bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of flucloxacillin-modified hepatocellular proteins: implications in flucloxacillin-induced liver injury
Authors: Ali Serat-E , Waddington James C , Lister Adam , Sison-Young Rowena , Jones Robert P , Rehman Adeeb H , Goldring Chris E P , Naisbitt Dean J , Meng Xiaoli 
Published: February 2023

Abstract
Flucloxacillin is a β-lactam antibiotic associated with a high incidence of drug-induced liver injury. Although expression of HLA-B*57:01 is associated with increased susceptibility, little is known of the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the provision of flucloxacillin-modified peptides that are presented to T-cells by the protein encoded by the risk allele. In this study, we have shown that flucloxacillin binds to multiple proteins within human primary hepatocytes, including major hepatocellular proteins (hemoglobin and albumin) and mitochondrial proteins. Inhibition of membrane transporters multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein (P-gp) appeared to reduce the levels of covalent binding. A diverse range of proteins with different functions was found to be targeted by flucloxacillin, including adaptor proteins (14-3-3), proteins with catalytic activities (liver carboxylesterase 1, tRNA-splicing endonuclease subunit Sen2, All-trans-retinol dehydrogenase ADH1B, Glutamate dehydrogenase 1 mitochondrial, Carbamoyl-phosphate synthase [ammonia] mitochondrial), and transporters (hemoglobin, albumin, and UTP-glucose-1-phosphate uridylyltransferase). These flucloxacillin-modified intracellular proteins could provide a potential source of neoantigens for HLA-B*57:01 presentation by hepatocytes. More importantly, covalent binding to critical cellular proteins could be the molecular initiating events that lead to flucloxacillin-induced cholestasis Data are available via ProteomeXchange with identifier PXD038581.
The Relationship Between Respiratory Complaints and Urine Aluminum Levels in Aluminum Factory Workers
Authors: BilgiN Cahit , Arbak Peri , Güleç Balbay Ege , Balbay Öner , Annakkaya Ali Nihat 
Published: February 2023

Objective
This prospective case-control study aimed to investigate the forms and conditions of respiratory effects in workers working in an Aluminum Profile Factory.

Methods
All male (42 person, mean age: 32.2 ± 6.9) workers working in an Aluminum Profile Factory were compared with 33 controls.

Results
The urinary aluminum levels of the workers were significantly higher than the control group. Complaints of cough, sputum, shortness of breath and wheezing were statistically significantly higher than the control group. In aluminum workers, those with dyspnea had a significantly higher urinary Al level than those without dyspnea.

Conclusions
It is thought that primary and secondary prevention are both important in the workplaces with aluminum exposure. Urinary aluminum level monitoring could be key to protecting the respiratory health of the workers.
By Nature, We're Doers and Problem Solvers
Authors: Castro Katherine C. , Fisher Alexandra B. , Geczik Ashley M. , Boyer Stacy L. , Resick Christian J. , Lee Jin , Davis Andrea L. , Taylor Jennifer A. , Allen Joseph A. 
Published: February 2023

Objective
The US fire service experienced increased demands due to COVID-19. This qualitative study explored the pandemic's impact on work-life balance and safety.

Methods
Five interviews and 10 focus groups were conducted with 15 fire departments in the COVID-19 RAPID Mental Health Assessment. Coding and multilevel content analysis were conducted in NVivo.

Results
Four department support themes were identified: emotional/social (33.1%), policy (28.4%), instrumental (22.9%), and informational (15.5%). Four work-life balance themes were identified: life (51.2%), children (18.1%), physiological (16.5%), and work (14.2%). We observed more departmental resources to help mitigate job demands within the work environment compared with those for work-life demands.

Conclusions
Job resources are needed to mitigate demands and improve safety culture and mental well-being of the fire service under normal conditions, and for the next pandemic, natural disaster, or long-term emergency.
Impedance Change as an Indicator of Cochlear Implant Failure
Authors: Pisa Justyn F. D. , Almutairi Walleed H. , Mackie Kristy , Stangherlin Daniela , Sulkers Jacob , Hochman Jordan B. 
Published: February 2023

Objective
In February 2020, Advanced Bionics initiated a field action notice to remove the MS Ultra (V1) implant from circulation. In this study, we quantify a single site’s incidence with device failure and examine the relationship between impedance change and declining speech perception.

Study Design
Retrospective/cohort study.

Setting
Tertiary healthcare center.

