bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Workload Associated With Learning Foot Core Exercises
Authors: Newsham Katherine
Published: September 2021

Patients and clinicians have expressed frustration when learning or teaching intrinsic foot muscle exercises. However, there is limited information on how patients perceive the workload of an exercise. This study evaluates participants’ perceptions of workload while learning intrinsic foot muscle exercises with or without neuromuscular electrical stimulation. Twenty-six individuals completed a 4-week supervised intrinsic foot muscle training program. Thirteen participants utilized neuromuscular electrical stimulation during the initial 2 weeks of training. Participant perceptions of workload, measured by the National Aeronautics and Space Administration Task Load Index, revealed decreasing load over 2 weeks and minimal load at 4 weeks. Inclusion of neuromuscular electrical stimulation did not affect perception of load of skill acquisition.
Hip Injury Profile and Time Missed From Participation in Male National Collegiate Athletic Association Division I Baseball Athletes
Authors: Bolia Ioanna K. , Bell Jennifer A. , Kang Hyunwoo P. , Haratian Aryan , Hasan Laith K. , Eppler Michael B. , Romano Russ , Tibone James E. , Gamradt Seth C. , Weber Alexander E.
Published: September 2021

Context: It is important to examine hip injury characteristics in baseball athletes in order to develop injury-specific prevention protocols. There is currently a lack of literature regarding collegiate baseball athletes. Objective: To report the hip injury characteristics and time missed from sport participation in National Collegiate Athletic Association Division I baseball players over a period of 5 years. Results: Forty-seven hip–groin injuries were recorded in 30 National Collegiate Athletic Association Division I baseball players. Pitchers had the highest number of hip–groin injuries (24/47, 51%), and outfielders had the longest time missed from baseball participation (33 days on average). The two most common types of hip–groin injuries were femoroacetabular impingement syndrome (14/47, 30%) and hip adductor strain (14/47, 30%). Days missed from baseball participation was 4.5 days (range: 4–7) for short-term injuries and 90 days (range: 46–131) for long-term injuries. Interpretations: Femoroacetabular impingement syndrome and adductor muscle strain were the predominant diagnoses in National Collegiate Athletic Association Division I baseball players with hip–groin injury; short-term injuries resulted in ∼5 days missed but recovery from a long-term injury took ∼3 months. Pitchers had the highest number of injuries (including adductor strain and femoroacetabular impingement syndrome).
Anomalous interfacial dynamics of single proton charges in binary aqueous solutions
Authors: Comtet Jean , Rayabharam Archith , Glushkov Evgenii , Zhang Miao , Avsar Ahmet , Watanabe Kenji , Taniguchi Takashi , Aluru Narayana R. , Radenovic Aleksandra
Published: September 2021

Single-molecule localization microscopy reveals a marked influence of solvation on interfacial proton charge dynamics.
100,000-spin coherent Ising machine
Authors: Honjo Toshimori , Sonobe Tomohiro , Inaba Kensuke , Inagaki Takahiro , Ikuta Takuya , Yamada Yasuhiro , Kazama Takushi , Enbutsu Koji , Umeki Takeshi , Kasahara Ryoichi , Kawarabayashi Ken-ichi , Takesue Hiroki
Published: September 2021

We constructed a large optical computer based on optical parametric oscillators coupled via measurement and feedback.
Learning the solution operator of parametric partial differential equations with physics-informed DeepONets
Authors: Wang Sifan , Wang Hanwen , Perdikaris Paris
Published: September 2021

Enabling the rapid emulation of parametric differential equations with physics-informed deep operator networks.
Microporous polymers with cascaded cavities for controlled transport of small gas molecules
Authors: Seong Jong Geun , Lee Won Hee , Lee Jongmyeong , Lee So Young , Do Yu Seong , Bae Joon Yong , Moon Sun Ju , Park Chi Hoon , Jo Hye Jin , Kim Ju Sung , Lee Kueir-Rarn , Hung Wei-Song , Lai Juin-Yih , Ren Yi , Roos Conrad J. , Lively Ryan P. , Lee Young Moo
Published: September 2021

Cascaded microporosity localized on membrane surfaces markedly improved selective transport of small molecules.
Reconciling evidence of oxidative weathering and atmospheric anoxia on Archean Earth
Authors: Johnson Aleisha C. , Ostrander Chadlin M. , Romaniello Stephen J. , Reinhard Christopher T. , Greaney Allison T. , Lyons Timothy W. , Anbar Ariel D.
Published: September 2021

New modeling of early Mo cycle places constraints on Archean O
2
.
Iron oxide nanoparticles augment the intercellular mitochondrial transfer–mediated therapy
Authors: Huang Ting , Zhang Tianyuan , Jiang Xinchi , Li Ai , Su Yuanqin , Bian Qiong , Wu Honghui , Lin Ruyi , Li Ni , Cao Hongcui , Ling Daishun , Wang Jinqiang , Tabata Yasuhiko , Gu Zhen , Gao Jianqing
Published: September 2021

Iron oxide nanoparticles could significantly promote the mitochondrial transfer from mesenchymal stem cells to the injured cells.
By the time we build robots that care for us, will we be able to care for them?
Authors: Murphy Robin R.
Published: September 2021

Klara and the Sun
by Kazuo Ishiguro is reviewed.
ULK1 inhibition promotes oxidative stress–induced differentiation and sensitizes leukemic stem cells to targeted therapy
Authors: Ianniciello Angela , Zarou Martha M. , Rattigan Kevin M. , Scott Mary , Dawson Amy , Dunn Karen , Brabcova Zuzana , Kalkman Eric R. , Nixon Colin , Michie Alison M. , Copland Mhairi , Vetrie David , Ambler Martin , Saxty Barbara , Helgason G. Vignir
Published: September 2021

