bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermo-Hydrodynamic Performance Evaluation of a Mini-Channel Inserted With TPMS-Based Porous Lattice
Authors: Rathore Surendra Singh , Mehta Balkrishna , Kumar Pradeep , Asfer Mohammed
Published: March 2024

The coupled pore-scale and Darcy-scale numerical simulations are used in this work to investigate heat transport and hydrodynamic characteristics within a porous channel constructed by using a primitive lattice based on triply-periodic-minimal-surface. The pore-scale simulation is used in void subdomain, whereas the microporous-solid subdomain is simulated by Darcy-scale simulation for a range of mass transfer rates 4×10−7 to 2×10−3 kg/s (corresponding Reynolds numbers 0.1<Re<500). The liquid-water (Pr=7) is used as the working fluid. The Darcy number and inertial drag coefficient are calculated using the pressure drop in the channel along with the heat transfer coefficient (Nusselt number) on both internal and external walls. The quantifiable deviation from local thermal equilibrium (LTE) is also established. The results reveal two distinct, namely passive and active regimes, depending upon the permeability of the microporous-solid subdomain. It is found that the Nusselt number is almost constant for permeability values Kμ<10−11m2(passive regime). However, significant variation is observed in the Nu for higher value of permeability Kμ≥10−11m2(active regime). The Darcy number and effective Nusselt number are found to be increasing, while the inertial drag coefficient and deviation from LTE are found to be decreasing with the permeability in the active regime only.
Quantification of Cartilage Poroelastic Material Properties Via Analysis of Loading-Induced Cell Death
Authors: Kotelsky Alexander , Carrier Joseph S. , Buckley Mark R.
Published: March 2024

Articular cartilage (AC) is a load-bearing tissue that covers long bones in synovial joints. The biphasic/poroelastic mechanical properties of AC help it to protect joints by distributing loads, absorbing impact forces, and reducing friction. Unfortunately, alterations in these mechanical properties adversely impact cartilage function and precede joint degeneration in the form of osteoarthritis (OA). Thus, understanding what factors regulate the poroelastic mechanical properties of cartilage is of great scientific and clinical interest. Transgenic mouse models provide a valuable platform to delineate how specific genes contribute to cartilage mechanical properties. However, the poroelastic mechanical properties of murine articular cartilage are challenging to measure due to its small size (thickness ∼ 50 microns). In the current study, our objective was to test whether the poroelastic mechanical properties of murine articular cartilage can be determined based solely on time-dependent cell death measurements under constant loading conditions. We hypothesized that in murine articular cartilage subjected to constant, sub-impact loading from an incongruent surface, cell death area and tissue strain are closely correlated. We further hypothesized that the relationship between cell death area and tissue strain can be used—in combination with inverse finite element modeling—to compute poroelastic mechanical properties. To test these hypotheses, murine cartilage-on-bone explants from different anatomical locations were subjected to constant loading conditions by an incongruent surface in a custom device. Cell death area increased over time and scaled linearly with strain, which rose in magnitude over time due to poroelastic creep. Thus, we were able to infer tissue strain from cell death area measurements. Moreover, using tissue strain values inferred from cell death area measurements, we applied an inverse finite element modeling procedure to compute poroelastic material properties and acquired data consistent with previous studies. Collectively, our findings demonstrate in the key role poroelastic creep plays in mediating cell survival in mechanically loaded cartilage and verify that cell death area can be used as a surrogate measure of tissue strain that enables determination of murine cartilage mechanical properties.
Fatigue-Life Prediction of the Optimized Savonius Vertical-Axis Wind Turbine Composite Blades
Authors: Ghoneam Sobhy M. , Hamada Ahmed A. , Sherif Taha S.
Published: March 2024

The sustainability of modern human civilization is significantly concerned with enhancing sustainable energy resources. Vertical-Axis Wind Turbines (VAWTs) gained a promising impact on the global energy mix due to their belief in sustainable energy solutions. This paper presents an integrated study of the dynamic performance and fatigue-life characteristics of the optimized Savonius-rotor VAWT composite blades. Furthermore, this paper introduces an experimental validation, numerical modeling, and visualization/verification study of the optimized VAWT composite blades and assesses its impact on the whole performance of the optimized Savonius VAWTs. Four combination levels of the optimal settings of the S-VAWT composite blade configurations are designed, modeled, simulated, and fabricated of Carbon/Glass—Polyester. The modal parameters such as natural frequency, mode shape, and damping factor are investigated using fast Fourier transformer (FFT) analyzer. The numerical finite element models (FEM) are generated to model, visualize, simulate, and predict the dynamic nature and fatigue-life characteristics of the optimal S-VAWT composite blade configurations. A correlation between the experimental and numerical results is established. The study findings highlight the significant impact of VAWT composite blades in enhancing the dynamic performance and fatigue-life characteristics of Savonius VAWTs. Furthermore, a small damage percentage of 2.8% predicted by the finite element analysis (FEA) for the optimal S-VAWT composite blade configuration validated the sustainability of the VAWT composite blade configurations in dynamic loading conditions.
Fieldwork campaigns and citizen science data increase the distributional range of the elusive Vipera monticola in Morocco
Authors: Martínez-Freiría Fernando , Bouazza Abdellah , Buldai Jon , Freitas Inês , Avella Ignazio , Scaramuzzi Andrea , Sioumpoura Katerina , Oliveira Duarte , Fahd Soumia
Published: March 2024

