bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview of Physical Activity Research Evolution in Africa: The Global Observatory for Physical Activity—GoPA!
Authors: Oyeyemi Adewale L. , Ramirez Varela Andrea , Lambert Estelle V. , Kohn Eduardo Ribes , Hallal Pedro C. , Pratt Michael
Published: February 2024

Objective: To describe the evolution of physical activity (PA) research in Africa, examine income and gender inequalities, and discuss future possibilities. Methods: A secondary analyses of the Global Observatory for Physical Activity data on PA research in Africa (1950–2019). Results: We identified 514 PA articles from 47 African countries in the past 70 years. Majority (83.1%) of the articles were published between 2012 and 2019. Fifteen countries had no publications. Six countries (South Africa [n = 156], Nigeria [n = 85], Ethiopia [n = 44], Ghana [n = 41], Kenya [n = 39], and Cameroon [n = 20]) accounted for about 75% of the publications. Most articles were observational (92.4%), single-country studies (78.4%), with male first (58.4%) and last authors (68%), and were classified as surveillance studies (45.1%). Few studies addressed interventions (5.8%) and policy (3.5%) or used device-based PA measurement (14.0%). The number of articles per country was positively related to human population level (r = .552, P = .000) and gross domestic product % spent on research and development (r = .301, P = .040). The publication rate per 100,000 people was positively related with the human development index (r = .349, P = .016) and negatively with the gender inequality index (r = −.360, P = .019). Conclusions: Our results provide an overview and status of PA research in Africa, highlighting country differences and gender inequalities in authorship. The findings may be used to benchmark the evolution of research in the region and to inform areas for improvement. There is an urgent need for more PA interventions and policy studies in Africa.
Impact of Prolonged Sport Stoppage on Knee Injuries in High School Athletes: An Ecological Study
Authors: Knapic Hannah , Shanley Ellen , Thigpen Charles A. , Prats-Uribe Albert , Fair Cynthia D. , Bullock Garrett S.
Published: February 2024

Context: In March 2020, public health concerns resulted in school closure throughout the United States. The prolonged sport cessation may affect knee injury risk in high school athletes. The purpose of this study was to describe and compare risk of knee injuries in high school athletes during 2019–2020 and 2020–2021 academic years, and stratify by gender, severity, mechanism of injury, injury type, and knee anatomic region. Design: Historical–prospective cohort study. Methods: This historical–prospective cohort study included 176 schools in 6 states matched by sport participation in control and COVID years from July 1, 2019 to June 30, 2021. Injury rates per 1000 athletes per year were calculated with 95% confidence intervals. A negative binomial regression was performed to assess potential differences in knee injuries between academic years. Results: 94,847 and 72,521 high school athletes participated in the 2019–2020 (19–20) and 2020–2021 (20–21) seasons. Knee injury risk was higher in the 20–21 season (19–20: 28.89% [27.82–29.96]; 20–21: 33.82% [32.50–35.14]). Risk increased for male athletes from 2019–2020 to 2020–2021 (19–20: 29.42% [28.01–30.83]; 20–21: 40.32% [38.89–41.75]). Female knee injury risk was similar between years (19–20: 25.78% [24.29–27.27]; 20–21: 26.03% [24.31–27.75]). Knee injuries increased by a ratio of 1.2 ([95% CI, 1.1–1.3], P < .001) during 2020–2021. Conclusions: Knee injury risk and relative risk increased among males in 2020–2021. Results indicate changes in knee injury risk following return from COVID shelter in place among high school athletes and implicate potential negative downstream effects of interrupted sports training and participation on high school injury risk.
The History of Physical Activity Promotion in Physical Education and Suggestions for Moving Forward
Authors: Centeio Erin E. , Brusseau Timothy A.
Published: February 2024

Physical activity (PA) is an essential component of the physical education classroom, whether it is used to practice motor skills, increase motor competence, or provide experience and opportunities to nurture lifelong PA participation. This chapter outlines the history of PA in the school setting, beginning with physical education and expanding through a Comprehensive School Physical Activity Program model including PA during the school day (e.g., recess and classroom-based activity), PA before and after school (including active commuting), staff involvement, and family and community engagement. We begin by discussing the theoretical underpinnings of PA in the school setting and then outline previous research around PA implications. Ideas and suggestions for how the field of physical education and PA in schools can move the field forward together to embrace PA during the school day while being culturally and socially just are presented. Finally, future directions and implications for research are discussed.
Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation
Authors: Erickson Emily C. , You Inchul , Perry Grace , Dugourd Aurelien , Donovan Katherine A. , Crafter Claire , Johannes Jeffrey W. , Williamson Stuart , Moss Jennifer I. , Ros Susana , Ziegler Robert E. , Barry Simon T. , Fischer Eric S. , Gray Nathanael S. , Madsen Ralitsa R. , Toker Alex
Published: February 2024

