bluuebunny/crossref_metadata_2025_split huggingface dataset:
Audit and group feedback in nursing home physician groups: lessons learned from a qualitative study
Authors: Yeung Gary Y. C. , Albers Charlotte A. W. , Smalbrugge Martin , de Bruijne Martine C. , Jepma Patricia , Joling Karlijn J. 
Published: February 2025

Abstract

Background
Audit and group feedback (A&F) is an instrument used to encourage healthcare professionals to improve the quality of care. Clinical practice was audited against a set of criteria and fed back to a group by a facilitator. The aim of this study was to gain a better understanding of how physician group feedback sessions in nursing homes were conducted and to what extent they resulted in action planning.

Methods
Fifteen group feedback sessions of the antibiotic A&F program within a nursing home network were audio-recorded, transcribed, and analyzed via the Framework Method for thematic analysis. The coding was performed using the existing Calgary A&F Framework and Cooke’s conceptual model of physician behaviors, and open inductive codes were added.

Results
Elements of the conceptual model and the Calgary A&F Framework occurred within all group feedback sessions. The relationships within the group and with the facilitators were important elements when moving a group from interpreting the results to formulating action plans. Physician groups responded positively to the audit data, particularly if they were among the best performing. The data were met with doubt by physicians who did not recognize their own practice. When exploring potential reasons for lower guideline adherence, groups often considered data quality or external factors such as the choice of non-adherent treatment by locum staff. The degree of reflection on personal factors as explanations for low adherence and the extent to which groups identified learning and improvement opportunities varied: some groups were able to formulate action plans to address data problems and knowledge gaps, whereas others scheduled a follow-up meeting to develop action plans for treatment or prescribing practice changes.

Conclusions
The facilitator was crucial in supporting the group in interpreting the results, steering the conversation towards sharing change cues, and helping the physician group in developing action plans. The degree of reflection and action planning varied by group. By implementing the lessons learned from this study, group feedback sessions can be refined, supporting participants in action planning.
PEX11B palmitoylation couples peroxisomal dysfunction with Schwann cells fail in diabetic neuropathy
Authors: Yang Yu Mei , Ma Hang Bin , Xiong Yue , Wu Qian , Gao Xiu Kui 
Published: February 2025

Abstract

Background
Diabetic neuropathy (DN) is a prevalent and painful complication of diabetes; however, the mechanisms underlying its pathogenesis remain unclear, and effective clinical treatments are lacking. This study aims to explore the role of peroxisomes in Schwann cells in DN.

Methods
The abundance of peroxisomes in the sciatic nerves of mice or Schwann cells was analyzed using laser confocal super-resolution imaging and western blotting. The RFP-GFP-SKL (Ser-Lys-Leu) probe was utilized to assess pexophagy (peroxisomes autophagy) levels. To evaluate the palmitoylation of PEX11B, the acyl-resin assisted capture (acyl-RAC) assay and the Acyl-Biotin Exchange (ABE) assay were employed. Additionally, MR (Mendelian randomization) analysis was conducted to investigate the potential causal relationship between DN and MS (Multiple sclerosis).

Results
There was a decrease in peroxisomal abundance in the sciatic nerves of diabetic mice, and palmitic acid (PA) induced a reduction in peroxisomal abundance by inhibiting peroxisomal biogenesis in Schwann cells. Mechanistically, PA induced the palmitoylation of PEX11B at C25 site, disrupting its self-interaction and impeding peroxisome elongation. Fenofibrate, a PPARα agonist, effectively rescued peroxisomal dysfunction caused by PA and restored the peroxisomal abundance in diabetic mice. Lastly, MR analysis indicates a notable causal influence of DN on MS, with its onset and progression intricately linked to peroxisomal dysfunction.

Conclusions
Targeting the peroxisomal biogenesis pathway may be an effective strategy for preventing and treating DN, underscoring the importance of addressing MS risk at the onset of DN.
Alpha-1 antitrypsin reduces inflammation and vasculopathy in mice with oxygen-induced retinopathy
Authors: Suphapimol Varaporn , Liu Yu-Han , Prato Sandro , Karnowski Alexander , Hardy Charles , Morelli Adriana Baz , Jayasimhan Abhirup , Deliyanti Devy , Wilkinson-Berka Jennifer L. 
Published: February 2025

Abstract

Background
Damage to the retinal vasculature is a major cause of vision loss and is influenced by a pro-inflammatory environment within retinal tissue. Alpha-1 antitrypsin (AAT) is a potent inhibitor of serine proteases and has anti-inflammatory properties. We hypothesised that AAT could reduce inflammation and vasculopathy in neovascular retinopathies including oxygen-induced retinopathy (OIR).

