bluuebunny/crossref_metadata_2025 huggingface dataset:
The Proper Scope of Behavioural Law and Economics
Authors: Engel Christoph
Published: February 2021

Behavioural law and economics applies the conceptual tools of behavioural economics to the analysis of legal problems and legal intervention. These models, and the experiments to test them, assume an institution-free state of nature. In modern societies, the law’s subjects never see this state of nature. However, a rich arrangement of informal and formal institutions creates generalised trust. If individuals are sufficiently confident that nothing too detrimental will happen, they are freed up to interact with strangers as if they were in a state of nature. This willingness dramatically reduces transaction cost and enables division of labour. If generalised trust can be assumed, simple economic models are appropriate, but they must be behavioural, since otherwise individuals would not want to run the risk of interaction.
The Normative Order of the Internet
Authors: Kettemann Matthias C.
Published: February 2021

Online anarchy? Far from it: as this study convincingly shows, norms matter online. In a tour de force, internet law expert Matthias C. Kettemann analyses the genesis, ontology, and legitimation of rule and rules on the internet. Innovatively, the study establishes the emergence of a normative order of the internet, an order that integrates norms materially and normatively connected to the use and development of the internet at three different levels (regional, national, international), of two types (privately and publicly authored), and of different character (from ius cogens to technical standards). Centrifugal forces contribute to normative redundancies (“normative froth”), real conflicts of norms between regulatory layers and geographically bounded normative spheres (“normative friction”), substantial structural problems (“normative fractures”), and political, commercial, and technological fragmentation of the internet. But these forces of normative disorder can be countered. As the study impressively shows, a normative turn has taken place on the internet. The rules on rule-making that have developed within the normative order of the internet explain, predict, and legitimize the creation of new norms through processes of self-learning normativity. These norms are then assessed for their internal coherence, consonance with other order norms, and consistency with the order’s finality. The normative order of the internet is based on and produces a liquefied system characterized by self-learning normativity. Thus a theory of normativity (“of the law”) that goes back to Kant needs to be fundamentally rethought: with norm-based self-organization as the principle of life that enables the transcendental constitution of normativityon the internet.
The Impact of Crisis Intervention Team Response, Dispatch Coding, and Location on the Outcomes of Police Encounters with Individuals with Mental Illnesses in Chicago
Authors: Watson Amy C , Owens Linda K , Wood Jennifer , Compton Michael T
Published: February 2021

The Crisis Intervention Team (CIT) model has been implemented in over 3,000 communities across the USA. Research to date has shown beneficial results in terms of officers’ knowledge, attitudes, self-efficacy, stigma, and force preferences. This study aimed to broaden the lens on the implementation context of CIT to examine whether factors in the environment and response process affect how calls are resolved. This study focused on several factors—CIT response, call location, and upstream decisions to pre-identify calls as mental health-related—that may impact call outcomes. Our findings suggest that CIT response, dispatch coding, and the places where calls originate play a role in shaping outcomes. More research is needed to unpack the effects of this wider CIT implementation environment.
Dry Needling for the Treatment of Tension-Type, Cervicogenic, or Migraine Headaches: A Systematic Review and Meta-Analysis
Authors: Pourahmadi Mohammadreza , Dommerholt Jan , Fernández-de-Las-Peñas César , Koes Bart Willem , Mohseni-Bandpei Mohammad Ali , Mansournia Mohammad Ali , Delavari Somayeh , Keshtkar Abbasali , Bahramian Mehrdad
Published: February 2021

Objective

Dry needling is a treatment technique used by clinicians to relieve symptoms in patients with tension-type headache (TTH), cervicogenic headache (CGH), or migraine. This systematic review’s main objective was to assess the effectiveness of dry needling on headache pain intensity and related disability in patients with TTH, CGH, or migraine.

Methods

Medline/PubMed, Scopus, Embase, PEDro, Web of Science, Ovid, Allied and Complementary Medicine Database/EBSCO, Cochrane Central Register of Controlled Clinical Trials, Google Scholar, and trial registries were searched until April 1, 2020, along with reference lists of eligible studies and related reviews. Randomized clinical trials or observational studies that compared the effectiveness of dry needling with any other interventions were eligible for inclusion. Three reviewers independently selected studies, extracted data, and assessed risk of bias. Random-effects meta-analyses were performed to produce pooled-effect estimates (Morris dppc2) and their respective CIs.

Results

Of 2715 identified studies, 11 randomized clinical trials were eligible for qualitative synthesis and 9 for meta-analysis. Only 4 trials were of high quality. Very low-quality evidence suggested that dry needling is not statistically better than other interventions for improving headache pain intensity in the short term in patients with TTH (SMD −1.27, 95% CI = −3.56 to 1.03, n = 230), CGH (SMD −0.41, 95% CI = −4.69 to 3.87, n = 104), or mixed headache (TTH and migraine; SMD 0.03; 95% CI = −0.42 to 0.48, n = 90). Dry needling provided significantly greater improvement in related disability in the short term in patients with TTH (SMD −2.28, 95% CI = −2.66 to −1.91, n = 160) and CGH (SMD −0.72, 95% CI = −1.09 to −0.34, n = 144). The synthesis of results showed that dry needling could significantly improve headache frequency, health-related quality of life, trigger point tenderness, and cervical range of motion in TTH and CGH.

