographics was then calculated, assuming no changes in care and in the associations between maternal characteristics and stillbirth over time.Main outcome measureStillbirth.ResultsCompared with 1983–1987, there were more women in older age groups giving birth, more nulliparous women, more indigenous women and women born in Oceania, Asia and Africa, more multiple pregnancies and more women with pre‐existing diabetes in 2014–2018. Despite this, the rate of stillbirth fell from 5.42 per 1000 births in 1983 to 1.72 per 1000 births in 2018 (P < 0.001). Applying the multivariable logistic regression equation, derived from the 1983–87 data, to each year, had there been no changes in care or in the associations between maternal characteristics and stillbirth, the rate of stillbirth would have increased by 12%, from 4.94 per 1000 in 1983 to 5.54 per 1000 in 2018, as a result of the change in maternal characteristics.ConclusionsPopulation rates of stillbirth are falling faster than is generally appreciated.Tweetable abstractPopulation reductions in stillbirth have been underestimated as a result of changing maternal characteristics.
Distribution of semen examination results 2020 – A follow up of data collated for the WHO semen analysis manual 2010
Authors: Campbell Martin J. , Lotti Francesco , Baldi Elisabetta , Schlatt Stefan , Festin Mario P. R. , Björndahl Lars , Toskin Igor , Barratt Christopher L. R. 
Published: February 2021

AbstractBackgroundIt is now 11 years since publication of the WHO 2010 guidelines for semen assessment values, and it is critical to determine whether they are still valid and/or whether they should be modified.ObjectivesTo utilise data published since 2010 and combine these with data used in the 2010 assessment to provide an updated and more comprehensive representation of the fertile man. This may be utilised to present an updated distribution of values for use by WHO in 2021.Materials and MethodsTwo specific analyses were performed namely, (1) Analysis 1: Examination of published data following publication of WHO 2010 [termed 2010–2020 data]. (2) Analysis 2: Examination of the data used to help formulate the 2010 distribution of values combined with the data from Analysis (1) [termed WHO 2020].ResultsIn total, data from more than 3500 subjects, from twelve countries and five continents were analysed. The 5th centile values for concentration, motility and morphology are: 16 × 106/ml, 30% progressive motility [42% total motility] and 4% normal forms.DiscussionThis study presents substantial additional information to establish more comprehensive and globally applicable lower reference values for semen parameters for fertile men although they do not represent distinct limits between fertile and subfertile men. There are still data missing from many countries and, some geographical regions are not represented. Moreover, the number of subjects although significant is still relatively low (<4000).ConclusionThese distributions of values now include semen analysis providing a more global representation of the fertile man. Increasing the number of subjects provides robust information that is also more geographically representative.
Developing a physiologically based pharmacokinetic model of apixaban to predict scenarios of drug–drug interactions, renal impairment and paediatric populations
Authors: Xu Ruijuan , Tang Hong , Chen Lin , Ge Weihong , Yang Jin 
Published: February 2021

AimsTo develop a physiologically based pharmacokinetic (PBPK) model for apixaban, an oral anticoagulant with a narrow therapeutic index, and to predict PK profiles and potential drug–drug interactions (DDIs) in patients with renal impairment and paediatrics.MethodsA whole‐body apixaban PBPK model was developed and validated in SimCYP for healthy adults with or without interacting drugs. The model was extended to renal impairment and paediatrics. Observed PK data in adults were compared with predicted data. The effect of renal function, age and DDIs on apixaban PK was investigated.ResultsThe PBPK model successfully predicted the PK of apixaban alone and under the influence of interacting drugs. For patients with renal impairment, the PBPK model successfully predicted the fold change in each impairment group; inhibitory DDI and renal impairment had a synergistic effect on the increase of apixaban exposure (e.g., almost 3‐fold increase of AUC in ketoconazole + severe renal impairment group). For infants younger than 1 year, the exposure of apixaban decreased with increased weight‐normalized clearance. For newborn infants, AUC of apixaban was >2‐fold higher than that in children older than 1 year. Meanwhile, the effect of DDI seems to be weakened while the effect of renal impairment might be enhanced in infants younger than 1 year.ConclusionOur study provides a reasonable approach to estimate the dose adjustment for the first use of apixaban in special populations with complex situations, which has the opportunity to make the clinical practice much safer.
Synthesizing external aggregated information in the presence of population heterogeneity: A penalized empirical likelihood approach
Authors: Sheng Ying , Sun Yifei , Huang Chiung‐Yu , Kim Mi‐Ok 
Published: February 2021

AbstractWith the increasing availability of data in the public domain, there has been a growing interest in exploiting information from external sources to improve the analysis of smaller scale studies. An emerging challenge in the era of big data is that the subject‐level data are high dimensional, but the external information is at an aggregate level and of a lower dimension. Moreover, heterogeneity and uncertainty in the auxiliary information are often not accounted for in information synthesis. In this paper, we propose a unified framework to summarize various forms of aggregated information via estimating equations and develop a penalized empirical likelihood approach to incorporate such information in logistic regression. When the homogeneity assumption is violated, we extend the method to account for population heterogeneity among different sources of information. When the uncertainty in the external information is not negligible, we propose a variance estimator adjusting for the uncertainty. The proposed estimators are asymptotically more efficient than the conventional penalized maximum likelihood estimator and enjoy the oracle property even with a diverging number of predictors. Simulation studies show that the proposed approaches yield higher accuracy in variable selection compared with competitors. We illustrate the proposed methodologies with a pediatric kidney transplant study.
Peptide allergen‐specific immunotherapy for allergic airway diseases—State of the art
Authors: Wraith David C. , Krishna Mamidipudi T. 
Published: February 2021

