bluuebunny/crossref_metadata_2025 huggingface dataset:
The tau oligomer antibody APNmAb005 detects early-stage pathological tau enriched at synapses and rescues neuronal loss in long-term treatments
Authors: Tai Hwan-Ching , Ma Haou-Tzong , Huang Shien-Chieh , Wu Meng-Fang , Wu Chia-Lin , Lai Yen-Ting , Li Zhong-Lin , Margolin Richard , Intorcia Anthony J. , Serrano Geidy E. , Beach Thomas G. , Nallani Madhaven , Navia Bradford , Jang Ming-Kuei , Tai Chin-Yin
Published: June 2022

Numerous tau immunotherapies are being developed against Alzheimer’s disease (AD), but it has been challenging to specifically target early-stage tau aggregates using conformation-dependent antibodies. Here, we report a monoclonal antibody, APNmAb005, that recognized a conformational epitope associated with tau oligomers. In AD brain extracts, mAb005 preferentially recognized oligomeric tau in the synapse over monomeric tau in the cytosol. In the prefrontal cortex and hippocampus, mAb005 immunoreactivity was strongly present in early-stage AD but surprisingly diminished in late-stage AD (Braak stage VI). mAb005 also recognized aggregates in 3R tauopathies (Pick’s disease) and 4R tauopathies (corticobasal degeneration and progressive supranuclear palsy), including those in astrocytes and oligodendrocytes. In rTg4510 mice (P301L tau), mAb005 immunoreactivity first appeared in distal neurites but much later in neuronal somas. Thus, the mAb005 epitope appears to be associated with early-stage oligomers of tau (esoTau) that accumulate around synapses in AD, which is also detectable in both 3R and 4R tauopathies. In cellular uptake models of tauopathy transmission, mAb005 blocked the formation of intracellular inclusions induced by incubation with rTg4510 mouse brain extracts. Long-term treatments with mAb005 in rTg4510 mice partially rescued synaptic and neuronal loss in the hippocampus without promoting overall tau clearance. Our data suggest that immunotherapies targeting esoTau enriched around synaptic sites may alleviate tau toxicity against synapses and neurons, which may be a promising treatment strategy against AD.

One Sentence Summary

A tau-conformer antibody recognizing synaptic oligomers and 3R, 4R, and mixed aggregates in humans rescues neuronal loss in mouse tauopathy models.
Deep brain cancer metastasis detection with wide-volume Raman spectroscopy through a single tapered fiber
Authors: Pisano Filippo , Masmudi-Martín Mariam , Andriani Maria Samuela , Cid Elena , Pisanello Marco , Balena Antonio , Collard Liam , Tantussi Francesco , Grande Marco , Sileo Leonardo , Gentile Francesco , De Angelis Francesco , De Vittorio Massimo , de La Prida Liset Menendez , Valiente Manuel , Pisanello Ferruccio
Published: June 2022

We propose a low-invasive method to enable implantable, large volume Raman spectroscopy in arbitrarily deep brain regions of the mouse brain. Using a single tapered fiber as thin as 1 μm at the tip, we identified diagnostic markers of brain metastasis - the most frequent brain tumor in human adults - with overall accuracy ≥ 90%. We view our approach as a promising complement to the existing palette of tools for optical interrogation of the brain.
Structural basis of ubiquitin-independent PP1 complex disassembly by p97
Authors: van den Boom Johannes , Meyer Hemmo , Saibil Helen
Published: June 2022

The AAA+ ATPase p97 (also called VCP, or Cdc48 in yeast) unfolds proteins and disassembles protein complexes in a myriad of cellular processes, but how a substrate complex needs to be loaded onto p97 by a dedicated substrate adapter and then disassembled by p97 has not been structurally visualized so far. Here we present cryo-EM structures of p97 in the process of disassembling a protein phosphatase-1 (PP1) complex by stripping off an inhibitory subunit. We show that PP1 and its partners SDS22 and inhibitor-3 (I3) bind to a peripheral N-domain of p97 via a direct contact between SDS22 and a groove in the N-domain. A density consistent with the SHP box of the p37 adapter binds to the same N-domain underneath the PP1 complex, while the p37-UBX domain is found on the adjacent N-domain. I3 is likely represented by three densities. One covers the PP1 catalytic site adjacent to SDS22, another is at the PP1 binding site for the RVXF motif in I3 pointing towards the p97 pore, and the third is a peptide threaded through the central channel of the spiral-shaped p97 hexamer. Our data show how p97 arranges a substrate complex between the N-domain and central channel, and then extracts one component by threading it through the channel to disassemble the complex.
PERIOD phosphorylation leads to feedback inhibition of CK1 activity to control circadian period
Authors: Philpott Jonathan M. , Freeberg Alfred M. , Park Jiyoung , Lee Kwangjun , Ricci Clarisse G. , Hunt Sabrina R. , Narasimamurthy Rajesh , Segal David H. , Robles Rafael , Cai Yao D. , Tripathi Sarvind , McCammon J. Andrew , Virshup David M. , Chiu Joanna C. , Lee Choogon , Partch Carrie L.
Published: June 2022