Morocco comprises most of the geographic range extent of Vipera monticola and the three subspecies described within this taxon. However, the distribution of this species is likely underestimated due to its low detectability. In this note, we use data collected through recent fieldwork campaigns and citizen science to update the distribution of V. monticola in Morocco, considering the distribution of the three described subspecies. We provide records for 45 vipers corresponding to 15 UTM 10x10 km cells (six new UTM 10x10 km cells), increasing by 8.8% the range of V. monticola in the country. Remarkable range increases occur for the subspecies V. monticola atlantica and V. monticola monticola, the latter confirmed by genetic assessment, as well as for V. monticola saintgironsi with a new record in Jbel Bou Naceur. We note the occurrence of habitat degradation across the species range, likely promoted by anthropogenic factors as deforestation, aridification and overgrazing. We also indicate Jbel Oukaimeden as a potential area to develop population-monitoring studies.
The Influence of High-Intensity Work on the Record Power Profile of Under-23, Pro Team, and World Tour Cyclists
Authors: Leo Peter , Mateo-March Manuel , Giorgi Andrea , Muriel Xabier , Javaloyes Alejandro , Barranco-Gil David , Pallarés Jesús G. , Lucia Alejandro , Mujika Iñigo , Valenzuela Pedro L.
Published: March 2024

Background: Durability (ie, the ability to attenuate the decline in performance after accumulated work) has been identified as a performance determinant in elite cyclists. The aim of the present study was to compare durability in elite cyclists of various performance levels, particularly after high-intensity work, referred to as “high-intensity durability.” Methods: Forty-nine (N = 49) male road cyclists were categorized as either under 23 years of age (U23) (N = 11), Pro Team (N = 13), or World Tour (N = 24). The participants’ critical power (CP) was assessed during the preseason. Thereafter, the participants’ maximum mean power (MMP) values were determined for efforts of different durations (from 5 s to 30 min) after different levels of accumulated work above CP (from 0 to 7.5 kJ·kg−1). Results: U23 cyclists showed a significant reduction of all relative MMP values for durations ≥1 minute after ≥5 kJ·kg−1 above CP compared with the “fresh” state (0 kJ·kg−1), whereas in Pro Team and World Tour cyclists, a significant reduction was not observed until 7.5 kJ·kg−1 above CP. In the “fresh” state, both Pro Team and particularly World Tour cyclists attained higher MMP values for efforts ≥10 minutes than U23 riders. However, more differences emerged with greater previous work levels, and indeed after 7.5 kJ·kg−1 above CP World Tour cyclists attained higher MMP values than both U23 and Pro Team cyclists for most efforts (≥30 s). Conclusion: Pro Team and particularly World Tour cyclists tolerate greater levels of accumulated work at high intensity, which might support the importance of high-intensity durability for performance.
Quantifying methane emissions from United States landfills
Authors: Cusworth Daniel H. , Duren Riley M. , Ayasse Alana K. , Jiorle Ralph , Howell Katherine , Aubrey Andrew , Green Robert O. , Eastwood Michael L. , Chapman John W. , Thorpe Andrew K. , Heckler Joseph , Asner Gregory P. , Smith Mackenzie L. , Thoma Eben , Krause Max J. , Heins Daniel , Thorneloe Susan
Published: March 2024

Methane emissions from solid waste may represent a substantial fraction of the global anthropogenic budget, but few comprehensive studies exist to assess inventory assumptions. We quantified emissions at hundreds of large landfills across 18 states in the United States between 2016 and 2022 using airborne imaging spectrometers. Spanning 20% of open United States landfills, this represents the most systematic measurement-based study of methane point sources of the waste sector. We detected significant point source emissions at a majority (52%) of these sites, many with emissions persisting over multiple revisits (weeks to years). We compared these against independent contemporaneous in situ airborne observations at 15 landfills and established good agreement. Our findings indicate a need for long-term, synoptic-scale monitoring of landfill emissions in the context of climate change mitigation policy.
Selection of experience for memory by hippocampal sharp wave ripples
Authors: Yang Wannan , Sun Chen , Huszár Roman , Hainmueller Thomas , Kiselev Kirill , Buzsáki György
Published: March 2024

Experiences need to be tagged during learning for further consolidation. However, neurophysiological mechanisms that select experiences for lasting memory are not known. By combining large-scale neural recordings in mice with dimensionality reduction techniques, we observed that successive maze traversals were tracked by continuously drifting populations of neurons, providing neuronal signatures of both places visited and events encountered. When the brain state changed during reward consumption, sharp wave ripples (SPW-Rs) occurred on some trials, and their specific spike content decoded the trial blocks that surrounded them. During postexperience sleep, SPW-Rs continued to replay those trial blocks that were reactivated most frequently during waking SPW-Rs. Replay content of awake SPW-Rs may thus provide a neurophysiological tagging mechanism to select aspects of experience that are preserved and consolidated for future use.
Design of a SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model
Authors: Tan Bin , Zhang Xiaoming , Ansari Ahmadullah , Jadhav Prakash , Tan Haozhou , Li Kan , Chopra Ashima , Ford Alexandra , Chi Xiang , Ruiz Francesc Xavier , Arnold Eddy , Deng Xufang , Wang Jun
Published: March 2024

