bluuebunny/crossref_metadata_2025_split huggingface dataset:
AeroVax: study protocol for a randomised, double-blind, placebo-controlled phase 2 trial to evaluate safety and immunogenicity of a next-generation COVID-19 vaccine delivered by inhaled aerosol to humans
Authors: Komorowski Adam S. , Mbuagbaw Lawrence , Jeyanathan Mangalakumari , Afkhami Sam , Swinton Marilyn , D'Agostino Michael R. , Howie Karen , Medina Maria Fe C. , Gauvreau Gail M. , Brister Danica L. , Satia Imran , Lichty Brian D. , Miller Matthew S. , Cameron Donald W. , Halperin Scott , Thabane Lehana , Loeb Mark , Xing Zhou , Smaill Fiona M. 
Published: January 2025

BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to have a significant impact worldwide, in part due to a reduction in neutralising antibody protection provided by vaccines targeting monovalent spike antigens related to immune escape. Development of vaccines amenable for respiratory mucosal delivery that provide broad and durable immunity are needed.ObjectiveThis study aims to determine the safety and immunogenicity of a single inhaled dose of a replication-deficient chimpanzee adenovirus type 68 vector expressing a trivalent transgene cassette of SARS-CoV-2 S1 domain of spike, nucleocapsid, and RNA polymerase genes (ChAd-triCoV/Mac).MethodsWe plan to recruit 350 non-pregnant adults aged 18–65 who have previously received three intramuscular SARS-CoV-2 mRNA vaccines in this 24-week, multicentre, double-blind, parallel group, phase II, two-sided superiority randomised controlled trial. Participants will be randomised 2:1 to receive either a single inhaled dose of ChAd-triCoV/Mac or placebo, both aerosolizedviathe AeroNeb® Solo vibrating mesh nebuliser. A subset of separately-randomised participants will undergo bronchoalveolar lavage (BAL). The co-primary outcome to be analysed in the per-protocol population is SARS-CoV-2 antigen-specific CD4+ and CD8+ T cell responses measured at 2 weeks in the peripheral blood; solicited adverse events (AEs) frequency to day 7 and unsolicited to day 28. In the BAL sub-study, the co-primary outcome will also include BAL fluid SARS-CoV-2 antigen-specific CD4+ and CD8+ T cell responses measured at 4 weeks.ConclusionThis placebo-controlled phase 2 randomised trial will test the safety and immunogenicity of an inhaled, nebulised ChAd-triCoV/Mac SARS-CoV-2 vaccine that is novel in its administration route and targeting of multiple viral epitopes. The results will provide further information regarding the mucosal T cell response to immunisation.
Lack of weight gain and increased mortality during and after treatment among adults with drug-resistant tuberculosis: a retrospective cohort study in Georgia, 2009–2020
Authors: Chakhaia Tsira , Blumberg Henry M , Kempker Russell R , Luo Ruiyan , Dzidzikashvili Nino , Chincharauli Mamuka , Tukvadze Nestan , Avaliani Zaza , Stauber Christine , Magee Matthew J. 
Published: January 2025

BackgroundWhile low body mass index (BMI) is associated with poor tuberculosis (TB) treatment outcomes, the impact of weight gain during TB treatment is unclear. To address this knowledge gap, we assessed if lack of weight gain is associated with all-cause mortality during and after TB treatment.MethodsWe conducted a retrospective cohort study among adults with newly diagnosed multi- or extensively drug-resistant (M/XDR) pulmonary TB in Georgia between 2009–2020. The exposure was a change in BMI during the first 3–6 months of TB treatment. All-cause mortality during and after TB treatment was assessed using the National Death Registry. We used competing-risk Cox proportional hazard models to estimate adjusted hazard ratios (aHR) between BMI change and all-cause mortality.ResultsAmong 720 adult participants, 21% had low BMI (<18.5 kg·m−2) at treatment initiation and 9% died either during (n=16) or after treatment (n=50). During the first 3–6 months of TB treatment, 17% lost weight and 14% had no weight change. Among 479 adults with normal baseline BMI (≥18.5–24.9 kg·m−2), weight loss was associated with an increased risk of death during TB treatment (aHR=5.25; 95%CI: 1.31–21.10). Among 149 adults with a low baseline BMI, no change in BMI was associated with increased post-TB treatment mortality (aHR=4.99; 95%CI: 1.25–19.94).ConclusionsWeight loss during TB treatment (among those with normal baseline BMI) or no weight gain (among those with low baseline BMI) was associated with increased rates of all-cause mortality. Our findings suggest that scaling up weight management interventions among those with M/XDR TB may be beneficial.
Exacerbation and Mortality Risk in Individuals with Bronchiectasis Post-COVID-19 Recovery
Authors: Kim Sang Hyuk , Kim Jong Seung , Kim Min Ji , Jin Sorin , Kim Bo-Guen , Moon Seong Mi , Yang Bumhee , Moon Ji-Yong , Min Kyung Hoon , Choi Hayoung , Lee Hyun 
Published: January 2025