ULK1 inhibition increases the sensitivity of leukemia stem cells to TKI therapy by modulating energy and redox balance.
CPEB alteration and aberrant transcriptome-polyadenylation lead to a treatable SLC19A3 deficiency in Huntington’s disease
Authors: Picó Sara , Parras Alberto , Santos-Galindo María , Pose-Utrilla Julia , Castro Margarita , Fraga Enrique , Hernández Ivó H. , Elorza Ainara , Anta Héctor , Wang Nan , Martí-Sánchez Laura , Belloc Eulàlia , Garcia-Esparcia Paula , Garrido Juan J. , Ferrer Isidro , Macías-García Daniel , Mir Pablo , Artuch Rafael , Pérez Belén , Hernández Félix , Navarro Pilar , López-Sendón José Luis , Iglesias Teresa , Yang X. William , Méndez Raúl , Lucas José J.
Published: September 2021

Altered CPEBs and mRNA polyadenylation lead to thiamine deficiency in the brains of patients and mice with Huntington’s disease.
Aberrant activation of m6A demethylase FTO renders HIF2α
low/−
clear cell renal cell carcinoma sensitive to BRD9 inhibitors
Authors: Zhang ChuanJie , Chen Lu , Lou WeiJuan , Su JunHui , Huang JingYi , Liu Ao , Xu Yang , He HongChao , Gao Yi , Xu DanFeng , Li QingQuan
Published: September 2021

Hypoxia-inducible factor 2α (HIF2α) antagonists are effective against clear cell renal cell carcinomas (ccRCCs) that highly express HIF2α. To identify potential drug targets in HIF2α
low/−
ccRCC, we constructed an epigenetic-focused single-guide RNA library and performed an in vivo CRISPR-Cas9 knockout screen in BALB/c nude mice transplanted with 786-O (HIF2α
high
) or Caki-2 (HIF2α
low/−
) cells. We found that the m6A demethylase fat mass and obesity-associated (
FTO
) gene was indispensable to the growth of HIF2α
low/−
but not HIF2α
high
ccRCC. Activation of FTO in HIF2α
low/−
ccRCC was caused by an increased intracellular α-ketoglutarate–to-succinate ratio and stabilized bromodomain-containing protein 9 (
BRD9
) messenger RNA via m6A demethylation. RNA sequencing and chromatin immunoprecipitation sequencing profiling further revealed that SRY-box transcription factor 17 (SOX17) recruited BRD9 to de novo super enhancers associated with genes that feature prominently in ccRCC pathogenesis, including
CCND1
,
VEGFR2
,
CDC20
,
SRC
, and
MAPK6
.
BRD9
knockdown or the BRD9-selective antagonist I-BRD9 suppressed the growth of HIF2α
low/−
but not HIF2α
high
ccRCC cells in vitro. In BALB/c nude mice bearing HIF2α
low/−
ccRCC cell line–derived xenografts and patient-derived tumor xenografts, I-BRD9 administration effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice with greater efficacy than sunitinib. Together, these findings indicate that BRD9 is a druggable target for treating HIF2α
low/−
ccRCC.
Oligo-heterotrophic Activity of
Marinobacter subterrani
Creates an Indirect Fe(II) Oxidation Phenotype in Gradient Tubes
Authors: Jain Abhiney , Bonis Benjamin M. , Gralnick Jeffrey A.
Published: September 2021

Gradient tubes are the most commonly used method to isolate and identify neutrophilic Fe(II)-oxidizing bacteria. The formation of oxidized iron bands in gradient tubes provides a compelling assay to ascribe the ability to oxidize Fe(II) to autotrophic bacteria whose growth is dependent on Fe(II) oxidation.
A Combination of Genomics, Transcriptomics, and Genetics Provides Insights into the Mineral Weathering Phenotype of Pseudomonas azotoformans F77
Authors: Wang Yuan-Li , Dong Wen , Xiang Kai-Xiang , Wang Qi , He Lin-Yan , Sheng Xia-Fang
Published: September 2021

Acid production and tolerance play important roles in effective and persistent mineral weathering in bacteria, although the molecular mechanisms governing acid production and acid tolerance in bacteria have not been fully elucidated. In this study, the molecular mechanisms underlying biotite (as a silicate mineral) weathering (dissolution) and acid tolerance of
P. azotoformans
F77 were characterized using genomics, transcriptomics, and genetics analyses.
Overexpression of Oxidoreductase YghA Confers Tolerance of Furfural in Ethanologenic Escherichia coli Strain SSK42
Authors: Jilani S. Bilal , Prasad Rajendra , Yazdani Syed Shams
Published: September 2021

Lignocellulosic biomass represents an inexhaustible source of carbon for second-generation biofuels. Thermo-acidic pretreatment of biomass is performed to loosen the lignocellulosic fibers and make the carbon bioavailable for microbial metabolism.
Performance Evaluation of the BD SARS-CoV-2 Reagents for the BD MAX System
Authors: Yanson Karen , Laviers William , Neely Lori , Lockamy Elizabeth , Castillo-Hernandez Luis Carlos , Oldfied Christopher , Ackerman Ronald , Ackerman Jamie , Ortiz Daniel A. , Pacheco Sixto , Simner Patricia J. , Young Stephen , McElvania Erin , Cooper Charles K.
Published: September 2021

Nucleic acid amplification testing (NAAT) for SARS-CoV-2 is the standard approach for confirming COVID-19 cases. This study compared results between two emergency use authorization (EUA) NAATs, with two additional EUA NAATs utilized for discrepant testing.
Improved Molecular Diagnosis and Culture of the Emerging Heteropathotype Enterohemorrhagic Escherichia coli O80:H2 Using Its Non-Melibiose-Fermenting and Antibiotic-Resistance Properties
Authors: Bizot Etienne , Cointe Aurélie , Smadja Natacha , Sergentet Delphine , Lefèvre Sophie , Weill François-Xavier , Levy Corinne , Cohen Robert , Mariani-Kurkdjian Patricia , Bonacorsi Stéphane
Published: September 2021