The emergence of SARS-CoV-2 variants and drug-resistant mutants calls for additional oral antivirals. The SARS-CoV-2 papain-like protease (PL
pro
) is a promising but challenging drug target. We designed and synthesized 85 noncovalent PL
pro
inhibitors that bind to a recently discovered ubiquitin binding site and the known BL2 groove pocket near the S4 subsite. Leads inhibited PL
pro
with the inhibitory constant K
i
values from 13.2 to 88.2 nanomolar. The co-crystal structures of PL
pro
with eight leads revealed their interaction modes. The in vivo lead Jun12682 inhibited SARS-CoV-2 and its variants, including nirmatrelvir-resistant strains with EC
50
from 0.44 to 2.02 micromolar. Oral treatment with Jun12682 improved survival and reduced lung viral loads and lesions in a SARS-CoV-2 infection mouse model, suggesting that PL
pro
inhibitors are promising oral SARS-CoV-2 antiviral candidates.
Vaccines to control tuberculosis in cattle
Authors: Michel Anita L.
Published: March 2024

The age-old cattle disease has resisted rigorous control, but the BCG vaccine may do better
The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis
Authors: Balasubramanian Arumugam , Hsu Alan Y. , Ghimire Laxman , Tahir Muhammad , Devant Pascal , Fontana Pietro , Du Gang , Liu Xing , Fabin Dang , Kambara Hiroto , Xie Xuemei , Liu Fei , Hasegawa Tomoya , Xu Rong , Yu Hongbo , Chen Mei , Kolakowski Steven , Trauger Sunia , Larsen Martin Røssel , Wei Wenyi , Wu Hao , Kagan Jonathan C. , Lieberman Judy , Luo Hongbo R.
Published: March 2024

Plasma membrane perforation elicited by caspase cleavage of the gasdermin D (GSDMD) N-terminal domain (GSDMD-NT) triggers pyroptosis. The mechanisms underlying GSDMD membrane translocation and pore formation are not fully understood. Here, using a proteomic approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner. S-palmitoylation of GSDMD at Cys
191
/Cys
192
(human/mouse), catalyzed by palmitoyl acyltransferases ZDHHC5 and ZDHHC9 and facilitated by reactive oxygen species (ROS), directly mediated membrane translocation of GSDMD-NT but not full-length GSDMD (GSDMD-FL). Palmitoylation of GSDMD-FL could be induced before inflammasome activation by stimuli such as lipopolysaccharide (LPS), consequently serving as an essential molecular event in macrophage priming. Inhibition of GSDMD palmitoylation suppressed macrophage pyroptosis and IL-1β release, mitigated organ damage, and enhanced the survival of septic mice. Thus, GSDMD-NT palmitoylation is a key regulatory mechanism controlling GSDMD membrane localization and activation, which may offer an additional target for modulating immune activity in infectious and inflammatory diseases.
Chagas disease in immunocompromised patients
Authors: Clark Eva H. , Messenger Louisa A. , Whitman Jeffrey D. , Bern Caryn
Published: March 2024

As Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of
Trypanosoma cruzi
infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for
T. cruzi
reactivation, which can be lethal. Evidence-based practices to prevent and manage
T. cruzi
reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various populations of immunocompromised individuals, including people with HIV and patients undergoing solid organ and hematopoietic stem cell transplantation.
HIV-1 capsid stability and reverse transcription are finely balanced to minimize sensing of reverse transcription products
via
the cGAS-STING pathway
Authors: Eschbach Jenna E. , Puray-Chavez Maritza , Mohammed Shawn , Wang Qiankun , Xia Ming , Huang Lin-Chen , Shan Liang , Kutluay Sebla B.
Published: March 2024

A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization
per se
does not completely block reverse transcription. Surprisingly, due to the combined effects of enhanced reverse transcription and defects in nuclear entry, two separate CA mutants that form hyperstable cores induced innate immune sensing more potently than destabilizing CA mutations. At low concentrations that allowed the accumulation of reverse transcription products, CA-targeting compounds GS-CA1 and lenacapavir measurably impacted CA lattice stability in cells and modestly enhanced innate immune sensing of HIV. Interestingly, innate immune activation observed with viruses containing unstable cores was abolished by low doses of lenacapavir. Innate immune activation observed with both hyperstable and unstable CA mutants was dependent on the cGAS-STING DNA-sensing pathway and reverse transcription. Overall, our findings demonstrate that CA lattice stability and reverse transcription are finely balanced to support reverse transcription and minimize cGAS-STING-mediated sensing of the resulting viral DNA.

