bluuebunny/crossref_metadata_2025 huggingface dataset:
The Anglican Tradition
Authors: McCoy Adam D.
Published: October 2020

Anglican monasticism began in the 1840s and was associated with the Anglo-Catholic movement. Women’s communities, which were focused on nursing, teaching, and social work, grew quickly, while men’s communities developed later and more slowly. Fears of Roman Catholicism initially caused new communities to avoid traditional forms of monasticism in favour of the more recent models of the Visitation, Daughters of Charity, and Mercy Sisters. Anglican monasticism quickly spread to North America, Africa, Asia, Australia, and Melanesia. The years since have seen the emergence of characteristically Anglican notions of community formation, rules, governance, and spirituality. The Second Vatican Council had a profound effect on the Anglo-Catholic movement, leading to significant changes in Anglican monastic communities—among them a greater willingness to experiment with different kinds of community life. Many areas of research are open.
The Architecture of the Ascetic Body
Authors: Coon Lynda
Published: October 2020

This chapter argues that the sensory, corporeal, and spatial practices of desert ascetics transmuted into a technique of Christian imperialism in the later Roman Empire. It is divided into two sections: ‘Fortress of the Ascetic Body’ and ‘Spatial Practice of the Ascetic Body’. The first section surveys ways in which the Christian body vanquished its classical counterpart through sensory, material, and spatial techniques. The second part of the chapter applies the corporeal theory established in the first section to build the architecture of the ascetic body, a new direction for scholarship in the field. The essay concludes by suggesting methods through which the material, sensory, and architectural world of late ancient asceticism travelled across the Alps to the monasteries of the early medieval North, where the ideal of the desert became part of the everyday experience of monks.
Monasticism in Latin America
Authors: Hernández Sandoval Bonar L.
Published: October 2020

This chapter provides an overview of the historiography of monasticism in late colonial and modern-day Latin America. Current scholarship focuses on three main areas: the effects of secularization on the economic and spiritual life of monastic orders; the appearance of new monastic sensibilities and definitions of what it means to be a monk and a nun in a postcolonial setting; and the symbiotic relationship between monasticism and Latin American societies. The chapter concludes by suggesting future areas of research, in the process calling for more attention to the relationship between monastics and indigenous peoples, as well as to the transnational links between monastic orders in Latin America, other parts of the Global South, and Western societies.
Society of behavior medicine mid-career leadership institute: a faculty perspective
Authors: Romero Regina E , Arline-Bradley Shavon , Johnson Susan , Tanenbaum Richard
Published: October 2020

This commentary describes the purpose, framework and methods for the opening two days of a year long leadership development program for diverse cohorts of mid-career professionals in academic medicine and behavioral science disciplines.
Exploring How Personal, Social, and Institutional Characteristics Contribute to Geriatric Medicine Subspecialty Decisions: A Qualitative Study of Trainees’ Perceptions
Authors: Raj Minakshi , Platt Jodyn E. , Anthony Denise L. , Fitzgerald James T. , Lee Shoou-Yih Daniel
Published: October 2020

Purpose

To explore internal medicine residents’ and geriatrics fellows’ perceptions of how personal, social, and institutional characteristics contribute to their professional identity and subspecialty decisions related to geriatric medicine.

Method

The authors conducted 23 in-depth, semistructured interviews with internal medicine residents, with and without an interest in geriatrics, and geriatrics fellows across 3 academic medical centers in the United States from October 2018 through June 2019. They then used a qualitative narrative approach to analyze the interview data.

Results

Trainees related personal experiences, such as exposure to physicians and experiences with grandparents, to their interest in medicine. Trainees with an interest in geriatrics at 2 institutions did not feel supported, or understood, by peers and mentors in their respective institutions but maintained their interest in the field. The following variations between institutions that are supportive and those that are not were noted: the number of geriatricians, the proximity of the institution to geriatrics clinics, and the ways in which institutional leaders portrayed the prestige of geriatric medicine. Institutional characteristics influenced trainees’ understanding of what it meant to be a doctor, what meaning they garnered from work as a physician, and their comfort with different types of complexity, such as those presented when providing care to older adults.

Conclusions

Institutional characteristics may be particularly important in shaping trainee interest in geriatric medicine. Institutions should encourage leadership training and opportunities for geriatricians so they can serve as role models and as hands-on mentors for trainees beginning in medical school. Increasing the number of geriatricians requires institutions to increase the value they place on geriatrics to generate a positive interest in this field among trainees. Institutions facilitating formation of professional identity and sense of purpose in work may consider engaging geriatricians in leadership and mentoring roles as well as curriculum development.
Impact of COVID-19 Related Policy Changes on Buprenorphine Dispensing in Texas
Authors: Thornton James Douglas , Varisco Tyler J. , Bapat Shweta S. , Downs Callie G. , Shen Chan
Published: October 2020

Objectives:

To measure the change in the daily number of patients receiving buprenorphine and buprenorphine prescribers during the early phase of the COVID-19 (SARS-CoV-2) pandemic in Texas.

Methods:

Counts of the number of patients filling and number of providers prescribing buprenorphine were calculated for each weekday between November 4, 2019 and May 12, 2020. The change in daily patients and prescribers between March 2, 2020 and May 12, 2020, was modeled as a change in slope compared to the baseline period using autoregressive, interrupted time series regression.