Patients
Forty-nine adult patients (52 devices) were implanted between October 2017 and December 2019, with the following exclusion criteria: <18 years of age, medical/surgical failures, and lack of English-language proficiency.

Interventions
Diagnostic.

Main Outcome Measures
Postoperative speech perception (AzBio sentence test) scores at 12 months postactivation were compared with repeat testing at 6- to 12-month intervals. Degree of change in impedances from 1 month postactivation was analyzed at similar intervals. Device failures were suspected when impedance levels on three or more electrodes dropped to <3.5 kΩ and AzBio scores declined >15%. Device failures were confirmed through analyses completed by the manufacturer.

Results
To date, 21% (11/52) of devices have met all three criteria for a confirmed failure with an average decline in speech perception of 27.7 ± 22%. The average length of time for detection of device failure was 21.9 ± 5 months postimplantation. An additional 7 devices (13%) are currently being monitored for failure but have not yet met full criteria. There was no predictive relationship between degree of impedance change and speech perception scores. Electrodes along the entire array (channels 1–16) can be affected.

Conclusions
Impedance values can be used as a reliable indicator of device malfunction, thus facilitating patient counseling and early intervention. No correlation was identified between impedance changes and speech perception scores.
Totally Implantable Hearing Implant Revision Surgery Indications and Outcomes
Authors: Shohet Jack , Bibee Jacqueline , Gende Deanna 
Published: February 2023

Objective
Analyze indications, findings, and outcomes of revision procedures for a totally implantable active middle ear implant (AMEI) over the past 17 years.

Study Design
Retrospective review.

Setting
Single institution, private practice setting.

Subjects
Adult patients using a totally implantable AMEI called the Esteem middle ear implant by Envoy Medical who needed revision to their original implant between 2005 and 2022. Thirty-nine patients had 60 revision procedures.

Intervention
History of a totally implantable AMEI revision procedure. Indications for revision were related to either surgical wound issues or reduced device function.

Outcome Measures
Device diagnostics, audiometric outcomes, and documented subjective report.

Results
Surgical site wound issues were readily corrected in the majority of patients; most had risk factors for wound breakdown. For sterile wound dehiscence, it was not always necessary to remove the sound processor for an extended time to promote healing. Outcomes for revision procedures because of device issues ranged from 31 to 100% success rate, depending on the cause of issue. The most common indication for revision was reduced device function caused by scar band and/or fibrotic tissue accumulation in the middle ear.

Conclusion
Revision of fully implantable AMEI can be successful for many indications. Appropriate preoperative device troubleshooting and medical evaluation is helpful in identifying the issue and determining surgical approach. Suboptimal device function and feedback can sometimes be improved by removing tissue around the implant, although permanency of this procedure varies among patients.
Recurrent Benign Paroxysmal Positional Vertigo in DFNB16 Patients with Biallelic STRC Gene Deletions
Authors: Achard Sophie , Campion Margaux , Parodi Marine , MacAskill Melissa , Hochet Baptiste , Simon François , Rouillon Isabelle , Jonard Laurence , Serey-Gaut Margaux , Denoyelle Françoise , Loundon Natalie , Marlin Sandrine 
Published: February 2023

Objective
Deletions of STRC gene (DFNB16) account for 12% of isolated congenital mild to moderate hearing loss (HL). In mice, the stereocilin protein, encoded by STRC, is present in the vestibular kinocilium embedded in the otoconial membrane of the utricular macula. Despite this, effects on vestibular function have not been widely investigated. The aim of this study was to investigate the prevalence of benign paroxysmal positional vertigo (BPPV) in a cohort of DFNB16 patients.

Study Design
Observational descriptive epidemiological study.

Setting
Single-center study, in a tertiary referral center.

Patients
Older than 5 years, with a genetic diagnosis of HL related to biallelic STRC gene deletions, diagnosed between 2015 and 2021

Intervention
Patients or their parents were interviewed to determine whether they had experienced vertigo or episodes of BPPV.

Main Outcome Measure
Criteria were at least five acute episodes of rotatory vertigo, each lasting less than 1 minute, episodes triggered by changes in specific head position, and an absence of neurological symptoms.

Results
Sixty-four patients having mild (33%) to moderate (66%) HL were included. Median age was 15 years (range, 6–48 yr). Prevalence of BPPV was 39% (25 of 64). Median age of first onset was 13 years (range, 3–18 yr).