Methods
Litters of C57BL/6J mice were randomised to develop OIR by exposure to high oxygen between postnatal days 7 to 12 resulting in vaso-obliteration (phase I OIR), and then room air from postnatal days 12 to 18 resulting in neovascularisation (phase II OIR). Control mice were exposed to room air. Separate cohorts of mice were administered control vehicle or human AAT (120 mg/kg) by intraperitoneal injection every second day in phase I or phase II OIR.

Results
In phase I OIR, plasma levels of AAT were reduced compared to room air controls, and AAT treatment reduced vaso-obliteration. In phase II OIR, AAT treatment influenced inflammation by reducing the density of ionised calcium binding adaptor protein 1 + cells (microglia/macrophages) and modulating their cell process length and reducing mRNA levels of tumour necrosis factor and monocyte chemoattractant protein-1, but not interleukin-1b and interleukin-6 in retina. Furthermore, AAT treatment reduced retinal neovascularisation, gliosis, vascular endothelial growth factor mRNA and protein expression, and vascular leakage, compared to OIR controls.

Conclusions
This research demonstrates the vasculo-protective actions of AAT, and thereby the potential of AAT as a therapeutic option for neovascular retinopathies.
TGF-β1 Induces Mucosal Mast Cell Genes and is Negatively Regulated by the IL-3/ERK1/2 Axis
Authors: Meurer Steffen K. , Bronneberg Gina , Penners Christian , Kauffmann Marlies , Braunschweig Till , Liedtke Christian , Huber Michael , Weiskirchen Ralf 
Published: February 2025

Abstract
Mast cells develop from the myeloid lineage and are released from the bone marrow as immature cells, which then differentiate at the destination tissue based on cues from the local environment. In the liver, mast cells are recruited in diseased states to fibrogenic surroundings rich in TGF-β1. The aim of this study was to investigate TGF-β1 signaling in primary and permanent mast cells to identify common and unique mechanisms. The TGF-β receptor repertoire is similar among mast cells, with high expression of type I and type II receptors and very low expression of type III receptors (Betaglycan and Endoglin). Downstream, TGF-β1 activates the SMAD2/3 signaling axis and also SMAD1/5 with target genes Smad6 and Id1 in a transient manner. Initially, TGF-β1 upregulates the transcription of mucosal mast cell effectors Mcpt1 and Mcpt2 in all analyzed mast cells. This upregulation is reduced in the presence of IL-3, which promotes proliferation. Inhibition of ERK1/2 activation reduces proliferation and mitigates the negative effect of IL-3 on Mcpt1 mRNA and protein expression in the immortalized mast cell line PMC-306 but not in bone marrow-derived mast cells. Therefore, extracellular signal-regulated kinases ERK1/2 are identified as a mutual switch between IL-3-driven proliferation and TGF-β1-promoted mucosal mast cell differentiation in PMC-306. In conclusion, TGF-β1 promotes a mucosal gene signature and inhibits proliferation in mast cells, with these effects being counter-regulated by IL-3/ERK1/2.

Graphical Abstract
Depression and anxiety in childhood-onset systemic lupus erythematosus: prevalence, associated factors, and impact on quality of life and family
Authors: Duangmala Pitsamai , Sontichai Watchareewan 
Published: February 2025

Abstract

Background
Depression and anxiety are common psychiatric manifestations in childhood-onset systemic lupus erythematosus (cSLE). This study aimed to determine the prevalence of clinically significant depression and anxiety, identify associated factors, and assess their impact on health-related quality of life (HRQOL) and family in patients with cSLE.

Methods
We conducted a cross-sectional study of cSLE patients, aged 8–18 years. Patients completed the Children’s Depression Inventory (CDI), Screening for Child Anxiety Related Disorders (SCARED), Pediatric Quality of Life Inventory Generic Core Scale (PedsQL-GC), and Visual Analog Scale of pain intensity. Their parents completed the Pediatric Quality of Life Family Impact module (PedsQL family impact).