Results:

The rate of change of daily buprenorphine prescriptions (β = −1.75, 95% CI = −5.8–2.34) and prescribers (β = −0.32, 95% CI = −1.47–0.82) declined insignificantly during the COVID-19 period compared to the baseline.

Conclusions:

Despite a 57% decline in ambulatory care utilization in the south-central US during March and April of 2020, health services utilization related to buprenorphine in Texas remained robust. Protecting access to buprenorphine as the COVID-19 pandemic continues to unfold will require intensive efforts from clinicians and policy makers alike. While the presented results are promising, researchers must continue monitoring and exploring the clinical and humanistic impact of COVID-19 on the treatment of substance use disorders.
Management of Postpartum Hemorrhage With a Mini-Sponge Tamponade Device
Authors: Rodriguez Maria I. , Bullard Mary , Jensen Jeffrey T. , Gregory Kenton , Vwalika Bellington , Barofsky Andrew D. , Marts Tola , Edelman Alison B.
Published: October 2020

BACKGROUND:

Postpartum hemorrhage is a leading cause of maternal mortality globally. A tamponade agent that can be quickly and easily placed in a range of settings could advance the treatment of atonic hemorrhage.

METHOD:

We adapted a highly effective trauma dressing for use in postpartum hemorrhage. This mini-sponge tamponade device is comprised of two components: compressed mini-sponges contained within a strong mesh pouch and a tubular applicator. Compressed mini-sponges rapidly absorb blood, expand within seconds, and exert sustained pressure uniformly to bleeding sites. The sponges are deployed within a mesh pouch to facilitate simple vaginal removal.

EXPERIENCE:

We successfully placed the mini-sponge device in nine patients experiencing postpartum hemorrhage after vaginal birth, with resolution of bleeding within 1 minute. The mean time to place the device was 62 seconds. Uterine fill was documented in all cases by ultrasound scan, and device placement was rated as “easy” to “very easy.” Mini-sponges were left in place on average for 1 hour (0.5 hours–14 hours). Bleeding did not recur. There were no adverse events; all patients remained afebrile and did not require subsequent surgical intervention.

CONCLUSION:

This study supports further evaluation of the mini-sponge device for the management of postpartum hemorrhage.

FUNDING:

This study was funded by OBSTETRX, Inc.
Successful rescue with videolaryngoscopy after failed fibroscopy in anticipated difficult airway: case series
Authors: González-Giraldo Daniela , Largo-Pineda Carlos Eriel , Zamudio-Burbano Mario Andrés
Published: October 2020

Introduction:

In the management of the anticipated difficult airway (DA), awake intubation is the strategy of choice. In this context, flexible fibroscopy is the tool most widely used as the first choice. However, there is always the rare case where it may fail.

Important findings:

Six successful rescue cases using videolaryngoscopy following failed fibroscopy in patients with anticipated DA, and 1 case of rescued extubation of an airway previously secured with fiberoptic bronchoscopy.

Conclusion:

Videolaringoscopy may be an adequate tool to use as a backup plan for the management of an anticipated DA.
Improving the identification of genitourinary syndrome of menopause through the utilization of the Day-to-Day Impact of Vaginal Aging questionnaire
Authors: Mastroianni Jennie , Thompson Julie A. , Shifren Jan L. , Zuckerman Andrea L. , Pereira Katherine
Published: October 2020

Objective:

Genitourinary syndrome of menopause (GSM) affects nearly 50% of postmenopausal women. Yet women fail to recognize GSM as a chronic condition and are reluctant to discuss their vaginal or sexual complaints with a health care provider. This quality improvement project implemented the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire to improve the identification and diagnosis of GSM in women ≥ 45 years of age presenting for an annual wellness examination or a vulvovaginal/genitourinary complaint.

Methods:

From October 2019 to February 2020, the DIVA questionnaire was distributed in a large women's health practice setting to women ≥ 45 years of age, for completion before their annual wellness visit or for evaluation of a GSM-related complaint. GSM diagnosis rates during the implementation period were compared with diagnosis rates during a 4-month period immediately preceding the implementation. Data collected during the implementation period were examined to evaluate if GSM diagnosis was more likely in patients who completed the DIVA questionnaire when compared to those women who did not complete the questionnaire.

Results:

Of the 175 women who met the inclusion criteria, 113 completed the DIVA questionnaire. Completion of the DIVA questionnaire demonstrated a relative percentage increase in GSM diagnosis by 30.7% when compared to the 4-month preimplementation period (10.1% to 13.2%, P = 0.231). This change was not statistically significant. During the implementation period, a statistically significant difference in GSM diagnosis was observed for patients who completed the DIVA questionnaire when compared to those patients who did not complete the questionnaire (37.2% vs 9.7%, P < 0.001). When results were stratified by visit type, women presenting for an annual wellness visit who completed the DIVA questionnaire had a higher GSM diagnosis rate than those who did not complete the questionnaire (37.2% vs 10%, P < 0.001). When results were stratified by menopausal status, GSM diagnosis rates were also more likely for postmenopausal women who completed the DIVA questionnaire when compared to those who did not complete the questionnaire (44.2% vs 8.5%, P < 0.001).

Conclusions:

The DIVA questionnaire is a brief, but comprehensive screening tool that can increase GSM identification and treatment, particularly for postmenopausal, and midlife women presenting for an annual wellness visit in a busy women's health practice setting.