More than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantially higher potency than our first-generation AKT degrader (INY-03-041), with both compounds outperforming catalytic AKT inhibition by GDC-0068. Using multiomic profiling and causal network integration in breast cancer cells, we demonstrated that the enhanced efficacy of INY-05-040 was associated with sustained suppression of AKT signaling, which was followed by induction of the stress mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). Further integration of growth inhibition assays with publicly available transcriptomic, proteomic, and reverse phase protein array (RPPA) measurements established low basal JNK signaling as a biomarker for breast cancer sensitivity to AKT degradation. Together, our study presents a framework for mapping the network-wide signaling effects of therapeutically relevant compounds and identifies INY-05-040 as a potent pharmacological suppressor of AKT signaling.
ALOX5 drives the pyroptosis of CD4
+
T cells and tissue inflammation in rheumatoid arthritis
Authors: Cai Hao , Zhang Jianhua , Xu Hua , Sun Weiwei , Wu Weijie , Dong Chen , Zhou Ping , Xue Chengbin , Nan Yunyi , Ni Yingchen , Wu Xinyuan , Gu Zhifeng , Chen Minhao , Wang Youhua
Published: February 2024

Pyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4
+
T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotriene A
4
(LTA
4
), were increased in CD4
+
T cells from patients with RA and, among patients with RA, were lowest in those in clinical remission. Knockdown or pharmacological inhibition of ALOX5 suppressed CD4
+
T cell pyroptosis and improved symptoms in two rodent models of RA. Mechanistically, the increase in ALOX5 activity in RA CD4
+
T cells enhanced the production of the LTA
4
derivative LTB
4
, which stimulated Ca
2+
influx through ORAI3 channels, leading to the activation of NLRP3 inflammasomes and pyroptosis. Our findings reveal a role for ALOX5 in RA and provide a molecular basis for further exploring the clinical utility of ALOX5 inhibition in RA and for using ALOX5 as a biomarker to distinguish active disease and remission in RA.
Coxiella burnetii
infection persistence in a goat herd during seven kidding seasons after an outbreak of abortions: the effect of vaccination
Authors: Zendoia Ion I. , Barandika Jesús F. , Cevidanes Aitor , Hurtado Ana , García-Pérez Ana L.
Published: February 2024

Coxiella burnetii
infection was monitored during seven kidding seasons (2017–2023) in a dairy goat herd that after an outbreak of Q fever abortions was vaccinated with an inactivated phase I vaccine. Due to the high infection rate just after the outbreak, only the replacement stock was vaccinated during the first three kidding seasons, and when the average herd immunity had decreased (fourth kidding season onwards), the whole herd was vaccinated. Vaginal swabs, feces, and milk were analyzed by PCR to monitor infection, and dust and aerosols were analyzed to measure
C. burnetii
environmental contamination. One year after the onset of the outbreak, a significant reduction in
C. burnetii
shedding loads was observed, but the percentage of shedding animals remained high until the third kidding season. By the seventh kidding season, no shedders were detected. The bacterial load excreted was significantly lower in vaccinated compared with unvaccinated animals, and in yearlings compared with multiparous.
C. burnetii
was detected by PCR in aerosols collected inside the animal premises throughout the study period except in the last season; whereas, aerosols collected outdoors tested negative in the last three kidding seasons. Viable
C. burnetii
was detectable in environmental dust collected inside the barn until the third kidding season following the outbreak. These results indicate that after an outbreak of Q fever, the risk of infection for humans and susceptible animals can remain high for at least three kidding seasons when the number of
C. burnetii
animal shedders is still high, even when bacterial excretion is low.

IMPORTANCE

Q fever is a zoonosis distributed worldwide. Ruminants are the main reservoir, and infection can cause high rates of abortion. After entering a farm,
Coxiella burnetii
infection can persist in the animal population over several lambing/kidding periods. Once infection is established in a herd, vaccination with the inactivated Phase I vaccine significantly reduces bacterial shedding, but although at low levels, excretion may continue to occur for several lambing/kidding seasons. The time that
C. burnetii
remains viable in the farm environment after an outbreak of Q fever determines the period when risk of infection is high for the people in close contact. This work showed that this period extends at least three kidding seasons after the outbreak. These results provided valuable information on the epidemiology of
C. burnetii
infection in goat herds and may help to develop guidelines for controlling the disease and reducing infection risk for susceptible people and animals.
A prototrophic suppressor of a
Vibrio fischeri
D-glutamate auxotroph reveals a member of the periplasmic broad-spectrum racemase family (BsrF)
Authors: Coppinger Macey N. , Laramore Kathrin , Popham David L. , Stabb Eric V.
Published: February 2024

Although bacterial peptidoglycan (PG) is highly conserved, some natural variations in PG biosynthesis and structure have evolved. Understanding the mechanisms and limits of such variation will inform our understanding of antibiotic resistance, innate immunity, and the evolution of bacteria. We have explored the constraints on PG evolution by blocking essential steps in PG biosynthesis in
Vibrio fischeri
and then selecting mutants with restored prototrophy. Here, we attempted to select prototrophic suppressors of a D-glutamate auxotrophic
murI racD
mutant. No suppressors were isolated on unsupplemented lysogeny broth salts (LBS), despite plating >10
11
cells, nor were any suppressors generated through mutagenesis with ethyl methanesulfonate. A single suppressor was isolated on LBS supplemented with iso-D-gln, although the iso-D-gln subsequently appeared irrelevant. This suppressor has a genomic amplification formed by the creation of a novel junction that fuses
proB
to a gene encoding a putative
b
road-
s
pectrum
r
acemase of

V.
f
ischeri

,
bsrF
. An engineered
bsrF
allele lacking the putative secretion signal (ΔSS-
bsrF
) also suppressed D-glu auxotrophy, resulting in PG that was indistinguishable from the wild type. The ΔSS-
bsrF
allele similarly suppressed the D-alanine auxotrophy of an
alr
mutant and restored prototrophy to a
murI alr
double mutant auxotrophic for both D-ala and D-glu. The ΔSS-
bsrF
allele increased resistance to D-cycloserine but had no effect on sensitivity to PG-targeting antibiotics penicillin, ampicillin, or vancomycin. Our work helps define constraints on PG evolution and reveals a periplasmic broad-spectrum racemase in
V. fischeri
that can be co-opted for PG biosynthesis, with concomitant D-cycloserine resistance.

