bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time management practice and associated factors among employees working in public health centers, Northwest Ethiopia: a mixed method study
Authors: Terefe Sisay , Yazachew Lake , Asmamaw Desale Bihonegn , Belachew Tadele Biresaw , Feleke Amsalu , Tafere Tesfahun Zemene , Yimer Ali , Negash Wubshet Debebe 
Published: October 2023

AbstractBackgroundWhile progressing towards universal health coverage, poor time management in the healthcare system had significant effect on an individual such as imbalance, job dissatisfaction, and work ineffectiveness and finally poor productivity of the organization will be resulted. Information about time management practice in the healthcare system is limited. Therefore, the objective of this study was to assess time management practice and associated factors among employees working in public health centers, Dabat District, Northwest Ethiopia.MethodsA facility-based cross-sectional mixed methods (quantitative and qualitative) study was conducted in Dabat District from May 27 to June 22, 2022. A simple random sampling technique was used to select 413 study subjects and for the qualitative data, six key informants were selected. Self-administered questionnaire was used for the quantitative study, and an interview guide was employed for the qualitative study. Epi-data version 4.6 and SPSS 26 software were used for data entry and analysis, respectively. Open Code 4.6 software was used for qualitative data analysis. Variables with p-value of < 0.05 in multivariable analysis were considered as significant associated factors.ResultsA total of 396 employees participated in the study with a response rate of 95.8%. The result showed that overall, 54.8% (95% CI: 49.5–59.6) of health employees had practiced good time management. The likelihood of good time management was higher among those health workers who had planning experience (AOR = 2.04, 95% CI: 1.22–3.4), low procrastination habit (AOR = 1.65 95% CI: 1.04–2.65), satisfied with performance appraisal (AOR: 1.7, 95% CI: 1.05–2.81), and satisfied with organizational policy and strategy (AOR: 2.6, 95% CI: 1.6–4.3). The qualitative result also showed that the existing performance appraisal practices were not linked to rewards or sanction planning.ConclusionThe overall time management practice of public health center employees was low compared with prior studies. Organizational policies, prior planning experience, procrastination, and performance appraisal were all significantly associated factors with time management practice. Therefore, health center managers need to set an intervention to address all of the following factors to enhance employees’ time management skills at public health centers like evidence-based performance appraisals, sharing organizational policies, and engaging in capacity building activities such as training in time management and planning.
Mechanical osteoarthritis of the hip in a one medicine concept: a narrative review
Authors: Tomé I. , Alves-Pimenta S. , Sargo R. , Pereira J. , Colaço B. , Brancal H. , Costa L. , Ginja M. 
Published: October 2023

AbstractHuman and veterinary medicine have historically presented many medical areas of potential synergy and convergence. Mechanical osteoarthritis (MOA) is characterized by a gradual complex imbalance between cartilage production, loss, and derangement. Any joint instability that results in an abnormal overload of the joint surface can trigger MOA. As MOA has a prevailing mechanical aetiology, treatment effectiveness can only be accomplished if altered joint mechanics and mechanosensitive pathways are normalized and restored. Otherwise, the inflammatory cascade of osteoarthritis will be initiated, and the changes may become irreversible. The management of the disease using non-steroidal anti-inflammatory drugs, analgesics, physical therapy, diet changes, or nutraceuticals is conservative and less effective. MOA is a determinant factor for the development of hip dysplasia in both humans and dogs. Hip dysplasia is a hereditary disease with a high incidence and, therefore, of great clinical importance due to the associated discomfort and significant functional limitations. Furthermore, on account of analogous human and canine hip dysplasia disease and under the One Medicine concept, unifying veterinary and human research could improve the well-being and health of both species, increasing the acknowledgement of shared diseases. Great success has been accomplished in humans regarding preventive conservative management of hip dysplasia and following One Medicine concept, similar measures would benefit dogs. Moreover, animal models have long been used to better understand the different diseases’ mechanisms. Current research in animal models was addressed and the role of rabbit models in pathophysiologic studies and of the dog as a spontaneous animal model were highlighted, denoting the inexistence of rabbit functional models to investigate therapeutic approaches in hip MOA.
Histological and ultrastructural characterization of the dorso-ventral skin of the juvenile and the adult starry puffer fish (Arothron stellatus, Anonymous 1798)
Authors: Madkour Fatma A. , Abdellatif Ahmed M. , Osman Yassein A. , Kandyel Ramadan M. 
Published: October 2023