Video Summary:

http://links.lww.com/MENO/A655.
Using the 6-min Walk Test to Monitor Peak Oxygen Uptake Response to Cardiac Rehabilitation in Patients With Heart Failure
Authors: Chirico Daniele , Davidson Travis W. , Terada Tasuku , Scott Kyle , Keast Marja-Leena , Reid Robert D. , Pipe Andrew L. , Reed Jennifer L.
Published: October 2020

Purpose:

We examined the agreement between peak oxygen uptake (V˙o2peak), estimated using prediction equations from the 6-min Walk Test (6MWT), and V˙o2peak measured using a cardiopulmonary exercise test (CPX) to estimate change in V˙o2peak in patients with heart failure (HF) enrolled in cardiac rehabilitation (CR).

Methods:

This was secondary analysis of 54 (including 9 women) patients with HF who completed a clinical CR program. Four previously published equations using 6MWT distance were used to estimate V˙o2peak and were compared with a CPX at baseline, follow-up, and change using the standard and modified Bland-Altman method. Analyses were repeated for quartiles of cardiorespiratory fitness (CRF) based on measured V˙o2peak from the CPX.

Results:

Bland-Altman plots revealed proportional bias between all prediction equations and the measured V˙o2peak. The difference between methods varied by the level of CRF, with overestimation of prediction equations at greater levels of CRF and underestimation at lower levels of CRF. This poor agreement remained when comparisons were made between the estimated and measured V˙o2peak values at quartiles of CRF, indicating prediction equations have limited ability to predict V˙o2peak at any level of CRF.

Conclusion:

Estimated V˙o2peak using 6MWT distance demonstrated poor agreement with measured V˙o2peak from a CPX. While distance ambulated on the 6MWT remains an important measure of physical performance in patients with HF, prediction equations using 6MWT distance are not appropriate to monitor changes in V˙o2peak following CR in patients with HF.
Long-term Cardiac Maintenance Programming
Authors: Christle Jeffrey W. , Baumgartner Michaela , Zelger Otto , Lammel Christoph , Haller Bernhard , Bjarnason-Wehrens Birna , Myers Jon , Hamm Larry F. , Froelicher Victor , Halle Martin , Pressler Axel
Published: October 2020

Purpose:

Greater than 65% of all cardiac mortality is related to coronary artery disease (CAD). Cardiac rehabilitation (CR) aims to reduce cardiovascular risk and number of hospital readmissions. Cardiac maintenance programs (CMPs) are designed to sustain or improve health after completing early CR. Although CMPs are supported by most national health guidelines, few long-term studies on these diverse programs have been performed.

Methods:

This was a retrospective repeated-measures analysis with case-controlled subanalysis. Within-subject differences for CMP participants were examined between enrollment and last clinical visit. Assessments included medical history, anthropometry, blood analysis, and cardiopulmonary exercise testing. A subset of 20 CMP participants were compared with 20 patients with CAD who chose not to participate in CMP, matched for age, sex, and follow-up duration.

Results:

A total of 207 patients (60 ± 9 yr, 16% female) were included for the primary analyses. Average follow-up was 6.3 ± 4.8 yr (range 4-20 yr). CMP participants reduced peak workload (1.76 ± 0.56 to 1.60 ± 0.58 W/kg; P < .001) and aerobic capacity (26.1 ± 6.2 to 24.6 ± 7.1 mL/kg/min; P = .003). High-density lipoprotein-cholesterol increased significantly (48 ± 12 to 51 ± 14 mg/dL; P < .001), whereas all other metabolic risk factors remained unaffected. Matched controls had higher functional capacity (2.35 ± 0.81 vs 1.56 ± 0.52 W/kg; P < .001) and lower body mass index (25.3 ± 3.6 vs 28.6 ± 3.9 kg/m2) at baseline, but no significant differences with respect to long-term efficacy were observed.

Conclusions:

Long-term participation in CMP did not result in maintaining functional capacity or cardiovascular risk profile in patients with CAD. However, compared with matched nonparticipants, CMP participants (are more deconditioned at baseline) but do not seem to deteriorate as quickly.
Cool Crosslinking: Riboflavin at 4°C for Pain Management After Crosslinking for Keratoconus Patients, A Randomized Clinical Trial
Authors: Toro-Giraldo Laura , Morales Flores Norma , Santana-Cruz Omar , Ramirez-Miranda Arturo , Navas Alejandro , Olivo-Payne Andrew , Lichtinger Alejandro , Jimenez-Corona Aida , Graue-Hernández Enrique O.
Published: October 2020

Purpose:

To explore corneal cooling as a method of pain management in corneal-accelerated collagen cross-linking.

Methods:

This was a prospective and interventional randomized clinical trial registered in the National Institutes of Health Clinical Trials through the identifier NCT030760770. The research was conducted at the Institute of Ophthalmology “Conde de Valenciana.” A total of 98 patients were randomly assigned to one of the following 2 groups: cold riboflavin (4°C) group or control group (riboflavin at room temperature). The inclusion criteria were patients of any sex, older than 18 years of age with keratoconus diagnosis who needed management with cross-linking in both eyes because of the evidence of progression. The exclusion criteria were patients who had cross-linking without epithelial debridement, unilateral cross-linking, or any other ocular pathologies besides keratoconus and any cognitive incapacity that would make the understanding of the pain test difficult. The main outcome measures were pain, tearing, photophobia, foreign body sensation, and irritation.

