bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression care trajectories and sustainable return to work among long-term sick-listed workers: a register-based study (The Norwegian GP-DEP Study)
Authors: Meling Heidi Marie , Baste Valborg , Ruths Sabine , Anderssen Norman , Haukenes Inger 
Published: February 2025

Abstract

Background
Depressive disorders can negatively impact work life sustainability for affected individuals. Little is known about depression care trajectories and their association with sustainable return to work (SRTW) after long-term sick leave. This study aimed to identify depression care trajectories during the first three months of sick leave among long-term sick-listed workers with depression and investigate their associations with SRTW.

Methods

Design
Nationwide cohort study using linked data from Norwegian health and population registries. Study population: All inhabitants of Norway aged 20–64 from 1 January 2009 to 1 April 2011, who were diagnosed with depression in general practice, and had reached three months consecutive sick leave (n = 13 624, 63.7% women). Exposure: Depression care trajectories during the first three months of initial sick leave, identified using group-based multi-trajectory modeling. Types of depression care included were general practitioner (GP) consults, GP longer consults and/or talking therapy, antidepressant medication (MED), and specialized mental healthcare. Outcome: SRTW, measured by accumulated all-cause sickness absence days during two-year follow-up after initial sick leave, with cutoffs at 0, ≤ 30, and ≤ 90 days. Analysis: Gender stratified generalized linear models, used to investigate the associations between depression care trajectories and SRTW, adjusting for sociodemographic factors and sick leave duration.

Results
Four depression care trajectory groups were identified: “GP 12 weeks” (37.2%), “GP 2 weeks” (18.6%), “GP & MED 12 weeks” (40.0%), and “Specialist, GP & MED 12 weeks” (8.7%). The “GP 12 weeks” group (reference) had the highest proportion attaining SRTW for both genders. Men in the “GP 2 weeks” group had a 12–14% lower likelihood for SRTW compared to the reference. Women in the “Specialist,GP & MED 12 weeks 12 weeks” group had a 19- 23% lower likelihood for SRTW compared to the reference.

Conclusion
The association between depression care trajectories and SRTW varies by gender. However, trajectories involving follow-up by the GP, including both standard and longer consults and/or talking therapy over 12 weeks, showed the highest likelihood of SRTW for both genders. Enhancing GP resources could improve SRTW outcomes by allowing more frequent and longer consultations or talking therapy.
Phenotype-based clusters, inflammation and cardiometabolic complications in older people before the diagnosis of type 2 diabetes: KORA F4/FF4 cohort study
Authors: Huemer Marie-Theres , Spagnuolo Maria C. , Maalmi Haifa , Wagner Robert , Bönhof Gidon J. , Heier Margit , Koenig Wolfgang , Rathmann Wolfgang , Prystupa Katsiaryna , Nano Jana , Ziegler Dan , Peters Annette , Roden Michael , Thorand Barbara , Herder Christian 
Published: February 2025

Abstract

Background
Using a data-driven approach, six clusters with different risk profiles and burden of complications were recently identified in middle-aged people before the diagnosis of type 2 diabetes (T2D). We aimed to investigate whether these clusters could be generalised to older people and if subclinical inflammation was related to their cardiometabolic risk profiles.

Methods
We assigned 843 participants of the KORA F4 study aged 61–82 years without T2D to the six previously defined phenotype-based clusters. Based on 73 biomarkers of subclinical inflammation, we derived an inflammation-related score (“inflammatory load”) using principal component analysis to assess subclinical inflammation. Risk factors, inflammatory load as well as prevalence and incidence of (pre)diabetes-related complications were compared between the clusters using pairwise comparisons and regression analyses.

Results
Clusters 1 and 2 had the lowest cardiometabolic risk, whereas clusters 5 and 6 the highest. T2D risk was highest in clusters 3, 4, 5, and 6 compared with the low-risk cluster 2 (age- and sex-adjusted ORs between 3.6 and 34.0). In cross-sectional analyses, there were significant between-cluster differences in chronic kidney disease (CKD), distal sensorimotor polyneuropathy (DSPN) and cardiovascular disease (all p < 0.045). In prospective analyses (mean follow-up time 6.5–8.3 years), clusters differed significantly in CKD and DSPN incidence, but not in incident CVD or all-cause mortality. The inflammatory load was highest in the high-risk cluster 5 and lowest in cluster 2. Adjustment for the inflammatory load had only a minor impact on the aforementioned differences in outcomes between clusters.