PERIOD (PER) and Casein Kinase 1δ regulate circadian rhythms through a phosphoswitch that controls PER stability and repressive activity in the molecular clock. CK1δ phosphorylation of the Familial Advanced Sleep Phase (FASP) serine cluster embedded within the Casein Kinase 1 binding domain (CK1BD) of mammalian PER1/2 inhibits its activity on phosphodegrons to stabilize PER and extend circadian period. Here, we show that the phosphorylated FASP region (pFASP) of PER2 directly interacts with and inhibits CK1δ. Co-crystal structures in conjunction with accelerated molecular dynamics simulations reveal how pFASP phosphoserines dock into conserved anion binding sites near the active site of CK1δ. Limiting phosphorylation of the FASP serine cluster reduces product inhibition, decreasing PER2 stability and shortens circadian period in human cells. We found that Drosophila PER also regulates CK1δ via feedback inhibition through the phosphorylated PER-Short domain, revealing a conserved mechanism by which PER phosphorylation near the CK1BD regulates CK1 kinase activity.
Humanized antibody potently neutralizes all SARS-CoV-2 variants by a novel mechanism
Authors: Luo Sai , Zhang Jun , Kreutzberger Alex J.B. , Eaton Amanda , Edwards Robert J. , Jing Changbin , Dai Hai-Qiang , Sempowski Gregory D. , Cronin Kenneth , Parks Robert , Ye Adam Yongxin , Mansouri Katayoun , Barr Maggie , Pishesha Novalia , Williams Aimee Chapdelaine , Francisco Lucas Vieira , Saminathan Anand , Peng Hanqin , Batra Himanshu , Bellusci Lorenza , Khurana Surender , Alam S. Munir , Montefiori David C. , Saunders Kevin O. , Tian Ming , Ploegh Hidde , Kirchhausen Tom , Chen Bing , Haynes Barton F. , Alt Frederick W.
Published: June 2022

SARS-CoV-2 Omicron variants have generated a world-wide health crisis due to resistance to most approved SARS-CoV-2 neutralizing antibodies and evasion of antibodies induced by vaccination. Here, we describe the SARS-CoV-2 neutralizing SP1-77 antibody that was generated from a humanized mouse model with a single human VH1-2 and Vκ1-33-associated with immensely diverse complementarity-determining-region-3 (CDR3) sequences. SP1-77 potently and broadly neutralizes SARS-CoV-2 variants of concern and binds the SARS-CoV-2 spike protein receptor-binding-domain (RBD) via a novel-CDR3-based mode. SP1-77 does not block RBD-binding to the ACE2-receptor or endocytosis step of viral entry, but rather blocks membrane fusion. Our findings provide the first mechanistic insight into how a non-ACE2 blocking antibody potently neutralizes SARS-CoV-2, which may inform strategies for designing vaccines that robustly neutralize current and future SARS-CoV-2 variants.
Cross-Protective Antibodies Against Common Endemic Respiratory Viruses
Authors: Cabán Madelyn , Rodarte Justas V. , Bibby Madeleine , Gray Matthew D. , Taylor Justin J. , Pancera Marie , Boonyaratanakornkit Jim
Published: June 2022

Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) are a major cause of death, morbidity, and health care costs worldwide, and they can exact a significant toll on immunocompromised patients, the elderly, and those with underlying lung disease. There is an unmet medical need for safe and effective medications for many of the viruses responsible for common respiratory viral infections in vulnerable patient populations. While a protective monoclonal antibody exists for RSV, clinical use is limited to high-risk infant populations. Here, we present the discovery, in vitro characterization, and in vivo efficacy testing of two cross-neutralizing monoclonal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV. The 3×1 antibody is capable of targeting multiple parainfluenza viruses; the MxR antibody shares features with other previously reported monoclonal antibodies that are capable of neutralizing both RSV and HMPV. We obtained structures using cryo-electron microscopy of these antibodies in complex with their antigens to 3.62 Å resolution for 3×1:HPIV3 and to 2.24 Å for MxR:RSV, providing a structural basis to corroborate our in vitro characterization of binding and neutralization. Together, a cocktail of 3×1 and MxR could have clinical utility in providing broad protection against four of the respiratory viruses that cause significant morbidity and mortality in at-risk individuals.
Human RAD52 stimulates the RAD51-mediated homology search
Authors: Muhammad Ali Akbar , Peterlini Thibault , Guirouilh-Barbat José , Veaute Xavier , Busso Didier , Lopez Bernard , Masson Jean-Yves , Mazon Gérard , Le Cam Eric , Dupaigne Pauline
Published: June 2022

Homologous recombination (HR) is a DNA repair mechanism of double strand breaks and blocked replication forks that involves a process of homology search and homologous pairing leading to the formation of synaptic intermediates whose architecture and dynamics are tightly regulated to ensure genome integrity. In this mechanism, RAD51 recombinase plays a central role and is supported by many partner including BRCA2 and RAD52. If the mediator function of BRCA2 to load RAD51 on RPA-covered ssDNA is well established, the role of RAD52 in HR, more precisely its interplay with BRCA2 is still far from understood. We have used Transmission Electron Microscopy combined with biochemistry to characterize the sequential participation of RPA, RAD52 and BRCA2 in the assembly of the RAD51 filament, its architecture and its activity. Despite our results confirm that RAD52 lacks a mediator activity, we observed that RAD52 can tightly bind to RPA-coated ssDNA, inhibit the mediator role of BRCA2 and form shorter RAD52- and RAD51-containing mixed filaments that are more efficient in subsequent homology search and formation of synaptic complexes and D-loops, resulting in more frequent multi-invasions as well. Through the characterization of the behavior of RAD52 and BRCA2, these results provide new molecular insights on the formation and regulation of presynaptic and synaptic intermediates during human HR.
Three-dimensional mitochondrial fission, fusion and depolarisation event location prediction for a high throughput analysis of fluorescence microscopy images
Authors: de Villiers James Garrett , Theart Rensu Petrus
Published: June 2022