Results:

At 2 hours post-op, pain in the case and control groups was 3.80 ± 3.00 and 8.08 ± 2.21 (P < 0.05), tearing was 1.56 ± 1.96 and 8.29 ± 2.42 (P < 0.05), photophobia was 5.44 ± 3.57 and 7.83 ± 2.64 (P < 0.05), foreign body sensation was 2.20 ± 2.78 and 6.54 ± 2.73 (P < 0.05), and irritation was 3.48 ± 2.98 and 6.79 ± 3.00 (P < 0.05), respectively. A statistical significant difference was maintained in pain values on day 1 (2.79 ± 3.09 and 4.91 ± 3.27 [P < 0.05]), 2 (2.54 ± 2.41 and 4.00 ± 2.43 [P < 0.05]), and 4 (0.45 ± 0.76 and 1.22 ± 1.67 [P < 0.05]).

Conclusions:

This study demonstrated that pain and associated symptoms decreased significantly in the riboflavin 4°C group.
Brief Report: Proportion and Predictors of Adult TB Contacts Accepting HIV Testing During an Active TB Case Finding Intervention in South Africa
Authors: Albaugh Nicholas W. , Nonyane Bareng A. S. , Mmolawa Lesego , Siwelana Tsundzukani , Lebina Limakatso , Dowdy David W. , Martinson Neil , Hanrahan Colleen F.
Published: October 2020

Background:

Many individuals at risk for HIV may be reached through active TB case finding interventions in areas with highly prevalent co-epidemics of TB/HIV.

Methods:

We analyzed data from a cluster-randomized trial of 2 TB case finding strategies: facility-based screening and contact investigation of newly identified TB cases. In both arms, on-site rapid HIV testing was offered to all contacts older than 18 months who did not self-report HIV-positive status. Those who were HIV infected were referred appropriately. All contacts 15 years and older were included in this analysis.

Results:

Among 2179 contacts identified, 50% (1092) accepted HIV testing and counselling, of whom 6.3% (68) tested HIV-positive. Contacts who were unemployed [adjusted prevalence ratio (aPR) 1.14, 95% confidence interval (CI): 1.04 to 1.25], had not been to a clinic (aPR 1.09, 95% CI: 1.02 to 1.18) or HIV tested (aPR 1.25, 95% CI: 1.14 to 1.39) 6 months before, and those reporting gastrointestinal symptoms (aPR 1.22, 95% CI: 0.98 to 1.52) and genitourinary symptoms (aPR 1.30, 95% CI: 1.17 to 1.45) were significantly associated with accepting HIV testing. Women [adjusted odds ratio (aOR) 2.19, 95% CI: 1.26 to 3.81], individuals with a past history of tuberculosis (aOR 1.96, 95% CI: 0.93 to 4.14), and those not HIV tested 6 months before (aOR 2.20, 95% CI: 1.28 to 3.79) were significantly associated with testing HIV-positive.

Conclusion:

Offering HIV testing in the context of active tuberculosis case finding represents an opportunity to identify a large proportion of previously undiagnosed individuals with HIV in a population that might otherwise not seek testing.
Comparison of 99mTc-Tilmanocept and Hybrid Indocyanine Green–99mTc-Albumin Nanocolloid Drainage in a Patient With Melanoma in the Scalp
Authors: Valhondo-Rama Raquel , Sánchez Izquierdo Nuria , Tapias Mesa Andrés , Perissinotti Andrés , Vidal-Sicart Sergi
Published: October 2020

We present the planar lymphoscintigraphies and SPECT/CT images of a 60-year-old man diagnosed as having melanoma (Breslow 1.8 mm) in left parietal scalp, close to head midline. Sentinel lymph node biopsy using 99mTc-tilmanocept was performed, but the surgery was canceled. Two weeks later, sentinel lymph node biopsy was repeated, but using the hybrid radiotracer indocyanine green–99mTc-albumin nanocolloid. The lymphatic drainage in left laterocervical region was similar with these 2 radiotracers, but on the right side, more sentinel lymph nodes were detected with nanocolloid compared with tilmanocept.
Mandibular Fracture in a Patient Taking a Direct Oral Anticoagulant
Authors: Sasaki Ryo , Okamoto Toshihiro , Sangu Noriko Miyamoto , Kudo Satoshi , Ando Tomohiro
Published: October 2020

A 74-year-old man presented with hemorrhage from the mandible after an injury caused by a 5 × 3 × 3-cm metal square column flying from a 45-ton press machine that struck the right side of his face. He is a known atrial fibrillation patient and is on rivaroxaban, a direct oral anticoagulant. An approximately 8-cm Y-shaped wound with persistent hemorrhage was observed in the right mandible, and the mandible was displaced between the right mandibular canine and first premolar. Although the patient showed no dyspnea, the sublingual region showed a slight dark purple swelling; fiberoptic nasal intubation was performed. Computed tomography at 3.5 hours after the injury revealed a comminuted fracture of the right mandibular body, edema at the floor of the mouth, nasal cavity, upper pharynx to hypopharynx, and the pharyngeal airway around the endotracheal tube. Open reduction and internal fixation were performed. Rivaroxaban was started again 3 days after surgery.
Calpain Activation and Organ Failure in Sepsis: Molecular Insights and Therapeutic Perspectives
Authors: Huang Yifan , Wang Grace , Peng Tianqing
Published: October 2020