Conclusions

Dry needling produces similar effects to other interventions for short-term headache pain relief, whereas dry needling seems to be better than other therapies for improvement in related disability in the short term.

Impact

Although further high-methodological quality studies are warranted to provide a more robust conclusion, our systematic review suggested that for every 1 or 2 patients with TTH treated by dry needling, 1 patient will likely show decreased headache intensity (number needed to treat [NNT] = 2; large effect) and improved related disability (NNT = 1; very large effect). In CGH, for every 3 or 4 patients treated by dry needling, 1 patient will likely exhibit decreased headache intensity (NNT = 4; small effect) and improved related disability (NNT = 3; medium effect).
Relationships Between Stepping-Reaction Movement Patterns and Clinical Measures of Balance, Motor Impairment, and Step Characteristics After Stroke
Authors: Pollock Courtney L , Hunt Michael A , Garland S Jayne , Ivanova Tanya D , Wakeling James M
Published: February 2021

Objective

Successful stepping reactions, led by either the paretic or nonparetic leg, in response to a loss of balance are critical to safe mobility poststroke. The purpose of this study was to measure sagittal plane hip, knee, ankle, and trunk kinematics during 2-step stepping reactions initiated by paretic and nonparetic legs of people who had stroke and members of a control group.

Methods

Principal component analysis (PCA) was used to reduce the data into movement patterns explaining interlimb coordination of the stepping and stance legs. Correlations among principal components loading scores and clinical measures of balance ability (as measured on the Community Balance and Mobility scale), motor impairment (as measured on the foot and leg sections of the Chedoke-McMaster Stroke Assessment), and step characteristics (length and velocity) were used to examine the effect of stroke on stepping reaction movement patterns.

Results

The first 5 principal components explained 95.9% of the movement pattern of stepping reactions and differentiated between stepping reactions initiated by paretic legs, nonparetic legs, or the legs of controls. Moderate-strong associations (ρ/r > 0.50) between specific principal component loading scores and clinical measures and step characteristics were dependent on the initiating leg. Lower levels of motor impairment, higher levels of balance ability, and faster and longer steps were associated with stepping reactions initiated by the paretic leg that comprised paretic leg flexion and nonparetic leg extension. Step initiation with the nonparetic leg showed associations between higher scores on clinical measures and movement patterns of flexion in both paretic and nonparetic legs.

Conclusions

Movement patterns of stepping reactions poststroke were influenced by the initiating leg. After stroke, specific movement patterns showed associations with clinical measures depending on the initiating leg, suggesting that these movement patterns are important to retraining of stepping reactions. Specifically, use of flexion patterning and assessment of between-leg pattern differentiation may be important aspects to consider during retraining of stepping reactions poststroke.

Impact

Evidence-based interventions targeting balance reactions are still in their infancy. This investigation of stepping reactions poststroke addresses a major gap in research.
Framings ofWg,1
Authors: Kupers Alexander , Randal-Williams Oscar
Published: February 2021

We compute the set of framings of $W_{g,1} = D^{2n} \# (S^{\,n} \times S^{\,n})^{\# g}$, up to homotopy and diffeomorphism relative to the boundary.
Exploring research impact models: A systematic scoping review
Authors: Razmgir Maryam , Panahi Sirous , Ghalichi Leila , Mousavi Seyed Ali Javad , Sedghi Shahram
Published: February 2021

This article explores the models and frameworks developed on “research impact’. We aim to provide a comprehensive overview of related literature through scoping study method. The present research investigates the nature, objectives, approaches, and other main attributes of the research impact models. It examines to analyze and classify models based on their characteristics. Forty-seven studies and 10 reviews published between 1996 and 2020 were included in the analysis. The majority of models were developed for the impact assessment and evaluation purposes. We identified three approaches in the models, namely outcome-based, process-based, and those utilized both of them, among which the outcome-based approach was the most frequently used by impact models and evaluation was considered as the main objective of this group. The process-based ones were mainly adapted from the W.K. Kellogg Foundation logic model and were potentially eligible for impact improvement. We highlighted the scope of processes and other specific features for the recent models. Given the benefits of the process-based approach in enhancing and accelerating the research impact, it is important to consider such approach in the development of impact models. Effective interaction between researchers and stakeholders, knowledge translation, and evidence synthesis are the other possible driving forces contributing to achieve and improve impact.
A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies
Authors: Oldroyd Alexander G S , Allard Andrew B , Callen Jeffrey P , Chinoy Hector , Chung Lorinda , Fiorentino David , George Michael D , Gordon Patrick , Kolstad Kate , Kurtzman Drew J B , Machado Pedro M , McHugh Neil J , Postolova Anna , Selva-O’Callaghan Albert , Schmidt Jens , Tansley Sarah , Vleugels Ruth Ann , Werth Victoria P , Aggarwal Rohit
Published: February 2021

Objectives

To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening.

Methods

A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review.

Results

Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud’s phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD −1189.96) or lactate dehydrogenase (WMD −336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers.