Conclusions
Our findings extend the knowledge about the previously identified six phenotype-based clusters in older people without T2D. Differences between clusters were more pronounced for T2D risk than for prevalent or incident (pre)diabetes-related complications and absent for mortality. The high cardiometabolic risk corresponded to the high inflammatory load in cluster 5 but not to the lower inflammatory load of high-risk clusters 3 and 6.

Graphical abstract
The clinical outcomes of anterior minimally invasive inverted PHILOS plate fixation for distal humeral shaft fractures
Authors: Fu Gang , Wang Shen’ao , Wu Weiqiang , Lin Fengfei , Li Renbin 
Published: February 2025

Abstract

Background
The unique anatomy and biomechanics of the distal humerus make distal humeral shaft fractures a significant challenge in orthopedic surgery. Conventional posterior surgical approaches are associated with risks such as iatrogenic radial nerve injury and increased soft tissue trauma.

Objective
This study aimed to assess the clinical efficacy of an inverted PHILOS plate using an anterior minimally invasive percutaneous approach for treating distal humeral shaft fractures.

Methods
We enrolled 32 patients with distal humeral shaft fractures. The surgical technique involved an anterior minimally invasive percutaneous application of an inverted PHILOS plate. Outcome measures included operative time, intraoperative blood loss, incision length, fracture healing time, and functional scores (Constant-Murley and Mayo Elbow Performance Scores). Postoperative complications, including nerve injury and nonunion, were documented.

Results
The mean operative time was 1.69 ± 0.66 h, with a median blood loss of 50 ml (IQR: 50–100 ml). The mean incision length was 10.9 ± 1.78 cm, and the mean time to fracture healing was 11.2 ± 3.68 weeks. Functional outcomes were satisfactory, with a mean Constant shoulder score of 92.69 ± 6.6 and a mean Mayo Elbow Performance Score of 91.4 ± 8.04. No instances of iatrogenic nerve injury or nonunion were observed.

Conclusion
The anterior minimally invasive percutaneous approach using an inverted PHILOS plate is an effective method for treating distal humeral shaft fractures. This technique minimizes soft tissue damage, reduces the risk of iatrogenic radial nerve injury, and ensures reliable fracture stabilization, thus offering a promising alternative to conventional posterior approaches.
MMP28 recruits M2-type tumor-associated macrophages through MAPK/JNK signaling pathway-dependent cytokine secretion to promote the malignant progression of pancreatic cancer
Authors: Dong Shi , Li Xin , Chen Zhou , Shi Huaqing , Wang Zhengfeng , Zhou Wence 
Published: February 2025

Abstract

Background
Crosstalk between pancreatic cancer cells and tumor-associated macrophages (TAMs) is a critical driver of malignant progression, and plays an important role in the low response rate to immunotherapy in patients with for pancreatic cancer. Although it is known that cancer cells induce TAM infiltration and M2 polarization, the underlying mechanisms remain elusive. Herein, we identified matrix metalloproteinase 28 (MMP28), a highly expressed protein, as a key regulator of this process.

Methods
Immunohistochemical staining and qRT-PCR were used to validate MMP28 as a potential marker for the prognosis of patients with pancreatic cancer. We evaluated the tumor-promoting effect of MMP28 in vitro with CCK-8, Transwell, and EdU assay and Western blotting and explored the potential mechanism of MMP28-induced M2 polarization of TAMs with a coculture system, immunofluorescence staining and flow cytometry. A subcutaneous graft tumor model was constructed to assess the tumor-promoting effect of MMP28 and its ability to induce M2 TAM infiltration.