Abstract
Background
The starry puffer fish (Arothron stellatus, Anonymous, 1798) is a poisonous tetradontidae fish inhabiting the Red sea. The skin constitutes an important defense against any external effects. The study aims to characterize the dorso-ventral skin of the juvenile and the adult starry puffer fish using light and scanning electron microscopies. Twenty specimens of juvenile and adult fresh fishes were used.

Results
The scanning electron microarchitecture of the skin of the juvenile and adult fish showed delicate irregular-shaped protrusions, and well-defined bricks-like elevations on the dorsal side and interrupted folds as well as irregular-shaped protrusions on the ventral side. In adult fish, the patterned microridges of the superficial and deep epithelial cells (keratinocytes) were larger and well-defined in the dorsal skin than in the ventral side, the contrary was seen in the juvenile fish. The microridges were arranged in a fingerprint or honeycomb patterns. The openings of the mucous cells were more numerous in the dorsal skin in both age stages but more noticeable in adult. Furthermore, the sensory cells were more dominant in the juveniles than the adults. The odontic spines were only seen in adult. Histologically, few taste buds were observed in the epidermis of the dorsal skin surface of the adult fish. Both mucous and club cells were embedded in the epidermis of the juvenile and adult fish with different shapes and sizes. Melanophores were observed at the dorsal skin of both juvenile and adult fishes while fewer numbers were noticed at the ventral surfaces. Several dermal bony plates with different shapes and sizes were demonstrated in the skin of both adult and juvenile fishes.

Conclusion
The structural variations of skin of the juvenile and adult fishes may reflect the various environmental difficulties that they confront.
Global-scale GWAS associates a subset of SNPs with animal-adapted variants in M. tuberculosis complex
Authors: Brenner Evan P. , Sreevatsan Srinand 
Published: October 2023

Abstract

Background
While Mycobacterium tuberculosis complex (MTBC) variants are clonal, variant tuberculosis is a human-adapted pathogen, and variant bovis infects many hosts. Despite nucleotide identity between MTBC variants exceeding 99.95%, it remains unclear what drives these differences. Markers of adaptation into variants were sought by bacterial genome-wide association study of single nucleotide polymorphisms extracted from 6,362 MTBC members from varied hosts and countries.

Results
The search identified 120 genetic loci associated with MTBC variant classification and certain hosts. In many cases, these changes are uniformly fixed in certain variants while absent in others in this dataset, providing good discriminatory power in distinguishing variants by polymorphisms. Multiple changes were seen in genes for cholesterol and fatty acid metabolism, pathways previously proposed to be important for host adaptation, including Mce4F (part of the fundamental cholesterol intake Mce4 pathway), 4 FadD and FadE genes (playing roles in cholesterol and fatty acid utilization), and other targets like Rv3548c and PTPB, genes shown essential for growth on cholesterol by transposon studies.

Conclusions
These findings provide a robust set of genetic loci associated with the split of variant bovis and variant tuberculosis, and suggest that adaptation to new hosts could involve adjustments in uptake and catabolism of cholesterol and fatty acids, like the proposed specialization to different populations in MTB lineages by alterations to host lipid composition. Future studies are required to elucidate how the associations between cholesterol profiles and pathogen utilization differences between hosts and MTBC variants, as well as the investigation of uncharacterized genes discovered in this study. This information will likely provide an understanding on the diversification of MBO away from humans and specialization towards a broad host range.
Walking the path of treatable traits in interstitial lung diseases
Authors: Amati Francesco , Spagnolo Paolo , Ryerson Christopher J. , Oldham Justin M. , Gramegna Andrea , Stainer Anna , Mantero Marco , Sverzellati Nicola , Lacedonia Donato , Richeldi Luca , Blasi Francesco , Aliberti Stefano 
Published: October 2023