Conclusion

Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.
A review of group-based methods for teaching statistics in higher education
Authors: Jones Elinor , Palmer Tom
Published: February 2021

The teaching of statistics in higher education in the UK is still largely lecture based. This is despite recommendations such as those given by the American Statistical Association’s Guidelines for Assessment and Instruction in Statistics Education report that more emphasis should be placed on active learning strategies where students take more responsibility for their own learning. One possible model is that of collaborative learning, where students learn in groups through carefully crafted ‘problems’, which has long been suggested as a strategy for teaching statistics. In this article, we review two specific approaches that fall under the collaborative learning model: problem- and team-based learning. We consider the evidence for changing to this model of teaching in statistics, as well as give practical suggestions on how this could be implemented in typical statistics classes in higher education.
Identification of 16SrII-V Phytoplasma Associated with Mungbean Phyllody Disease in Taiwan
Authors: Chen Yen-Ming , Chien Yuan-Yu , Chen Yuh-Kun , Liao Pei-Qing , Tan Choon-Meng , Chiu Yi-Ching , Tai Chao-Feng , Yang Jun-Yi
Published: February 2021

Mungbean (Vigna radiata (L.) R. Wilczek), an important legume crop in Asia, is primarily cultivated in the central-southern region of western Taiwan. In 2020, mungbean exhibiting typical phytoplasma-induced disease symptoms such as witches’ broom, phyllody, virescence, and proliferation was observed in Yunlin County, Taiwan. Moreover, the seed harvested from diseased plants displayed premature germination. Transmission electron microscopy examination of leaf veins prepared from symptomatic mungbean demonstrated that the occlusion of sieve tubes resulted from the accumulation of phytoplasma-like bodies in sieve elements along with filament-like structures in sieve pores. The association of phytoplasma in symptomatic mungbean was confirmed by PCR analyses of the 16S ribosomal RNA (rRNA) and immunodominant membrane protein genes. Further analyses of the 16S rRNA-based phylogenetic tree and the iPhyClassifier-based virtual restriction fragment length polymorphism study demonstrated that the phytoplasma-associated mungbean phyllody disease identified in this study belongs to the 16SrII-V subgroup. BLAST analysis and the phylogenetic analysis indicated that the SAP11-like protein identified in mungbean phyllody disease is identical to peanut witches’ broom phytoplasma SAP11, which explains the witches’ broom phenotype observed in symptomatic mungbean. The results described in this report confirm that the 16SrII-V phytoplasma, a widely distributed phytoplasma associated with peanut witches’ broom disease in Taiwan, has also infected mungbean. This is not only the first instance of mungbean phyllody disease found in Taiwan but also the first instance of mungbean phyllody disease caused by 16SrII-V subgroup phytoplasma.
A Stable Quantitative Trait Locus on Chromosome 5BL Combined with Yr18 Conferring High-Level Adult Plant Resistance to Stripe Rust in Chinese Wheat Landrace Anyuehong
Authors: Long Li , Yao Fangjie , Guan Fangnian , Cheng Yukun , Duan Luyao , Zhao Xuyang , Li Hao , Pu Zhien , Li Wei , Jiang Qiantao , Wei Yuming , Ma Jian , Kang Houyang , Dai Shoufen , Qi Pengfei , Xu Qiang , Deng Mei , Zheng Youliang , Jiang Yunfeng , Chen Guoyue
Published: February 2021

Chinese wheat landrace Anyuehong (AYH) has displayed high levels of stable adult plant resistance (APR) to stripe rust for >15 years. To identify quantitative trait loci (QTLs) for stripe rust resistance in AYH, a set of 110 recombinant inbred lines (RILs) was developed from a cross between AYH and susceptible cultivar Taichung 29. The parents and RILs were evaluated for final disease severity (FDS) in six field tests with a mixture of predominant Puccinia striiformis f. sp. tritici races at the adult plant stage and genotyped via the wheat 55K single-nucleotide polymorphism (SNP) array to construct a genetic map with 1,143 SNP markers. Three QTLs, designated as QYr.AYH-1AS, QYr.AYH-5BL, and QYr.AYH-7DS, were mapped on chromosome 1AS, 5BL, and 7DS, respectively. RILs combining three QTLs showed significantly lower FDS compared with the lines in other combinations. Of them, QYr.AYH-5BL and QYr.AYH-7DS were stably detected in all environments, explaining 13.6 to 21.4% and 17.6 to 33.6% of phenotypic variation, respectively. Compared with previous studies, QYr.AYH-5BL may be a new QTL, whereas QYr.AYH-7DS may be Yr18. Haplotype analysis revealed that QYr.AYH-5BL is probably present in 6.2% of the 323 surveyed Chinese wheat landraces. The kompetitive allele specific PCR (KASP) markers for QYr.AYH-5BL were developed by the linked SNP markers to successfully confirm the effects of the QTL in a validation population derived from a residual heterozygous line and were further assessed in 38 Chinese wheat landraces and 92 cultivars. Our results indicated that QYr.AYH-5BL with linked KASP markers has potential value for marker-assisted selection to improve stripe rust resistance in breeding programs.
Desulfovibrio subterraneus sp. nov., a mesophilic sulfate-reducing deltaproteobacterium isolated from a deep siliceous mudstone formation
Authors: Ueno Akio , Tamazawa Satoshi , Tamamura Shuji , Murakami Takuma , Kiyama Tamotsu , Inomata Hidenori , Amano Yuki , Miyakawa Kazuya , Tamaki Hideyuki , Naganuma Takeshi , Kaneko Katsuhiko
Published: February 2021