IMPORTANCE

In HIV-1 particles, the dimeric RNA genome and associated viral proteins and enzymes are encased in a proteinaceous lattice composed of the viral capsid protein. Herein, we assessed how altering the stability of this capsid lattice through orthogonal genetic and chemical approaches impacts the induction of innate immune responses. Specifically, we found that decreasing capsid lattice stability results in more potent sensing of viral reverse transcription products, but not the genomic RNA, in a cGAS-STING-dependent manner. The recently developed capsid inhibitors lenacapavir and GS-CA1 enhanced the innate immune sensing of HIV-1. Unexpectedly, due to increased levels of reverse transcription and cytosolic accumulation of the resulting viral cDNA, capsid mutants with hyperstable cores also resulted in the potent induction of type I interferon-mediated innate immunity. Our findings suggest that HIV-1 capsid lattice stability and reverse transcription are finely balanced to minimize exposure of reverse transcription products in the cytosol of host cells.
IFN-λ drives distinct lung immune landscape changes and antiviral responses in human metapneumovirus infection
Authors: Sojati Jorna , Parks Olivia B. , Zhang Yu , Walters Sara , Lan Jie , Eddens Taylor , Lou Dequan , Fan Li , Chen Kong , Oury Tim D. , Williams John V.
Published: March 2024

Human metapneumovirus (HMPV) is a primary cause of acute respiratory infection, yet there are no approved vaccines or antiviral therapies for HMPV. Early host responses to HMPV are poorly characterized, and further understanding could identify important antiviral pathways. Type III interferon (IFN-λ) displays potent antiviral activity against respiratory viruses and is being investigated for therapeutic use. However, its role in HMPV infection remains largely unknown. Here, we show that IFN-λ is highly upregulated during HMPV infection
in vitro
in human and mouse airway epithelial cells and
in vivo
in mice. We found through several immunological and molecular assays that type II alveolar cells are the primary producers of IFN-λ. Using mouse models, we show that IFN-λ limits lung HMPV replication and restricts virus spread from upper to lower airways but does not contribute to clinical disease. Moreover, we show that IFN-λ signaling is predominantly mediated by CD45
-
non-immune cells. Mice lacking IFN-λ signaling showed diminished loss of ciliated epithelial cells and decreased recruitment of lung macrophages in early HMPV infection along with higher inflammatory cytokine and interferon-stimulated gene expression, suggesting that IFN-λ may maintain immunomodulatory responses. Administration of IFN-λ for prophylaxis or post-infection treatment in mice reduced viral load without inflammation-driven weight loss or clinical disease. These data offer clinical promise for IFN-λ in HMPV treatment.

IMPORTANCE

Human metapneumovirus (HMPV) is a common respiratory pathogen and often contributes to severe disease, particularly in children, immunocompromised people, and the elderly. There are currently no licensed HMPV antiviral treatments or vaccines. Here, we report novel roles of host factor IFN-λ in HMPV disease that highlight therapeutic potential. We show that IFN-λ promotes lung antiviral responses by restricting lung HMPV replication and spread from upper to lower airways but does so without inducing lung immunopathology. Our data uncover recruitment of lung macrophages, regulation of ciliated epithelial cells, and modulation of inflammatory cytokines and interferon-stimulated genes as likely contributors. Moreover, we found these roles to be distinct and non-redundant, as they are not observed with knockout of, or treatment with, type I IFN. These data elucidate unique antiviral functions of IFN-λ and suggest IFN-λ augmentation as a promising therapeutic for treating HMPV disease and promoting effective vaccine responses.
Evaluation of vector susceptibility in
Aedes aegypti
and
Culex pipiens pallens
to Tibet orbivirus
Authors: Ren Nanjie , Jin Qianqian , Wang Fei , Huang Doudou , Yang Cihan , Zaman Wahid , Salazar Ferdinand Villanueva , Liu Qiyong , Yuan Zhiming , Xia Han
Published: March 2024

Mosquito-borne viruses cause various infectious diseases in humans and animals. Tibet orbivirus (TIBOV), a newly identified arbovirus, efficiently replicates in different types of vertebrate and mosquito cells, with its neutralizing antibodies detected in cattle and goats. However, despite being isolated from
Culicoides
midges
, Anopheles,
and
Culex
mosquitoes, there has been a notable absence of systematic studies on its vector competence. Thus, in this study,
Aedes aegypti
and
Culex pipiens pallens
were reared in the laboratory to measure vector susceptibility through blood-feeding infection. Furthermore, RNA sequencing was used to examine the overall alterations in the
Ae. aegypti
transcriptome following TIBOV infection. The results revealed that
Ae. aegypti
exhibited a high susceptibility to TIBOV compared to
Cx. p. pallens
. Effective replication of the virus in
Ae. aegypti
midguts occurred when the blood-feeding titer of TIBOV exceeded 10
5
plaque-forming units mL
−1
. Nevertheless, only a few TIBOV RNA-positive samples were detected in the saliva of
Ae. aegypti
and
Cx. p. pallens
, suggesting that these mosquito species may not be the primary vectors for TIBOV. Moreover, at 2 dpi of TIBOV, numerous antimicrobial peptides downstream of the Toll and Imd signaling pathways were significantly downregulated in
Ae. aegypti
, indicating that TIBOV suppressed mosquitos’ defense to survive in the vector at an early stage. Subsequently, the stress-activated protein kinase JNK, a crucial component of the MAPK signaling pathway, exhibited significant upregulation. Certain genes were also enriched in the MAPK signaling pathway in TIBOV-infected
Ae. aegypti
at 7 dpi.

