bluuebunny/crossref_metadata_2025_split huggingface dataset:
What do medical students and their clinical preceptors understand by primary health care in South Africa? A qualitative study
Authors: Mabuza Langalibalele Honey , Moshabela Mosa 
Published: October 2023

Abstract
Background
The definition of Primary Health Care (PHC) issued by the World Health Organisation in 1978 indicated that essential health care should be made accessible to individuals and their communities close to where they live and work. In 1992 Starfield articulated the four pillars of PHC: the patient’s first contact with healthcare, comprehensive care, coordinated care and continuous care. Using this literature guidance, this study sought to explore what undergraduate medical students and their clinical preceptors understood by PHC in four South African medical schools.

Methods
A qualitative study using the phenomenological design was conducted among undergraduate medical students and their clinical preceptors. The setting was four medical schools in South Africa (Sefako Makgatho Health Sciences University, Walter Sisulu University and the University of KwaZulu-Natal and the Witwatersrand University). A total of 27 in-depth interviews were conducted among the clinical preceptors and 16 focus group discussions among the students who were in their clinical years of training (MBChB 4–6). Interviews were digitally recorded and transcribed verbatim, followed by thematic data analysis using the MAXQDA 2020 (Analytics Pro) software.

Results
Four themes were identified in which there were similarities between the students and their preceptors regarding their understanding of PHC: (1) PHC as the patient’s first contact with the healthcare system; (2) comprehensive care; (3) coordination of care and (4) continuity of care. A further two themes were identified in which these two groups were not of similar understanding: (5) PHC as a level or an approach to healthcare and (6) the role of specialist clinical preceptors in PHC.

Conclusions
Medical students and their clinical preceptors displayed an understanding of PHC in line with four pillars articulated by Starfield and the WHO definition of PHC. However, there remains areas of divergence, on which the medical schools should follow the guidance provided by the WHO and Starfield for a holistic understanding of PHC.
The effect of a simulation-based training program in basic life support on the knowledge of Palestinian nurses: a quasi-experimental study in governmental hospitals
Authors: Fahajan Yousef , Emad Osama J. , Albelbeisi Ahmed Hassan , Albelbeisi Ali , Shnena Yasmin Abu , Khader Ayda , Kakemam Edris 
Published: October 2023

Abstract
Background
Basic Life Support (BLS) plays an important role in increasing the survival rate of hospitalized heart attack patients. There are no previous studies on the effect of BLS training among Palestinian nurses. This study aimed to evaluate the effect of simulation-based BLS training program on nurses’ knowledge Palestinian nurses at governmental hospitals.

Methods
A quasi-experimental, pre & post-test design was used. 700 nurses were recruited proportionally using a simple random sampling method among 2980 nurses from 13 public hospitals in the Gaza Strip. This study was conducted from June to August 2022. A practical BLS test consisting of 10 multiple-choice questions according to American Heart Association guidelines (2020) was collected and sociodemographic characteristics. SPSS software, version 24 was used for the statistical analysis. Descriptive statistics and weighted mean were used. T-Test and One-way analysis of variance (ANOVA) were applied to determine differences in means among groups.

Results
Most of the participating nurses (55.7%) were male, while (44.3%) were female. The majority of nurses (84.4%) are under 40 years of age. The weighted mean scores in the pre-test ranged from 52.2 to 75.1% and the mean scores was (6.16 ± 1.97). After applying conventional BLS training, the weighted mean scores ranged from 85.6 to 97.3% and the mean scores was (9.19 ± 1.04). The study revealed that the nurses’ knowledge increased after applying simulation-based training program. The mean of knowledge scores was statistically significant between the pre and post-test on the basis of the current work hospital (P-value < 0.001).

Conclusion
This study affords significant evidence of the positive effects of the BLS training program in improving nurses’ knowledge; we recommend advanced BLS training for all healthcare providers, doctors, and nurses working in hospitals and healthcare centers. Nursing managers can implement systematic strategies to enhance nurses’ knowledge and practice in BLS to target low-scoring Governorates.
Intermittent hypoxia therapy ameliorates beta-amyloid pathology via TFEB-mediated autophagy in murine Alzheimer's disease
Authors: Wang Xueting , Xie Yuqi , Chen Guijuan , Lu Yapeng , Wang Dan , Zhu Li 
Published: October 2023

Abstract
Background
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Impaired autophagy in plaque-associated microglia (PAM) has been reported to accelerate amyloid plaque deposition and cognitive impairment in AD pathogenesis. Recent evidence suggests that the transcription factor EB (TFEB)-mediated activation of the autophagy–lysosomal pathway is a promising treatment approach for AD. Moreover, the complementary therapy of intermittent hypoxia therapy (IHT) has been shown to upregulate autophagy and impart beneficial effects in patients with AD. However, the effect of IHT on PAM remains unknown.