AbstractInterstitial lung diseases (ILDs) are complex and heterogeneous diseases. The use of traditional diagnostic classification in ILD can lead to suboptimal management, which is worsened by not considering the molecular pathways, biological complexity, and disease phenotypes. The identification of specific “treatable traits” in ILDs, which are clinically relevant and modifiable disease characteristics, may improve patient’s outcomes. Treatable traits in ILDs may be classified into four different domains (pulmonary, aetiological, comorbidities, and lifestyle), which will facilitate identification of related assessment tools, treatment options, and expected benefits. A multidisciplinary care team model is a potential way to implement a “treatable traits” strategy into clinical practice with the aim of improving patients’ outcomes. Multidisciplinary models of care, international registries, and the use of artificial intelligence may facilitate the implementation of the “treatable traits” approach into clinical practice. Prospective studies are needed to test potential therapies for a variety of treatable traits to further advance care of patients with ILD.
SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier
Authors: Stüdle Chiara , Nishihara Hideaki , Wischnewski Sven , Kulsvehagen Laila , Perriot Sylvain , Ishikawa Hiroshi , Schroten Horst , Frank Stephan , Deigendesch Nikolaus , Du Pasquier Renaud , Schirmer Lucas , Pröbstel Anne-Katrin , Engelhardt Britta 
Published: October 2023

AbstractBackgroundAs a consequence of SARS-CoV-2 infection various neurocognitive and neuropsychiatric symptoms can appear, which may persist for several months post infection. However, cell type-specific routes of brain infection and underlying mechanisms resulting in neuroglial dysfunction are not well understood.MethodsHere, we investigated the susceptibility of cells constituting the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP) to SARS-CoV-2 infection using human induced pluripotent stem cell (hiPSC)-derived cellular models and a ChP papilloma-derived epithelial cell line as well as ChP tissue from COVID-19 patients, respectively.ResultsWe noted a differential infectibility of hiPSC-derived brain microvascular endothelial cells (BMECs) depending on the differentiation method. Extended endothelial culture method (EECM)-BMECs characterized by a complete set of endothelial markers, good barrier properties and a mature immune phenotype were refractory to SARS-CoV-2 infection and did not exhibit an activated phenotype after prolonged SARS-CoV-2 inoculation. In contrast, defined medium method (DMM)-BMECs, characterized by a mixed endothelial and epithelial phenotype and excellent barrier properties were productively infected by SARS-CoV-2 in an ACE2-dependent manner. hiPSC-derived brain pericyte-like cells (BPLCs) lacking ACE2 expression were not susceptible to SARS-CoV-2 infection. Furthermore, the human choroid plexus papilloma-derived epithelial cell line HIBCPP, modeling the BCSFB was productively infected by SARS-CoV-2 preferentially from the basolateral side, facing the blood compartment. Assessment of ChP tissue from COVID-19 patients by RNA in situ hybridization revealed SARS-CoV-2 transcripts in ChP epithelial and ChP stromal cells.ConclusionsOur study shows that the BCSFB of the ChP rather than the BBB is susceptible to direct SARS-CoV-2 infection. Thus, neuropsychiatric symptoms because of COVID-19 may rather be associated with dysfunction of the BCSFB than the BBB. Future studies should consider a role of the ChP in underlying neuropsychiatric symptoms following SARS-CoV-2 infection.
Nuclear respiratory factor 1 drives hepatocellular carcinoma progression by activating LPCAT1-ERK1/2-CREB axis
Authors: Liu Ran , Yin Chuanzheng , Zhao Peng , Guo Bing , Ke Wenbo , Zheng Xichuan , Xie Dawei , Wang Yaofeng , Wang Gengqiao , Jia Yinzhao , Gao Yang , Hu Wenjun , Liu Gang Logan , Song Zifang 
Published: October 2023

Abstract
Background
Nuclear respiratory factor 1 (NRF1) is a transcription factor that participates in several kinds of tumor, but its role in hepatocellular carcinoma (HCC) remains elusive. This study aims to explore the role of NRF1 in HCC progression and investigate the underlying mechanisms.