Enterohemorrhagic
Escherichia coli
(EHEC) O80:H2, belonging to sequence type ST301, is among the main causes of hemolytic and uremic syndrome in Europe, a major concern in young children. Aside from the usual intimin and Shiga toxin virulence factors (VFs), this emerging serotype possesses a mosaic plasmid combining extra-intestinal VF- and antibiotic resistance-encoding genes.
Convergent HIV-1 Evolution upon Targeted Destabilization of the gp120-gp41 Interface
Authors: Torrents de la Peña Alba , del Moral Sánchez Iván , Burger Judith A. , Bontjer Ilja , Isik Gözde , Eggink Dirk , van Gils Marit J. , Sanders Rogier W.
Published: September 2021

A successful HIV-1 vaccine most likely requires an envelope glycoprotein (Env) component, as Env is the only viral protein on the surface of the virus and the target for neutralizing antibodies. However, HIV Env is metastable and flexible because of the weak interactions between the Env subunits, complicating the generation of recombinant mimics of native Env.
Structures of Foot-and-Mouth Disease Virus with Bovine Neutralizing Antibodies Reveal the Determinant of Intraserotype Cross-Neutralization
Authors: He Yong , Li Kun , Wang Li , Sun Zixian , Cao Yimei , Li Pinghua , Sun Pu , Bao Huifang , Zhou Shasha , Wang Sheng , Bai Xingwen , Liu Xuerong , Zhao Lixia , Fan Xiuli , Liu Zaixin , Lu Zengjun , Yang Cheng , Lou Zhiyong
Published: September 2021

Foot-and-mouth disease virus (FMDV) causes a highly contagious and economically devastating disease in cloven-hoofed animals, and neutralizing antibodies play critical roles in the defense against viral infections. Here, we isolated a bovine antibody (R55) using the single B cell antibody isolation technique.
Evolution of Antibodies to Native Trimeric Envelope and Their Fc-Dependent Functions in Untreated and Treated Primary HIV Infection
Authors: Nagel Lauren , Kant Sanket , Leeks Christopher , Routy Jean-Pierre , Tremblay Cécile , Thomas Réjean , Szabo Jason , Côté Pierre , Trottier Benoit , LeBlanc Roger , Rouleau Danielle , Dupuy Franck P. , Bernard Nicole F. ,   for the investigators in Montreal Primary HIV Infection cohort
Published: September 2021

Closed-conformation envelope is expressed on the surface of HIV-infected cells. Antibodies targeting this conformation and that support FcDFs have the potential to control HIV.
Sugar-Phosphate Toxicities
Authors: Boulanger Erin F. , Sabag-Daigle Anice , Thirugnanasambantham Pankajavalli , Gopalan Venkat , Ahmer Brian M. M.
Published: September 2021

Accumulation of phosphorylated intermediates during cellular metabolism can have wide-ranging toxic effects on many organisms, including humans and the pathogens that infect them. These toxicities can be induced by feeding an upstream metabolite (a sugar, for instance) while simultaneously blocking the appropriate metabolic pathway with either a mutation or an enzyme inhibitor.
Host-Environment Interplay Shapes Fungal Diversity in Mosquitoes
Authors: Tawidian Patil , Coon Kerri L. , Jumpponen Ari , Cohnstaedt Lee W. , Michel Kristin
Published: September 2021

The Asian tiger mosquito,
Aedes albopictus
, is the dominant mosquito species in the United States and an important vector of arboviruses of major public health concern. One aspect of mosquito control to curb mosquito-borne diseases has been the use of biological control agents such as fungal entomopathogens.
mSphere of Influence: How I Learned to Love Bacteria and their Tangled Evolutionary Tree
Authors: Levin Tera C.
Published: September 2021

Tera Levin works in the fields of evolution, microbiology, and genetics, studying how adaptation shapes the molecular interactions between eukaryotic hosts and bacterial pathogens. In this mSphere of Influence article, she reflects on how the paper “Population genomics of early events in the ecological differentiation of bacteria” by Shapiro et al. (B.
Early Neonatal Meconium Does Not Have a Demonstrable Microbiota Determined through Use of Robust Negative Controls with
cpn
60-Based Microbiome Profiling
Authors: Dos Santos Scott J. , Pakzad Zahra , Elwood Chelsea N. , Albert Arianne Y. K. , Gantt Soren , Manges Amee R. , Dumonceaux Tim J. , Maan Evelyn J. , Hill Janet E. , Money Deborah M. ,   The Maternal Microbiome Legacy Project Team
Published: September 2021

Much like the recent placental microbiome controversy, studies of neonatal meconium reporting bacterial communities within the fetal and neonatal gut imply that microbial colonization begins prior to birth. However, recent work has shown that placental microbiomes almost exclusively represent contamination from lab reagents and the environment.
A New Thienopyrimidinone Chemotype Shows Multistage Activity against Plasmodium falciparum, Including Artemisinin-Resistant Parasites
Authors: Bosson-Vanga Henriette , Primas Nicolas , Franetich Jean-François , Lavazec Catherine , Gomez Lina , Ashraf Kutub , Tefit Maurel , Soulard Valérie , Dereuddre-Bosquet Nathalie , Le Grand Roger , Donnette Mélanie , Mustière Romain , Amanzougaghene Nadia , Tajeri Shahin , Suzanne Peggy , Malzert-Fréon Aurélie , Rault Sylvain , Vanelle Patrice , Hutter Sébastien , Cohen Anita , Snounou Georges , Roques Pierre , Azas Nadine , Lagardère Prisca , Lisowski Vincent , Masurier Nicolas , Nguyen Michel , Paloque Lucie , Benoit-Vical Françoise , Verhaeghe Pierre , Mazier Dominique
Published: September 2021