Conclusions
This study showed recurrent BPPV and early age of onset in patients with biallelic STRC gene deletions. BPPV may be associated with the HL phenotype in patients with STRC gene deletions. It is important to inform patients and families of this potential risk such that appropriate management can be proposed.
Oxidized phospholipid oxPAPC induces a Th1-like phenotype in regulatory T cells and inhibits their protective function in atherosclerosis
Authors: Appleton Brenna D. , Palmer Sydney A. , Smith Harrison P. , Stephens Lilly E. , Major Amy S. 
Published: February 2023

AbstractBackgroundRegulatory T cells (Tregs) are protective in atherosclerosis but reduced during disease progression due to cell death and loss of stability. However, the mechanisms of Tregdysfunction remain unknown. Oxidized phospholipids (oxPLs) are abundant in atherosclerosis and can activate innate immune cells, but there is limited information regarding their impact on T cells. Given Tregloss during atherosclerosis progression and oxPL levels in the plaque microenvironment, we sought to determine whether oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), an oxPL associated with atherosclerotic plaques, alters Tregdifferentiation and function.MethodsNaïve CD4+T cells were cultured under Treg,Th1, and Th17 polarizing conditions with or without oxPAPC and assessed by flow cytometry. Gene expression in oxPAPC-treated Tregswas analyzed by bulk RNA sequencing. Functional studies of oxPAPC-induced Tregswere performed by co-culturing Tregswith CTV-labeled CD8+cellsin vitro. In vivosuppression of atherosclerosis was evaluated by adoptively transferring control or oxPAPC-treated Tregsto hyperlipidemicLdlr-/-mice.ResultsCompared to controls, oxPAPC-treated Tregswere less viable but expressed higher levels of the Th1-associated markers T-bet, CXCR3, and IFN-γ. Th1 and Th17 skewing cultures were unaltered by oxPAPC. IFN-γ is linked to Treginstability, thus Tregpolarization experiments were repeated usingIfngr1-/-CD4+T cells. IFNγR1 deficiency did not improve cell viability in oxPAPC-treated Tregs, however, T-bet and IFN-γ expression was not increased suggesting a role for IFN-γ signaling. OxPAPC-treated Tregswere less suppressivein vitro, and adoptive transfer studies in hyperlipidemicLdlr-/-mice showed that oxPAPC-induced Tregspossessed altered tissue homing and were insufficient to inhibit atherosclerosis progression.ConclusionsOxPAPC elicits Treg-specific changes that induce a Th1-like phenotype dependent on IFN-γ signaling. This is biologically relevant as oxPAPC-treated Tregsare unable to reduce atherosclerosis progression inLdlr-/-mice. This study supports a role for oxPLs in negatively impacting Tregdifferentiation and atheroprotective function.
Industrial chicory genome gives insights into the molecular timetable of anther development and male sterility
Authors: Waegneer Evelien , Rombauts Stephane , Baert Joost , Dauchot Nicolas , De Keyser Annick , Eeckhaut Tom , Haegeman Annelies , Liu Chang , Maudoux Olivier , Notté Christine , Staelens Ariane , Van der Veken Jeroen , Van Laere Katrijn , Ruttink Tom 
Published: February 2023

ABSTRACTIndustrial chicory (Cichorium intybusvar.sativum) is a biannual crop mostly cultivated for extraction of inulin, a fructose polymer used as a dietary fiber. F1hybrid breeding is a promising breeding strategy in chicory but crucially relies on stable self-incompatibility. Here, we report the assembly and annotation of a new industrial chicory reference genome. Additionally, we performed RNA-Seq on subsequent stages of flower bud development of a fertile line and two cytoplasmic male sterile (CMS) clones. Comparison of fertile and CMS flower bud transcriptomes combined with morphological microscopic analysis of anthers, provided a molecular understanding of anther development and identified key genes in a range of underlying processes, including tapetum development, sink establishment, pollen wall development and anther dehiscence. We also described the role of phytohormones in the regulation of these processes under normal fertile flower bud development. In parallel, we evaluated which processes are disturbed in CMS clones and could contribute to the male sterile phenotype. Taken together, this study provides a state-of-the-art industrial chicory reference genome, an annotated and curated candidate gene set related to anther development and male sterility as well as a detailed molecular timetable of flower bud development in fertile and CMS lines.
The clustering of multiple health and lifestyle behaviours among Swedish adolescents: A person-oriented analysis
Authors: Jonsson Kenisha Russell , Corell Maria , Löfstedt Petra , Adjei Nicholas Kofi 
Published: February 2023