BackgroundIndividuals with bronchiectasis have an increased risk of exacerbation by coronavirus 2019 (COVID-19), even after recovery from COVID-19. However, the impact of COVID-19 severity on severe exacerbation and mortality remains uncertain.MethodsWe enrolled 48 342 individuals diagnosed with bronchiectasis between January 1, 2015 and October 7, 2020 from Korea National Health Insurance Service. Of these individuals, 2711 with bronchiectasis were identified as also having recovered from COVID-19. A COVID-19 and matched cohort (n=2711 for both) were established after 1:1 propensity matching. The exposure was COVID-19 (non-severe and severe), and outcomes were severe exacerbation of bronchiectasis and death following the COVID-19 recovery date.ResultsDuring a median follow-up of 70 days (interquartile range [IQR], 31–216 days) for severe exacerbation and a median of 71 days (IQR, 32–129 days) for death, including 14 days of recovery time, the incidence of severe exacerbation and death were 402.2/10 000 person-years and 342.9/10 000 person-years in the COVID-19 cohort. Although the COVID-19 cohort did not show higher risk of severe exacerbation, the cohort exhibited a significantly higher risk of mortality (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.06–2.01) compared with the matched cohort. In a stratified analysis, the severe COVID-19 cohort showed a significantly higher risk of severe exacerbation (aHR 2.38, 95% CI 1.25–4.51) and mortality (aHR 2.99, 95% CI 2.08–4.28) compared with the matched cohort.ConclusionThe risk of severe exacerbation and mortality in individuals with bronchiectasis was increased after recovery from COVID-19, particularly in those who experienced severe COVID-19.
Upper lobe CT imaging features improve prediction of lung function decline in COPD
Authors: Makimoto Kalysta , Virdee Sukhraj , Koo Meghan , Hogg James C. , Bourbeau Jean , Tan Wan C. , Kirby Miranda 
Published: January 2025

BackgroundIt is unknown if prediction models for lung function decline using computed tomography (CT) imaging-derived features from the upper-lobes improve performance compared to globally-derived features in individuals at risk of and with COPD.Materials and MethodsIndividuals at risk (current or former smokers) and those with COPD from the Canadian Cohort Obstructive Lung Disease (CanCOLD), a retrospective study, were investigated. A total of 103 CT features were extracted globally and regionally, and were used with 12 clinical features (demographics, questionnaires, and spirometry) to predict rapid lung function decline for individuals at risk and those with COPD. Machine learning models were evaluated in a hold-out test set using the area under the receiver operating characteristic curve (AUC) with DeLong's test for comparison.ResultsA total of 780 participants were included (n=276 at risk; n=298 GOLD 1 COPD; n=206 GOLD 2+ COPD). For predicting rapid lung function decline in those at risk, the upper-lobe CT model obtained a significantly higher AUC (AUC=0.80) than the lower-lobe CT model (AUC=0.63) and global model (AUC=0.66; p<0.05). For predicting rapid lung function decline in COPD, there was no significant differences between the upper-lobe (AUC=0.63), lower-lobe (AUC=0.59) or global CT features model (AUC=059; p>0.05).ConclusionCT features extracted from the upper-lobes obtained significantly improved prediction performance compared to globally extracted features for rapid lung function decline in early/mild COPD.
Suture button systems for coronoid fracture fixation: a biomechanical time-zero pilot study
Authors: Lappen Sebastian , Kadantsev Pavel , Bohnet Daniel , Geyer Stephanie , Hinz Maximilian , Marx Christian , Braun Sepp , Siebenlist Sebastian 
Published: January 2025

Abstract
Purpose
This study aims to describe a fixation technique for coronoid fractures using suture buttons, and to biomechanically evaluate this technique in comparison to screw fixation as a time-zero pilot study.