Sepsis is a severe systemic response to infection; its ensuing organ failure commonly portends an unfavorable prognosis. Despite the fact that sepsis has been studied for decades, the molecular mechanisms underlying sepsis-induced organ dysfunction remain elusive and more complex than previously thought, and effective therapies are extremely limited. Calpain is a type of calcium-dependent cysteine protease that includes dozens of isoforms. Calpain, as well as its endogenous-specific inhibitor calpastatin, have been implicated in the pathogenesis of sepsis-induced organ dysfunction. Further, there is an accumulating body of evidence supporting the beneficial effect of calpain inhibition or regulation on multiple organ failure in sepsis. Better understanding of the underlying molecular mechanisms is helpful in the development of calpain/calpastatin-targeted therapeutic strategies to protect against sepsis-induced organ injury. The aim of this review is to summarize the recent literature and evidence surrounding the role of the calpain/calpastatin system in the process of organ dysfunction caused by sepsis—including regulation of cell death, modulation of inflammatory response, and disruption of critical proteins—to provide guidance for future research and therapy development.
Model Adequacy Tests for Likelihood Models of Chromosome-Number Evolution
Authors: Rice Anna , Mayrose Itay
Published: October 2020

Chromosome number is a central feature of eukaryote genomes. Deciphering patterns of chromosome-number change along a phylogeny is central to the inference of whole genome duplications and ancestral chromosome numbers. ChromEvol is a probabilistic inference tool that allows the evaluation of several models of chromosome-number evolution and their fit to the data. However, fitting a model does not necessarily mean that the model describes the empirical data adequately. This vulnerability may lead to incorrect conclusions when model assumptions are not met by real data.

Here, we present a model adequacy test for likelihood models of chromosome-number evolution. The procedure allows to determine whether the model can generate data with similar characteristics as those found in the observed ones.

We demonstrate that using inadequate models can lead to inflated errors in several inference tasks. Applying the developed method to 200 angiosperm genera, we find that in many of these, the best-fitted model provides poor fit to the data. The inadequacy rate increases in large clades or in those in which hybridizations are present.

The developed model adequacy test can help researchers to identify phylogenies whose underlying evolutionary patterns deviate substantially from current modelling assumptions and should guide future methods developments.
A dense linkage map for a large repetitive genome: discovery of the sex-determining region in hybridising fire-bellied toads (Bombina bombinaandB. variegata)
Authors: Nürnberger Beate , Baird Stuart J.E. , Čížková Dagmar , Bryjová Anna , Mudd Austin B. , Blaxter Mark L. , Szymura Jacek M.
Published: October 2020

Hybrid zones that result from secondary contact between diverged populations offer unparalleled insight into the genetic architecture of emerging reproductive barriers and so shed light on the process of speciation. Natural selection and recombination jointly determine their dynamics, leading to a range of outcomes from finely fragmented mixtures of the parental genomes that facilitate introgression to a situation where strong selection against recombinants retains large unrecombined genomic blocks that act as strong barriers to gene flow. In the hybrid zone between the fire-bellied toadsBombina bombinaandB. variegata(Anura: Bombinatoridae), two anciently diverged and ecologically distinct taxa meet and produce abundant, fertile hybrids. The dense linkage map presented here enables genomic analysis of the selection-recombination balance that keeps the two gene pools from merging into one. We mapped 4,775 newly developed marker loci from bait-enriched genomic libraries in F2 crosses. The enrichment targets were selected from a draft assembly of theB. variegatagenome, after filtering highly repetitive sequences. We developed a novel approach to infer the most likely diplotype per sample and locus from the raw read mapping data, which is robust to over-merging and obviates arbitrary filtering thresholds. Large-scale synteny betweenBombinaandXenopus tropicalissupports the resulting linkage map. By assessing the sex of late-stage F2 tadpoles from histological sections, we also identified the sex-determining region in theBombinagenome to 7 cM on LG5, which is homologous toX. tropicalischromosome 5, and inferred male heterogamety, suggestive of an XY sex determination mechanism. Interestingly, chromosome 5 has been repeatedly recruited as a sex chromosome in anurans with XY sex determination.
Hearing loss is associated with gray matter differences in older adults at risk for and with Alzheimer’s disease
Authors: Giroud N. , Pichora-Fuller M. K. , Mick P. , Wittich W. , Al-Yawer F. , Rehan S. , Orange J.B. , Phillips N. A.
Published: October 2020

Using data from the COMPASS-ND study we investigated associations between hearing loss and hippocampal volume as well as cortical thickness in older adults with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s dementia (AD). SCD participants with greater pure-tone HL exhibited lower hippocampal volume, but more cortical thickness in the left superior temporal gyrus and right pars opercularis. Greater speech-in-noise reception thresholds were associated with lower cortical thickness bilaterally across much of the cortex in AD. The AD group also showed a trend towards worse speech-in-noise thresholds compared to the SCD group.

Highlights

In SCD, greater pure-tone hearing loss was associated with lower right hippocampal volume.

Pure-tone hearing loss was not associated with brain atrophy in MCI or AD.

Individuals with AD exhibited a trend towards poorer speech-in-noise (SiN) thresholds than SCD.