IMPORTANCE

Tibet orbivirus (TIBOV) is an understudied arbovirus of the genus
Orbivirus
. Our study is the first-ever attempt to assess the vector susceptibility of this virus in two important mosquito vectors,
Aedes aegypti
and
Culex pipiens pallens
. Additionally, we present transcriptome data detailing the interaction between TIBOV and the immune system of
Ae. aegypti
, which expands the knowledge about orbivirus infection and its interaction with mosquitoes.
Bacillus subtilis
remains translationally active after CRISPRi-mediated replication initiation arrest
Authors: Muñoz-Gutierrez Vanessa , Cornejo Fabián A. , Schmidt Katja , Frese Christian K. , Halte Manuel , Erhardt Marc , Elsholz Alexander K. W. , Turgay Kürşad , Charpentier Emmanuelle
Published: March 2024

Initiation of bacterial DNA replication takes place at the origin of replication (
oriC
), a region characterized by the presence of multiple DnaA boxes that serve as the binding sites for the master initiator protein DnaA. This process is tightly controlled by modulation of the availability or activity of DnaA and
oriC
during development or stress conditions. Here, we aimed to uncover the physiological and molecular consequences of stopping replication in the model bacterium
Bacillus subtilis
. We successfully arrested replication in
B. subtilis
by employing a clustered regularly interspaced short palindromic repeats interference (CRISPRi) approach to specifically target the key DnaA boxes 6 and 7, preventing DnaA binding to
oriC
. In this way, other functions of DnaA, such as a transcriptional regulator, were not significantly affected. When replication initiation was halted by this specific artificial and early blockage, we observed that non-replicating cells continued translation and cell growth, and the initial replication arrest did not induce global stress conditions such as the SOS response.

IMPORTANCE

Although bacteria constantly replicate under laboratory conditions, natural environments expose them to various stresses such as lack of nutrients, high salinity, and pH changes, which can trigger non-replicating states. These states can enable bacteria to (i) become tolerant to antibiotics (persisters), (ii) remain inactive in specific niches for an extended period (dormancy), and (iii) adjust to hostile environments. Non-replicating states have also been studied because of the possibility of repurposing energy for the production of additional metabolites or proteins. Using clustered regularly interspaced short palindromic repeats interference (CRISPRi) targeting bacterial replication initiation sequences, we were able to successfully control replication initiation in
Bacillus subtilis
. This precise approach makes it possible to study non-replicating phenotypes, contributing to a better understanding of bacterial adaptive strategies.
Clozapine-induced pneumonitis mimicking an atypical pneumonia
Authors: Vaselli Natasha Marcella , Du Preez Stanley , Jasenthu Kankanamage Nuwan
Published: March 2024

Clozapine is an antipsychotic used for treatment-resistant schizophrenia with a significant side effect profile, including agranulocytosis, myocarditis and fever. Clozapine-induced fever often occurs in the first 2 weeks of treatment and settle after a few days. We report a case of a woman in her mid-30s who developed fever and infective symptoms suggestive of an atypical pneumonia while on clozapine titration. She was on clozapine for 16 days before developing high-grade fever, dry cough, diarrhoea, headache and photophobia with a very high CRP. We performed an extensive infection workup that returned negative results except for bilateral upper lobe ground glass changes of the lungs on CT. Despite antibiotic therapy, which would cover an atypical pneumonia, her CRP remained elevated and her fever persisted. Focus was directed to clozapine-induced pneumonitis as the cause for her symptoms. Her antibiotics were ceased, and clozapine was downtitrated. With the adjustment of her clozapine dose, her fevers and associated symptoms resolved, and CRP downtrended. Her fevers did not return when clozapine was uptitrated in the community subsequently. Clozapine-induced fever or other immune-allergic reactions should be systematically considered when patients develop fever during the initiation phase of clozapine therapy. Ruling out infective causes is desirable prior to attributing fevers to clozapine especially when they are accompanied by infective symptoms and high inflammatory markers. Careful downtitration of clozapine should be considered rather than abrupt cessation in managing clozapine-induced fevers and subsequent slow uptitration could be considered.
Delirium and incident dementia in hospital patients in New South Wales, Australia: retrospective cohort study
Authors: Gordon Emily H , Ward David D , Xiong Hao , Berkovsky Shlomo , Hubbard Ruth E
Published: March 2024

Objectives

To determine the strength and nature of the association between delirium and incident dementia in a population of older adult patients without dementia at baseline.

Design

Retrospective cohort study using large scale hospital administrative data.

Setting

Public and private hospitals in New South Wales, Australia between July 2001 and March 2020.

Participants

Data were extracted for 650 590 hospital patients aged ≥65 years. Diagnoses of dementia and delirium were identified from ICD-10 (international classification of diseases, 10th revision) codes. Patients with dementia at baseline were excluded. Delirium-no delirium pairs were identified by matching personal and clinical characteristics, and were followed for more than five years.