This paper documents the development of a novel method to predict the occurrence and exact locations of mitochondrial fission, fusion and depolarisation events in three dimensions. These occurrence and location of these events were successfully predicted with a three-dimensional version of the Pix2Pix generative adversarial network (GAN) as well as a three-dimensional adversarial segmentation network called the Vox2Vox GAN. The Pix2Pix GAN predicted the locations of mitochondrial fission, fusion and depolarisation events with accuracies of 35.9%, 33.2% and 4.90%, respectively. Similarly, the Vox2Vox GAN achieved accuracies of 37.1%, 37.3% and 7.43%. The accuracies achieved by the networks in this paper are too low for the immediate implementation of these tools in life science research. They do however indicate that the networks have modelled the mitochondrial dynamics to some degree of accuracy and may therefore still be helpful as an indication of where events might occur if time lapse sequences are not available. The prediction of these morphological mitochondrial events have, to our knowledge, never been achieved before in literature. The results from this paper can be used as a baseline for the results obtained by future work.
Multimodal X-ray probe station at 9C beamline of Pohang Light Source-II
Authors: Ham Daseul , Lee Su Yong , Choi Sukjune , Oh Ho Jun , Noh Do Young , Kang Hyon Chol
Published: June 2022

In this study, the conceptual design and performance of a multimodal X-ray probe station recently installed at the 9C coherent X-ray scattering beamline of the Pohang Light Source-II are presented. The purpose of this apparatus is to measure coherent X-ray diffraction, X-ray fluorescence and electrical properties simultaneously. A miniature vacuum probe station equipped with a four-point probe was mounted on a six-axis motion hexapod. This can be used to study the structural and chemical evolution of thin films or nanostructures, as well as device performance including electronic transport properties. This probe station also provides the capability of varying sample environments such as gas atmosphere using a mass-flow-control system and sample temperatures up to 600°C using a pyrolytic boron nitride heater. The in situ annealing of ZnO thin films and the performance of ZnO nanostructure-based X-ray photodetectors are discussed. These results demonstrate that a multimodal X-ray probe station can be used for performing in situ and operando experiments to investigate structural phase transitions involving electrical resistivity switching.
A new mixed-valence CuI/CuII three-dimensional coordination polymer constructed with an N,O-donor ligand generated via solvothermal synthesis: structural features and magnetic properties
Authors: Kochel Andrzej , Hołyńska Małgorzata , Twaróg Kamil , Jezierska Aneta , Panek Jarosław J. , Wojaczyński Jacek
Published: June 2022

A new mixed-valence CuI/CuII three-dimensional coordination polymer, poly[[diaquabis[μ4-2-(pyrazin-2-yl)quinoline-4-carboxylato]dicopper(I)copper(II)] bis(tetrafluoridoborate)], {[Cu3(C14H8N3O2)2(H2O)2](BF4)2}
n
, was synthesized and characterized, with 2-(pyrazin-2-yl)quinoline-4-carboxylic acid being employed as a linker ligand. The ligand was isolated as its hydrochloride salt, 4-carboxy-2-(pyrazin-2-yl)quinolin-1-ium chloride dihydrate, C14H10N3O2
+·Cl−·2H2O. The compounds show luminescence at 550 nm for the ligand and at 565 nm for the polymer at 297 K. The ligand structure was rationalized by means of quantum-chemical calculations, which led to a similar conformation to that determined from X-ray diffraction studies.
Structure determination and Hirshfeld surface analysis of new cocrystal and salt forms of 5-aminotetrazole with hydroxy- and nitro-substituted carboxylic acids
Authors: Nirmal Ram Jeyaraman Selvaraj , Sathya Udhayasuriyan , Gomathi Sundaramoorthy , Cordes David Bradford
Published: June 2022

Two new crystalline solids, namely, 5-aminotetrazole–3,5-dihydroxybenzoic acid–water (1/4/6), CH3N5·4C7H6O4·6H2O (I), and 5-aminotetrazolium 3,5-dinitrosalicylate, CH4N5
+·C7H3N2O7
− (II), have been synthesized and characterized by single-crystal X-ray diffraction and Hirshfeld surface analysis. The crystal packing arrangements of I and II are governed by N—H...O and O—H...O hydrogen-bonding interactions. In cocrystal I, adjacent acid molecules are linked through O—H...O hydrogen bonds, forming a dimer with an R
2
2(8) motif. In salt II, the tetrazolium cation and acid anion are linked through N—H...O hydrogen bonds to also form a dimer with an R
2
2(8) motif. Further N—H...O and O—H...O hydrogen bonds help to stabilize the crystal packing, along with aromatic π–π stacking interactions in I and carbonyl...π interactions in II. The Hirshfeld surface analysis and fingerprint plots reveal that O...H/H...O interactions contribute 34.4% of the total interactions in the crystal packing of cocrystal I and 36.7% in salt II.
Jouska: a lesson on financial (il)literacy of Indonesian millennials?
Authors: Soepriyanto Gatot , Limijaya Amelia
Published: June 2022

Learning outcomes

The learning outcomes are as follows: Students/participants can understand the type of financial fraud pertaining to the case; Students/participants can analyse the case using the fraud triangle perspective; students/participants can describe detection/anticipation strategies to prevent such acts from taking place in the future; students/participants can evaluate the case using the ethical decision-making framework; and students/participants can comprehend the importance of financial literacy when investing, especially in this digital era.