Results
Of 91 patients, the median disease duration was 3.4 years (IQR 3.5), and the median SLE disease activity index 2000 score was 2 (IQR 6). The prevalence of clinically significant depression (CDI > 15) and clinically significant anxiety (SCARED ≥ 25) were 31.9% and 49.5%, respectively. Coexisting clinically significant depression and anxiety were found in 26 patients (28.6%). In multivariable analyses, older age at diagnosis was associated with clinically significant depression (OR 1.56, 95% CI 1.12–2.16, p = 0.008), while organ damage (OR 4.27, 95% CI: 1.19–15.31, p = 0.026) and pain score (OR 1.61, 95% CI: 1.11–2.32, p = 0.012) were associated with clinically significant anxiety. Patients with clinically significant depression or anxiety had significantly lower PedsQL-GC and PedsQL family impact scores compared to those without these symptoms.

Conclusions
These results suggest that depression and anxiety are prevalent in cSLE and have negative impacts on HRQOL and family. Physicians should be aware of the presence of these psychological symptoms, particularly in patients with risk factors. Providing psychological counseling and prompt referral to psychiatrists could enhance HRQOL and family functioning.
Impact of intravenous immunoglobulin treatment on peripheral blood cells in children with Kawasaki disease complicated with coronary artery lesion
Authors: Zhao Junshan , Ma Yingying , Xin Li , Wang Lijun , Gao Hongliang 
Published: February 2025

Abstract

Background
Kawasaki disease (KD) primarily affects young children and can lead to coronary artery lesions. Intravenous immunoglobulin (IVIG) treatment is essential; however, it may fail in 10-20% of cases, increasing the risk of complications. Complete blood count (CBC) tests can help assess disease severity and predict risks. This study investigated the impact of IVIG on peripheral blood cells, including neutrophil count, platelet-lymphocyte ratio, hemoglobin level, mean platelet volume (MPV), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), in children with KD complicated by coronary artery lesions (CALs).

Methods
This retrospective analysis included children diagnosed with typical KD. The neutrophil count, hemoglobin level, platelet-lymphocyte ratio, MPV, ESR, and CRP were compared between those with (CAL+) and without (CAL−) CALs during the acute phase, as well as at 7 days, 1 month, and 2 months after normalizing body temperature with IVIG.

Results
A total of 76 children with KD were analyzed, including 30 with CAL+. CAL+ and CAL− patients exhibited elevated neutrophil counts during the acute phase, with no significant differences (P > 0.05) between groups. After IVIG treatment, CAL− patients demonstrated a more pronounced reduction in neutrophil count (P < 0.05) than CAL+ patients. Hemoglobin levels differed significantly during the acute phase (P < 0.05) but were comparable post-treatment (P > 0.05) between CAL+ and CAL− patients. The platelet-lymphocyte ratio varied significantly between groups during the acute phase and 1-month post-treatment (P < 0.05). Mean ESR and CRP levels were significantly elevated at all time points in the CAL+ group compared with the CAL− group. No significant differences in MPV were observed between groups.

Conclusions
After IVIG treatment, CAL− patients demonstrated a more important reduction in neutrophil count than CAL+ patients after IVIG. Pediatric patients with KD and CAL+ showed lower hemoglobin and platelet-lymphocyte ratio and higher ESR and CRP compared with CAL−, suggesting that they may serve as indicators for CAL in pediatric patients with KD.
Sex-specific role of epigenetic modification of a leptin upstream enhancer in adipose tissue
Authors: Müller Luise , Oelkrug Rebecca , Mittag Jens , Hoffmann Anne , Ghosh Adhideb , Noé Falko , Wolfrum Christian , Guiu Jurado Esther , Klöting Nora , Dietrich Arne , Blüher Matthias , Kovacs Peter , Krause Kerstin , Keller Maria 
Published: February 2025

Abstract

Objective
Maternal hormonal status can have long-term effects on offspring metabolic health and is likely regulated via epigenetic mechanisms. We elucidated the effects of maternal thyroid hormones on the epigenetic regulation of leptin (Lep) transcription in adipose tissue (AT) and subsequently investigated the role of DNA methylation at a Lep upstream enhancer (UE) in adipocyte biology.