Methods
An O’Driscoll type 2 anteromedial coronoid facet (AMCF) fracture was simulated in 20 fresh-frozen human elbows. The specimens were randomized into two groups and fracture fixation was performed with either a suture button system or a 3.5 mm cannulated screw. Ultimate load-to-failure (N) was then tested for each specimen.

Results
The mean load-to-failure was 322.6 ± 75.9 N for suture button fixation and 314.2 ± 85.9 N for screw fixation. The differences were not statistically significant (p = 0.432). Additional fracturing of the coronoid fragment was observed in two specimens with screw fixation.

Conclusion
Promising biomechanical evaluations show that this fixation technique using suture buttons in the treatment of coronoid fractures provides equal construct stability as screw fixation. Further studies are required to fully validate this procedure.
Impact of hopelessness on migration intentions of nursing students: a path analysis
Authors: Berşe Soner , Karacan Emine , Zivdir Yeşılyurt Pelin , Güngörmüş Zeynep 
Published: January 2025

Abstract

Background
Brain drain refers to the migration of qualified professionals to developed countries in search of better living and working conditions, and has become a global concern, particularly in the healthcare sector. Migration of highly skilled nurses results in increased workload for the remaining nursing staff, limited access to quality healthcare services, and contributes to disparities in healthcare. Therefore, nursing students represent a critical demographic group for understanding the drivers of brain drain in the healthcare sector.

Purpose
This study aimed to assess the levels of hopelessness experienced by nursing students in Turkey throughout their education and to examine the impact of hopelessness on their decisions to move abroad.

Materials and methods
The study was conducted on 795 students enrolled in the nursing departments of two public universities in Gaziantep. Data were collected using a Demographic Data Form, the Beck Hopelessness Scale, and the Attitudes Towards Brain Drain Scale. The data were analyzed using the SPSS 24.0 statistical software.

Results
57% of the nursing students considered moving abroad, with 20.2% preferring Germany. The primary reasons for their desire to migrate included poor living conditions (11.1%), economic problems (12.9%), unfavorable working conditions (8.3%), and educational challenges (5.4%). The findings highlight the significant role of future hopelessness in influencing the migration intentions of nursing students.

Conclusion
More than half of Turkish nursing students consider moving abroad to seek better working conditions, higher living standards, financial gains and educational opportunities, with Germany being their top destination country. Despite low levels of hopelessness observed among the students, the tendency for migration persisted. A retention policy needs to be developed with strategic actions to prevent nurses from migrating to other countries.

Clinical trial number
not applicable.
Semi-field experiments reveal contrasted predation and movement patterns of aquatic macroinvertebrate predators of Anopheles gambiae larvae
Authors: Onen Hudson , Kaindoa Emmanuel W. , Nkya Joel , Limwagu Alex , Kaddumukasa Martha A. , Okumu Fredros O. , Kayondo Jonathan K. , Akol Anne M. , Tripet Frédéric 
Published: January 2025

Abstract
Background
Members of the Anopheles gambiae complex are major malaria vectors in sub-Saharan Africa. Their larval stages inhabit a variety of aquatic habitats in which, under natural circumstances, they are preyed upon by different taxa of aquatic macroinvertebrate predators. Understanding the potential impact of predators on malaria vector larval population dynamics is important for enabling integrated local mosquito control programmes with a stronger emphasis on biocontrol approaches. This study experimentally evaluated the predation efficacy and foraging strategy of three common aquatic macroinvertebrate predators of An. gambiae, diving beetles (Coleoptera), backswimmers (Hemiptera), and dragonfly nymphs (Odonata) in a semi-field system in South-Eastern Tanzania.

Methods
An array of alternating small and large basins used as aquatic habitats was created in two compartments of a semi-field system and filled with well water. Field-collected adult diving beetles, backswimmers or dragonfly nymphs were randomly assigned to these habitats and Anopheles arabiensis larvae were added as prey in half of the habitats. The number of mosquito larvae consumed, predator mobility across habitats and mortality were recorded at 24, 48 and 72 h.