Case overview/synopsis

This case discusses the investment funds mismanagement accusations addressed to PT Jouska Finansial Indonesia (Jouska). Jouska is a financial planner business that was immensely popular among Indonesian young investors. It actively posted interesting content on its social media accounts, gaining attention from the millennial and Gen Z generations. However, in 2020, many of its clients reported and filed complaints that their portfolio values decreased significantly because of Jouska’s decision to invest their funds in low-quality stocks. Jouska was also alleged to violate its role as a financial planner by being able to perform several activities that fell under the authority of investment managers. This case attracted the attention of authorities so that the Investment Alert Task Force (SWI) stopped Jouska’s operational activities and initiated an investigation into the case. SWI also blocked Jouska’s websites, applications and social media accounts, in cooperation with the Ministry of Communication and Information. Despite settlement agreements that Jouska claimed had been offered to several clients, at the end of 2020 some of its clients and former clients filed a formal lawsuit. As of January 2021, several alleged criminal actions attributed to Jouska were still under investigation, comprised of money laundering, clients’ funds embezzlement, fraud, and insider trading. In October 2021, Aakar’s status was a suspect in the allegations. This case is another example of investment misconduct or fraud; to put it another way, it is the effect. It is expected that the participants can deliberate other perspectives during the discussion that could be the cause of such a case, hence viewing it holistically.

Complexity academic level

Undergraduate level.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 1: Accounting and Finance.
Dementia and the aging population: cognitive screening within correctional health
Authors: Washington Lance
Published: June 2022

Purpose

The purpose of this study was to examine the literature surrounding dementia in the aging correctional population and assess the role of cognitive screening related to dementia detection within corrections. The literature regarding the role of dementia within the justice continuum is scant. Furthermore, correctional health researchers have not reached a consensus on the best age to administer cognitive screening in older persons or prioritizes a screening tool for the early detection of dementia.

Design/methodology/approach

A key search term list including dementia screening and was developed to review the literature surrounding dementia and the aging correctional population. PubMed, Criminal Justice Abstracts (Ebsco) and the National Criminal Justice Reference Service were used within the academic search. A gray literature search using these same search terms was conducted reviewing criminal justice federal agencies and organizations for additional information on the dementia experience within correctional settings. Snowballing was used to capture relevant theoretical and empirical knowledge.

Findings

Shortages in aging specialized health-care staffing presents a barrier for the clinical interpretation of Montreal Cognitive Assessment (MoCA) results. Correctional officers are also identified as useful candidates within the administration of cognitive screening with proper training. The MoCA may be the optimal cognitive screening tool for dementia, until an original cognitive screening tool is created specific to the correctional population. An age of 55 years or older may serve as the best cutoff score for classifying incarcerated individuals as older persons, and screening should be prioritized for these individuals. Finally, new specialized programs related to dementia within correctional settings are identified.

Research limitations/implications

A limitation of this research is the conflicting opinions among researchers regarding the use of general cognitive screening tools within the correctional setting.

Originality/value

This research can inform correctional organizational policy and practices regarding the screening of older persons suspected of dementia. Most notably, this research proposes that correctional settings should incorporate the MoCA within initial screening of all individuals 55 years of age or older, enriching the job design of correctional officer's job positions to include cognitive testing, and for correctional settings to provide dementia and age-associated training for correctional officers. Finally, this paper informs future research in the development of a cognitive assessment tool specific to the correctional population.
Time is of the essence: a systematic literature review of temporality in information systems development research
Authors: O'Connor Mairead , Conboy Kieran , Dennehy Denis
Published: June 2022

Purpose

The purpose of this paper is to identify, classify and analyse temporality in information systems development (ISD) literature.

Design/methodology/approach

The authors address the temporality and ISD research gap by using a framework – which classifies time into three categories: conceptions of time, mapping activities to time and actors relating to time. The authors conduct a systematic literature review which investigates time in ISD within the Senior Scholars' Basket, Information Technology & People (IT&P), and top two information systems conferences over the past 20 years. The search strategy resulted in 9,850 studies of which 47 were identified as primary papers.

Findings

The results reveal that ISD research is ill equipped for contemporary thinking around time. This systematic literature review (SLR) contributes to ISD by finding the following gaps in the literature: (1) clock time is dominant and all other types of time are under-researched; (2) contributions to mapping activities to time is lacking and existing studies focus on single ISD projects rather multiple complex ISD projects; (3) research on actors relating to time is lacking; (4) existing ISD studies which contribute to temporal characteristics are fragmented and lack integration with other categories of time and (5) ISD methodology papers lack contributions to temporal characteristics and fail to acknowledge and contribute to time as a multifaceted interrelated concept.

Originality/value

This work has developed the first SLR on temporality in ISD. This study provides a starting point for ISD researchers and ISD practitioners to test commonly held temporal assumptions of ISD researchers and practitioners.
The first stage of an exploratory study into the UK fire and rescue services working with children and young people who set fires
Authors: Foster Joanna
Published: June 2022

Purpose

This paper aims to outline the first stages of an exploratory study into how the UK fire and rescue services (FRSs) identify those children and young people who require psychosocial interventions to address their firesetting behaviour.