Results
The relevant results of this study revealed a strong correlation between MMP28 expression and TAM infiltration, with a predominance of M2-polarized TAMs in pancreatic cancer tissues. Mechanistic investigations demonstrated that MMP28 promotes the secretion of multiple cytokines, including IL-8 and VEGFA through the activation of the MAPK/JNK signaling pathway. These cytokines act as potent chemoattractants and polarizing factors for TAMs. Additionally, we discovered an interaction between MMP28 and ANXA2, which contributes to the regulation of TAM recruitment and polarization. In vivo studies confirmed the critical role of MMP28 in tumor growth and TAM infiltration. Depletion of macrophages, inhibition of JNK, or neutralization of IL-8 and VEGFA significantly suppressed tumor progression. Transcriptomic analysis suggested that IL-8 and VEGFA induce M2 TAM polarization by modulating TAM amino acid metabolism.

Conclusions
Collectively, our findings elucidate a novel mechanism by which pancreatic cancer cells manipulate the tumor microenvironment through MMP28-dependent cytokine secretion, promoting TAM infiltration and M2 polarization. These results highlight MMP28 as a promising therapeutic target for pancreatic cancer.

Graphical Abstract
Schematic overview of the mechanisms by which MMP28 promotes the migration and polarization of TAMs. High levels of MMP28 promote the secretion of IL-8 and VEGFA by cancer cells by mediating the phosphorylation of the MAPK/JNK signalling pathway and then recruiting TAMs. IL-8 and VEGFA subsequently induce amino acid metabolism alterations in TAMs by binding to relevant receptors on TAMs, which ultimately promote the polarization of TAMs to the M2 phenotype. In addition, ANXA2 increases MMP28-mediated M2 TAM infiltration by interacting with MMP28.
The lncRNA MIR181A1HG in extracellular vesicles derived from highly metastatic colorectal cancer cells promotes liver metastasis by remodeling the extracellular matrix and recruiting myeloid-derived suppressor cells
Authors: Gu Yichao , Mi Yushuai , Cao Yifan , Yu Kuan , Zhang Zihao , Lian Peng , Li Dawei , Qin Jing , Zhao Senlin 
Published: February 2025

Abstract

Background
Colorectal liver metastasis (CRLM) is the main cause of death in colorectal cancer (CRC) patients worldwide. In the initial stage of metastasis, primary tumors provide the necessary conditions for metastasis by shaping the local microenvironment of the target organ, forming “premetastatic niches” (PMNs), and extracellular vesicles (EVs) play important roles in shaping PMNs. Therefore, investigating the EVs involved in the regulation of PMNs and their mechanism is highly valuable for the further understanding of CRLM.

Methods
Transmission electron microscopy and differential ultracentrifugation were used to verify the existence of exosomes. In vivo and in vitro assays were used to identify the roles of MIR181A1HG in EVs in CRLM. RNA pull-down and dual-luciferase reporter assays were used to clarify the mechanism by which MIR181A1HG in EVs regulated the crosstalk between CRC cells and hepatic stellate cells (HSCs).

Results
We demonstrated that the lncRNA MIR181A1HG was progressively upregulated in tissues, serum EVs from healthy normal controls to CRC and paired liver metastatic groups. Additionally, we verified that HNRNPA2B1 mediated the packaging of MIR181A1HG into CRC cell-derived EVs, which in turn functioned as a ceRNA by sponging miR373-3p to activate HSCs via the TGFβRII/Smad2/3 signaling pathway. Furthermore, activated HSCs could secrete the chemokine CXCL12 to promote CRLM by remodeling the extracellular matrix and recruiting myeloid-derived suppressor cells in the liver, which resulted in liver metastasis.

Conclusions
MIR181A1HG in EVs from highly metastatic CRC cells promoted CRLM by activating HSCs to form PMNs in the liver, which contributes to the further understanding of the mechanism of CRLM and provides potential predictive markers for CRLM.
Another potential etiology for cardiac manifestation after snakebite
Authors: Aoki Yoshihiro , Smith Chris , Ariyoshi Koya 
Published: February 2025