This work reports a new chemical structure that (i) displays activity against the human malaria parasite
Plasmodium falciparum
at 3 stages of the parasitic cycle (blood stage, hepatic stage, and sexual stages), (ii) remains active against parasites that are resistant to the first-line treatment recommended by the World Health Organization (WHO) for the treatment of severe malaria (artemisinins), and (iii) reduces transmission of the parasite to the mosquito vector in a mouse model. This new molecule family could open the way to the conception of novel antimalarial drugs with an original multistage mechanism of action to fight against
Plasmodium
drug resistance and block interhuman transmission of malaria.
Isolation, Screening, and Degradation Characteristics of a Quinclorac-Degrading Bacterium, Strain D, and Its Potential for Bioremediation of Rice Fields Polluted by Quinclorac
Authors: Huang Siqi , Pan Jiuyue , Tuwang Mancuo , Li Hongyan , Ma Chenyi , Chen Mingxue , Lin Xiaoyan
Published: September 2021

QNC-degrading bacteria have been isolated from different environments, but there are no reports of
Cellulosimicrobium cellulans
strains that degrade QNC. In this study, a previously unidentified bacterial strain that degrades QNC, strain D, was screened from paddy soil.
Antimicrobial Resistance and Type III Secretion System Virulotypes of Pseudomonas aeruginosa Isolates from Dogs and Cats in Primary Veterinary Hospitals in Japan: Identification of the International High-Risk Clone Sequence Type 235
Authors: Hayashi Wataru , Izumi Katsutoshi , Yoshida Satoshi , Takizawa Shino , Sakaguchi Kanae , Iyori Keita , Minoshima Ken-ichi , Takano Shinya , Kitagawa Maki , Nagano Yukiko , Nagano Noriyuki
Published: September 2021

Pseudomonas aeruginosa
is an environmentally ubiquitous and important opportunistic human pathogen responsible for life-threatening health care-associated infections. Because of its extensive repertoire of virulence determinants and intrinsic and acquired resistance mechanisms, the organism could be one of the most clinically and epidemiologically important causes of morbidity and mortality.
Adaptation to Fluconazole via Aneuploidy Enables Cross-Adaptation to Amphotericin B and Flucytosine in Cryptococcus neoformans
Authors: Yang Feng , Gritsenko Vladimir , Lu Hui , Zhen Cheng , Gao Lu , Berman Judith , Jiang Yuan-ying
Published: September 2021

Cryptococcosis is a globally distributed invasive fungal infection caused by infections with
Cryptococcus neoformans
or
Cryptococcus gattii
. Only three classes of therapeutic drugs are clinically available for treating cryptococcosis: polyenes (amphotericin B), azoles (fluconazole), and pyrimidine analogues (flucytosine).
Drug Target Validation of the Protein Kinase
AEK1,
Essential for Proliferation, Host Cell Invasion, and Intracellular Replication of the Human Pathogen Trypanosoma cruzi
Authors: Chiurillo Miguel A. , Jensen Bryan C. , Docampo Roberto
Published: September 2021

Chagas disease affects 6 to 7 million people in the Americas, and its treatment has been limited to drugs with relatively high toxicity and low efficacy in the chronic phase of the infection. New validated targets are needed to combat this disease. In this work, we report the chemical and genetic validation of the protein kinase AEK1, which is essential for cytokinesis and infectivity, using a novel gene editing strategy.
Mutations in the Methyltransferase Motifs of L Protein Attenuate Newcastle Disease Virus by Regulating Viral Translation and Cell-to-Cell Spread
Authors: Li Xiao , Sun Lu , Zhao Jing , Tu Kaihang , Xue Jia , Guo Xin , Zhang Guozhong
Published: September 2021

Newcastle disease virus (NDV) is an important pathogen that is widespread globally. Research on its pathogenic mechanism is an important means of improving prevention and control efforts.
Viewpoint: digital paediatrics—so close yet so far away
Authors: Hensel Kai O , Powell John
Published: September 2021

Technology is driving a revolution in healthcare, but paediatric services have not fully harnessed the potential. Digital health solutions yet to achieve their promise in paediatrics include electronic health records, decision support systems, telemedicine and remote consultations, despite the accelerated uptake during the COVID-19 pandemic. There are also significant potential benefits in digitally enabled research, including systems to identify and recruit participants online or through health records, tools to extract data points from routine data sets rather than new data collection, and remote approaches to outcome measurement. Children and their families are increasingly becoming digital health citizens, able to manage their own health and use of health services through mobile apps and wearables such as fitness trackers. Ironically, one barrier to the uptake of these technologies is that the fast pace of change in this area means the evidence base behind many of these tools remains underdeveloped. Clinicians are often sceptical of innovations which appear largely driven by enthusiasts rather than science. Rigorous studies are needed to demonstrate safety and effectiveness. Regulators need to be agile and responsive. Implementation needs adequate resource and time, and needs to minimise risks and address concerns, such as worries over losing human contact. Digital health care needs to be embedded in medical education and training so that clinicians are trained in the use of innovations and can understand how to embed within services. In this way, digital paediatrics can deliver benefits to the profession, to services and to our patients.
Intermediate-term outcomes of the Aurolab aqueous drainage implant in neovascular glaucoma
Authors: Gnanavelu Subathra , Puthuran George Varghese , Chiranjeevi Kousalya Pavani , Wijesinghe Hiruni Kaushalya , Reddy Vishnuvardhan , Mani Iswarya , Krishnadas Subbaiah Ramasamy , Gedde Steven Jon
Published: September 2021

Purpose

To assess the outcomes of the non-valved Aurolab aqueous drainage implant (AADI) in neovascular glaucoma (NVG).

Methods

Data of consecutive patients with NVG who underwent AADI and had a minimum follow-up of 2 years were included. The primary outcome measure was the cumulative rate of surgical failure defined as intraocular pressure (IOP) >21 mm Hg or reduced <20% below baseline, IOP ≤5 mm Hg, reoperation for glaucoma or a complication, or loss of light perception vision.