Main outcome measures

Cox proportional hazards models and Fine-Gray hazard models were used to estimate the associations of delirium with death and incident dementia, respectively. Delirium-outcome dose-response associations were quantified, all analyses were performed in men and women separately, and sensitivity analyses were conducted.

Results

The study included 55 211 matched pairs (48% men, mean age 83.4 years, standard deviation 6.5 years). Collectively, 58% (n=63 929) of patients died and 17% (n=19 117) had a newly reported dementia diagnosis during 5.25 years of follow-up. Patients with delirium had 39% higher risk of death (hazard ratio 1.39, 95% confidence interval 1.37 to 1.41) and three times higher risk of incident dementia (subdistribution hazard ratio 3.00, 95% confidence interval 2.91 to 3.10) than patients without delirium. The association with dementia was stronger in men (P=0.004). Each additional episode of delirium was associated with a 20% increased risk of dementia (subdistribution hazard ratio 1.20, 95% confidence interval 1.18 to 1.23).

Conclusions

The study findings suggest delirium was a strong risk factor for death and incident dementia among older adult patients. The data support a causal interpretation of the association between delirium and dementia. The clinical implications of delirium as a potentially modifiable risk factor for dementia are substantial.
Effectiveness, reach, uptake and feasibility of digital health interventions for adults with venous thromboembolism: protocol of a systematic review and meta-analysis
Authors: Fu Yan , Pu Hongji , Wang Yanjie , Lu Xinwu , Qiu Peng , Hu Min , Cheng Yong
Published: March 2024

Introduction

Prevention of recurrence after an episode of venous thromboembolism (VTE), and also the post-thrombotic syndrome (PTS), is still a recognised challenge. In this meta-analysis, we will summarise existing evidence to compare intelligent system follow-up and routine follow-up for patients with VTE.

Methods and analysis

Relevant randomised controlled trials (RCTs) and cohort studies will be included from the following databases: MEDLINE/PubMed, Web of Science and the Cochrane Library. The last search time will be 31 March 2024. Two reviewers will independently identify RCTs and cohort studies according to eligibility and exclusion criteria. The risk of bias of included cohort studies will be assessed with the Newcastle-Ottawa Scale, Methodological Index of Non-Randomised Studies, and the risk of bias of RCTs will be assessed with and Cochrane Collaboration’s tool. The primary outcomes include overall survival rate and PTS incidence rate. The Grades of Recommendations, Assessment, Development and Evaluation tool will be used to assess the level of evidence for outcome from RCTs. RevMan V.5.4 software will be used to pool outcomes.

Ethics and dissemination

Ethical approval was obtained from Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine Science Research Ethics Committee (SH9H-2023-T466-1). The findings will be disseminated to the public through conference presentations and publication in peer-reviewed scientific journals.

PROSPERO registration number

CRD42023410644.
Correlates of post-traumatic stress disorder among adult residents of conflict-affected communities in Cross River State, Nigeria: a cross-sectional study
Authors: Awa Theresa Mark , Ugbe Ugbe Maurice-Joel , Onwusaka Obiageli Chiezey , Abua Eucheria Ekugeni , Esu Ekpereonne Babatunde
Published: March 2024

Background

Conflict-affected communities in Nigeria experience a range of problems. These experiences have been associated with different types of mental disorders, most notably, post-traumatic stress disorder (PTSD).

Aim

This study sought to assess PTSD and its associated factors among adults in conflict-affected communities in Odukpani Local Government Area (LGA), Cross River State, Nigeria.

Methods

A cross-sectional study was conducted using non-probability and probability sampling techniques. The sample size for this study was 486 conflict-affected adults. The symptoms of PTSD were assessed using the Harvard Trauma Questionnaire and a semistructured questionnaire was employed to collect data on sociodemographic and trauma-related characteristics. Data were analysed using descriptive statistics, χ2and multivariable logistic regression.

Results

The prevalence of PTSD in conflict-affected communities in Odukpani LGA, Cross River State, Nigeria was 73.9%. The multivariate analysis revealed that higher educational attainment (AOR 5.66; p<0.001; 95% CI 2.37 to 13.54), family size >4 (AOR 1.72; p=0.03; 95% CI 1.06 to 2.77), discrimination because of present status (AOR 1.96; p=0.03; 95% CI 1.26 to 3.06) and family history of mental illnesses (AOR 2.08; p=0.002; 95% CI 1.31 to 3.31) showed statistically significant relationships with PTSD in the study population.

Conclusion

A multisectoral approach for creating and routinely arranging mental health interventions and aid programmes aimed at improving social outcomes such as employment, living conditions and social networks for conflict-affected communities is recommended.
The association of degree of polypharmacy before and after among hospitalised internal medicine patients and clinical outcomes: a retrospective, population-based cohort study
Authors: Jonsdottir Freyja , Blondal Anna B , Gudmundsson Adalsteinn , Bates Ian , Stevenson Jennifer Mary , Sigurdsson Martin I
Published: March 2024

Objectives

To determine the prevalence and incidence of polypharmacy/hyperpolypharmacy and which medications are most prescribed to patients with varying burden of polypharmacy.

Design

Retrospective, population-based cohort study.

Setting

Iceland.