In AD, greater atrophy across large portions of the cortex was associated with greater SiN thresholds.
Near-Fibre Electromyography
Authors: Piasecki Mathew , Estruch Oscar Garnés C. , Stashuk Daniel W
Published: October 2020

Near fibre electromyography (NFEMG) is the use of specifically high-pass filtered motor unit potential (MUPs) (i.e. near fibre MUPs (NFMs)) extracted from needle-detected EMG signals for the examination of changes in motor unit (MU) morphology and electrophysiology caused by neuromuscular disorders or ageing. The concepts of NFEMG, the parameters used, including NFM duration and dispersion, which relates to fibre diameter variability and/or endplate scatter, and a new measure of neuromuscular junction transmission (NMJ) instability, NFM segment jitter, and the methods for obtaining their values are explained. Evaluations using simulated needle-detected EMG data and exemplary human data are presented, described and discussed. The data presented demonstrate the ability of using NFEMG parameters to detect changes in MU fibre diameter variability, end plate scatter, and neuromuscular transmission time variability. These changes can be detected prior to alterations of MU size, numbers or muscle recruitment patterns.
Modelling testing and response strategies for COVID-19 outbreaks in remote Australian Aboriginal communities
Authors: Hui Ben B. , Brown Damien , Chisholm Rebecca H. , Geard Nicholas , McVernon Jodie , Regan David G.
Published: October 2020

Background

Remote Australian Aboriginal and Torres Strait Islander communities have potential to be severely impacted by COVID-19, with multiple factors predisposing to increased transmission and disease severity. Our modelling aims to inform optimal public health responses.

Methods

An individual-based simulation model represented communities ranging from 100 to 3,500 people, comprised of large interconnected households. A range of strategies for case finding, quarantining of contacts, testing, and lockdown were examined, following the silent introduction of a case.

Results

Multiple secondary infections are likely present by the time the first case is identified. Quarantine of close contacts, defined by extended household membership, can reduce peak infection prevalence from 60-70% to around 10%, but subsequent waves may occur when community mixing resumes. Exit testing significantly reduces ongoing transmission.

Concurrent lockdown of non-quarantined households for 14 days is highly effective for epidemic control and reduces overall testing requirements; peak prevalence of the initial outbreak can be constrained to less than 5%, and the final community attack rate to less than 10% in modelled scenarios. Lockdown also mitigates the effect of a delay in the initial response. Compliance with lockdown must be at least 80-90%, however, or epidemic control will be lost.

Conclusions

A SARS-CoV-2 outbreak will spread rapidly in remote communities. Prompt case detection with quarantining of extended-household contacts and a 14-day lockdown for all other residents, combined with exit testing for all, is the most effective strategy for rapid containment. Compliance is crucial, underscoring the need for community supported, culturally sensitive responses.
Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks
Authors: Schneider William M. , Luna Joseph M. , Hoffmann H.-Heinrich , Sánchez-Rivera Francisco J. , Leal Andrew A. , Ashbrook Alison W. , Le Pen Jérémie , Michailidis Eleftherios , Ricardo-Lax Inna , Peace Avery , Stenzel Ansgar F. , Lowe Scott W. , MacDonald Margaret R. , Rice Charles M. , Poirier John T.
Published: October 2020

The COVID-19 pandemic has claimed the lives of more than one million people worldwide. The causative agent, SARS-CoV-2, is a member of theCoronaviridaefamily, which are viruses that cause respiratory infections of varying severity. The cellular host factors and pathways co-opted by SARS-CoV-2 and other coronaviruses in the execution of their life cycles remain ill-defined. To develop an extensive compendium of host factors required for infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E), we performed parallel genome-scale CRISPR knockout screens. These screens uncovered multiple host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, SREBP signaling, and glycosylphosphatidylinositol biosynthesis, as well as an unexpected requirement for several poorly characterized proteins. We identified an absolute requirement for the VTT-domain containing protein TMEM41B for infection by SARS-CoV-2 and all other coronaviruses. This humanCoronaviridaehost factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus spillover events.

HIGHLIGHTS

Genome-wide CRISPR screens for SARS-CoV-2, HCoV-OC43, HCoV-NL63, and HCoV-229E coronavirus host factors.

Parallel genome-wide CRISPR screening uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles.

Coronaviruses co-opt multiple biological pathways, including glycosaminoglycan biosynthesis, SREBP signaling, and glycosylphosphatidylinositol biosynthesis and anchoring, among others.

TMEM41B - a poorly understood factor with roles in autophagy and lipid mobilization - is a critical pan-coronavirus host factor.
Interactions among mTORC, AMPK, and SIRT: A Computational Model for Cell Energy Balance and Metabolism
Authors: Sadria Mehrshad , Layton Anita T.
Published: October 2020

Key proteins such as mTORC, AMPK, and sirtuins are known to play an essential role in the management of metabolic stress and ageing mechanisms. An impairment in these mechanisms is commonly associated with cellular ageing and degenerative diseases. To understand the complex interactions of ageing□related signalling pathways and environmental signals, and the impacts on lifespan and health-span, we developed a computational model of ageing signalling pathways. The model includes (i) the insulin/IGF-1 pathway, which couples energy and nutrient abundance to the execution of cell growth and division, (ii) mTORC1 and amino acid sensors, (iii) the Preiss-Handler and salvage pathways, which regulate the metabolism of NAD+ and the NAD+-consuming factor SIRT1, (iv) the energy sensor AMPK, and (v) transcription factors FOXO and PGC-1α. Key findings include the clinically important role of PRAS40, sestrin2, and diet in the treatment of cancers and other diseases, and a potential link between SIRT1-activating compounds and premature autophagy. The model can be used as an essential component to simulate gene manipulation, therapies (e.g., rapamycin and wortmannin), calorie restrictions, and chronic stress, and to assess their functional implications on longevity and ageing□related diseases.