Results
The presence of An. gambiae larvae in habitats significantly increased the survival of backswimmer and dragonfly nymphs, which are not mobile. In contrast, diving beetles survived well under any initial condition by preferentially flying away from habitats without prey to nearby larger habitats with prey. The larval predation rates of predacious diving beetle, backswimmer and dragonfly nymphs were stable over time at a mean of 3.2, 7.0 and 9.6 larvae consumed each day.

Conclusion
This study demonstrates that aquatic macroinvertebrate predators display adaptive foraging behaviour in response to prey presence and aquatic habitat size. It also confirms the ability of these predators to significantly reduce An. gambiae larval densities in aquatic habitats, thus their potential for consideration as additional biocontrol tools for mosquito population reduction.
Preimplantation genetic testing for four families with severe combined immunodeficiency: Three unaffected livebirths
Authors: Zhang Lingyun , Feng Lei , Shi Hao , Niu Wenbin , Wang Yanchi , Bu Bei , Liu Yidong , Bao Xiao , Song Wenyan , Jin Haixia , Sun Yingpu 
Published: January 2025

Abstract
Purpose
Severe combined immunodeficiency (SCID) is a set of rare monogenic inherited diseases that together represent the most severe form of the primary immunodeficiency disease phenotype. Preimplantation genetic testing for monogenic defects (PGT-M) is an effective reproductive technology strategy to prevent disease-causing gene mutations from being transmitted to offspring. The aim of this study was to report the use of PGT-M strategy based on karyomapping in four families to avoid the birth of SCID children.

Methods
Four couples underwent the PGT-M strategy due to SCID. The strategy of PGT-M started with a biopsy of the trophectoderm cells of embryos, and the whole genome was amplified by multiple replacement amplification (MDA). Then, the single nucleotide polymorphisms (SNPs) in the region upstream and downstream of the mutation site were subsequently identified via karyomapping, and the results were analyzed via SNPs linkage analysis. The aneuploids of the embryos were identified simultaneously. Finally, prenatal amniocentesis was used to verify the validity of the PGT-M results.

Results
We identified three novel variants (case1: IL2RG c.720_726delGAGCCAC; case 3: RAG2 c.770 C > T; and case 4: LIG4 c.1347 A > T). All four couples with SCID pathogenic gene mutations were subjected to karyomapping linkage analysis, and embryos with the pathogenic gene mutation were successfully identified. Euploid blastocysts without pathogenic alleles were transplanted, and healthy offspring were ultimately born. Prenatal diagnosis also confirmed the validity of our results.

Conclusion
This study revealed that karyomapping is an efficient approach for identifying SCID. Through PGT-M with karyomapping linkage analysis, healthy babies were born to families carrying mutations in the SCID pathogenic gene.
Crohn’s disease, irritable bowel syndrome, and chronic fatigue: the importance of communication and symptom management—a case report
Authors: Haedrich Johannes , Huber Roman 
Published: January 2025

Abstract
Background
Crohn’s disease and irritable bowel syndrome may both cause abdominal pain and diarrhea. Irritable bowel syndrome not only is an important differential diagnosis for Crohn’s disease but also occurs in one out of three patients with Crohn’s disease in remission in parallel. If not adequately diagnosed and treated, additional functional symptoms such as fatigue and/or muscle pain may develop, indicating a more severe course.

Case presentation
A 64-year-old Caucasian male with long-standing, widely inactive Crohn’s disease presented with persistent diarrhea, bloating, abdominal pain, general fatigue, unexplained hip pain, and frequent shivering with cold extremities, which had worsened following a gastrointestinal infection and psychological stress. A plausible explanation of his symptoms, based on an understanding of mind–body interactions, the autonomic nervous system, and temperature regulation, combined with symptom relief, was associated with rapid and sustainable improvement. After 2.5 years of follow-up, the patient is almost symptom-free.