Results

We included 85 eyes of 85 patients with NVG, with a mean age of 61.2±9.3 years. The most common aetiologies were proliferative diabetic retinopathy (n=43) and central retinal vein occlusion (n=24). The mean IOP decreased from 36.8±12.5 mm Hg at baseline to 15.8±7.5 mm Hg at 2-year follow-up (p<0.001) and the number of IOP-lowering medications reduced from 3.4±0.8 to 1.5±1.1 (p<0.001). The cumulative rate of failure increased from 3.1% (95% CI 1.1% to 11.8%) at 1 year to 33.8% (95% CI 20.4% to 52.5%) at 2 years. Multivariable analysis showed that eyes with open angles had a lower risk of failure (HR 0.17, 95% CI 0.10 to 1.03, p=0.09). The logarithm of minimum angle of resolution visual acuity declined from 0.98±0.7 to 1.8±1.0 at 2 years (p<0.001).

Conclusion

Approximately one-third of NVG eyes that received the AADI failed after 2 years of follow-up similar to other series. Early AADI implantation at the open angle stage of NVG may yield better results.
An essential accessory
Authors: Prince David , Popuri Radha , Majumdar Avik
Published: September 2021

A young adult male was referred for a second opinion of deranged liver biochemistry. He initially presented two years prior with abdominal pain, lethargy and fevers due to a segment two pyogenic liver abscess. He received empirical antibiotic therapy to resolution. Computed tomography for abscess follow-up revealed an intrahepatic inferior vena cava thrombus. He was anti-coagulated with warfarin. He was lupus anticoagulant positive and had a highly positive beta-2 glycoprotein antibody on serial measurement and was diagnosed with anti-phospholipid syndrome. On current review, the patient had no clinical stigmata of chronic liver disease. There were dilated veins on the supraumbilical abdominal and chest walls. There was mild hepatomegaly but no splenomegaly. Laboratory investigations revealed mildly cholestatic liver function tests with hyperbilirubinaemia (40μmol/L) but no liver synthetic dysfunction. Serological screening did not reveal any cause of chronic liver disease. The patient underwent multiphase abdominal CT and formal hepatic venography. What is the diagnosis and describe the hepatic venous outflow?
Prevalence of dry eye in patients with systemic lupus erythematosus: a meta-analysis
Authors: Wang Lixiang , Xie Yan , Deng Yingping
Published: September 2021

Objectives

To investigate dry eye disease (DED) in patients affected by systemic lupus erythematosus (SLE).

Methods

We conducted a systematic search of the literature on PubMed, EMBASE and the Cochrane Library databases from conception to 30 April 2020 for studies related to dry eye, secondary Sjögren’s syndrome (sSS) and SLE. Original full-text articles with the number of patients diagnosed with SLE of over 15 were included. The risk of bias was evaluated with a validated critical appraisal tool which assessed study quality based on confounding factors, selection bias, bias related to measurement and bias related to data analysis. Data were extracted and pooled to evaluate the overall prevalence of DED with the random-effect model and sSS with the fixed effect model.

Results

A total of 29 studies were included and 18 273 participants were involved. The pooled data showed that the overall prevalence of DED was 16% (95% CI 10% to 21%, p<0.001) in patients of SLE. Dry eye symptoms and abnormal Schirmer’s test were found in 26% (95% CI 20% to 32%, p<0.001) and 24% (95% CI 14% to 34%, p<0.001) of patients with SLE, respectively. 12% (95% CI 9% to 15%, p<0.001) of patients also met the criteria of sSS. The OR of DED in patients with SLE was 4.26 (95% CI 3.47 to 5.05, p<0.001) compared with healthy controls. The meta-regression analysis showed that the sample size (p=0.004) and study location (p=0.022) could be the source of heterogeneity.

Conclusions

DED and sSS are both common in patients with SLE.
What factors are associated with ambulance use for non-emergency problems in children? A systematic mapping review and qualitative synthesis
Authors: Proctor Alyesha , Baxter Helen , Booker Matthew James
Published: September 2021

Objective

To explore what factors are associated with ambulance use for non-emergency problems in children.

Methods

This study is a systematic mapping review and qualitative synthesis of published journal articles and grey literature. Searches were conducted on the following databases, for articles published between January 1980 and July 2020: MEDLINE, EMBASE, PsycINFO, CINAHL and AMED. A Google Scholar and a Web of Science search were undertaken to identify reports or proceedings not indexed in the above. Book chapters and theses were searched via the OpenSigle, EThOS and DART databases. A literature advisory group, including experts in the field, were contacted for relevant grey literature and unpublished reports. The inclusion criteria incorporated articles published in the English language reporting findings for the reasons behind why there are so many calls to the ambulance service for non-urgent problems in children. Data extraction was divided into two stages: extraction of data to generate a broad systematic literature ‘map’, and extraction of data from highly relevant papers using qualitative methods to undertake a focused qualitative synthesis. An initial table of themes associated with reasons for non-emergency calls to the ambulance for children formed the ‘thematic map’ element. The uniting feature running through all of the identified themes was the determination of ‘inappropriateness’ or ‘appropriateness’ of an ambulance call out, which was then adopted as the concept of focus for our qualitative synthesis.

Results

There were 27 articles used in the systematic mapping review and 17 in the qualitative synthesis stage of the review. Four themes were developed in the systematic mapping stage: socioeconomic status/geographical location, practical reasons, fear of consequences and parental education. Three analytical themes were developed in the qualitative synthesis stage including practicalities and logistics of obtaining care, arbitrary scoring system and retrospection.

Conclusions

There is a lack of public and caregiver understanding about the use of ambulances for paediatrics. There are factors that appear specific to choosing ambulance care for children that are not so prominent in adults (fever, reassurance, fear of consequences). Future areas for attention to decrease ambulance activation for paediatric low-acuity reports were highlighted as: identifying strategies for helping caregivers to mitigate perceived risk, increasing availability of primary care, targeted education to particular geographical areas, education to first-time parents with infants and providing alternate means of transportation.