Participants

Including patients (≥18 years) admitted to internal medicine services at Landspitali – The National University Hospital of Iceland, between 1 January 2010 with a follow-up of clinical outcomes through 17 March 2022.

Main outcomes measures

Participants were categorised into medication use categories of non-polypharmacy (<5), polypharmacy (5–10) and hyperpolypharmacy (>10) based on the number of medications filled in the year predischarge and postdischarge. The primary outcome was prevalence and incidence of new polypharmacy. Secondary outcomes were mortality, length of hospital stay and re-admission.

Results

Among 85 942 admissions (51% male), the median (IQR) age was 73 (60–83) years. The prevalence of preadmission non-polypharmacy was 15.1% (95% CI 14.9 to 15.3), polypharmacy was 22.9% (95% CI 22.6 to 23.2) and hyperpolypharmacy was 62.5% (95% CI 62.2 to 62.9). The incidence of new postdischarge polypharmacy was 33.4% (95% CI 32.9 to 33.9), and for hyperpolypharmacy was 28.9% (95% CI 28.3 to 29.5) for patients with preadmission polypharmacy. Patients with a higher level of medication use were more likely to use multidose drug dispensing and have a diagnosis of adverse drug reaction. Other comorbidities, including responsible subspeciality and estimates of comorbidity and frailty burden, were identical between groups of varying polypharmacy. There was no difference in length of stay, re-admission rate and mortality.

Conclusions

Preadmission polypharmacy/hyperpolypharmacy and postdischarge new polypharmacy/hyperpolypharmacy is common amongst patients admitted to internal medicine. A higher level of medication use category was not found to be associated with demographic, comorbidity and clinical outcomes. Medications that are frequently inappropriately prescribed were among the most prescribed medications in the group. An increased focus on optimising medication usage is needed after hospital admission.

Trial registration number

NCT05756400.
Community-based interventions targeting multiple forms of malnutrition among adolescents in low-income and middle-income countries: protocol for a scoping review
Authors: Kurniawan Adi Lukas , Ranisavljev Marijana , Partap Uttara , Shinde Sachin , Ferrero Elisabetta , Ostojic Sergej , Mkwanazi Ntombizodumo , Alangea Deda Ogum , Neumann Christine , Liu Shuyan , Bärnighausen Till , Fawzi Wafaie W.
Published: March 2024

Background

Adolescent malnutrition is a significant public health challenge in low-income and middle-income countries (LMICs), with long-term consequences for health and development. Community-based interventions have the potential to address multiple forms of malnutrition and improve the health outcomes of adolescents. However, there is a limited understanding of the content, implementation and effectiveness of these interventions. This scoping review aims to synthesise evidence on community-based interventions targeting multiple forms of malnutrition among adolescents in LMICs and describe their effects on nutrition and health.

Methods and analysis

A comprehensive search strategy will be implemented in multiple databases including MEDLINE (through PubMed), Embase, CENTRAL (through Cochrane Library) and grey literature, covering the period from 1 January 2000 to 14 July 2023. We will follow the Participants, Concept and Context model to design the search strategy. The inclusion criteria encompass randomised controlled trials and quasi-experimental studies focusing on adolescents aged 10–19 years. Various types of interventions, such as micronutrient supplementation, nutrition education, feeding interventions, physical activity and community environment interventions, will be considered. Two reviewers will perform data extraction independently, and, where relevant, risk of bias assessment will be conducted using standard Cochrane risk-of-bias tools. We will follow the PRISMA Extension for Scoping Reviews checklist while reporting results.

Ethics and dissemination

The scope of this scoping review is restricted to publicly accessible databases that do not require prior ethical approval for access. The findings of this review will be shared through publications in peer-reviewed journals, and presentations at international and regional conferences and stakeholder meetings in LMICs.

Scoping review registration

The final protocol was registered prospectively with the Open Science Framework on 19 July 2023 (https://osf.io/t2d78).
Associations between use of diabetes technology and diabetes distress: a Danish cross-sectional survey of adults with type 1 diabetes
Authors: Lorenzen Johanne Triantafyllou , Madsen Kristoffer Panduro , Cleal Bryan , Joensen Lene Eide , Nørgaard Kirsten , Pedersen-Bjergaard Ulrik , Schmidt Signe , Rytter Karen , Willaing Ingrid
Published: March 2024

Introduction

The study aimed to investigate independent and combined associations between insulin delivery method (insulin pump therapy (IPT) vs multiple daily injections (MDI)), glucose monitoring method (intermittently scanned continuous glucose monitoring (isCGM) and real-time continuous glucose monitoring (rtCGM) vs blood glucose metre (BGM)) and diabetes distress (DD) in adults with type 1 diabetes (T1D).

Research design and methods

We combined data from two Danish questionnaire-based surveys, the Steno Tech Survey (n=1591) and the Type 1 Diabetes Distress Scale (T1-DDS) validation survey (n=4205), in which individuals aged ≥18 years with T1D were invited to participate. The 28-item T1-DDS was used to measure DD and DD scores were categorised as little or no distress (score <2.0), moderate distress (2.0–2.9) and high distress (score ≥3.0). Associations between insulin delivery, glucose monitoring methods and DD were assessed using linear regression.