Abstract
This letter discusses the possibility of Takotsubo cardiomyopathy (TTC) as an alternative diagnosis in a recently reported case of acute myocardial infarction following a hump-nosed viper bite. The patient’s presentation, including delayed chest tightness, elevated troponin, ECG changes, and normal coronary arteries, coupled with complete recovery within 3 months, strongly suggests TTC. Multiple case reports have documented the association between snakebites and TTC, with proposed pathophysiological mechanisms including sympathetic surge from pain and stress, direct cardiotoxic effects of venom, and inflammatory mediators during envenomation. The excessive catecholamine response may trigger transient cardiac dysfunction characteristic of TTC. Recognizing TTC as a potential complication of snakebites has important clinical implications, as its management and prognosis differ from acute coronary syndrome. Understanding this association may enhance diagnostic approaches and treatment strategies in similar cases, particularly when normal coronary arteries and complete cardiac recovery are observed.
Impact of the hierarchical medical system on the perceived quality of primary care in China: a quasi-experimental study
Authors: Zhao Yaxin , Zhai Xiaohui , Zhou Zhongliang , Peng Zixuan , Shen Chi , Fan Xiaojing , Lai Sha , Coyte Peter C. 
Published: February 2025

Abstract

Background
Although the implementation of a hierarchical medical system (HMS) has been shown to improve the allocation of medical resources and patient health-seeking behaviour, its role in patient’s perceived quality of primary care remains unexplored. This study aimed to assess the impact of HMS implementation on rural and urban residents’ perceived quality of primary care.

Methods
Data were obtained from the China Family Panel Study for 2012, 2014, 2016, and 2018. A total of 40,011 rural and 22,482 urban residents were included in the research participants for analysis. This study adopted a quasi-natural experimental design, and the multiple-period difference-in-differences method was used to capture changes in patient’s perceived quality of primary care before and after the introduction of HMS.

Results
We found that HMS implementation declined the perceived quality of primary care by an average of 18% among rural residents (OR: 0.82, 95% CI 0.68–0.99), while there was no significant change among urban residents (OR: 1.13, 95% CI 0.87–1.46). There was a 24% reduction in the perceived quality of primary care (OR: 0.76, 95% CI 0.61–0.96) one year after HMS among rural residents, and there was no statistically significant difference two years after HMS. After HMS implementation, the level of perceived quality of primary care by rural patients with chronic diseases decreased by 72% (OR: 0.28, 95% CI 0.11–0.78).

Conclusions
HMS has a limited effect on improving residents’ perceived quality of primary care, especially for those living in rural areas. Policymakers are suggested to establish a quality monitoring system that incorporates patient experience as an essential standard to systematically evaluate the impacts of the HMS, with more efforts being put into helping vulnerable groups such as residents under 60 years old and patients with chronic diseases.
Haematological and serum biochemical derangements induced by acute exposure to didecyl dimethyl ammonium bromide in Gallus gallus domesticus
Authors: Abdul Bello Ayema , Isa Hamza Ibrahim , Shittu Muftau 
Published: February 2025

Abstract

Background
Infectious diseases have negatively impacted poultry productivity, thereby causing economic losses and international trade embargoes. Several chemical cocktails are being employed to ‘treat’ such diseases that have defied known interventions. Quaternary ammonium compounds are amongst such chemicals being used to disinfect drinking water of poultry, with a premise of therapeutic effect. Such extra-label use has limited toxicological data. We set out to determine the haematological and serum biochemical derangements associated with acute oral exposure to didecyl dimethyl ammonium bromide (DDAB), in 6-week-old Isa Brown pullets. The pullets were haphazardly assigned into control (n = 10) and DDAB (n = 10) exposed groups. The exposure group was administered, with the aid of an insulin syringe, a single oral dose of DDAB at 360 mg/kg, determined from a previous acute toxicity study.

Results
Following monitoring for toxic signs and/or death during 14 days, blood samples were collected for analyses. Haematological analyses, determined following established principles, revealed significant (p < 0.05) increases in packed cell volume, total erythrocyte counts and monocytes, but decreased heterophil and eosinophil counts, in the birds administered DDAB. Serum biochemical assay for aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities, appraised using appropriate ELISA kits (Randox® Laboratories), revealed significant (p < 0.05) elevations in these enzymes. Malondialdehyde level was significantly (p < 0.05) raised but glutathione concentration and catalase activity were significantly (p < 0.05) decreased. Urea and creatinine were significantly (p < 0.05) increased.