PROSPERO registration number

CRD42019160395.
Outpatient parenteral antimicrobial therapy (OPAT) versus inpatient care in the UK: a health economic assessment for six key diagnoses
Authors: Dimitrova Maria , Gilchrist Mark , Seaton R A
Published: September 2021

Objectives

To compare costs associated with different models of outpatient parenteral antimicrobial therapy (OPAT) delivery with costs of inpatient (IP) care across key infection groups managed via OPAT in the UK.

Design

A cost-minimisation design was used due to evidence of similarities in patient and treatment outcomes between OPAT and IP care. A bottom-up approach was undertaken for the evaluation of OPAT associated costs. The British Society of Antimicrobial Chemotherapy National Outcomes Registry System was used to determine key infection diagnoses, mean duration of treatment and most frequent antibiotics used.

Setting

Several OPAT delivery settings were considered and compared with IP care.

Interventions

OPAT models considered were OP clinic model, nurse home visits, self (or carer)-administration by a bolus intravenous, self-administration by a commercially prefilled elastomeric device, continuous intravenous infusion of piperacillin with tazobactam or flucloxacillin with elastomeric device as OP once daily and, specifically for bone and joint and diabetic foot infections, complex outpatient oral antibiotic therapies.

Results

Base case and a range of scenario results showed all evaluated OPAT service delivery models to be less costly than IP stay of equivalent duration. The extent of savings varied by OPAT healthcare delivery models. Estimated OPAT costs as a proportion of IP costs were estimated at 0.23–0.53 (skin and soft-tissue infections), 0.34–0.46 (complex urinary tract infections), 0.23–0.51 (orthopaedic infections), 0.24–0.42 (diabetic foot infections) 0.40–0.56 (exacerbations of bronchiectasis) and 0.25–0.42 (intra-abdominal infections). Partial or full complex oral antibiotic therapies in orthopaedic or diabetic foot infections costs were estimated to be 0.13–0.26 of IP costs. Main OPAT costs were associated with staff time and antimicrobial medications.

Conclusions

OPAT is a cost-effective use of National Health Service resources for the treatment of a range of infections in the UK in patients who can be safely managed in a non-IP setting.
Added value of functional neuroimaging to assess decision-making capacity of older adults with neurocognitive disorders: protocol for a prospective, monocentric, single-arm study (IMAGISION)
Authors: Tannou Thomas , Godard-Marceau Aurelie , Joubert Sven , Daneault Serge , Kergoat Marie-Jeanne , Magnin Eloi , Comte Alexandre , Gabriel Damien , Vidal Chrystelle , Pazart Lionel , Aubry Regis
Published: September 2021

Introduction

Assessment of decision-making capacity (DMC) is essential in daily life as well as for defining a person-centred care plan. Nevertheless, in ageing, especially if signs of dementia appear, it becomes difficult to assess decision-making ability and raises ethical questions. Currently, the assessment of DMC is based on the clinician’s evaluation, completed by neuropsychological tests. Functional MRI (fMRI) could bring added value to the diagnosis of DMC in difficult situations.

Methods and analysis

IMAGISION is a prospective, monocentric, single-arm study evaluating fMRI compared with clinical assessment of DMC. The study will begin during Fall 2021 and should be completed by Spring 2023. Participants will be recruited from a memory clinic where they will come for an assessment of their cognitive abilities due to decision-making needs to support ageing in place. They will be older people over 70 years of age, living at home, presenting with a diagnosis of mild dementia, and no exclusion criteria of MRI. They will be clinically assessed by a geriatrician on their DMC, based on the neuropsychological tests usually performed. Participants will then perform a behavioural task in fMRI (Balloon Analogue Risk Task) to analyse the activation areas. Additional semistructured interviews will be conducted to explore real life implications. The main analysis will study concordance/discordance between the clinical classification and the activation of fMRI regions of interest. Reclassification as ‘capable’, based on fMRI, of patients for whom clinical diagnosis is ‘questionable’ will be considered as a diagnostic gain.

Ethics and dissemination

IMAGISION has been authorised by a research ethics board (Comité de Protection des Personnes, Bordeaux, II) in France, in accordance with French legislation on interventional biomedical research, under the reference IDRCB number 2019-A00863-54, since 30 September 2020. Participants will sign an informed consent form. The results of the study will be presented in international peer-reviewed scientific journals, international scientific conferences and public lectures.

Trial registration number

NCT03931148
Assessment of an intervention to optimise antenatal management of women admitted with preterm labour and intact membranes using amniocentesis-based predictive risk models: study protocol for a randomised controlled trial (OPTIM-PTL Study)
Authors: Cobo Teresa , Aldecoa Victoria , Bartha Jose Luis , Bugatto Fernando , Paz Carrillo-Badillo María , Comas Carmina , Diago-Almeda Vicente , Ferrero Silvia , Goya Maria , Herraiz Ignacio , Martí-Malgosa Laia , Olivella Anna , Paulés Cristina , Vives Àngels , Figueras Francesc , Palacio Montse , Gratacós Eduard
Published: September 2021

Introduction

The majority of women admitted with threatened preterm labour (PTL) do not delivery prematurely. While those with microbial invasion of the amniotic cavity (MIAC) represent the highest risk group, this is a condition that is not routinely ruled out since it requires amniocentesis. Identification of low-risk or high-risk cases might allow individualisation of care, that is, reducing overtreatment with corticosteroids and shorten hospital stay in low-risk women, while allowing early antibiotic therapy in those with MIAC. Benefits versus risks of amniocentesis-based predictor models of spontaneous delivery within 7 days and/or MIAC have not been evaluated.