IMPORTANCE

D-Amino acids are used and produced by organisms across all domains of life, but often, their origins and roles are not well understood. In bacteria, D-ala and D-glu are structural components of the canonical peptidoglycan cell wall and are generated by dedicated racemases Alr and MurI, respectively. The more recent discovery of additional bacterial racemases is broadening our view and deepening our understanding of D-amino acid metabolism. Here, while exploring alternative PG biosynthetic pathways in
Vibrio fischeri
, we unexpectedly shed light on an unusual racemase, BsrF. Our results illustrate a novel mechanism for the evolution of antibiotic resistance and provide a new avenue for exploring the roles of non-canonical racemases and D-amino acids in bacteria.
RBM14 inhibits the replication of porcine epidemic diarrhea virus by recruiting p62 to degrade nucleocapsid protein through the activation of autophagy and interferon pathway
Authors: Wang Xiaoquan , Tong Wu , Yang Xinyu , Zhai Huanjie , Qin Wenzhen , Liu Changlong , Zheng Hao , Yu Hai , Tong Guangzhi , Zhang Zhendong , Kong Ning , Shan Tongling
Published: February 2024

Porcine epidemic diarrhea virus (PEDV) results in PED, which is an infectious intestinal disease with the representative features of diarrhea, vomiting, and dehydration. PEDV infects neonatal piglets, causing high mortality rates. Therefore, elucidating the interaction between the virus and host in preventing and controlling PEDV infection is of immense significance. We found a new antiviral function of the host protein, RNA-binding motif protein 14 (RBM14), which can inhibit PEDV replication via the activation of autophagy and interferon (IFN) signal pathways. We found that RBM14 can recruit cargo receptor p62 to degrade PEDV nucleocapsid (N) protein through the RBM14-p62-autophagosome pathway. Furthermore, RBM14 can also improve the antiviral ability of the hosts through interacting with mitochondrial antiviral signaling protein to induce IFN expression. These results highlight the novel mechanism underlying RBM14-induced viral restriction. This mechanism leads to the degradation of viral N protein via the autophagy pathway and upregulates IFN for inhibiting PEDV replication; thus, offering new ways for preventing and controlling PED.

IMPORTANCE

Porcine epidemic diarrhea virus (PEDV) is a vital reason for diarrhea in neonatal piglets, which causes high morbidity and mortality rates. There is currently no effective vaccine or drug to treat and prevent infection with the PEDV. During virus infection, the host inhibits virus replication through various antiviral factors, and at the same time, the virus antagonizes the host’s antiviral reaction through its own encoded protein, thus completing the process of virus replication. Our study has revealed that the expression of RNA-binding motif protein 14 (RBM14) was downregulated in PEDV infection. We found that RBM14 can recruit cargo receptor p62 to degrade PEDV N protein via the RBM14-p62-autophagosome pathway and interacted with mitochondrial antiviral signaling protein and TRAF3 to activate the interferon signal pathway, resulting in the inhibition of PEDV replication.
Nsp1 facilitates SARS-CoV-2 replication through calcineurin-NFAT signaling
Authors: Lui Wai-Yin , Ong Chon Phin , Cheung Pak-Hin Hinson , Ye Zi-Wei , Chan Chi-Ping , To Kelvin Kai-Wang , Yuen Kit-San , Jin Dong-Yan
Published: February 2024

SARS-CoV-2, the causative agent of COVID-19, has been intensely studied in search of effective antiviral treatments. The immunosuppressant cyclosporine A (CsA) has been suggested to be a pan-coronavirus inhibitor, yet its underlying mechanism remained largely unknown. Here, we found that non-structural protein 1 (Nsp1) of SARS-CoV-2 usurped CsA-suppressed nuclear factor of activated T cells (NFAT) signaling to drive the expression of cellular DEAD-box helicase 5 (DDX5), which facilitates viral replication. Nsp1 interacted with calcineurin A (CnA) to displace the regulatory protein regulator of calcineurin 3 (RCAN3) of CnA for NFAT activation. The influence of NFAT activation on SARS-CoV-2 replication was also validated by using the Nsp1-deficient mutant virus. Calcineurin inhibitors, such as CsA and VIVIT, inhibited SARS-CoV-2 replication and exhibited synergistic antiviral effects when used in combination with nirmatrelvir. Our study delineated the molecular mechanism of CsA-mediated inhibition of SARS-CoV-2 replication and the anti-SARS-CoV-2 action of calcineurin inhibitors.