Design/methodology/approach

A purposive sample (N = 53) representing all the UK FRSs was recruited. Participants completed an online survey to establish the type of firesetting intervention provided, if any; the training and policies available to staff who identify those clients requiring psychosocial interventions and what influences this decision-making.

Findings

Decision-making on how to identify clients requiring psychosocial interventions was dominated by professional judgement informed by practitioner training and experience alone, which is subject to human error and bias. Some staff undertaking this risk-critical work have no access to training and/or written guidance to assist their decision-making. Nearly 30% of participants (N = 14) deemed national firesetting policy as not useful in identifying the type of firesetting intervention needed. The development of a risk assessment tool, training and national written guidance were considered the three main ways staff could be helped in identifying those clients requiring psychosocial interventions.

Practical implications

The implications are as follows: the development of a risk assessment tool for fire and rescue service staff working with children and young people who set fires, a requirement for all fire and rescue staff working with children and young people who set fires to receive mandatory training in this specialist field of work, all FRSs to offer firesetting intervention services to children and young people, all FRSs to have written firesetting policies that assist staff in their identification of firesetting risk and national firesetting guidance for FRSs that assists staff in their identification of firesetting risk and the tenets of defensible decision-making.

Originality/value

To the best of the author’s knowledge, this is the first study to look at how the UK FRSs identify those children and young people requiring psychosocial interventions to address their firesetting behaviour. The 100% completion rate to the online survey suggests the findings are generalisable across all the UK FRSs, providing the FRS professional body with an opportunity to instigate the changes their frontline practitioners and managers have identified.
Early Financial Education, Financial Literacy, and Gender Equity in Finance*
Authors: Bae Kyounghun , Jang Ga‐Young , Kang Hyoung‐Goo , Tan Pearleen
Published: June 2022

This study investigates how to promote gender equity in finance through early financial education using survey responses gathered in Singapore. The empirical tests for the effect of financial education on financial literacy suggest that women who receive early financial education better understand the compounding effect of interest rates on loans, portfolio diversification, and mortgage payments. The impact of early financial education on financial behavior is also evident in women's increased participation in the stock market, insurance activities, and savings habits. The implications can be used to guide policymakers charged with promoting gender equity through early financial education.
Pair-Switching Rerandomization
Authors: Zhu Ke , Liu Hanzhong
Published: June 2022

Rerandomization discards assignments with covariates unbalanced in the treatment and control groups to improve estimation and inference efficiency. However, the acceptance-rejection sampling method used in rerandomization is computationally inefficient. As a result, it is time-consuming for rerandomization to draw numerous independent assignments, which are necessary for performing Fisher randomization tests and constructing randomization-based confidence intervals. To address this problem, we propose a pair-switching rerandomization (PSRR) method to draw balanced assignments efficiently. We obtain the unbiasedness and variance reduction of the difference-in-means estimator and show that the Fisher randomization tests are valid under PSRR. Moreover, we propose an exact approach to invert Fisher randomization tests to confidence intervals, which is faster than the existing methods. In addition, our method is applicable to both nonsequentially and sequentially randomized experiments. We conduct comprehensive simulation studies to compare the finite-sample performance of the proposed method with that of classical rerandomization. Simulation results indicate that PSRR leads to comparable power of Fisher randomization tests and is 3–23 times faster than classical rerandomization. Finally, we apply the PSRR method to analyze two clinical trial datasets, both of which demonstrate the advantages of our method.
Population demography maintains biogeographic boundaries
Authors: Schmidt Chloé , Muñoz Gabriel , Lancaster Lesley T. , Lessard Jean‐Philippe , Marske Katharine A. , Marshall Katie E. , Garroway Colin J.
Published: June 2022

Global biodiversity is organised into biogeographic regions that comprise distinct biotas. The contemporary factors maintaining differences in species composition between regions are poorly understood. Given evidence that populations with sufficient genetic variation can adapt to fill new habitats, it is surprising that more homogenisation of species assemblages across regions has not occurred. Theory suggests that expansion across biogeographic regions could be limited by reduced adaptive capacity due to demographic variation along environmental gradients, but this possibility has not been empirically explored. Using three independently curated data sets describing continental patterns of mammalian demography and population genetics, we show that populations near biogeographic boundaries have lower effective population sizes and genetic diversity, and are more genetically differentiated. These patterns are consistent with reduced adaptive capacity in areas where one biogeographic region transitions into the next. That these patterns are replicated across mammals suggests they are stable and generalisable in their contribution to long‐term limits on biodiversity homogenisation. Understanding the contemporary processes that maintain compositional differences among regional biotas is crucial for our understanding of the current and future organisation of global biodiversity.
Statistical analysis based reactive power optimization using improved differential evolutionary algorithm
Authors: Kumar Lalit , Kar Manoj Kumar , Kumar Sanjay
Published: June 2022