Methods and analysis

This will be a Spanish randomised, multicentre clinical trial in singleton pregnancies (23.0–34.6 weeks) with PTL, conducted in 13 tertiary centres. The intervention arm will consist in the use of amniocentesis-based predictor models: iflow risk,hospital discharge within 24 hours of results with no further medication will be recommended. Ifhigh risk,antibiotics will be added to standard management. The control group will be managed according to standard institutional protocols, without performing amniocentesis for this indication. The primary outcome will be total antenatal doses of corticosteroids, and secondary outcomes will be days of maternal stay and the occurrence of clinical chorioamnionitis. A cost analysis will be undertaken. To observe a reduction from 90% to 70% in corticosteroid doses, a reduction in 1 day of hospital stay (SD of 2) and a reduction from 24% to 12% of clinical chorioamnionitis, a total of 340 eligible patients randomised 1 to 1 to each study arm is required (power of 80%, with type I error α=0.05 and two-sided test, considering a dropout rate of 20%). Randomisation will be stratified by gestational age and centre.

Ethics and dissemination

Prior to receiving approval from the Ethics Committee (HCB/2020/1356) and the Spanish Agency of Medicines and Medical Devices (AEMPS) (identification number: 2020-005-202-26), the trial was registered in the European Union Drug Regulating Authorities Clinical Trials database (2020-005202-26). AEMPS approved the trial as a low-intervention trial. All participants will be required to provide written informed consent. Findings will be disseminated through workshops, peer-reviewed publications and national/international conferences.

Protocol version

V.4 10 May 2021.

Trial registration numbers

NCT04831086and Eudract number 2020-005202-26.
Metformin in the management of antipsychotic-induced weight gain in adults with psychosis: development of the first evidence-based guideline using GRADE methodology
Authors: Fitzgerald Ita , O'Connell Jean , Keating Dolores , Hynes Caroline , McWilliams Stephen , Crowley Erin K
Published: September 2021

Background

Adjunctive metformin is the most well-studied intervention in the pharmacological management of antipsychotic-induced weight gain (AIWG). Although a relatively unaddressed area, among guidelines recommending consideration of metformin, prescribing information that would facilitate its applied use by clinicians, for example, provision of a dose titration schedule is absent. Moreover, recommendations differ regarding metformin’s place in the hierarchy of management options. Both represent significant barriers to the applied, evidence-based use of metformin for this indication.

Objective

To produce a guideline solely dedicated to the optimised use of metformin in AIWG management, using internationally endorsed guideline methodology.

Methods

A list of guideline key health questions (KHQs) was produced. It was agreed that individual recommendations would be ‘adopted or adapted’ from current guidelines and/or developed de novo, in the case of unanswered questions. A systematic literature review (2008–2020) was undertaken to identify published guidelines and supporting (or more recent) research evidence. Quality appraisal was undertaken using the Appraisal of Guidelines Research and Evaluation II tool, A Measurement Tool to Assess Systematic Reviews (AMSTAR) assessment,and the Cochrane Risk of Bias 2 tool, where appropriate. Assessment of evidence certainty and recommendation development was undertaken using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Findings

We confirmed that no published guideline—of appropriate quality, solely dedicated to the use of metformin to manage AIWG was available. Recommendations located within other guidelines inadequately addressed our KHQs.

Conclusion

All 11 recommendations and 7 supporting good practice developed here were formulated de novo.

Clinical implications

These recommendations build on the number and quality of recommendations in this area, and facilitate the optimised use of metformin when managing AIWG.
Founder mutation in myosin-binding protein C with an early onset and a high penetrance in males
Authors: Méndez Irene , Fernández Ana Isabel , Espinosa Maria Ángeles , Cuenca Sofía , Lorca Rebeca , Rodríguez José Fernando , Tamargo Maria , García-Montero Marta , Gómez Cristina , Vilches Silvia , Vázquez Nélida , Álvarez Reyes , Medrano Constancio , Yotti Raquel , Fernández-Avilés Francisco , Bermejo Javier
Published: September 2021

Objective

One of the challenges in hypertrophic cardiomyopathy (HCM) is to determine the pathogenicity of genetic variants and to establish genotype/phenotype correlations. This study aimed to: (1) demonstrate thatMYBPC3c.2149–1G>A is a founder pathogenic variant, (2) describe the phenotype and clinical characteristics of mutation carriers and (3) compare these patients with those with the most frequent pathogenic HCM variants:MYBPC3p.Arg502Trp/Gln.

Methods

We reviewed genetic tests performed in HCM probands at our institution. We carried out transcript analyses to demonstrate the splicing effect, and haplotype analyses to support the founder effect ofMYBPC3c.2149–1G>A. Carriers with this mutation were compared with those fromMYBPC3p.Arg502Trp/Gln in terms of presentation features, imaging and outcomes.

Results

MYBPC3c.2149–1G>A was identified in 8 of 570 probands and 25 relatives. Penetrance was age and sex dependent, 50.0% of the carriers over age 36 years and 75.0% of the carriers over 40 years showing HCM. Penetrance was significantly higher in males: in carriers older than 30 years old, 100.0% of males vs 50.0% of females had a HCM phenotype (p=0.01). Males were also younger at diagnosis (32±13 vs 53±10 years old, p<0.001).MYBPC3c.2149–1G>A resulted in an abnormal transcript that led to haploinsufficiency and was segregated in two haplotypes. However, both came from one founder haplotype. Affected carriers showed a better functional class and higher left ventricular ejection fraction (LVEF) than patients withMYBPC3p.Arg502Trp/Gln (p<0.05 for both). Nevertheless, the rate of major adverse outcomes was similar between the two groups.