Results

Among 2068 adults with T1D who responded to one of the surveys, the use of IPT was associated with a lower total T1-DDS score (−0.09, 95% CI 0.16 to −0.03) compared with MDI and adjusted for glucose monitoring method. The use of CGM was associated with a higher total T1-DDS score (0.11, 95% CI 0.05 to 0.18) compared with BGM and adjusted for the insulin delivery method. IPT was still associated with a lower T1-DDS score, regardless of being combined with BGM (−0.17, 95% CI −0.28 to −0.06) or CGM (−0.13, 95% CI −0.21 to −0.05), compared with MDI with CGM. No association was found between the type of CGM (isCGM vs rtCGM) and DD among either IPT or MDI users when restricting analysis to individuals using CGM.

Conclusions

Among Danish adults with T1D, the use of IPT was associated with lower levels of DD, while CGM use was associated with higher levels of DD. DD should be addressed when introducing people with T1D to diabetes technology, CGM in particular.

Trial registration number

NCT04311164(Results).
Efficacy and safety of traditional Chinese manual therapy (Tuina) in patients with non-specific chronic low back pain: a study protocol for a randomised controlled trial
Authors: Cao Ben , Fang Sitong , Wu Zhiwei , Zhou Xin , Kong Lingjun , Zhu Qingguang , Zhu Bowen , Tang Cheng , Fang Min
Published: March 2024

Introduction

Non-pharmacological interventions play a crucial role in the management of non-specific chronic low back pain (NSCLBP). One prime example is Tuina, a traditional Chinese manual therapy that incorporates pressing, kneading and rubbing techniques to alleviate physical discomfort and enhance overall well-being. It serves as a widely used technique in China and other East Asian countries. However, the effectiveness and safety of Tuina for managing NSCLBP have not been substantiated through rigorous clinical research. We sought to carry out a randomised controlled trial with an open-label design, blinded assessors and parallel arms to assess the effectiveness and safety of Tuina as a treatment for NSCLBP. The trial aims to provide high-quality evidence regarding the efficacy and safety of Tuina in improving outcomes for patients with NSCLBP.

Methods and analysis

A total of 150 patients aged 18–60 years with NSCLBP will be recruited. Participants will be randomly assigned to one of the two groups. Both groups will receive standard health education. In addition, the treatment group will receive Tuina therapy, while the control group will participate in core stability exercises. Each group will undergo a total of 18 interventions over 6 weeks, with the interventions administered three times per week. The primary outcome measure is the patient’s pain intensity, assessed using the Numerical Rating Scale, at week 6 following randomisation. Secondary outcomes encompass disability (measured by the Roland-Morris Disability Questionnaire), quality of life (assessed using the EuroQoL-5 dimensions questionnaire), adverse emotions (evaluated with the Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia and Depression Anxiety Stress Scale), biomechanical outcomes, socioeconomic indicators (medication use, healthcare utilisation and absenteeism), patient satisfaction, treatment adherence and other relevant factors.

The statistical analysis will follow the intention-to-treat principle. Two-way repeated measures analysis of variance will be used to compare the clinical data across different time points within both groups.

Ethics and dissemination

The study protocol has received approval from the Ethics Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (2023-1366-133-01). All study participants will be required to give written informed consent. The findings of the study will be submitted to a peer-reviewed journal for publication and presented at scientific conferences. Additionally, the participants will receive copies of the results.

Trial registration number

ChiCTR2300076257.
How can we improve Comprehensive Geriatric Assessment for older people living with frailty in primary care and community settings? A qualitative study
Authors: Mahmoud Aseel , Goodwin Victoria A , Morley Naomi , Whitney Julie , Lamb Sarah E , Lyndon Helen , Creanor Siobhan , Frost Julia
Published: March 2024

Objective

With advancing age comes the increasing prevalence of frailty and increased risk of adverse outcomes (eg, hospitalisation). Evidence for comprehensive geriatric assessment (CGA), a multidimensional holistic model of care, is mixed in community settings. Uncertainties remain, such as the key components of CGA, who delivers it, and the use of technology. This study aimed to understand the perspectives, beliefs and experiences, of both older people and health professionals, to improve the current CGA and explore factors that may impact on CGA delivery in community settings.

Design

A qualitative interview study was conducted with older people and healthcare professionals (HCPs) identified using a maximum variation strategy. Data were analysed using an abductive analysis approach. The non-adoption, abandonment, scale-up, spread and sustainability framework and the theoretical framework of acceptability guided the categorisation of the codes and identified categories were mapped to the two frameworks.

Setting

England, UK.

Results

27 people were interviewed, constituting 14 older people and 13 HCPs. We identified limitations in the current CGA: a lack of information sharing between different HCPs who deliver CGA; poor communication between older people and their HCPs and a lack of follow-up as part of CGA. When we discussed the potential for CGA to use technology, HCPs and older people varied in their readiness to engage with it.

Conclusions

Viable solutions to address gaps in the current delivery of CGA include the provision of training and support to use digital technology and a designated comprehensive care coordinator. The next stage of this research will use these findings, existing evidence and stakeholder engagement, to develop and refine a model of community-based CGA that can be assessed for feasibility and acceptability.