Results
NRF1 was overexpressed and hyperactive in HCC tissue and cell lines and high expression of NRF1 indicated unfavorable prognosis of HCC patients. NRF1 promoted proliferation, migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, NRF1 activated ERK1/2-CREB signaling pathway by transactivating lysophosphatidylcholine acyltransferase 1 (LPCAT1), thus promoting cell cycle progression and epithelial mesenchymal transition (EMT) of HCC cells. Meanwhile, LPCAT1 upregulated the expression of NRF1 by activating ERK1/2-CREB signaling pathway, forming a positive feedback loop.

Conclusions
NRF1 is overexpressed in HCC and promotes HCC progression by activating LPCAT1-ERK1/2-CREB axis. NRF1 is a promising therapeutic target for HCC patients.
The Study of Ketamine for Youth Depression (SKY-D): study protocol for a randomised controlled trial of low-dose ketamine for young people with major depressive disorder
Authors: Schwartz Orli S. , Amminger Paul , Baune Bernard T. , Bedi Gillinder , Berk Michael , Cotton Sue M. , Daglas-Georgiou Rothanthi , Glozier Nick , Harrison Ben , Hermens Daniel F. , Jennings Emma , Lagopoulos Jim , Loo Colleen , Mallawaarachchi Sumudu , Martin Donel , Phelan Bethany , Read Nikki , Rodgers Anthony , Schmaal Lianne , Somogyi Andrew A. , Thurston Lily , Weller Amber , Davey Christopher G. 
Published: October 2023

Abstract
Background
Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD).

Methods
SKY-D is a double-masked, randomised controlled trial funded by the Australian Government’s National Health and Medical Research Council (NHMRC). Participants aged between 16 and 25 years (inclusive) with moderate-to-severe MDD will be randomised to receive either low-dose ketamine (intervention) or midazolam (active control) via subcutaneous injection once per week for 4 weeks. The primary outcome is change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment. Further follow-up assessment will occur at 8 and 26 weeks from treatment commencement to determine whether treatment effects are sustained and to investigate safety outcomes.

Discussion
Results from this trial will be important in determining whether low-dose subcutaneous ketamine is an effective treatment for young people with moderate-to-severe MDD. This will be the largest randomised trial to investigate the effects of ketamine to treat depression in young people.

Trial registration
Australian and New Zealand Clinical Trials Registry ID: ACTRN12619000683134. Registered on May 7, 2019. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377513.
Community-based type 2 diabetes care by lay village health workers in rural Lesotho: protocol for a cluster-randomized trial within the ComBaCaL cohort study (ComBaCaL T2D TwiC)
Authors: Gerber Felix , Gupta Ravi , Lejone Thabo Ishmael , Tahirsylaj Thesar , Lee Tristan , Kohler Maurus , Haldemann Maria Ines , Räber Fabian , Chitja Mamakhala , Manthabiseng Molulela , Khomolishoele Makhebe , Mota Mota , Bane Matumaole , Sematle Pauline Mamorontsane , Makabateng Retselisitsoe , Mphunyane Madavida , Phaaroe Sejojo , Basler Dave , Kindler Kevin , Seelig Eleonora , Briel Matthias , Chammartin Frédérique , Labhardt Niklaus Daniel , Amstutz Alain 
Published: October 2023

Abstract
Background
Type 2 diabetes (T2D) poses a growing public health burden, especially in low- and middle-income countries (LMICs). Task-shifting to lay village health workers (VHWs) and the use of digital clinical decision support systems (CDSS) are promising approaches to tackle the current T2D care gap in LMICs. However, evidence on the effectiveness of lay worker-led T2D care models, in which VHWs initiate and monitor drug treatment in addition to community-based screening and referral services, is lacking.