Results
Pregnant mice treated with triiodothyronine (T3) produced offspring with reduced body weight, total fat mass, and gonadal white adipose tissue (gWAT) mass at 6 months of age (treatment: N = 8; control: N = 12). Compared with control offspring, exclusively female offspring of T3-treated mothers presented lower Lep mRNA levels and higher Lep UE methylation in gWAT. In murine preadipocytes, targeted demethylation of the Lep UE via a dCas9-SunTag-TET1 system reduced methylation by ~ 20%, but this effect was insufficient to alter Lep expression or lipid accumulation after differentiation. In human omental visceral AT (OVAT) samples from the Leipzig Obesity BioBank (LOBB, N = 52), LEP UE methylation was associated with body fat percentage, and mediation analysis indicated that leptin serum levels partially mediate this association exclusively in females.

Conclusion
Findings from the animal model suggest that maternal thyroid hormones influence offspring gWAT Lep expression in a sex-specific manner, potentially through changes in Lep UE methylation. However, in vitro experiments indicate that Lep UE methylation alone is not sufficient to regulate Lep expression or adipocyte lipid accumulation. In humans with obesity, LEP UE methylation is associated with body fat percentage, with leptin serum levels potentially acting as a mediator exclusively in females.
Bibliometric analysis on the research focus of otolaryngological surgery
Authors: Ren Liyan , Yin Yanli , Wang Fang , Zhu Hongbo , Han Li , Liang Tao , Ping Fumin 
Published: February 2025

Abstract
An investigation was carried out to assess the scholarly impact of scientific papers in otolaryngological surgery from 2010 to 2023 using their frequency of citations as a measure. The investigation focused on the 100 most cited papers, collecting data on the year of publication, country of origin, journal source, paper type, and research field. The publications were distributed across 55 out of the 160 journals in the field, and each piece received citations ranging from 131 to 1775. Most (54.1%) of these papers were classified within medicine. The United States became the primary source country for these papers, providing 68 publications. A peak of 20 papers were published in 2011, marking the highest amount. In the US, the journal “Otolaryngology Head And Neck Surgery” has the impact factor 7.8 and has significantly advanced the field. With nine publications, R.M. Rosenfeld was found to be the author with the most publications. Overall, the probability of a paper referenced on otolaryngological surgery is influenced by factors such as the language in which it is published, the country it originates from, and the journal it is sourced from. These factors demonstrate the complex nature of academic influence in this field.
Neuropathological stages of neuronal, astrocytic and oligodendrocytic alpha-synuclein pathology in Parkinson’s disease
Authors: Otero-Jimenez Maria , Wojewska Marcelina J. , Binding Lawrence P. , Jogaudaite Simona , Gray-Rodriguez Sandra , Young Alexandra L. , Gentleman Steve , Alegre-Abarrategui Javier 
Published: February 2025

Abstract
Alpha-synucleinopathies are neurodegenerative diseases characterized by the spread of alpha-synuclein (α-syn) aggregates throughout the central nervous system in a stereotypical manner. These diseases include Lewy body disease (LBD), which encompass Dementia with Lewy bodies (DLB), Parkinson’s Disease (PD), and Parkinson’s Disease Dementia (PDD), and Multiple System Atrophy (MSA). LBD and MSA chiefly contain α-syn aggregates in neurons and oligodendrocytes, respectively, although glial α-syn pathology in LBD is increasingly being recognized. Semi-quantitative and machine learning-based quantifications of neuronal, oligodendrocytic and astrocytic α-syn pathology were implemented on a cohort of LBD and MSA post-mortem tissue samples. The neuroanatomical distribution of each cell-type specific α-syn pathology was evaluated using conditional probability matrices and Subtype and Stage Inference (SuStaIn) algorithm. We revealed extensive glial α-syn pathology in LBD, emphasizing the disease- and region-specific profile of astrocytic α-syn pathology, which was absent in MSA and minimal in the substantia nigra of LBD. Furthermore, we have described distinct morphologies of astrocytic α-syn pathology, which were found to correlate with the density of astrocytic α-syn inclusions. Astrocytic α-syn pathology was mainly centered in the amygdala and exhibited a unique stereotypical progression whilst oligodendrocytes displayed a distribution akin to the established neuronal progression pattern. SuStaIn modeling was further used to test for heterogeneity in the spatiotemporal progression, revealing that a subset of cases might follow an alternative pattern. Based on these findings, we introduce a novel multimodal progression framework that integrates, for the first time, the temporal and spatial progression of astrocytic and oligodendrocytic α-syn pathology alongside neuronal pathology in PD, providing further information regarding the role of neurons and glia in disease pathogenesis.
Microbial profiling of black soldier fly larvae reared on substrates supplemented with different mineral sources originating from phosphorus recycling technologies
Authors: Reyer Henry , Mielenz Manfred , Daş Gürbüz , Metges Cornelia C. , Wimmers Klaus 
Published: February 2025