ABSTRACTBackgroundKnowledge of the distribution, prevalence, and clustering of multiple health and lifestyle related behaviours (HLBs) among adolescents can inform the development of more effective health-promoting policies and interventions. We therefore assessed the clustering of multiple HLBs among 11, 13 and 15-year-old Swedish adolescents and examined the socioeconomic and demographic correlates of each cluster.MethodsWe used data from the 2017/2018 Swedish Health Behaviour in School-aged Children (HBSC) study to conduct sex and age-stratified latent class analysis (LCA). The LCA was based on five HLBs: eating behaviour and habits (EBH), physical activity (PA), tobacco usage (TU), alcohol consumption (AC) and sleeping habits and patterns (SHPs). Multinomial logistic regression models were used to assess the associations between the identified clusters and the socioeconomic and demographic characteristics of adolescents and their parents.ResultsHealth behaviours varied by age and sex. Four distinct clusters were identified based on sex: cluster 1 (Mixed eating behaviours and habits, physical activity and low alcohol consumption), cluster 2 Healthy lifestyle behaviours), cluster 3 (Unhealthy lifestyle behaviours), and cluster 4 (Breakfast, low alcohol consumption and tobacco usage). In the age-stratified analyses, three clusters were identified: cluster 1 (Unhealthy lifestyle behaviours), cluster 2 (Moderately healthy lifestyle behaviours) and cluster 3 (Healthy lifestyle behaviours). The multinomial analysis showed that sex, age, family situation and perceived family wealth were strong predictors of health behaviours. In particular, unhealthy behaviours showed the most frequent associations with socioeconomic disadvantage, having a migrant background and living in reconstructed families or single parent households.ConclusionsHealth behaviours vary significantly based on socioeconomic and demographic factors. Targeted policy and interventions programmes can effectively improve HLBs among vulnerable and at-risk adolescents.
Improved cognition after high-intensity exercise paired with motor practice in individuals with stroke and older adults: A randomized controlled trial
Authors: Greeley Brian , Larssen Beverley C. , Ferris Jennifer , Yeganeh Negin Motamed , Andrushko Justin W. , Chau Briana , Jones Christina B. , Peters Sue , Campbell Kristin L. , Neva Jason L. , Boyd Lara A. 
Published: February 2023

AbstractIntroductionStroke is a leading cause of long-term disability resulting in cognitive and motor impairments. Exercise may improve cognition and motor function. We paired multiple bouts of high-intensity interval training (HIIT) exercise with motor practice to positively affect cognitive and motor function after stroke and age-matched controls.MethodsUsing a randomized controlled parallel group design, 31 individuals with chronic stroke and 41 older adult controls were randomized to either 23 minutes of HIIT exercise or rest prior to completing motor task practice using their paretic/non-dominant arm across five days. Primary outcomes were reaction time and motor function. Assessors were blinded to the intervention group. Trail Making Test-A and B (TMT-A, TMT-B), and object hit and avoid (OHA) were used to assess processing speed and inhibitory control.ResultsAll participants showed evidence of motor learning; HIIT exercise did not confer an additional benefit. For stroke participants, motor function (p= .047), but not motor impairment, improved. The stroke exercise group displayed significant reductions in TMT-A completion time (p= .026). Exercise with motor practice also led to a reduced number of distractors hit (p =.035) in the OHA task for both participant groups. There were no adverse events.ConclusionsFive days of HIIT exercise paired with motor practice led to improved processing speed for individuals with stroke. Both participant, exercise groups showed improved visuospatial skills and inhibitory control. Together, HIIT exercise paired with motor practice appears to be a safe and effective means of enhancing cognitive-motor skills after stroke and in older adults.Trial RegistryClinicalTrials.gov, ID:NCT02980796Trial registry nameThe Influence of Exercise on Neuroplasticity and Motor Learning After Stroke (EX-ML3)
CDK5 activity in retinal pigment epithelium contributes to gap junction dynamics during phagocytosis
Authors: Fadjukov Julia , Wienbar Sophia , Milićević Nemanja , Hakanen Satu , Vihinen-Ranta Maija , Ihalainen Teemu O. , Schwartz Gregory W. , Nymark Soile 
Published: February 2023