This study presents a novel improved differential evolutionary (IDE) algorithm for optimizing reactive power management (RPM) problems. The effectiveness of IDE algorithm is tested on different unimodal and multimodal benchmark functions. The objective function of the RPM is considered as the minimization of active power losses. Initially, the power flow analysis approach is employed to detect the optimal position of flexible AC transmission system (FACTS) devices. The proposed method is used to determine the optimal value of control variables such as generator's reactive power generation, transformer tap settings, and reactive power sources. Furthermore, the efficacy of the IDE approach is compared with other promising optimization methods such as variants of differential evolution algorithm, moth flame optimization (MFO), brainstorm‐based optimization algorithm (BSOA), and particle swarm optimization (PSO) on various IEEE standard test bus (i.e., IEEE‐30, ‐57, ‐118, and ‐300) systems with active and reactive loading incorporating FACTS devices. A Static VAR compensator (SVC) for shunt compensation and a thyristor‐controlled series compensator (TCSC) for series compensation were used as FACTS devices. The proposed IDE method significantly reduces the active power loss, that is, 55.65% in IEEE 30, 39.68% in IEEE 57, 16.32% in IEEE 118, and 8.56% in IEEE 300 bus system at nominal loading. Finally, the statistical analysis such as Wilcoxon signed‐rank test (WSRT) and ANOVA test were thoroughly analysed to demonstrate the firmness and accuracy of the proposed technique.
James Hutton's concept of time: that of Leibniz, not Newton
Authors: Thomas Roger D. K.
Published: June 2022

It is well known that James Hutton's approach to the study of what would later be known as Earth science was significantly influenced by the work of Isaac Newton. But it is hardly appreciated, except perhaps in continental Europe, that Gottfried Leibniz had as much or greater influence on Hutton's ‘natural philosophy’ and even his methods of research and analysis. Nowhere is this more apparent than in the shaping of Hutton's understanding of the nature of time itself.
The lost titan of Cauvery
Authors: Pal Saurabh , Ayyasami Krishnan
Published: June 2022

In 1987, authors P. Yadagiri and K. Ayyasami described a giant dinosaur, Bruhathkayosaurus matleyi, from the Late Cretaceous beds of the Cauvery Basin, India. Unfortunately, the fossil remains of this giant had disintegrated into dust before they reached the repository, making B. matleyi a dubious species. Gigantism is one of the many characteristic features of dinosaurs that grab public attention, and there is much fossil evidence that suggests gigantism was not limited to any specific group of dinosaurs. Nevertheless, this characteristic feature was very advanced and extensive among sauropod dinosaurs, which belonged to a group of long necked herbivorous dinosaurs. Sauropods evolved from basal saurischian dinosaurs about 200 Ma and survived until the K/Pg (Cretaceous–Palaeogene) mass extinction event, about 66 Ma. By the Late Jurassic period, many colossal size sauropods had evolved, such as Supersaurus, Diplodocus, Barosaurus, etc. but together with other Diplodocidae, they went extinct by the end of the Late Jurassic. During the Cretaceous, a new clade of sauropod dinosaurs evolved, the Titanosauria. The Titanosauria diversified into various genera, and in terms of size, they ranged from a 6‐m‐long Magyarosaurus, to the 35‐m‐long Argentinosaurus. Most of these giant titanosaurs, including Argentinosaurus, alongside Patagotitan, Dreadnoughtus, Puertasaurus, and Futalognkosaurus, are known from South America, making this continent truly a ‘land of giants’ during the Cretaceous. However, the latest discoveries of this group indicate that supersized titanosaurs were not just restricted to South America, with Paralititan from Africa and Australotitan from Australia. Loss of the fossil remains of B. matleyi has raised not only questions upon the validity of the species, but also questions the notion that any supersized dinosaur lived in India. Here we critically review pieces of evidence in support of supersize dinosaur remains from Southern India.
Histological features of Clostridioides difficile colitis in patients with inflammatory bowel disease
Authors: Sweeney Jacob R. , Crawford Carl V. , Yantiss Rhonda K.
Published: June 2022

Aims

Patients with inflammatory bowel disease (IBD) are at increased risk for Clostridioides difficile infection, although clinically important infections can be difficult to recognise. C. difficile infection does not produce pseudomembranes when it occurs in IBD patients. These individuals may also be colonised by the organism, in which case diarrhoeal symptoms are not necessarily attributed to C. difficile. We performed this study to determine whether any features distinguished C. difficile‐associated colitis from an IBD flare.

Methods and results

We reviewed the clinical, endoscopic and biopsy findings from 50 patients with established IBD and worsening diarrhoea, including 22 with concurrent positive C. difficile stool toxin polymerase chain reaction (PCR) assays and 28 with negative C. difficile assay results. We found that C. difficile‐infected patients had symptoms and endoscopic findings that were indistinguishable from active IBD. Although most biopsy samples from patients with C. difficile infection showed chronic active colitis indistinguishable from IBD, some displayed neutrophilic infiltrates unaccompanied by plasma cell‐rich inflammation involving superficial (41%) and crypt (18%) epithelium as well as neutrophilic infiltrates within lamina propria distant from foci of cryptitis (32%). All three of these features were significantly more common among infected than uninfected patients (4, 0 and 4%; P = 0.002, P = 0.03 and P = 0.02, respectively).