A novel mesophilic sulfate-reducing bacterium, strain HN2T, was isolated from groundwater sampled from the subsurface siliceous mudstone of the Wakkanai Formation located in Horonobe, Hokkaido, Japan. The bacterium was Gram-negative and vibrio-shaped, and its motility was conferred by a single polar flagellum. Cells had desulfoviridin. Catalase and oxidase activities were not detected. It grew in the temperature range of 25–40 °C (optimum, 35 °C) and pH range of 6.3–8.1 (optimum, pH 7.2–7.6). It used sulfate, thiosulfate, dimethyl sulfoxide, anthraquinone-2,6-disulfonate, Fe3+, and manganese oxide, but not elemental sulfur, nitrite, nitrate, or fumarate as electron acceptors. The strain showed weak growth with sulfite as the electron acceptor. Fermentative growth with pyruvate, lactate and cysteine was observed in the absence of sulfate, but not with malate or fumarate. NaCl was not required, but the strain tolerated up to 40 g l–1. Strain HN2T did not require vitamins. The major cellular fatty acids were iso-C15 : 0 (23.8 %), C18 : 1
 ω9t (18.4 %), C18 : 0 (15.0 %), C16 : 0 (14.5 %), and anteiso-C17 :0 (10.1 %). The major respiratory quinone was menaquinone MK-6(H2). The G+C content of the genomic DNA was 56.7 mol%. Based on 16S rRNA gene sequence analysis, the closest phylogenetic relative of strain HN2T is

Desulfovibrio psychrotolerans

JS1T (97.0 %). Digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) values of the strains HN2T and

D. psychrotolerans

JS1T were 22.2 and 79.8 %, respectively. Based on the phenotypic and molecular genetic evidence, we propose a novel species, D. subterraneus sp. nov. with the type strain HN2T (=DSM 101010T=NBRC 112213T).
Effect of low-passage number on dengue consensus genomes and intra-host variant frequencies
Authors: Fung Christian K. , Li Tao , Pollett Simon , Alera Maria Theresa , Yoon In-Kyu , Hang Jun , Macareo Louis , Srikiatkhachorn Anon , Ellison Damon , Rothman Alan L. , Fernandez Stefan , Jarman Richard G. , Maljkovic Berry Irina
Published: February 2021

Intra-host single nucleotide variants (iSNVs) have been increasingly used in genomic epidemiology to increase phylogenetic resolution and reconstruct fine-scale outbreak dynamics. These analyses are preferably done on sequence data from direct clinical samples, but in many cases due to low viral loads, there might not be enough genetic material for deep sequencing and iSNV determination. Isolation of the virus from clinical samples with low-passage number increases viral load, but few studies have investigated how dengue virus (DENV) culture isolation from a clinical sample impacts the consensus sequence and the intra-host virus population frequencies. In this study, we investigate consensus and iSNV frequency differences between DENV sequenced directly from clinical samples and their corresponding low-passage isolates. Twenty five DENV1 and DENV2 positive sera and their corresponding viral isolates (T. splendens inoculation and C6/36 passage) were obtained from a prospective cohort study in the Philippines. These were sequenced on MiSeq with minimum nucleotide depth of coverage of 500×, and iSNVs were detected using LoFreq. For both DENV1 and DENV2, we found a maximum of one consensus nucleotide difference between clinical sample and isolate. Interestingly, we found that iSNVs with frequencies ≥5 % were often preserved between the samples, and that the number of iSNV positions, and sample diversity, at this frequency cutoff did not differ significantly between the sample pairs (clinical sample and isolate) in either DENV1 or DENV2 data. Our results show that low-passage DENV isolate consensus genomes are largely representative of their direct sample parental viruses, and that low-passage isolates often mirror high frequency within-host variants from direct samples.
Top-down effects in motor generalization
Authors: Poh Eugene , Al-Fawakhiri Naser , Tam Rachel , Taylor Jordan A. , McDougle Samuel D.
Published: February 2021

To generate adaptive movements we must generalize what we have previously learned to novel situations. The generalization of adapted movements has typically been framed as a consequence of neural tuning functions that overlap for similar movement kinematics - what might be considered bottom-up generalization. However, as is true in many domains of human behavior, generalization can also be framed as the result of deliberate decisions about how to act (top-down generalization). Here we attempt to broaden the scope of theories about motor generalization, hypothesizing that part of the typical motor generalization function can be characterized as a consequence of top-down decisions concerning the subjective similarity of different movement contexts. We tested this proposal by having participants make explicit similarity ratings over both traditional kinematic contextual dimensions (movement direction) and more abstract contextual dimensions (target shape), and perform a visuomotor adaptation generalization task where trials varied over those dimensions. Across five experiments, we measured the relationship between subjective similarity ratings and motor generalization. In some cases this link was rather strong, though it was determined by both task-relevance and explicit instruction. These results support a broadening of the descriptive framework used to understand the generalization of motor behaviors and support a more careful deployment of instructions in generalization studies.