Conclusions

MYBPC3c.2149–1G>A splicing variant is a founder mutation. Affected males show an early onset of HCM and with higher penetrance than women. Carriers show better functional class and higher LVEF thanMYBPC3p.Arg502Trp/Gln carriers, but a similar rate of major adverse outcomes.
Frailty for neurologists: a practical guide
Authors: Pollock Lucy , Smith Matthew
Published: September 2021

Neurologists increasingly care for people with significant frailty in both clinic and ward settings. Such care demands a balanced approach to investigation, diagnosis and treatment, as well-intentioned actions can produce adverse effects. This article presents a practical approach to the identification and management of patients with frailty and neurological conditions. We address medicines optimisation, common causes of deterioration in those with frailty, communication, decisions about intensity of treatment, and shared decision-making including ethical aspects of withholding or withdrawing life-prolonging treatment, with a view to improving the experience both of people living with frailty and of the teams who care for them.
The influence of a basic military training diet on whole blood fatty acid profile and the Omega-3 Index of Australian Army recruits
Authors: Peoples Gregory E. , Larsen Penelope , Bowes Heather M. , Coombes Jarrin , Drain Jace R. , Groeller Herbert , McLennan Peter L.
Published: September 2021

This study described the whole blood fatty acid profile and Omega-3 Index (O3I) of Australian Army recruits at the commencement and completion of basic military training (BMT). Eighty males (17–34 y, 77.4 ± 13.0 kg, 43.5 ± 4.3 mL/kg/min) and 37 females (17–45 y, 64.3 ± 8.8 kg, 39.3 ± 2.7 mL/kg/min) volunteered to participate (N = 117). Whole blood samples of each recruit were collected using a finger prick in weeks 1 and 11 (n = 82) and analysed via gas chromatography for the relative proportions of each fatty acid (mean [95% confidence interval]). The macronutrient characteristics of the diet offerings was also determined. At commencement there was a low omega-3 status (sum of omega-3; 4.95% [4.82–5.07]) and O3I (5.03% [4.90–5.16]) and no recruit recorded an O3I >8% (desirable). The omega-6/omega-3 (7.04 [6.85–7.23]) and arachidonic acid/eicosapentaenoic acid (AA/EPA) (18.70 [17.86–19.53]) ratios for the cohort were also undesirable. The BMT mess menu provided a maximum of 190 mg/day of EPA and 260 mg/day of docosahexaenoic acid (DHA). The O3I of the recruits was lower by week 11 (4.62% [4.51–4.78], p < 0.05), the omega-6/omega-3 increased (7.27 [7.07–7.47], p < 0.05) and the AA/EPA remained elevated (17.85 [16.89–18.81]). In conclusion, Australian Army recruits’ omega-3 status remained undesirable during BMT and deserves nutritional attention.

Novelty: Australian Army recruits’ Omega-3 Index, at the commencement of BMT, was reflective of the Western-style diet. The BMT diet offered minimum opportunity for daily EPA and DHA consumption. Every recruit experienced a further reduction of their Omega-3 Index during BMT.
Stoichiomorphic halogen-bonded cocrystals: a case study of 1,4-diiodotetrafluorobenzene and 3-nitropyridine
Authors: Hajjar Christelle , Nag Tamali , Al Sayed Hashim , Ovens Jeffrey S. , Bryce David L.
Published: September 2021

The concept of variable stoichiometry cocrystallization is explored in halogen-bonded systems. Three novel cocrystals of 1,4-diiodotetrafluorobenzene and 3-nitropyridine with molar ratios of 1:1, 2:1, and 1:2, respectively, are prepared by slow evaporation methods. Single-crystal X-ray diffraction analysis reveals key differences between each of the nominally similar cocrystals. For instance, the 1:1 cocrystal crystallizes in the P21/n space group and features a single chemically and crystallographically unique halogen bond between iodine and the pyridyl nitrogen. The 2:1 cocrystal crystallizes in the [Formula: see text] space group and features a halogen bond between iodine and one of the nitro oxygens in addition to an iodine–nitrogen halogen bond. The 1:2 cocrystal crystallizes with a large unit cell (V = 9896 Å3) in the Cc space group and features 10 crystallographically distinct iodine-nitrogen halogen bonds. Powder X-ray diffraction experiments carried out on the 1:1 and 2:1 cocrystals confirm that gentle grinding does not alter the crystal forms. 1H → 13C and 19F → 13C cross-polarization magic angle spinning (CP/MAS) NMR experiments performed on powdered samples of the 1:1 and 2:1 cocrystals are used as spectral editing tools to select for either the halogen bond acceptor or donor, respectively. Carbon-13 chemical shifts in the cocrystals are shown to change only very subtly relative to pure solid 1,4-diiodotetrafluorobenzene, but the shift of the carbon directly bonded to iodine nevertheless increases, consistent with halogen bond formation (e.g., a shift of +1.6 ppm for the 2:1 cocrystal). This work contributes new examples to the field of variable stoichiometry cocrystal engineering with halogen bonds.
The impact of COVID-19 on the mental health of Canadian children and youth
Authors: Vaillancourt Tracy , Szatmari Peter , Georgiades Katholiki , Krygsman Amanda
Published: September 2021

Children and youth flourish in environments that are predictable, safe, and structured. The COVID-19 pandemic has disrupted these protective factors making it difficult for children and youth to adapt and thrive. Pandemic-related school closures, family stress, and trauma have led to increases in mental health problems in some children and youth, an area of health that was already in crisis well before COVID-19 was declared a global pandemic. Because mental health problems early in life are associated with significant impairment across family, social, and academic domains, immediate measures are needed to mitigate the potential for long-term sequalae. Now more than ever, Canada needs a national mental health strategy that is delivered in the context in which children and youth are most easily accessible—schools. This strategy should provide coordinated care across sectors in a stepped care framework and across a full continuum of mental health supports spanning promotion, prevention, early intervention, and treatment. In parallel, we must invest in a comprehensive population-based follow-up of Statistics Canada’s Canadian Health Survey on Children and Youth so that accurate information about how the pandemic is affecting all Canadian children and youth can be obtained. It is time the Canadian government prioritizes the mental health of children and youth in its management of the pandemic and beyond.