IMPORTANCE

Cyclosporine A (CsA), commonly used to inhibit immune responses, is also known to have anti-SARS-CoV-2 activity, but its mode of action remains elusive. Here, we provide a model to explain how CsA antagonizes SARS-CoV-2 through three critical proteins: DDX5, NFAT1, and Nsp1. DDX5 is a cellular facilitator of SARS-CoV-2 replication, and NFAT1 controls the production of DDX5. Nsp1 is a viral protein absent from the mature viral particle and capable of activating the function of NFAT1 and DDX5. CsA and similar agents suppress Nsp1, NFAT1, and DDX5 to exert their anti-SARS-CoV-2 activity either alone or in combination with Paxlovid.
The
Caenorhabditis elegans
proteome response to two protective
Pseudomonas
symbionts
Authors: Pees Barbara , Peters Lena , Treitz Christian , Hamerich Inga K. , Kissoyan Kohar A. B. , Tholey Andreas , Dierking Katja
Published: February 2024

The
Caenorhabditis elegans
natural microbiota isolates
Pseudomonas lurida
MYb11 and
Pseudomonas fluorescens
MYb115 protect the host against pathogens through distinct mechanisms. While
P. lurida
produces an antimicrobial compound and directly inhibits pathogen growth,
P. fluorescens
MYb115 protects the host without affecting pathogen growth. It is unknown how these two protective microbes affect host biological processes. We used a proteomics approach to elucidate the
C. elegans
response to MYb11 and MYb115. We found that both
Pseudomonas
isolates increase vitellogenin protein production in young adults, which confirms previous findings on the effect of microbiota on
C. elegans
reproductive timing. Moreover, the
C. elegans
responses to MYb11 and MYb115 exhibit common signatures with the response to other vitamin B
12
-producing bacteria, emphasizing the importance of vitamin B
12
in
C. elegans
-microbe metabolic interactions. We further analyzed signatures in the
C. elegans
response specific to MYb11 or MYb115. We provide evidence for distinct modifications in lipid metabolism by both symbiotic microbes. We could identify the activation of host-pathogen defense responses as an MYb11-specific proteome signature and provide evidence that the intermediate filament protein IFB-2 is required for MYb115-mediated protection. These results indicate that MYb11 not only produces an antimicrobial compound but also activates host antimicrobial defenses, which together might increase resistance to infection. In contrast, MYb115 affects host processes such as lipid metabolism and cytoskeleton dynamics, which might increase host tolerance to infection. Overall, this study pinpoints proteins of interest that form the basis for additional exploration into the mechanisms underlying
C. elegans
microbiota-mediated protection from pathogen infection and other microbiota-mediated traits.

IMPORTANCE

Symbiotic bacteria can defend their host against pathogen infection. While some protective symbionts directly interact with pathogenic bacteria, other protective symbionts elicit a response in the host that improves its own pathogen defenses. To better understand how a host responds to protective symbionts, we examined which host proteins are affected by two protective
Pseudomonas
bacteria in the model nematode
Caenorhabditis elegans
. We found that the
C. elegans
response to its protective symbionts is manifold, which was reflected in changes in proteins that are involved in metabolism, the immune system, and cell structure. This study provides a foundation for exploring the contribution of the host response to symbiont-mediated protection from pathogen infection.
Draft genome sequence of
Bacillus velezensis
strains AOA1 and AKS2, the potential plant growth-promoting rhizobacteria
Authors: Babalola Olubukola Oluranti , Akanmu Akinlolu Olalekan , Ayangbenro Ayansina Segun
Published: February 2024

This report describes the draft genome sequence of
Bacillus velezensis
strains AOA1 and AKS2 isolated from maize rhizosphere soil in South Africa.
Bacillus velezensis
plays important biological roles as plant growth promoting rhizobacterium (PGPR).
Bacillus velezensis
strains also exhibit numerous biotechnological application potentials in agriculture and diverse industrial settings.
Draft genome sequences of 21
Pedobacter
strains isolated from amphibian specimens
Authors: Zumkeller Celine M. , Bletz Molly C. , Rakotoarison Andolalao , Sabino-Pinto Joana , Reiter Silke , Spohn Marius , Schwengers Oliver , Goesmann Alexander , Vences Miguel , Mihajlovic Sanja , Schäberle Till F.
Published: February 2024

The genomes of 21
Pedobacter
strains isolated from the European salamander
Salamandra salamandra
and different Madagascan frog species were sequenced using Illumina sequencing. Here, we report their draft genome sequences (~4.7–7.2 Mbp in size) to allow comparative genomics and taxonomic assignment of these strains.
Development of a duplex droplet digital PCR assay for the detection of
Burkholderia cepacia
complex and
Stenotrophomonas maltophilia
in bloodstream infections
Authors: Liu Chunmei , He Ziqiang , Kong Mimi , Jin Dong
Published: February 2024