Author Summary

In cellular ageing, mitochondrial function declines over time, which affects normal mechanisms of cells and organisms and leads to myriad of degenerative diseases and other health problems. To investigate the mechanisms that affect the ageing process, we focus on pathways that play a key role in the management of metabolic stress: the mTORC, AMPK, and sirtuins pathways. Our goal is to understand the complex interactions of ageing and metabolism related signalling pathways and environmental signals, and the impacts on lifespan and health-span. To accomplish that goal, we developed a computational model of signalling pathways related to ageing and metabolism. By conducting model simulations, we have unraveled the clinically important role of PRAS40, sestrin2, and diet in the treatment of cancers and other diseases, and a double-edged sword effect of SIRT1-activating compounds in their use as a health remedy. We view this model as an essential step towards a tool for studying metabolism, longevity, and ageing-related diseases. By extending the present model as appropriate, we can simulate gene manipulation, therapies (e.g., rapamycin and wortmannin), calorie restrictions, and chronic stress,.
Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGF-β responses through SKI stabilization
Authors: Gori Ilaria , George Roger , Purkiss Andrew G. , Strohbuecker Stephanie , Randall Rebecca A. , Ogrodowicz Roksana , Carmignac Virginie , Faivre Laurence , Joshi Dhira , Kjaer Svend , Hill Caroline S.
Published: October 2020

Shprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated with enhanced TGF-β signaling. In SGS patients, heterozygous point mutations have been mapped to the transcriptional corepressor SKI, which is a negative regulator of TGF-β signaling that is rapidly degraded upon ligand stimulation. The molecular consequences of these mutations, however, are not understood. Here we use a combination of structural biology, genome editing and biochemistry to show that SGS mutations in SKI abolish its binding to phosphorylated SMAD2 and SMAD3. This results in stabilization of SKI and consequently attenuation of TGF-β responses, in both knockin cells expressing an SGS mutation, and in fibroblasts from SGS patients. Thus, we reveal that SGS is associated with an attenuation of TGF-β-induced transcriptional responses, and not enhancement, which has important implications for other Marfan-related syndromes.
Creating Clear and Informative Image-based Figures for Scientific Publications
Authors: Jambor Helena , Antonietti Alberto , Alicea Bradly , Audisio Tracy L. , Auer Susann , Bhardwaj Vivek , Burgess Steven J. , Ferling Iuliia , Gazda Małgorzata Anna , Hoeppner Luke H. , Ilangovan Vinodh , Lo Hung , Olson Mischa , Mohamed Salem Yousef , Sarabipour Sarvenaz , Varma Aalok , Walavalkar Kaivalya , Wissink Erin M. , Weissgerber Tracey L.
Published: October 2020

Scientists routinely use images to display data. Readers often examine figures first; therefore, it is important that figures are accessible to a broad audience. Many resources discuss fraudulent image manipulation and technical specifications for image acquisition; however, data on the legibility and interpretability of images are scarce. We systematically examined these factors in non-blot images published in the top 15 journals in three fields; plant sciences, cell biology and physiology (n=580 papers). Common problems included missing scale bars, misplaced or poorly marked insets, images or labels that were not accessible to colorblind readers, and insufficient explanations of colors, labels, annotations, or the species and tissue or object depicted in the image. Papers that met all good practice criteria examined for all image-based figures were uncommon (physiology 16%, cell biology 12%, plant sciences 2%). We present detailed descriptions and visual examples to help scientists avoid common pitfalls when publishing images. Our recommendations address image magnification, scale information, insets, annotation, and color and may encourage discussion about quality standards for bioimage publishing.
NOX4 links metabolic regulation in pancreatic cancer to endoplasmic reticulum redox vulnerability and dependence on PRDX4
Authors: Jain Pallavi , Dvorkin-Gheva Anna , Mollen Erik , Xie Michael , Jessa Fatima , Dhavarasa Piriththiv , Chung Stephen , Brown Kevin R. , Jang Gun Ho , Notta Faiyaz , Moffat Jason , Hedley David , Boutros Paul C. , Wouters Bradly G. , Koritzinsky Marianne
Published: October 2020

Pancreatic ductal adenocarcinoma (PDAC) is an almost universally fatal malignancy and there is an urgent need for new therapeutic targets. PDAC cells harbor genetic alterations and display metabolic changes that render them vulnerable to perturbations in redox homeostasis. Peroxiredoxin 4 (PRDX4) supports redox homeostasis by metabolizing H2O2 in the endoplasmic reticulum (ER). Based on functional genomics, we found that PDAC cell lines are dependent on PRDX4 for their growth and survival. We validated this dependency in established and primary PDAC cells, as well as 3D models and orthotopic xenografts. Cell death induced by PRDX4 depletion was accompanied by increased levels of reactive oxygen species (ROS), DNA damage and a DNA-PKcs-governed DNA damage response. As such, PRDX4 depletion also sensitized cells and tumors to ionizing radiation. The source of ROS that created a dependency on PRDX4 was attributed to NADPH oxidase 4 (NOX4), which localizes to the ER membrane. The functional requirement for PRDX4 was correlated with cellular NADPH levels across different models of PDAC and could be rescued by depletion of NOX4 or NADPH. As such, this study has identified NOX4 as a link between metabolic deregulation and ER-specific redox vulnerability in PDAC. Since PRDX4 is not an essential gene in normal tissues, our work also suggests that PRDX4 represents a novel therapeutic target for pancreatic cancer that may be particularly potent in combination with radiotherapy.
The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression
Authors: Kaya-Çopur Aynur , Marchiano Fabio , Hein Marco Y. , Alpern Daniel , Russeil Julie , Luis Nuno Miguel , Mann Matthias , Deplancke Bart , Habermann Bianca H. , Schnorrer Frank
Published: October 2020