Methods
We are conducting a cluster-randomized trial nested within the Community-Based Chronic Disease Care Lesotho (ComBaCaL) cohort study (NCT05596773) using the trial within cohort (TwiC) design to assess the effectiveness of a VHW-led, CDSS-assisted T2D care model in rural Lesotho. Participants are non-pregnant members of the ComBaCaL cohort study with T2D. The ComBaCaL cohort study is conducted in approximately 100 villages in two rural districts in Lesotho and is managed by trained and supervised VHWs. In intervention villages, VHWs offer a community-based T2D care package including lifestyle counselling, first-line oral antidiabetic, lipid-lowering, and antiplatelet treatment guided by a tablet-based CDSS to participants who are clinically eligible, as well as treatment support to participants who prefer or clinically require facility-based T2D care. In control clusters, all participants will be referred to a health facility for T2D management. The primary endpoint is the mean glycosylated haemoglobin (HbA1c) 12 months after enrolment. Secondary endpoints include the 10-year risk for cardiovascular events estimated using the World Health Organization risk prediction tool.

Discussion
The trial was launched on May 13, 2023, and has enrolled 226 participants at the date of submission (October 6, 2023). To our knowledge, the trial is the first to assess task-shifting of T2D care to VHWs at the community level, including the prescription of first-line antidiabetic, lipid-lowering, and antiplatelet medication in sub-Saharan Africa, and will thus provide the missing evidence on the effectiveness of such a T2D care model in this setting. The study is operating within the established Lesotho VHW programme. Similar community health worker programmes which exist across sub-Saharan Africa may benefit from the findings.

Trial registration
ClinicalTrials.gov NCT05743387. Registered on February 24 2023.
Prognostic value of the prognostic nutritional index for patients with acute myocardial infarction undergoing percutaneous coronary intervention with variable glucose metabolism statuses: a retrospective cohort study
Authors: Ling Xuebin , Lin Chufen , Liu Jin , He Yibo , Yang Yongquan , Lu Na , Jie Wei , Liu Yong , Chen Shiqun , Guo Junli 
Published: October 2023

Abstract
Background
The prognostic nutritional index (PNI) and different glucose metabolisms have been separately reported to be correlated with long-term prognosis in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). However, PNI application in patients with an impaired glucose metabolism has not been well validated, especially in pre-diabetic patients. This study evaluated whether PNI influences a long-term risk of mortality along different glucose metabolism statuses.

Methods
A total of 17,697 patients with AMI and a history of PCI were enrolled in this retrospective observational cohort study from January 2007 to December 2020. Three subgroups with different glucose metabolism statuses, including normal glucose regulation (NGR), pre-diabetes mellitus (pre-DM), and diabetes mellitus (DM), were divided into three groups according to the tertiles of PNI, respectively.

Results
All-cause mortality occurred in 2613 (14.8%) patients within a median of 4.1 years of follow-up. Upon analyzing the Kaplan–Meier plots for the NGR, pre-DM, and DM groups, the incidence of all-cause or cardiovascular mortality in the low PNI (PNI-L, ≤ 42.7) subgroup was significantly higher than that in the median PNI (PNI-M, > 42.7 and ≤ 48.2) and high PNI (PNI-H, > 48.2) subgroups (all, P < 0.001). After adjusting for confounding factors, the hazard ratio (HR) for all-cause mortality in the PNI-L group significantly increased compared to that in the PNI-H subgroups of the NGR group (HR, 1.35; 95% CI 1.14–1.66; P < 0.001), pre-DM group (HR, 1.29; 95% CI 1.02–1.62; P < 0.001), and DM group (HR, 1.36; 95% CI 1.13–1.63; P < 0.001). Given that there was evidence of interactions between PNI and different glucose statuses (P for interaction < 0.001), patients were divided into nine subgroups, and we found that DM patients with PNI-L statuses had the highest risk of all-cause mortality compared to NGR patients with PNI-H statuses (HR, 1.69; 95% CI 1.42–2.01; P < 0.001).

Conclusion
Lower PNI is a significant and independent risk factor for all-cause mortality in AMI patients undergoing PCI with different glucose metabolism statuses, and this risk further increases with DM compared to NGR or pre-DM statuses.