Burkholderia cepacia
complex (BCC) and
Stenotrophomonas maltophilia
are nosocomial pathogens that cause various infections and exhibit high resistance to multiple antimicrobial agents. In this study, we aimed to develop a duplex droplet digital PCR (ddPCR) assay for detecting BCC and
S. maltophilia
in bloodstream infections. We optimized the experimental conditions by setting the annealing temperature to 51°C and determining the optimal concentrations of primers and probes, as well as the thermal cycle numbers. The feasibility of the duplex ddPCR reaction system with the optimal conditions was established and verified through parallel reactions with reference strains of BCC and
S. maltophilia
. The specificity of the assay, tested with 33 reference strains, was found to be 100%. The duplex ddPCR assay demonstrated good repeatability and could detect as low as 5.35 copies/reaction of BCC and 7.67 copies/reaction of
S. maltophilia
. This level of sensitivity was consistent in the simulated blood and blood bottle samples. We compared nucleic acid extraction methods and found that the Chelex-100 boiling method and kit extraction method exhibited similar detection sensitivity, suggesting the potential application of the Chelex-100 boiling method in the ddPCR assay. In the clinical samples, the duplex ddPCR assay accurately detected BCC and
S. maltophilia
in 58 cases. In conclusion, our study successfully developed a duplex ddPCR assay that provides accurate and convenient detection of BCC and
S. maltophilia
in bloodstream infections.

IMPORTANCE

Burkholderia cepacia
complex (BCC) and
Stenotrophomonas maltophilia
are implicated in a wide range of infections, including bloodstream infections (BSIs), pneumonia, and meningitis, and often exhibit high intrinsic resistance to multiple antimicrobial agents, limiting therapeutic options. The gold standard for diagnosing bloodstream infections remains blood culture. However, current blood culture detection and positivity rates do not meet the “rapid diagnosis” required for the diagnosis and treatment of critically ill patients with BSIs. The digital droplet PCR (ddPCR) method is a potentially more powerful tool in the diagnosis of BSIs compared to other molecular methods due to its greater sensitivity, specificity, accuracy, and reproducibility. In this study, a duplex ddPCR assay for the detection of BCC and
S. maltophilia
in BSIs was developed.
Clinical characteristics and outcomes of pleural aspergillosis: a review of 13 cases
Authors: Zhang Jing , Gao Xing-Lin , Wu Jian , Chen Jing-Jing
Published: February 2024

Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), which mostly occurs in the immunocompromised host. The clinical condition is critical, especially to those who develop bronchopleural fistula. This study aimed to assess the characteristics and the prognosis of aspergillus pleurisy. Clinical data from 13 patients diagnosed with aspergillus pleurisy in our hospital from January 2000 to December 2022 were retrospectively studied. Thirteen patients with
Aspergillus
pleurisy were included. There were 10 males and 3 females, with a median age of 65 (range: 18–79) years. Bronchopleural fistula was present in eight patients. A proven diagnosis of
Aspergillus
pleurisy was based on positive pleural fluid culture in seven cases and histopathological examination of pleural biopsies in six cases. Four patients refused further treatment and were discharged from the hospital against medical advice. Nine cases recovered and were discharged after multiple antifungal treatments (systemic and topical antifungal therapies, pleural drainage and irrigation, and surgical repair). During follow-up, one patient, who suffered underlying bronchiectasis, died of massive hemoptysis 2 years after discharge. The remaining eight cases are still under close follow-up, with a median follow-up of 5.4 (range: 1.3–18.9) years. The prognosis of aspergillus pleurisy complicated with bronchopleural fistula is poor. Thoracic surgery, especially lung resection, is a risk factor associated with the incidence of
Aspergillus
pleurisy. Systemic antifungal therapy and adequate pleural irrigation could improve the prognosis.

IMPORTANCE

Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), associated with a poor prognosis. The morbidity and mortality of this condition have not been thoroughly studied, and recent research on this topic is limited. The current study included 13 patients diagnosed with Aspergillus pleurisy, with the majority presenting concomitantly with a bronchopleural fistula. Among these patients, nine had a history of thoracic surgery, including lung transplantation and lobectomy. Four patients refused further treatment and were discharged against medical advice, while one patient succumbed to massive hemoptysis 2 years after discharge. This case series provides essential insights into Aspergillus pleurisy and evaluates the therapeutic strategy based on a limited cohort.
Pairing and Collective Excitations in Ising Superconductors
Authors: Semenov A. G.
Published: February 2024

Two-dimensional Ising superconductivity formed in NbSe2, MoS2, WS2, etc. transition-metal dichalcogenides is considered. For the superconducting state, the effective low-energy action for phases of the order parameters has been obtained and collective modes in the system have been studied. It has been shown that the system contains not only the Goldstone mode but also the Leggett mode with a mass related to the difference between the singlet and triplet pairing constants. The effect of a low magnetic field parallel to the plane of the system has also been discussed.
Outpatient and primary care direct provocation challenges for antibiotic allergy in children
Authors: Grewal Anjum , Jay Nicola
Published: February 2024

Objective

To evaluate the use of a questionnaire-based decision-making algorithm to triage children with reported antibiotic allergies to proceed directly to an oral provocation challenge.

Design

Cohort study.

Setting

Children aged 2–16 years attending paediatric emergency department over 1 year (1 June 2018 till 31 May 2019) or identified from four primary care centres in Sheffield with a recorded antibiotic allergy and no previous testing.

Participants

313 children with 325 recorded antibiotic allergies.

Exposure

Clinical decision-making algorithm used to either exclude, directly delabel or stratify children to oral antibiotic challenge in outpatient department or primary care practice.