AbstractRetinal pigment epithelium (RPE) at the back of the eye is a monolayer of cells with an extensive network of gap junctions that contributes to retinal health in a multitude of ways. One of those roles is the phagocytosis of photoreceptor outer segments. This renewal is under circadian regulation and peaks after light onset. Connexin 43 (Cx43) is the most predominantly expressed gap junction protein in RPE. In this study, we examine how gap junctions and specifically, Cx43 phosphorylation, contribute to phagocytosis in both human embryonic stem cell derived RPE and mouse RPE monolayers. We show that both Rac1 and CDK5 have differences in protein localization at different points in phagocytosis, and that by using their effectors, the capability of RPE for phagocytosis changes. CDK5 has not yet been reported in RPE tissue, and here we show that it likely regulates Cx43 localization and resulting electrical coupling. We find that gap junctions in RPE are temporally highly dynamic during phagocytosis and that regulation of gap junctions via phosphorylation is likely critical for maintaining eye health.
Population genetics in the early emergence of the Omicron SARS-CoV-2 variant in the provinces of South Africa
Authors: Contreras-González María Fernanda , Castelán-Sánchez Hugo G. , Diaz-Valenzuela Erik , Cibrián-Jaramillo Angélica 
Published: February 2023

AbstractPopulation genetic analyses of viral genome populations provide insight into the emergence and evolution of new variants of SARS-CoV-2. In this study, we use a population genetic approach to examine the evolution of the Omicron variant of SARS-CoV-2 in four provinces of South Africa (Eastern Cape, Gauteng, KwaZulu-Natal, and Mpumalanga) during the first months before emergence and after early spread. Our results show that Omicron polymorphisms increase sharply from September to November. We found differences between SARS-CoV-2 populations from Gauteng and Kwazulu-Natal and viruses from the Eastern Cape, where allele frequencies were higher, suggesting that natural selection may have contributed to the increase in frequency or that this was the site of origin. We found that the frequency of variants N501Y, T478K, and D614G increased in the spike in November compared with other mutations, some of which are also present in other animal hosts. Gauteng province was the most isolated, and most genetic variation was found within populations. Our population genomic approach is useful for small-scale genomic surveillance and identification of novel allele-level variants that can help us understand how SARS-CoV-2 will continue to adapt to humans and other hosts.
Defining the Burden of Disease of RSV in Europe: estimates of RSV-associated hospitalisations in children under 5 years of age. A systematic review and modelling study
Authors: Del Riccio Marco , Spreeuwenberg Peter , Osei-Yeboah Richard , Johannesen Caroline K. , Fernandez Liliana Vazquez , Teirlinck Anne C. , Wang Xin , Heikkinen Terho , Bangert Mathieu , Caini Saverio , Campbell Harry , Paget John 
Published: February 2023

AbstractBackgroundRespiratory syncytial virus (RSV) infections cause an estimated 22-50 million episodes of acute lower respiratory infections (ALRI) every year in children younger than 5 years. To date, no overall estimate of RSV-associated hospitalisations in children under 5 years has been published for the European Union (EU). Through statistical modelling, we estimated the RSV hospitalisation burden in children under 5 years of age in EU countries and Norway, by age group and country.MethodsWe collated national RSV-associated hospitalisation estimates calculated using linear regression models in children under 5 years via the RESCEU project for Denmark, England, Finland, Norway, the Netherlands and Scotland during 2006-2018. A systematic literature review was conducted to collect additional estimates. Using the multiple imputation and nearest neighbour matching extrapolation methods, we estimated RSV-associated hospitalisation rates in all EU countries.ResultsAdditional estimates for Spain and France were found in the literature and added to the analysis. We estimated that an average of 245,244 (95%CI 224,688-265,799) hospital admissions with a respiratory infection per year were associated with RSV in children under the age of 5, with most cases occurring among children aged less than 1 year (75%). Infants aged less than 2 months represented the most affected group (71.6 per 1,000 children; 95%CI: 66.6-76.6). The hospitalisation rates varied widely across countries: for example, estimated rates in the 0-2 months age group ranged from 47.4 (37.5-57.3) per 1,000 in the Netherlands to 98.3 (88.5-108.1) per 1,000 in France.ConclusionTo our knowledge, this is the first attempt to estimate the overall RSV hospitalisation burden in children under the age of 5 years in the EU. Our findings will help support decisions regarding prevention efforts, and they will also represent an important benchmark to understand changes in the RSV burden following the introduction of RSV immunisation programs in Europe.