Methods
8-Month-old APP/PS1 mice were treated with IHT for 28 days. Spatial learning memory capacity and anxiety in mice were investigated. AD pathology was determined by the quantity of nerve fibers and synapses density, numbers of microglia and neurons, Aβ plaque deposition, pro-inflammatory factors, and the content of Aβ in the brain. TFEB-mediated autophagy was determined by western blot and qRT-PCR. Primary microglia were treated with oligomeric Aβ 1–42 (oAβ) combined with IHT for mechanism exploration. Differential genes were screened by RNA-seq. Autophagic degradation process of intracellular oAβ was traced by immunofluorescence.

Results
In this study, we found that IHT ameliorated cognitive function by attenuating neuronal loss and axonal injury in an AD animal model (APP/PS1 mice) with beta-amyloid (Aβ) pathology. In addition, IHT-mediated neuronal protection was associated with reduced Aβ accumulation and plaque formation. Using an in vitro PAM model, we further confirmed that IHT upregulated autophagy-related proteins, thereby promoting the Aβ autophagic degradation by PAM. Mechanistically, IHT facilitated the nuclear localization of TFEB in PAM, with TFEB activity showing a positive correlation with Aβ degradation by PAM in vivo and in vitro. In addition, IHT-induced TFEB activation was associated with the inhibition of the AKT–MAPK–mTOR pathway.

Conclusions
These results suggest that IHT alleviates neuronal damage and neuroinflammation via the upregulation of TFEB-dependent Aβ clearance by PAM, leading to improved learning and memory in AD mice. Therefore, IHT may be a promising non-pharmacologic therapy in complementary medicine against AD.

Graphical Abstract
Saharan dust induces NLRP3-dependent inflammatory cytokines in an alveolar air-liquid interface co-culture model
Authors: Bredeck Gerrit , Dobner Jochen , Stahlmecke Burkhard , Fomba Khanneh Wadinga , Herrmann Hartmut , Rossi Andrea , Schins Roel P. F. 
Published: October 2023

Abstract
Background
Epidemiological studies have related desert dust events to increased respiratory morbidity and mortality. Although the Sahara is the largest source of desert dust, Saharan dust (SD) has been barely examined in toxicological studies. Here, we aimed to assess the NLRP3 inflammasome-caspase-1-pathway-dependent pro-inflammatory potency of SD in comparison to crystalline silica (DQ12 quartz) in an advanced air-liquid interface (ALI) co-culture model. Therefore, we exposed ALI co-cultures of alveolar epithelial A549 cells and macrophage-like differentiated THP-1 cells to 10, 21, and 31 µg/cm² SD and DQ12 for 24 h using a Vitrocell Cloud system. Additionally, we exposed ALI co-cultures containing caspase (CASP)1−/− and NLRP3−/− THP-1 cells to SD.

Results
Characterization of nebulized DQ12 and SD revealed that over 90% of agglomerates of both dusts were smaller than 2.5 μm. Characterization of the ALI co-culture model revealed that it produced surfactant protein C and that THP-1 cells remained viable at the ALI. Moreover, wild type, CASP1−/−, and NLRP3−/− THP-1 cells had comparable levels of the surface receptors cluster of differentiation 14 (CD14), toll-like receptor 2 (TLR2), and TLR4. Exposing ALI co-cultures to non-cytotoxic doses of DQ12 and SD did not induce oxidative stress marker gene expression. SD but not DQ12 upregulated gene expressions of interleukin 1 Beta (IL1B), IL6, and IL8 as well as releases of IL-1β, IL-6, IL-8, and tumor necrosis factor α (TNFα). Exposing wild type, CASP1−/−, and NLRP3−/− co-cultures to SD induced IL1B gene expression in all co-cultures whereas IL-1β release was only induced in wild type co-cultures. In CASP1−/− and NLRP3−/− co-cultures, IL-6, IL-8, and TNFα releases were also reduced.