Abstract

Background
Innovations to establish agricultural value chains utilising side streams and their reintegration into the feed and food supply are of great importance. Recyclates derived from biomass and waste are therefore becoming increasingly important as sources of nutrients. The larvae of the black soldier fly (BSF; Hermetia illucens) demonstrate considerable potential as livestock feed due to their ability to utilise a wide range of organic substrates. In this study, BSF larvae (BSFL) were reared on four different substrates: chicken feed diet (CD), high-fibre Gainesville fly diet (FD), or FD supplemented either with biochar (FD + BCH) or single superphosphate (FD + SSP) recyclates from sewage sludge processing. To validate the hypothesis that endogenous and substrate-associated microbiota significantly contribute to substrate conversion, the microbiota profiles of BSFL gut and frass were analysed by 16S rRNA gene amplicon sequencing. Results were associated to the different substrates as well as body composition, growth performance data, and mineral concentration of the larvae.

Results
The CD substrate was superior in terms of larval growth, although it caused a lower microbial alpha diversity in the larval intestine and frass compared to FD, with a dominance of Morganellaceae and families of Lactobacillales. The addition of the two sewage sludge derived products to the FD substrate significantly increased the calcium content of BSFL, while the phosphorus content was only increased by the addition of SSP. The shifts in the microbiota profiles of BSFL gut and frass indicated that BCH contributed to the regulation of the microbial milieu with suppressing the growth of potentially pathogenic microbes. The addition of SSP resulted in an enrichment of microorganisms with attributed phosphate-solubilising properties such as Pseudomonas and fungal species, likely being responsible for improving the bioavailability of phosphorus from the substrate.

Conclusions
The results demonstrate the high adaptability of the BSFL and its ability to change the substrate through specific microbiota in such a way that conditions are created for an optimal nutrient supply and thus growth of the larvae.
Depression, anxiety, stress, sleep quality, and life satisfaction among undergraduate medical students in the Gaza Strip: a cross-sectional survey
Authors: Aldabbour Belal , Jaradat Roa , Aljbour Omar , Abdo Mahmoud , Aljbour Jumana , Dayya Alaa Abo , Dabbour Asad Mohammad , Abuabada Amal 
Published: February 2025

Abstract

Background
Medical students suffer above-average rates of depression, anxiety, stress, poor sleep, and life dissatisfaction, which impacts their performance. In addition to the demands of medical study, medical students in the Gaza Strip face coping with life in an area marred by chronic conflict and poverty.

Methods
This cross-sectional study assessed medical students at the two medical schools in the Gaza Strip. Students were randomized according to university, sex, and academic level. Screening employed the DASS21, PSQI, and SWLS instruments. Ordinal logistic regression was used to investigate predictors of anxiety, stress, depression, sleep quality, and SWLS stage. Potential predictors of poor sleep quality were assessed by binary logistic regression, and multivariable logistic regression was implemented to determine the effect of covariates.

Results
Three hundred sixty-two medical students participated. Different stages of depression, anxiety, and stress symptoms were prevalent in 69%, 77.3%, and 65.2% of students, respectively. Poor sleep quality was prevalent in 77.9% of students, and 46.1% of medical students were dissatisfied with their lives. Low income was associated with higher rates of extremely severe anxiety and with higher rates of moderate depression. Poor sleep quality was associated with higher rates of all-stage anxiety, stress, and depression in univariate regression and with higher odds of moderate anxiety and mild, moderate, and extremely severe depression in multivariable regression.

Conclusions
Medical students in the Gaza Strip suffer from high rates of depression and anxiety symptoms, stress, poor sleep, and life dissatisfaction compared to several other countries and the pooled global prevalence. Medical schools in Gaza should put forward strategies to limit the psychological burdens perceived by their students.