Main outcome measures

To assess the safety of using the questionnaire-based algorithm for proceeding to a direct oral provocation challenge.

The secondary outcomes were to look for associations and predictive factors in positive challenges and to assess parent/carer acceptability of the service by using Likert Scale.

Results

Successful contact was made with 200 children, of which 153 children could be evaluated based on inclusion criteria, engagement and availability of medical records.

15 children were directly delabelled based on history and records. 138 children underwent challenges in outpatient and primary care. 6% of challenges were reactive with a mild, delayed reaction. Overall, a delabelling rate of 91% was achieved. There were no clear predictors for a positive challenge.

Conclusion

Our questionnaire-based algorithm for stratifying children with antibiotic allergies to proceed directly to an oral outpatient or primary care challenge was found to be safe, feasible and acceptable.
Effectiveness, barriers and facilitating factors of strategies for active delabelling of patients with penicillin allergy labels: a systematic review protocol
Authors: Nürnberg Hannah , Khatamzas Elham , Denkinger Claudia , Krause Tabea , Oetken Lars , Rauer Sophie , Rapp Amelie , Hoppe-Tichy Torsten , Morath Benedict
Published: February 2024

Introduction

Up to 15% of adult patients in the clinical setting report to be allergic to penicillin. However, in most cases, penicillin allergy is not confirmed. Due to the negative aspects associated with erroneous penicillin allergy, the implementation of active delabelling processes for penicillin allergy is an important part of antibiotic stewardship programmes. Depending on the clinical setting, different factors need to be considered during implementation. This review examines the effectiveness of different delabelling interventions and summarises components and structures that facilitate, support or constrain structured penicillin allergy delabelling.

Methods and analysis

This review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The databases MEDLINE (via PubMed), EMBASE and Cochrane Library were searched for studies reporting on any intervention to identify, assess or rule out uncertain penicillin allergy. To improve completeness, two further databases are also searched for grey literature. Study design, intervention type, professional groups involved, effectiveness, limitations, barriers, facilitating factors, clinical setting and associated regulatory factors will be extracted and analysed. In addition, exclusion criteria for participation in the delabelling intervention and criteria for not delabelling penicillin allergy will be summarised. In case of failed protocols, these are highlighted and quantitatively analysed if possible. Two independent reviewers will perform the screening process and data extraction. Discordant decisions will be resolved through review by a third reviewer. Bias assessment of the individual studies will be performed using the Newcastle Ottawa Scale.

Ethics and dissemination

Because individual patient-related data are not analysed, an ethical approval is not required. The review will be published in a peer-reviewed scientific journal.
Immune regulation and blood–brain barrier permeability in cerebral small vessel disease: study protocol of the INflammation and Small Vessel Disease (INSVD) study – a multicentre prospective cohort study
Authors: Low Audrey , van Winden Sanne , Cai Lupei , Kessels Roy P C , Maas Marnix C , Morris Robin G , Nus Meritxell , Tozer Daniel J , Tuladhar Anil , van der Kolk Anja , Wolters Rowan , Mallat Ziad , Riksen Niels P , Markus Hugh , de Leeuw Frank‐Erik
Published: February 2024

Introduction

The INflammation and Small Vessel Disease (INSVD) study aims to investigate whether peripheral inflammation, immune (dys)regulation and blood–brain barrier (BBB) permeability relate to disease progression in cerebral small vessel disease (SVD). This research aims to pinpoint specific components of the immune response in SVD relating to disease progression. This could identify biomarkers of SVD progression, as well as potential therapeutic targets to inform the development and repurposing of drugs to reduce or prevent SVD, cognitive decline and vascular dementia.

Methods and analysis

INSVD is a prospective observational multicentre cohort study in individuals with symptomatic SVD. This longitudinal study combines comprehensive immunophenotyping of the peripheral blood immune compartment with advanced neuroimaging markers of SVD and BBB permeability. The main SVD marker of interest is white matter microstructure as determined by diffusion tensor imaging, a valuable marker of disease progression owing to its sensitivity to early alterations to white matter integrity. The research is being conducted in two sites—in the UK (Cambridge) and the Netherlands (Nijmegen)—with each site recruiting 100 participants (total n=200). Participants undergo clinical and cognitive assessments, blood draws, and brain MRI at baseline and 2-year follow-up.

Ethics and dissemination

This study received ethical approval from the local ethics boards (UK: East of England—Cambridge Central Research Ethics Committee (REC) ref: 22/EE/00141, Integrated Research Application System (IRAS) ID: 312 747. Netherlands: Medical Research Ethics Committee (MREC) Oost-Nederland, ref: 2022-13623, NL-number: NL80258.091.22). Written informed consent was obtained from all subjects before the study. Any participant-derived benefits resulting from this research, such as new insights into disease mechanisms or possible novel therapies, will be disseminated to study participants, patient groups and members of the public.

Trial registration number

NCT05746221.
Clinical manifestations and prognostic factors analysis of patients hospitalised with acute exacerbation of idiopathic pulmonary fibrosis and other interstitial lung diseases
Authors: Ba Cuirong , Wang Huijuan , Jiang Chunguo , Shi Xuhua , Jin Jiawei , Fang Qiuhong
Published: February 2024

Background

Acute exacerbation (AE) is a life-threatening condition taking place not only in idiopathic pulmonary fibrosis (IPF) but also in interstitial lung diseases (ILD) other than IPF (non-IPF ILD). This study aims to compare the clinical manifestations between patients hospitalised with AE-IPF and AE-non-IPF ILD, and further analyse the risk factors related to in-hospital mortality.