Conclusions
At the dose studied, DDAB traversed the digestive tract barrier and accessed systemic circulation to induce haemato-biochemical derangement in chickens. Liver and kidney functions were adversely affected while oxidative distress was induced. Strict adherence to manufacturer’s recommended doses should be practised while using this chemical in water sanitation and other applications in poultry farms.
Unraveling the structural and functional consequences of non-synonymous single-nucleotide polymorphisms (nsSNPs) in human SOCS2: an in silico approach
Authors: Hossain Tanvir , Islam Md. Nur , Hossain Md. Anwar , Rahman Md. Mofizur , Islam Mohammed Mafizul , Gupta Shipan Das 
Published: February 2025

Abstract

Background
The protein from suppressors of cytokine signaling (SOCS) family regulates immune response by modulating the signaling pathways of cytokines. SOCS2, a member of this family, plays an important role in regulating growth hormone receptors, the JAK-STAT pathway, energy homeostasis, and other biological processes. Multiple non-synonymous SNPs (nsSNPs) have been found in the SOCS2 gene, which could affect protein function. However, there is limited understanding of disease susceptibility and abnormal functioning associated with these mutated SOCS2 gene.

Results
In this study, we examined nsSNPs in the human SOCS2 gene to evaluate their effects on protein stability, structure, and function through in silico approaches. SIFT; PhD-SNP, PROVEAN, PMut, PANTHER, PolyPhen-2, SNPs&GO, I-Mutant 3.0, and MUpro were the bioinformatics tools used to forecast the most harmful SNPs. ConSurf found the eight nsSNPs (L71F, G102R, G51E, G47R, R96Q, Y49H, P155Q, and I171S) to be present in highly conserved region, thus affecting their protein stability. The Project HOPE analysis predicts the 3D structure of the eight respective mutated proteins and assesses their potential molecular impact on protein function and structure. After a series of analysis, three mutants (G47R, Y49H, and I171S) were subjected to molecular dynamic simulation, principal component analysis, and free energy landscape to understand their impact during the course of mutation. The STRING algorithm was used to predict protein–protein interactions. Finally, KM plotter analysis showed that deregulation of SOCS2 gene expression has a significant impact on the patients’ survival rate of different types of cancers.

Conclusion
Our study has identified the eight most high-risk SNPs of SOCS2 gene that may contribute to diseases development associated with growth hormone signaling, immune dysregulation, and other energy metabolism.
Pain, Quality of Life, and Mental Health in Adults with X-linked Hypophosphatemia: A Cross-sectional Study
Authors: Diaz-delCastillo Marta , Espersen Rasmus Bundgaard , Beck-Nielsen Signe Sparre , Rejnmark Lars , Heegaard Anne-Marie 
Published: February 2025

Abstract

Objective
Hereditary hypophosphatemic disorders such as X-linked hypophosphatemia (XLH) are rare phosphate wasting disorders that cause abnormal bone mineralization, which manifests as bone deformities and dental problems. Pain, stiffness, and fatigue are the main symptoms reported by adult patients with XLH, interfering with their quality of life and activities of daily living. Here we provide a comprehensive evaluation of pain and health related quality of life in patients with XLH.

Design and Methods
In this cross-sectional study, 49 adult patients with XLH and 42 healthy sex- and age- matched control participants underwent pressure algometry to determine pain sensitivity. In addition, we collected patient-reported outcome data on pain, quality of life, and mental health through the following questionnaires: (1) Brief Pain Inventory-Short Form, (2) SF-36v2™ Health Survey, (3) painDETECT, (4) Functional Assessment of Cancer Therapy—Bone Pain, (4) Pain Catastrophizing Scale, (5) Generalized Anxiety Disorder 7 and (6) Patient Health Questionnaire 9.

Results
Patients with XLH present altered skin but not bone mechanical pressure pain thresholds, which may suggest referred pain through sensitization mechanisms. Questionnaire data highlight significantly higher pain scores in patients with XLH, which correlate with depression scores. Additionally, patients with XLH report decreased quality of life and mental health, increased pain catastrophizing thinking, and anxiety.

Conclusion
Our results suggest that using patient-reported outcomes is important to understand the pain phenotype and mental health in patients with XLH and can be helpful to dictate treatment aimed at improving their pain and quality of life.