Conclusions
Since surfactants can decrease the toxicity of poorly soluble particles, the higher potency of SD than DQ12 in this surfactant-producing ALI model emphasizes the importance of readily soluble SD components such as microbial compounds. The higher potency of SD than DQ12 also renders SD a potential alternative particulate positive control for studies addressing acute inflammatory effects. The high pro-inflammatory potency depending on NLRP3, CASP-1, and IL-1β suggests that SD causes acute lung injury which may explain desert dust event-related increased respiratory morbidity and mortality.
Pure platelet-rich plasma promotes semaphorin-3A expression: a novel insight to ameliorate intervertebral disk degeneration in vitro
Authors: Huang Jie , Lian Shi-lin , Han Jia-heng , Lu Zheng-cao , Ding Yu 
Published: October 2023

Abstract
Introduction
Intervertebral disk degeneration (IVDD) can be effectively treated using platelet-rich plasma (PRP). While the exact process is fully understood, it is believed that using pure PRP (P-PRP) without leukocytes is a better option for preventing IVDD. Semaphorin-3A (Sema3A), an inhibitor of angiogenesis and innervation, is essential for preserving IVDD’s homeostasis. Whether PRP prevents IVDD by modifying Sema3A has yet to receive much research. This work aims to clarify how P-PRP affects Sema3A when IVDD develops in vitro.

Methods
Nucleus pulposus cells (NPCs) isolated from 8-week-old male Sprague-Dawley rats were exposed to 10 ng/ml IL-1β and then treated with P-PRP or leukocyte platelet-rich plasma (L-PRP) in vitro, followed by measuring cell proliferation, apoptosis and microstructures, inflammatory gene and Sema3A expression, as well as anabolic and catabolic protein expression by immunostaining, quantitative real-time polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assay (ELISA).

Results
In comparison with L-PRP, P-PRP had a higher concentration of growth factors but a lower concentration of inflammatory substances. P-PRP increased the proliferation of NPCs, while IL-1 relieved the amount of apoptosis due to its intervention. Anabolic genes, aggrecan, and collagen II had higher expression levels. MMP-3 and ADAMTS-4, two catabolic or inflammatory genes, showed lower expression levels. Sema3A activity was enhanced after P-PRP injection, whereas CD31 and NF200 expression levels were suppressed.

Conclusions
P-PRP enhanced the performance of NPCs in IVDD by modifying the NF-κB signaling pathway and encouraging Sema3A expression, which may offer new therapy options for IVDD.

The translational potential of this article
The findings provide a new therapeutic target for the treatment of IVDD and show a novel light on the probable mechanism of PRP and the function of Sema3A in the progression of IVDD.
Bad research is not all bad
Authors: Hamilton Fergus , Arnold David , Lilford Richard 
Published: October 2023

AbstractIn this commentary, we discuss a recent article in Trials that raised concerns about the number of poorly performed randomised trials in the medical literature and discuss the trials literature more widely. Although we all aim for higher methodological standards in trials, we argue that (i) the idea that ‘most randomised trials are bad’, which the recent article concludes is an overly simplistic representation of the situation, and (ii) the suggestion that an increased focus on methodological review during trial development (e.g. ethical boards performing some assessment of the methodologists on a trial), while well meaning, may have negative unintended consequences. We therefore propose that (a) trials should be assessed on their merits and weaknesses, including an assessment of risk of bias but placing that in a wider context; (b) we should recognise that although the methodological conduct of trials is of utmost importance, interventions that aim to improve this could have unintended consequences—such as bureaucracy—that have an overall negative effect; and (c) we should therefore generate an evidence base for policy interventions to improve conduct of trials rather than applying arbitrary rules.
Trichinella spiralis excretory/secretory products from adult worms inhibit NETosis and regulate the production of cytokines from neutrophils
Authors: Wang Jing , Tang Bin , You Xihuo , Cai Xuepeng , Jia Wanzhong , Liu Xiaolei , Liu Mingyuan , Jin Xuemin , Ding Jing 
Published: October 2023