Conclusions
This case report exemplifies the interrelation between organic (Crohn’s disease) and functional diseases (irritable bowel syndrome, chronic fatigue syndrome, and somatoform pain). It further demonstrates that these connections may be overlooked in daily practice and that providing a plausible explanation in combination with symptom relief may be important for patients with functional syndromes.
A novel treatment strategy with hyperbaric oxygen of chronic osteomyelitis and pseudoarthrosis in a child with congenital hereditary sensory and autonomic neuropathy type 4 congenital insensitivity to pain with anhidrosis syndrome: a case report
Authors: Kjellberg Anders , Gustafsson Rebecca , Antonsson Pavel , Hedelin Henrik 
Published: January 2025

Abstract
Background
Congenital insensitivity to pain with anhidrosis is a rare but devastating hereditary disease. Congenital insensitivity to pain with anhidrosis is caused by a mutation in the neurotrophic receptor tyrosine kinase 1 gene (NRTK1). The condition is characterized by multiple injuries, recurrent infections, and mental retardation.

Case presentation
A 7-year-old Kurdish female patient, with a known case of congenital insensitivity to pain with anhidrosis, presented with a left tibial fracture, complicated by incorrect healing, osteomyelitis, and pseudoarthrosis spanning over a number of years. The osteomyelitis and pseudoarthrosis eventually healed after treatment with a combination of a long course of antibiotics, CERAMENT with gentamicin, and 40 sessions of hyperbaric oxygen treatment at 2.4 bar, 113 minutes with two air breaks. This is the first reported case of using hyperbaric oxygen treatment in children with congenital insensitivity to pain with anhidrosis. We discuss potential mechanistic explanations of the association between healing and hyperbaric oxygen treatment.

Conclusion
Hyperbaric oxygen treatment may be considered in other cases of complicated infections or treatment-resistant pseudoarthrosis in patients with this rare disease.
Sarcolemma resilience and skeletal muscle health require O-mannosylation of dystroglycan
Authors: Hord Jeffrey M. , Burns Sarah , Willer Tobias , Goddeeris Matthew M. , Venzke David , Campbell Kevin P. 
Published: January 2025

Abstract
Background
Maintaining the connection between skeletal muscle fibers and the surrounding basement membrane is essential for muscle function. Dystroglycan (DG) serves as a basement membrane extracellular matrix (ECM) receptor in many cells, and is also expressed in the outward-facing membrane, or sarcolemma, of skeletal muscle fibers. DG is a transmembrane protein comprised of two subunits: alpha-DG (α-DG), which resides in the peripheral membrane, and beta-DG (β-DG), which spans the membrane to intracellular regions. Extensive post-translational processing and O-mannosylation are required for α-DG to bind ECM proteins, which is mediated by a glycan structure known as matriglycan. O-mannose glycan biosynthesis is initiated by the protein O-mannosyltransferase 1 (POMT1) and POMT2 enzyme complex and leads to three subtypes of glycans called core M1, M2, and M3. The lengthy core M3 is capped with matriglycan. Genetic defects in post-translational O-mannosylation of DG interfere with its receptor function and result in muscular dystrophy with central nervous system and skeletal muscle pathophysiology.

Methods
To evaluate how the loss of O-mannosylated DG in skeletal muscle affects the development and progression of myopathology, we generated and characterized mice in which the Pomt1 gene was specifically deleted in skeletal muscle (Pomt1skm) to interfere with POMT1/2 enzyme activity. To investigate whether matriglycan is the primary core M glycan structure that provides the stabilizing link between the sarcolemma and ECM, we generated mice that retained cores M1, M2, and M3, but lacked matriglycan (conditional deletion of like-acetylglucosaminyltransferase 1; Large1skm). Next, we restored Pomt1 using gene transfer via AAV2/9-MCK-mPOMT1 and determined the effect on Pomt1skm pathophysiology.

Results
Our data showed that in Pomt1skm mice O-mannosylated DG is required for sarcolemma resilience, remodeling of muscle fibers and muscle tissue, and neuromuscular function. Notably, we observed similar body size limitations, sarcolemma weakness, and neuromuscular weakness in Large1skm mice that only lacked matriglycan. Furthermore, our data indicate that genetic rescue of Pomt1 in Pomt1skm mice limits contraction-induced sarcolemma damage and skeletal muscle pathology.

Conclusions
Collectively, our data indicate that DG modification by Pomt1/2 results in core M3 capped with matriglycan, and that this is required to reinforce the sarcolemma and enable skeletal muscle health and neuromuscular strength.