Conclusions

Although colonic biopsies from IBD patients with C. difficile infection usually lack features that aid distinction from colitic flares, some cases show an acute colitis pattern not seen in IBD alone. When identified in biopsies from symptomatic IBD patients, these changes should alert pathologists to the possibility of this clinically important infection.
Diagnostic criteria and evolving molecular characterisation of pulmonary neuroendocrine carcinomas
Authors: Williams Jessica F , Vivero Marina
Published: June 2022

Neuroendocrine carcinomas of the lung are currently classified into two categories: small‐cell lung carcinoma and large‐cell neuroendocrine carcinoma. Diagnostic criteria for small‐cell and large‐cell neuroendocrine carcinoma are based solely on tumour morphology; however, overlap in histologic and immunophenotypic features between the two types of carcinomas can potentially make their classification challenging. Accurate diagnosis of pulmonary neuroendocrine carcinomas is paramount for patient management, as clinical course and treatment differ between small‐cell and large‐cell neuroendocrine carcinoma. Molecular‐genetic, transcriptomic, and proteomic data published over the past decade suggest that small‐cell and large‐cell neuroendocrine carcinomas are not homogeneous categories but rather comprise multiple groups of distinctive malignancies. Nuances in the susceptibility of small‐cell lung carcinoma subtypes to different chemotherapeutic regimens and the discovery of targetable mutations in large‐cell neuroendocrine carcinoma suggest that classification and treatment of neuroendocrine carcinomas may be informed by ancillary molecular and protein expression testing going forward. This review summarizes the current diagnostic criteria, prognostic and predictive correlates of classification, and evidence of previously unrecognised subtypes of small‐cell and large‐cell neuroendocrine carcinoma.
Characterization and growth mechanisms of adhesion‐induced microcavities during debonding of softened glass
Authors: Zhou Jian , Xu Hongkun , Zhu Chenyu , Li Lihua , Ng Man Cheung , Liu Kun
Published: June 2022

The glass/mold interaction is crucial for controlling the surface quality of high‐precision glass products and elongating the lifespan of precious molds in hot forming techniques. Here we employ the probe tack test to separate a typical glass molding interface composed of N‐BK7 glass and tungsten carbide molds at different temperatures from 655 to 690°C. The macroscale debonding behavior translates from interfacial fracture to cohesive bulk deformation as temperature increases. The glass surfaces after debonding are covered by numerous randomly distributed cavities in micrometer. With temperature increasing, the maximum depth of microcavities greatly increases from less than 0.5 to over 10 μm; the area fraction overall increases and reaches 15% at maximum. These microcavities could result from the development of localized deformation at the gas‐trapping spots, due to the separation of the adhesive glass/mold interface. A large‐sized cavity evolves from the cyclic growth and coalescence of small cavities. For the interfacial fracture cases, cavities mainly propagate as cracks along the interface, and thus develop into shallow disc‐like shapes. However, for the cohesive cases, cavities prefer to grow in the bulk. The growth bifurcation could be governed by the competition between strain energy release rate and viscoelastic complex modulus.
Applying gelatine:chitosan film loaded with nanoemulsified garlic essential oil/α‐tocopherol as active packaging of sliced Omega‐3‐rich mortadella
Authors: Pérez‐Córdoba Luis J. , Pinheiro Ana C. , de Núñez de Villavicencio‐Ferrer Margarita , Trindade Marco A. , Sobral Paulo J. A.
Published: June 2022

The effect of using gelatine:chitosan (G:Ch) based films as carriers of nanoemulsified garlic essential oil/α‐tocopherol (0.4% v/v) on the shelf‐life and sensory acceptance of sliced omega‐3‐rich mortadella stored at 6 ± 1 °C for 7 days, was investigated. Three treatments were evaluated: mortadella packed with active (T1) and passive films (T2) and without (T3) films. T1 presented the highest effectiveness against the inoculated Listeria monocytogenes and Pseudomonas aeruginosa and retarded spoilage bacteria growth. The colour coordinates, pH and Aw of T1 were affected by the active film. TBARs values from T2 and T3 overcame the threshold of 1.0 mg MDA kg−1 sample at day 5. Panellists scored all sensory attributes between 6 (slightly liked) and 7 (moderately liked) within all treatments. The active G:Ch films developed has the potential to be used as good preservative carrier in sliced mortadella during refrigerated storage, and thus, this product can be processed without synthetic preservative.
SARS‐CoV‐2 infection rate in Antananarivo frontline health care workers, Madagascar
Authors: Ratovoson Rila , Raberahona Mihaja , Razafimahatratra Rado , Randriamanantsoa Lova , Andriamasy Emmanuel Harizaka , Herindrainy Perlinot , Razanajatovo Norosoa , Andriamandimby Soa Fy , Rakotonaivo Andoniaina , Randrianarisaona Fanirisoa , Dussart Philippe , Heraud Jean Michel , de Randria Mamy Jean de Dieu , Schoenhals Matthieu , Randremanana Rindra Vatosoa
Published: June 2022

Background

Health care workers (HCWs) represent a vulnerable population during epidemic periods. Our cohort study aimed to estimate the risk of infection and associated factors among HCWs during the first wave of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in Madagascar.

Methods

A prospective cohort study was carried out in three hospitals that oversaw the first cases of COVID‐19. Monthly ELISA‐based serological tests were conducted, and nasopharyngeal swabs were collected in the case of symptoms linked to COVID‐19 for RT–PCR analysis. Survival analyses were used to determine factors associated with SARS‐CoV‐2 infection.

Results

The study lasted 7 months from May 2020. We included 122 HCWs, 61.5% of whom were women. The median age was 31.9 years (IQR: 26.4–42.3). In total, 42 (34.4%) had SARS‐CoV‐2 infections, of which 20 were asymptomatic (47.6%). The incidence of SARS‐CoV‐2 infection was 9.3% (95% CI [6.5–13.2]) person‐months. Sixty‐five HCWs presented symptoms, of which 19 were positive by RT–PCR. When adjusted for exposure to deceased cases, infection was more frequent in HCWs younger than 30 years of age (RR = 4.9, 95% CI [1.4–17.2]).