Significance Statement

Generalization describes the transfer of knowledge from one context to another, and is typically thought to result from a higher-order inference process. However, in the motor adaptation domain, generalization is thought to arise from neural representations tuned to low-level kinematics. To bridge these differing views, we measured peoples’ subjective similarity judgements of different task contexts during sensorimotor adaptation. We found that motor generalization was closely linked to participant’s subjective judgements, and that explicit instructions about the consequential dimension of different contexts further shaped generalization. These findings emphasize that in addition to low level kinematic considerations, top-down inferences about which action to take in a given context should be considered as another key component of motor generalization.
How reacted USA with the first case of Bubonic Plague on 21 August?
Authors: Saire Josimar Edinson Chire , Cruz Jimy Oblitas
Published: February 2021

The present work studies the reactions of citizens from United States of America (USA) during the first cases of Bubonic Plague in the territory on August 2020, during pandemic generated by Covid-19. The interest of the study is analyze the posts of users from all the states of USA following a Text Mining approach. The collection of data is performed through Twitter Application Program Interface (API) of Twitter, considering keywords: bubonic plague and black death. The results show the states with highest number of coronavirus has more publication than others and the interest about treatments, political issues and public health.
SARS CoV-2 nucleoprotein enhances the infectivity of lentiviral spike particles
Authors: Mishra Tarun , Sreepadmanabh M , Ramdas Pavitra , Sahu Amit K , Kumar Atul , Chande Ajit
Published: February 2021

The establishment of SARS CoV-2 spike-pseudotyped lentiviral (LV) systems has enabled the rapid identification of entry inhibitors and neutralizing agents, alongside allowing for the study of this emerging pathogen in BSL-2 level facilities. While such frameworks recapitulate the cellular entry process in ACE2+ cells, they are largely unable to factor in supplemental contributions by other SARS CoV-2 genes. To address this, we performed an unbiased ORF screen and identified the nucleoprotein (N) as a potent enhancer of spike-pseudotyped LV particle infectivity. We further demonstrate that this augmentation by N renders LV spike particles less vulnerable to the neutralizing effects of a human IgG-Fc fused ACE2 microbody. Biochemical analysis revealed that the spike protein is better enriched in virions when the particles are produced in the presence of SARS CoV-2 nucleoprotein. Importantly, this improvement in infectivity is achieved without a concomitant increase in sensitivity towards RBD binding-based neutralization. Our results hold important implications for the design and interpretation of similar LV pseudotyping-based studies.
Fear and death anxiety among Latin American doctors during the Covid-19 pandemic
Authors: Indacochea-Cáceda Sonia , Torres-Malca Jenny Raquel , Vera-Ponce Víctor Juan , Pérez Miguel A. , De La Cruz-Vargas Jhony A.
Published: February 2021

Introduction

A patient’s death elicits various feelings arise in doctors such as impotence and guilt that could trigger physical or psychological symptoms. Despite its impact, few studies have explored anxiety and fear of death among physicians.

Objective

To evaluate perceptions and responses to one’s mortality among Latin American physicians treating COVID-19 patients.

Methodology

This cross-sectional study utilized the Collet-Lester Modified Fear of Death Scale and the Death Anxiety Scale (DAS) to collect data from physicians in Latin America.

Results

219 doctors from Peru, Mexico, Argentina, Colombia, and Bolivia filled out the online questionnaire. Fear of death among the sample population ranged from 56.2% to 90%. Furthermore, the prevalence of “High Anxiety” was 80.8%. A statistically significant association was found between fear according to age and time of graduation (p = 0.010 and p = 0.020, respectively). No differences were found by gender, age, and country of origin or practice.

Conclusion

Physicians experience feelings of helplessness and guilt upon the death of a patient and those feelings can trigger physical or psychological symptoms. For these states of fear and anxiety about death, more frequent in times of pandemic, doctors must be prepared, and institutions must provide them with the necessary means to help them overcome these difficult times.
LifeSim: A Lifecourse Dynamic Microsimulation Model of the Millennium Birth Cohort in England
Authors: Skarda Ieva , Asaria Miqdad , Cookson Richard
Published: February 2021

We present a dynamic microsimulation model for childhood policy analysis that models developmental, economic, social and health outcomes from birth to death for each child in the Millennium Birth Cohort (MCS) in England, together with public costs and a summary wellbeing measure. The model is a discrete event simulation in discrete time (annual periods), implemented in R, which progresses 100,000 individuals through each year of their lives from birth in the year 2000 to death. From age 0 to 18 the model draws observational data from the MCS, with explicit modelling of only a few derived outcomes (mental health, conduct disorder, mortality, health-related quality of life, public costs and a general wellbeing metric). During adulthood, all outcomes are modelled dynamically using explicit networks of stochastic process equations, with separate networks for working age and retirement. Our equations are parameterised using effect estimates from existing studies combined with target outcome levels from up-to-date administrative and survey data. We present our baseline projections and a simple validation check against external data from the British Cohort Study 1970 and Understanding Society survey.
Emerin self-assembly and nucleoskeletal coupling regulate nuclear envelope mechanics against stress
Authors: Fernandez Anthony , Bautista Markville , Wu Liying , Pinaud Fabien
Published: February 2021