Methods

Clinical data of 406 patients hospitalised with AE-IPF (93 cases) and AE-non-IPF ILD (313 cases) were retrospectively collected. Clinical features were compared between the two groups. Risk factors related to in-hospital mortality in patients with overall AE-ILD, AE-IPF and AE-non-IPF ILD were identified by multiple logistic regression analyses, respectively, and assessed by receiver operating characteristic curve.

Results

In addition to having more smokers and males, the AE-IPF group also had more respiratory failure on admission, comorbidities of pulmonary hypertension (PAH) or coronary artery disease/heart failure, a longer history of pre-existing ILD. Comorbidity of coronary heart disease/heart failure, respiratory failure at admission, neutrophil (N)%, serum hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH) and low cholesterol levels were independent risk factors for patients with AE-ILD, while respiratory failure on admission, N%, serum HBDH, urea nitrogen, LDH and low albumin levels were risk factors for the AE-non-IPF ILD group, and fever, N% and PAH were the AE-IPF group’s. Among them, HBDH 0.758 (sensitivity 85.5%, specificity 56%, cut-off 237.5 U/L) for patients with AE-ILD; N% 0.838 (sensitivity 62.5%, specificity 91.18%, cut-off 83.55%) for the AE-IPF group and HBDH 0.779 (sensitivity 86.4%, specificity 55.1%, cut-off 243.5 U/L) for the AE-non-IPF ILD group were the risk factors with the highest area under the curve.

Conclusions

Clinical characteristics differ between patients with AE-IPF and AE-non-IPF ILD. HBDH outperformed LDH in predicting the prognosis for patients with AE-ILD and AE-non-IPF ILD. N% was an independent predictor of death in-hospital in all three groups, especially in the AE-IPF group.
Navigating implementation barriers: a holistic approach to improving exertional heat stroke management
Authors: Hosokawa Yuri , Akama Takao
Published: February 2024

Objectives

To assess the shift in medical volunteers’ perception and practice surrounding exertional heat stroke (EHS) prehospital management after the Tokyo 2020 Olympic Games.

Methods

An online survey was sent to medical volunteers assigned to work at high EHS risk events during the Tokyo 2020 Olympic Games. Surveys were sent at the time of initial training, immediately after the Games, and one year after the Games. The survey investigated medical volunteers’ perceptions and practices regarding the assessment of rectal temperature and the use of whole-body cold water immersion (CWI) as prehospital management of EHS. In addition, an open-ended question was prepared to examine barriers and facilitators of their chosen perception and/or behaviour.

Results

The lack of knowledge about rectal temperature assessment improved over time, but the actual implementation did not. Meanwhile, increased utilisation of CWI was observed 1 year after the Games. The lack of equipment, apprehension towards rectal temperature assessment, the perception of difficulty getting patient consent, concerns for hypothermic overshoot and the number of required medical providers were raised as barriers to implementation.

Conclusion

Some improvements were observed in perception and practice; however, further organisational and financial support is warranted for a broader skill transfer and implementation.
Is the UN receiving ethical approval for its research with human participants?
Authors: Torrance Robert James , Mormina Maru , Sayeed Sadath , Kessel Anthony , Yoon Chang Ho , Cislaghi Beniamino
Published: February 2024

This paper examines the institutional mechanisms supporting the ethical oversight of human participant research conducted by the United Nations (UN). The UN has served an instrumental role in shaping international standards on research ethics, which invariably require ethical oversight of all research studies with human participants. The authors’ experiences of conducting research collaboratively with UN agencies, in contrast, have led to concern that the UN frequently sponsors, or participates in, studies with human participants that have not received appropriate ethical oversight. It is argued that the institutional mechanisms in place to prevent research with human participants from being undertaken by the UN without ethical oversight do not, at present, extend substantively beyond the provision of guidelines and online training offered by a minority of UN bodies. The WHO and UNICEF are identified as notable exceptions, having implemented various measures to prevent health research with human participants from being undertaken without ethical oversight. Yet, it is highlighted that the WHO and UNICEF are not the only UN bodies that undertake health research with human participants and there are countless actors under the umbrella of the UN system that are regularly involved in non-health research with human participants. Arguments for the pursuit of the highest standard of ethical oversight by UN bodies are presented. Moving forward, the paper asks the question: is it time for the UN to set the standards for the oversight of ethical oversight?
Tsunami-tendenko follows the antiextinction principle, not utilitarianism
Authors: Cato Susumu , Oshitani Ken
Published: February 2024