Conclusion

Our results indicate a high incidence of infection with SARS‐CoV‐2 among HCWs, with a high proportion of asymptomatic cases. Young HCWs are more likely to be at risk than others. Greater awareness among young people is necessary to reduce the threat of infection among HCWs.
The rhizosphere microbiome: Plant–microbial interactions for resource acquisition
Authors: Pantigoso Hugo A. , Newberger Derek , Vivanco Jorge M.
Published: June 2022

While horticulture tools and methods have been extensively developed to improve the management of crops, systems to harness the rhizosphere microbiome to benefit plant crops are still in development. Plants and microbes have been coevolving for several millennia, conferring fitness advantages that expand the plant’s own genetic potential. These beneficial associations allow the plants to cope with abiotic stresses such as nutrient deficiency across a wide range of soils and growing conditions. Plants achieve these benefits by selectively recruiting microbes using root exudates, positively impacting their nutrition, health and overall productivity. Advanced knowledge of the interplay between root exudates and microbiome alteration in response to plant nutrient status, and the underlying mechanisms there of, will allow the development of technologies to increase crop yield. This review summarizes current knowledge and perspectives on plant–microbial interactions for resource acquisition and discusses promising advances for manipulating rhizosphere microbiomes and root exudation.
Preferences for redistribution
Authors: Mengel Friederike , Weidenholzer Elke
Published: June 2022

We survey the literature on preferences for redistribution. We discuss different ways the literature has measured these preferences and review literature on the different determinants of preferences for redistribution. These range from institutions and demographic factors to fairness views and social preferences. Income inequality is, perhaps unsurprisingly, one of the most important determinants of preferences for redistribution. While our survey is largely focused on the economics literature, we also review some work from political science, sociology, and psychology.
Impact of in vitro fertilization‐embryo transfer on mother‐to‐infant transmission in women with chronic HBV infection
Authors: Yi Wei , Li Minghui , Sun Fangfang , Lu Huihui , Zeng Zhan , Bi Xiaoyue , Yang Liu , Lin Yanjie , Cao Xiuzhen , Hu Yuhong , Zhou Mingfang , Zhang Lu , Lu Yao , Wan Gang , Xie Yao
Published: June 2022

Background and Aims

In vitro fertilization‐embryo transfer (IVF‐ET) may increase the risk of mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV). The purpose of this study was to investigate the impact and safety of IVF‐ET on MTCT in women with chronic HBV infection (CHB).

Methods

The data of 298 women who got pregnant by IVF‐ET and their 375 children were collected retrospectively. Mothers were divided into the CHB group (n = 224) and the control group (HBsAg negative, n = 74). After birth, newborns were routinely vaccinated with the hepatitis B vaccine, and infants in the CHB group were injected with hepatitis B immunoglobulin within 2 h after birth. Demographic information, clinical data and laboratory test results were collected. The primary outcome measures were the MTCT rate of HBV, and the secondary outcome measures were the safety of the mother and infant.

Results

There was no case of HBV MTCT in all 282 newborns born in the CHB group and 93 neonates born in the control group. Of the two groups, the birth weight (3056.74 ± 601.65 vs. 2926.24 ± 704.86, P = .083), length (49.22 ± 1.97 vs. 48.74 ± 3.09, P = .167), 5‐min Apgar score (9.97 ± 0.21 vs. 9.90 ± 0.51, P = .212), days of pregnancy (265.70 ± 12.73 vs. 262.02 ± 17.50, P = .064) and neonatal malformation rate (0.71% vs. 0, P = 1.000) were similar. Two cases of neonatal malformation occurred in the CHB group. The incidences of pregnancy and childbirth complications were similar between the two groups.

Conclusion

IVF‐ET does not increase the risk of MTCT in women with chronic HBV infection, and it is safe for mothers and infants.
Auditory‐motor mapping training: Testing an intonation‐based spoken language treatment for minimally verbal children with autism spectrum disorder
Authors: Chenausky Karen V. , Norton Andrea C. , Tager‐Flusberg Helen , Schlaug Gottfried
Published: June 2022

We tested an intonation‐based speech treatment for minimally verbal children with autism (auditory‐motor mapping training, AMMT) against a nonintonation–based control treatment (speech repetition therapy, SRT). AMMT involves singing, rather than speaking, two‐syllable words or phrases. In time with each sung syllable, therapist and child tap together on electronic drums tuned to the same pitches, thus coactivating shared auditory and motor neural representations of manual and vocal actions, and mimicking the “babbling and banging” stage of typical development. Fourteen children (three females), aged 5.0–10.8, with a mean Autism Diagnostic Observation Schedule‐2 score of 22.9 (SD = 2.5) and a mean Kaufman Speech Praxis Test raw score of 12.9 (SD = 13.0) participated in this trial. The main outcome measure was percent syllables approximately correct. Four weeks post‐treatment, AMMT resulted in a mean improvement of +12.1 (SE = 3.8) percentage points, compared to +2.8 (SE = 5.7) percentage points for SRT. This between‐group difference was associated with a large effect size (Cohen's d = 0.82). Results suggest that simultaneous intonation and bimanual movements presented in a socially engaging milieu are effective factors in AMMT and can create an individualized, interactive music‐making environment for spoken‐language learning in minimally verbal children with autism.