Emerin is an integral nuclear envelope protein participating in the maintenance of nuclear shape. When mutated or absent, emerin causes X-linked Emery-Dreifuss muscular dystrophy (EDMD). To define how emerin takes parts in molecular scaffolding at the nuclear envelope and helps protect the nucleus against mechanical stress, we established its nanoscale organization using single molecule tracking and super-resolution microscopy. We show that emerin monomers form localized oligomeric nanoclusters stabilized by both lamin A/C and SUN1 at the LINC complex. Interactions of emerin with nuclear actin and BAF additionally modulate its membrane mobility and its ability to oligomerize. In nuclei subjected to mechanical challenges, the mechanotransducing functions of emerin are coupled to changes in its oligomeric state, and the incremental self-assembly of emerin determines nuclear shape adaptation against forces. We also show that the abnormal nuclear envelope deformations induced by EDMD emerin mutants stem from an improper formation of lamin A/C and LINC complex-stabilized emerin oligomers. These findings place emerin at the center of the molecular processes that regulate nuclear shape remodeling in response to mechanical challenges.
Spontaneous Transmembrane Pore Formation by Short-chain Synthetic Peptide
Authors: Koneru Jaya Krishna , Prakashchand Dube Dheeraj , Dube Namita , Ghosh Pushpita , Mondal Jagannath
Published: February 2021

Amphiphilicβ-peptides, which are synthetically designed short-chain helical foldamer ofβ-amino acids, are established potent biomimetic alternatives of natural antimicrobial peptides. An intriguing question is: how does the distinct molecular architecture of these short-chain and rigid synthetic peptides translates to its potent membrane disruption ability? Here, we address this question via a combination of all atom and coarse-grained molecular dynamics simulations of the interaction of mixed phospholipid bilayer with an antimicrobial 10-residue globally amphiphilic helicalβ-peptide at wide range of concentrations. The simulation demonstrates that multiple copies of this synthetic peptide, initially placed in aqueous solution, readily self-assemble and adsorb at membrane interface. Subsequently, beyond a threshold peptide-to-lipid ratio, the surface-adsorbed oligomeric aggregate moves inside the membrane and spontaneously forms stable water-filled transmembrane pore via a cooperative mechanism. The defects induced by these pores lead to the dislocation of interfacial lipid head groups, membrane thinning and substantial water leakage inside the hydrophobic core of the membrane. A molecular analysis reveals that, despite having a short architecture, these synthetic peptides, once inside the membrane, would stretch themselves towards the distal leaflet in favour of potential contact with polar head groups and interfacial water layer. The pore formed in coarse-grained simulation was found to be resilient upon structural refinement. Interestingly, the pore-inducing ability was found to be elusive in a non-globally amphiphilic sequence isomer of the sameβ-peptide, indicating strong sequence dependence. Taken together, this work put forward key perspectives of membrane-activity of minimally designed synthetic biomimetic oligomers relative to the natural antimicrobial peptides.

STATEMENT OF SIGNIFICANCE

The development of bacterial resistance to conventional antibiotics is a major concern towards public health. Antimicrobial peptides, which provide a natural defence against a large range of pathogens, including bacteria and fungi, are emerging as a sustainable substitute of antibiotics. However, serious issues with the naturally occurring antimicrobial peptides which have prevented their wide-spread appreciations are their susceptibility to degradation and lack of specificity for microbial targets. In this regard, synthetic biomimetic peptides are coming up as a viable alternative. In this work we provide clarity on how these synthetic antimicrobial peptides, which often involves distinctly short architecture, acts on the membrane. We show that despite its short architecture, a 10-residue biomimetic peptide,β-peptide, can spontaneously form stable membrane-spanning pore and induce water-leakage inside the membrane.
Akkermansia muciniphilasecretome promotes α-synuclein aggregation in enteroendocrine cells
Authors: Amorim Neto Dionísio Pedro , Bosque Beatriz Pelegrini , Pereira de Godoy João Vitor , Rodrigues Paulla Vieira , Meneses Dario Donoso , Tostes Katiane , Costa Tonoli Celisa Caldana , González-Billault Christian , de Castro Fonseca Matheus
Published: February 2021

The notion that the gut microbiota play a role in neurodevelopment, behavior and outcome of neurodegenerative disorders is recently taking place. A number of studies have consistently reported a greater abundance ofAkkermansia muciniphilain Parkinson’s disease (PD) fecal samples. Nevertheless, a functional link betweenA.muciniphilaand sporadic PD remained unexplored. Here, we investigated whetherA.muciniphilasecretome could initiate the misfolding process of α-synuclein (αSyn) in enteroendocrine cells (EECs), which are part of the gut epithelium and possess many neuron-like properties. We found thatA.muciniphilasecretome is directly modulated by mucin, induces intracellular calcium (Ca2+) release, and causes increased mitochondrial Ca2+uptake in EECs, which in turn leads to production of reactive oxygen species (ROS) and αSyn aggregation. However, these events were efficiently inhibited once we buffered mitochondrial Ca2+. Thereby, these molecular insights provided here offer evidence that bacterial secretome is capable of inducing αSyn aggregation in enteroendocrine cells.