Skeletal muscles are composed of gigantic cells called muscle fibers, packed with force-producing myofibrils. During development the size of individual muscle fibers must dramatically enlarge to match with skeletal growth. How muscle growth is coordinated with growth of the contractile apparatus is not understood. Here, we use the largeDrosophilaflight muscles to mechanistically decipher how muscle fiber growth is controlled. We find that regulated activity of core members of the Hippo pathway is required to support flight muscle growth. Interestingly, we identify Dlg5 and Slmap as regulators of the STRIPAK phosphatase, which negatively regulates Hippo to enable post-mitotic muscle growth. Mechanistically, we show that the Hippo pathway controls timing and levels of sarcomeric gene expression during development and thus regulates the key components that physically mediate muscle growth. Since Dlg5, STRIPAK and the Hippo pathway are conserved a similar mechanism may contribute to muscle or cardiomyocyte growth in humans.
Accounting for epistasis improves genomic prediction of phenotypes with univariate and bivariate models across environments
Authors: Vojgani Elaheh , Pook Torsten , Martini Johannes W.R. , Hölker Armin C. , Mayer Manfred , Schön Chris-Carolin , Simianer Henner
Published: October 2020

We compared the predictive ability of various prediction models for a maize dataset derived from 910 doubled haploid lines from European landraces (Kemater Landmais Gelb and Petkuser Ferdinand Rot), which were tested in six locations in Germany and Spain. The compared models were Genomic Best Linear Unbiased Prediction (GBLUP) as an additive model, Epistatic Random Regression BLUP (ERRBLUP) accounting for all pairwise SNP interactions, and selective Epistatic Random Regression BLUP (sERRBLUP) accounting for a selected subset of pairwise SNP interactions. These models have been compared in both univariate and bivariate statistical settings within and across environments. Our results indicate that modeling all pairwise SNP interactions into the univariate/bivariate model (ERRBLUP) is not superior in predictive ability to the respective additive model (GBLUP). However, incorporating only a selected subset of interactions with the highest effect variances in univariate/bivariate sERRBLUP can increase predictive ability significantly compared to the univariate/bivariate GBLUP. Overall, bivariate models consistently outperform univariate models in predictive ability. Over all studied traits, locations, and landraces, the increase in prediction accuracy from univariate GBLUP to univariate sERRBLUP ranged from 5.9 to 112.4 percent, with an average increase of 47 percent. For bivariate models, the change ranged from −0.3 to +27.9 percent comparing the bivariate sERRBLUP to the bivariate GBLUP. The average increase across traits and locations was 11 percent. This considerable increase in predictive ability achieved by sERRBLUP may be of interest for “sparse testing” approaches in which only a subset of the lines/hybrids of interest is observed at each location.

Key Message

The prediction accuracy of genomic prediction of phenotypes can be increased by only including top ranked pairwise SNP interactions into the prediction models.
Complete genome sequencing ofAcinetobacter baumanniiAC1633 andAcinetobacter nosocomialisAC1530 unveils a large multidrug resistant plasmid encoding the NDM-1 and OXA-58 carbapenemases
Authors: Alattraqchi Ahmed Ghazi , Rani Farahiyah Mohd. , Rahman Nor Iza A. , Ismail Salwani , Cleary David W. , Clarke Stuart C. , Yeo Chew Chieng
Published: October 2020

Carbapenem-resistantAcinetobacterspp. are considered priority drug-resistant human pathogenic bacteria. The genomes of two carbapenem-resistantAcinetobacterspp. clinical isolates obtained from the same tertiary hospital in Terengganu, Malaysia, namelyA. baumanniiAC1633 andA. nosocomialisAC1530, were sequenced. Both isolates were found to harbor the carbapenemase genesblaNDM-1andblaOXA-58in a large (ca. 170 kb) plasmid designated pAC1633-1 and pAC1530, respectively, that also encodes genes that confer resistance to aminoglycosides, sulfonamides, and macrolides. The two plasmids were almost identical except for the insertion of ISAba11and an IS4family element in pAC1633-1, and ISAba11along withrelBEtoxin-antitoxin genes flanked by inversely orientated pdif(XerC/XerD) recombination sites in pAC1530. TheblaNDM-1gene was encoded in aTn125composite transposon structure flanked by ISAba125whereasblaOXA-58was flanked by ISAba11and ISAba3downstream and a partial ISAba3element upstream within a pdifmodule. The presence of conjugative genes in plasmids pAC1633-1/pAC1530 and their discovery in two distinct species ofAcinetobacterfrom the same hospital are suggestive of conjugative transfer but mating experiments failed to demonstrate transmissibility under standard laboratory conditions. Comparative sequence analysis strongly inferred that pAC1633-1/pAC1530 was derived from two separate plasmids in an IS1006-mediated recombination or transposition event.A. baumanniiAC1633 also harbored three other plasmids designated pAC1633-2, pAC1633-3 and pAC1633-4. Both pAC1633-3 and pAC1633-4 are cryptic plasmids whereas pAC1633-2 is a 12,651 bp plasmid of the GR8/GR23 Rep3-superfamily group that encodes thetetA(39)tetracycline resistance determinant in a pdifmodule.