AbstractAllergen‐specific immunotherapy (AIT) is the only means of altering the natural immunological course of allergic diseases and achieving long‐term remission. Pharmacological measures are able to suppress the immune response and/or ameliorate the symptoms but there is a risk of relapse soon after these measures are withdrawn. Current AIT approaches depend on the administration of intact allergens, often comprising crude extracts of the allergen. We propose that the challenges arising from current approaches, including the risk of serious side‐effects, burdensome duration of treatment, poor compliance and high cost, are overcome by application of peptides based on CD4+ T cell epitopes rather than whole allergens. Here we describe evolving approaches, summarize clinical trials involving peptide AIT in allergic rhinitis and asthma, discuss the putative mechanisms involved in their action, address gaps in evidence and propose future directions for research and clinical development.
Transanal opening of the intersphincteric space: a novel sphincter‐sparing procedure to treat 325 high complex anal fistulas with long‐term follow‐up
Authors: Garg Pankaj , Kaur Baljit , Menon Geetha R. 
Published: February 2021

AbstractAimSepsis in the intersphincteric plane behaves like an abscess in a closed space and is present in most complex fistulas. Ignoring this sepsis is a cause of recurrence. Complex fistulas can be successfully managed by transanal opening of the intersphincteric space (TROPIS) into the anal canal. The long‐term efficacy of the TROPIS procedure was analysed in an exclusive cohort of high complex anal fistulas.MethodsAll consecutive patients operated for a high complex fistula‐in‐ano were included prospectively. Preoperative MRI scans were obtained for all the patients. The intersphincteric space and internal opening was laid open into the anal canal while preserving the external sphincter. The external tracts were thoroughly curetted and cleaned. Fistula healing rate and objective incontinence scores (preoperatively and during long‐term follow‐up) were analysed.ResultsA total of 325 patients (age 39.9 ± 10.9 years, 292 men) were operated with TROPIS and had a follow‐up of 7–67 months (median 36 months). In the cohort, 67.4% (219) had recurrent fistulas, 82.8% (269) had multiple tracts, 36.3% (118) had horseshoe tracts, 37.5% (122) had associated abscesses and 24% (78) were supralevator fistulas. Nineteen patients were excluded. Fistulas healed completely in 78.4% (240/306) of patients and did not heal in 21.6% (66/306) of patients. 36/66 of these patients were operated again and the fistulas healed in 28 patients. Thus, the overall healing rate was 87.6% (268/306). The mean preoperative and postoperative incontinence scores were 0.085 ± 0.35 and 0.119 ± 0.48 respectively (P = 0.38). The healing rate of fistulas with associated acute abscesses was similar to the fistulas without abscesses (87% vs. 88%, P = 0.85).ConclusionTransanal opening of the intersphincteric space is a safe and highly effective sphincter‐sparing procedure to manage high complex fistulas‐in‐ano.
Development of directed and random exploration in children
Authors: Meder Björn , Wu Charley M. , Schulz Eric , Ruggeri Azzurra 
Published: February 2021

AbstractAre young children just random explorers who learn serendipitously? Or are even young children guided by uncertainty‐directed sampling, seeking to explore in a systematic fashion? We study how children between the ages of 4 and 9 search in an explore–exploit task with spatially correlated rewards, where exhaustive exploration is infeasible and not all options can be experienced. By combining behavioral data with a computational model that decomposes search into similarity‐based generalization, uncertainty‐directed exploration, and random exploration, we map out developmental trajectories of generalization and exploration. The behavioral data show strong developmental differences in children's capability to exploit environmental structure, with performance and adaptiveness of sampling decisions increasing with age. Through model‐based analyses, we disentangle different forms of exploration, finding signature of both uncertainty‐directed and random exploration. The amount of random exploration strongly decreases as children get older, supporting the notion of a developmental “cooling off” process that modulates the randomness in sampling. However, even at the youngest age range, children do not solely rely on random exploration. Even as random exploration begins to taper off, children are actively seeking out options with high uncertainty in a goal‐directed fashion, and using inductive inferences to generalize their experience to novel options. Our findings provide critical insights into the behavioral and computational principles underlying the developmental trajectory of learning and exploration.
Hitler's theology: A cautionary tale for today's peril
Authors: Hinlicky Paul R. 
Published: February 2021

AbstractIn this article the author updates and renews his thesis from 2013 about the Weimarization of American political culture. He argues that fascism is an endemic modern possibility that has a theological dimension that becomes visible when the left‐right ideological binary descending from the French Revolution is set aside. Reviewing the evidence from Hitler's Table Talks, he shows how Hitler both understood himself as a progressive change agent and envisioned writing a new theology for triumphant Nazism in retirement. The article concludes by drawing upon Giorgio Agamben's analysis of Nazi biopolitics in Homo Sacer to point towards a messianic alternative.