SYNOPSIS FIGURE DESCRIPTION

The secretome isolated from the commensal gut bacteriumAkkermansia muciniphilatriggers intracellular Ca2+signaling in enteroendocrine cells, leading to increased mitochondrial Ca2+uptake. Mitochondrial Ca2+overload leads to ROS generation culminating with αSyn phosphorylation and aggregation (left panel). All these events were inhibited once mitochondrial Ca2+is buffered (right panel).

Gram-negative gut bacteriumAkkermansia muciniphilais consistently found more abundant in Parkinson’s disease patients.

Akkermansia muciniphilaprotein secretome composition is directly modulated by mucin and induces an IP3-independent endoplasmic reticulum (ER)-calcium release in enteroendocrine cells.

This Ca2+release is triggered by direct activation of Ryanodine Receptors leading to increased mitochondrial Ca2+uptake.

Mitochondrial Ca2+overload leads to ROS generation culminating with αSyn aggregation.

Buffering mitochondrial Ca2+efficiently inhibitsA.muciniphila-induced αSyn aggregation in enteroendocrine cells.
Association of Germline BRCA Pathogenic Variants with Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data
Authors: Turan Volkan , Lambertini Matteo , Lee Dong-Yun , Wang Erica T , Clatot Florian , Karlan Beth Y , Demeestere Isabelle , Bang Heejung , Oktay Kutluk
Published: February 2021

Purpose

To determine whether germline BRCA pathogenic variants (gBRCA) are associated with decreased ovarian reserve.

Materials and Methods

An individual patient-data meta-analysis was performed using 5 datasets on 828 evaluable women who were tested for gBRCA. Of those, 250 carried gBRCA while 578 had tested negative and served as controls. Of the women with gBRCA, four centers studied those affected with breast cancer (n=161) and one studied unaffected individuals (n=89). The data were adjusted for the center, age, body mass index, smoking and oral contraceptive pill use before the final analysis. Anti-mullerian hormone (AMH) levels in affected women were drawn before pre-systemic therapy.

Results

Mean ages of women with vs. without gBRCA1/2 (34.1± 4.9 vs. 34.3± 4.8 years; p=0.48), and with gBRCA1 vs gBRCA2 (33.7± 4.9 vs. 34.6± 4.8 years; p=0.16) were similar. After the adjustments, women with gBRCA1/2 had significantly lower AMH levels compared to controls (23% lower; 95% CI: 4-38%, p=0.02). When the adjusted analysis was limited to affected women (157 with gBRCA vs. 524 without, after exclusions), the difference persisted (25% lower; CI: 9-38%, p=0.003). The serum AMH levels were lower in women with gBRCA1 (33% lower; CI: 12-49%, p=0.004) but not gBRCA2 compared to controls (7% lower; CI: 31% lower to 26% higher, p=0.64).

Conclusions

Young women with gBRCA pathogenic variants, particularly of those affected and with gBRCA1, have lower serum AMH levels compared to controls. They may need to be preferentially counselled about the possibility of shortened reproductive lifespan due to diminished ovarian reserve.

Context

Key objective

DNA repair deficiency is emerging as a joint mechanism for breast cancer and reproductive aging. Recent studies showed that ovarian reserve maybe lower in women with BRCA pathogenic variants (gBRCA) due to DNA repair deficiency. However, clinical studies using the most sensitive serum ovarian reserve marker Anti-Mullerian-Hormone (AMH) provided mixed results. Given the heterogeneity of the data from clinical studies, we performed an individual patient data (IPD) meta-analysis to determine if gBRCA are associated with lower ovarian reserve.

Knowledge generated

gBRCA are associated with diminished ovarian reserve, as determined by serum AMH and this association is restricted to gBRCA1. This finding is firmer for affected women as this IPD meta-analysis predominantly studied those with breast cancer.

Relevance

Women with gBRCA may have shortened reproductive life span due to diminished ovarian reserve and should be proactively counseled for fertility preservation especially if faced with chemotherapy or delaying childbearing.
Effects of THAM Nasal Alkalinization on Airway Microbial Communities: A Pilot Study
Authors: Holliday Zachary M. , Launspach Janice L. , Durairaj Lakshmi , Singh Pradeep K. , Zabner Joseph , Stoltz David A.
Published: February 2021

Objectives

In cystic fibrosis (CF), loss of CFTR-mediated bicarbonate secretion reduces the airway surface liquid (ASL) pH causing airway host defense defects. Aerosolized sodium bicarbonate can reverse these defects, but its effects are short-lived. Aerosolized tromethamine (THAM) also raises the ASL pH but its effects are much longer lasting. In this pilot study, we tested the hypothesis that nasally administered THAM would alter the nasal bacterial composition in adults with and without CF.

Methods

Subjects (n=32 total) received intranasally administered normal saline or THAM followed by a wash out period prior to receiving the other treatment. Nasal bacterial cultures were obtained prior to and after each treatment period.

Results

At baseline, nasal swab bacterial counts were similar between non-CF and CF subjects, but CF subjects had reduced microbial diversity. Both nasal saline and THAM were well-tolerated. In non-CF subjects, nasal airway alkalinization decreased both the total bacterial density and the gram-positive bacterial species recovered. In both non-CF and CF subjects, THAM decreased the amount of C. accolens detected, but increased the amount of C. pseudodiphtheriticum recovered on nasal swabs. A reduction in S. aureus nasal colonization was also found in subjects who grew C. pseudodiphtheriticum.