This paper examines the concept of ‘tsunami-tendenko,’ a guideline suggesting that individuals prioritise their own safety over aiding others during large-scale disasters. Kodama defends tsunami-tendenko against accusations of egoism by arguing that the principle can be justified ethically on consequentialist (or more precisely, utilitarian) grounds. Kodama asserts that attempting to assist others during such disasters heightens the risk of ‘tomo-daore,’ where both the rescuer and the victim may perish. He claims that having people focus solely on saving themselves can maximise the overall number of lives saved. However, we challenge Kodama’s assertion that utilitarianism inherently favours tsunami-tendenko over mutual assistance during disasters. Instead, this paper proposes an alternative ethical foundation for tsunami-tendenko grounded in the ‘antiextinction principle,’ which prioritises minimising the potential for catastrophic outcomes. When considering the ethics of responding to disaster, it is important to distinguish between maximising the number of lives saved (utilitarianism) and minimising the risk of tomo-daore (antiextinction principle). This distinction may be overlooked if the distribution of probabilities is not considered. We conclude that the antiextinction principle aligns more naturally with tsunami-tendenko, emphasising the avoidance of catastrophic outcomes—a concern not always addressed by utilitarianism. Therefore, tsunami-tendenko should be regarded as a societal guideline aimed at preserving community sustainability by averting total destruction.
The Defence General Practitioner: an Updated Definition and Model
Authors: Holland Toby James , Smith M , King K
Published: February 2024

The geopolitical setting has changed significantly since the definition of UK Armed Forces General Practice was published in 2012. New operating models require medical services to provide smaller teams operating at greater reach from secondary care and logistical support. The Defence Medical Services have reorganised to meet these changing needs. Defence general practices (DGPs) are key enablers of the Defence strategic effort, both integral to deployed units, in preparing forces for deployment and managing their rehabilitation back to fitness. A formal role performance statement (RPS) has been created to guide the training and development of DGPs to meet these changing requirements. The RPS details the additional scope of practice, beyond the national GP licensing standard, in which DGPs work. In this article, we compare and contrast the RPS with the previous definition of a DGP. The resultant updated model recharacterises the extended roles into five themes of DGP built on the foundation of the Royal College of General Practitioners curriculum. This new model provides the platform on which to develop the clinical specialty over the next decade and highlights avenues for educational interventions to develop future generations of DGPs.
Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis
Authors: Xie Wenhui , Hou Yue , Xiao Shiyu , Zhang Xiaolin , Zhang Zhuoli
Published: February 2024

Background

Dysregulation of several inflammatory cytokines including tumour necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed to investigate the association of disease-modifying antirheumatic drugs (DMARDs) therapy for RA with risk of incident dementia.

Methods

Electronic database searches of PubMed, EMBASE and Cochrane Library were performed. Observational studies that assessed the association of dementia with DMARDs in RA were included. Pooled risk ratios (RRs) with 95% CIs were used as summary statistic. The certainty of evidence was judged by using the Grading of Recommendations Assessment, Development and Evaluation system.

Results

Overall, 14 studies involving 940 442 patients with RA were included. Pooled RR for developing dementia was 0.76 (95% CI 0.72 to 0.80) in patients taking biological DMARDs overall versus those taking conventional synthetic DMARDs, with 24% for TNF inhibitors (RR 0.76, 95% CI 0.71 to 0.82), 24% for non-TNF biologics (RR 0.76, 95% CI 0.70 to 0.83), separately. There was a significant subgroup effect among different types of TNF inhibitors (RR 0.58 [95%CI 0.53 to 0.65], 0.65 [95% CI 0.59 to 0.72], 0.80 [95% CI 0.72 to 0.88] for etanercept, adalimumab, infliximab, respectively; p value between groups=0.002). However, compared with non-users of DMARDs or investigative treatment, no significant effect on dementia incidence was observed in those receiving conventional synthetic DMARDs overall (RR 0.84, 95% CI 0.59 to 1.20), methotrexate (RR 0.78, 95% CI 0.54 to 1.12), hydroxychloroquine (RR 0.95, 95% CI 0.63 to 1.44), except for sulfasalazine (RR 1.27, 95% CI 1.06 to 1.50).

Conclusions

Biological DMARDs for RA are associated with decreased dementia risk, while protective effect is not observed in conventional synthetic DMARDs. Controlled clinical trials on TNF inhibitors are necessary to test their neuroprotective potentials.
Perspectives on the reclassification of taxa in the Arceuthobium campylopodum complex (Viscaceae)
Authors: Kenaley Shawn C. , Mathiasen Robert L.
Published: February 2024

The taxonomic classification of dwarf mistletoes ( Arceuthobium spp., Viscaceae) in series Campylopoda requires a multi-trait approach, integrating plant genetics, morphologies, and phenologies as well as their host and geographic distributions. Thus, competing interpretations on the contribution of these traits to defining species and subspecies boundaries has spurred considerable debate. Accordingly, the recent reclassification of 12 previously recognized species in ser. Campylopoda to separate subspecies of Arceuthobium campylopodum in the Flora of North America (FNA) has furthered this debate. We contend that these taxa deserve separate species recognition, while subspecies described prior to and after the recombination of ser. Campylopoda taxa in the FNA also deserve recognition. Herein, we provide evidence that the treatment in the FNA does not adequately reflect the diverse morphological, geographic, host, and phenological differences across the series, and hence, we maintain that the reclassification of ser. Campylopoda taxa was not justified according to empirical evidence published prior to and following the FNA treatment. We conclude our critique of the FNA treatment of ser. Campylopoda by advocating for the continued application of the Hawksworth and Wiens’ classification system, with minor modifications to the constitution of the series.