Conclusions

This study shows that aerosolized THAM is safe and well-tolerated and that nasal airway alkalinization alters the composition of mucosal bacterial communities.
Inequities in childhood immunisation coverage associated with socioeconomic, geographic, maternal, child, and place of birth characteristics in Kenya
Authors: Allan Simon , Adetifa Ifedayo M. O. , Abbas Kaja
Published: February 2021

Background

The global Immunisation Agenda 2030 highlights coverage and equity as a strategic priority goal to reach high equitable immunisation coverage at national levels and in all districts. We estimated inequities in full immunisation coverage associated with socioeconomic, geographic, maternal, child, and place of birth characteristics among children aged 12-23 months in Kenya.

Methods

We analysed full immunisation coverage (1-dose BCG, 3-dose DTP-HepB-Hib (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B), 3-dose polio, 1-dose measles, and 3-dose pneumococcal vaccines) of 3,943 children aged 12–23 months from the 2014 Kenya Demographic and Health Survey. We disaggregated mean coverage by socioeconomic (household wealth, religion, ethnicity), geographic (place of residence, province), maternal (maternal age at birth, maternal education, maternal marital status, maternal household head status), child (sex of child, birth order), and place of birth characteristics, and estimated inequities in full immunisation coverage using bivariate and multivariate logistic regression.

Results

Immunisation coverage ranged from 82% [81–84] for the third dose of polio to 97.4% [96.7–98.2] for the first dose of DTP-HepB-Hib, while full immunisation coverage was 68% [66–71] in 2014. After controlling for other background characteristics through multivariate logistic regression, children of mothers with primary school education or higher have at least 54% higher odds of being fully immunised compared to children of mothers with no education. Children born in clinical settings had 41% higher odds of being fully immunised compared to children born in home settings. Children in the Coast, Western, Central, and Eastern regions had at least 74% higher odds of being fully immunised compared to children in the North Eastern region, while children in urban areas had 26% lower odds of full immunisation compared to children in rural areas. Children in the middle and richer wealth quintile households were 43–57% more likely to have full immunisation coverage compared to children in the poorest wealth quintile households. Children who were sixth born or higher had 37% lower odds of full immunisation compared to first-born children.

Conclusions

Children of mothers with no education, born in home settings, in regions with limited health infrastructure, living in poorer households, and of higher birth order are associated with lower rates of full immunisation. Targeted programmes to reach under-immunised children in these subpopulations will lower the inequities in childhood immunisation coverage in Kenya.
Neurological mechanism of sensory deficits after developmental exposure to non-dioxin-like polychlorinated biphenyls (PCBs)
Authors: Brun Nadja R. , Panlilio Jennifer M. , Zhang Kun , Zhao Yanbin , Ivashkin Evgeny , Stegeman John J. , Goldstone Jared V.
Published: February 2021

The most abundant polychlorinated biphenyl (PCB) congeners found in the environment and in humans are neurotoxic. This is of particular concern for early life stages because the exposure of the more vulnerable developing nervous system to chemicals can result in neurobehavioral disorders. To uncover currently unknown links between PCB target mechanisms and neurobehavioral deficits, we investigated the effects of the non-dioxin-like (NDL) congener PCB153 on neuronal morphology and synaptic transmission linked to the proper execution of a sensorimotor response using zebrafish as a vertebrate model. Zebrafish that were exposed during development to concentrations similar to those found in human cord blood and PCB contaminated sites showed a delay in startle response. A similar delay was observed for other NDL congeners but not for the potent dioxin-like congener PCB126. Morphological and biochemical data demonstrate that while exposure to PCB153 induced swelling of afferent sensory neurons, the disruption of dopaminergic and GABAergic signaling is the dominant mechanism associated with motor movement. The effects on important and broadly conserved signaling mechanisms in vertebrates suggest that NDL PCBs may contribute to neurodevelopmental abnormalities in humans and, with the startle response being critical for the survival of fish, to evolutionary adaptation in wildlife.
Flexible analysis of TSS mapping data and detection of TSS shifts with TSRexploreR
Authors: Policastro Robert A. , McDonald Daniel J. , Brendel Volker P. , Zentner Gabriel E.
Published: February 2021

Heterogeneity in transcription initiation has important consequences for transcript stability and translation, and shifts in transcription start site (TSS) usage are prevalent in various disease and developmental contexts. Accordingly, numerous methods for global TSS profiling have been developed, including our recently published Survey of TRanscription Initiation at Promoter Elements with high-throughput sequencing (STRIPE-seq), a method to profile transcription start sites (TSSs) on a genome-wide scale with minimal cost and time. In parallel to our development of STRIPE-seq, we built TSRexploreR, an R package for end-to-end analysis of TSS mapping data. TSRexploreR provides functions for TSS and TSR detection, normalization, correlation, visualization, and differential TSS/TSR analysis. TSRexploreR is highly interoperable, accepting the data structures of TSS and TSR sets generated by several existing tools for processing and alignment of TSS mapping data, such as CAGEr for Cap Analysis of Gene Expression (CAGE) data. Lastly, TSRexploreR implements a novel approach for the detection of shifts in TSS distribution.