AbstractUpon encountering exogenous pathogens, polymorphonucleocytes (PMNs) engage in various processes to destroy them, including releasing neutrophil extracellular traps (NETs) that trap pathogens and induce phagocytosis and cytokine production. Parasites have unique strategies with which to evade the host's immune response. However, the strategy employed by Trichinella spiralis in response to the reaction of PMNs has yet to be elucidated. This study explored the effect of excretory/secretory products (ESP) on three major functions: NETs, phagocytosis, and cytokine production. Specifically, PMNs were pre-treated with the ESP of 3-day-old adults and then stimulated with phorbol 12-myristate 13-acetate (PMA). We found that in PMNs pretreated with ESP, PMA-induced NET generation was suppressed by ESP. ROS production is a hallmark of PMA-induced NETosis. The LDH assay results showed that ESP inhibits NETs by suppressing ROS rather than promoting PMN death. Furthermore, ESP enhanced Escherichia coli engulfment by PMNs, improving overall phagocytic function. Finally, cytokine analysis revealed an increase in pro-inflammatory cytokine IL-1β, and other cytokines (IL-10, TNF-α), while IL-4 displayed a significant reduction. In conclusion, this study has unraveled T. spiralis' evasion and regulation mechanisms against innate immune cells, providing insights into parasite strategies to manipulate host immunity, potentially informing new treatments for NET-related autoimmune diseases.
Graphical Abstract
Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement
Authors: Mizgier Nikola A. , Jones Charlie E. , Furano Anthony V. 
Published: October 2023

AbstractL1 (LINE1) non-LTR retrotransposons are ubiquitous genomic parasites and the dominant transposable element in humans having generated about 40% of their genomic DNA during their ~ 100 million years (Myr) of activity in primates. L1 replicates in germ line cells and early embryos, causing genetic diversity and defects, but can be active in some somatic stem cells, tumors and during aging. L1 encodes two proteins essential for retrotransposition: ORF2p, a reverse transcriptase that contains an endonuclease domain, and ORF1p, a coiled coil mediated homo trimer, which functions as a nucleic acid chaperone. Both proteins contain highly conserved domains and preferentially bind their encoding transcript to form an L1 ribonucleoprotein (RNP), which mediates retrotransposition. However, the coiled coil has periodically undergone episodes of substantial amino acid replacement to the extent that a given L1 family can concurrently express multiple ORF1s that differ in the sequence of their coiled coils. Here we show that such distinct ORF1p sequences can become entangled forming heterotrimers when co-expressed from separate vectors and speculate on how coiled coil entanglement could affect coiled coil evolution.
Spatial clusters of extended-spectrum beta-lactamase-producing Escherichia coli causing community-onset bacteriuria due to repeat infections: cluster analysis from a large urban medical center, San Francisco, 2014–2020
Authors: Raphael Eva , Inamdar Pushkar P. , Belmont Cheyenne , Shariff-Marco Salma , Huang Alison J. , Chambers Henry F. 
Published: October 2023

AbstractBackgroundUrinary tract infections caused by extended-spectrum beta-lactamase (ESBL)-producingEscherichia coli(ESBL-E. coli) may occur as outbreaks due to common-source exposures. Yet, it is currently unknown if they cluster geographically as would be expected as part of an outbreak.MethodsWe collected electronic health record data on all patients living in San Francisco with culture-documented community-onsetE. colibacteriuria in a safety-net public healthcare system from January 2014 to March 2020 (diagnosed < 48 h after hospital admission or in outpatient clinical settings without a hospitalization in the past 90 days). We assessed the presence of spatial clusters of (1) ESBL-E. colibacteriuria episodes, and (2) individuals with any ESBL-E. colibacteriuria episode, with Global and Local Moran’s I. We evaluated differences in prevalence of bacteriuria recurrence by ESBL-production by Poisson regression.ResultsOut of 4,304 unique individuals, we identified spatial clusters of ESBL-E. colibacteriuria episodes (n = 461) compared to non-ESBL-E. colibacteriuria episodes (n = 5477; Global Moran’s p < 0.001). Spatial clusters of individuals with any bacteriuria caused by ESBL-E. coliwere not identified (p = 0.43). Bacteriuria recurrence was more likely to occur with ESBL-E. coli(odds ratio [OR] 2.78, 95% confidence interval [95% CI] 2.10, 3.66, p < 0.001), particularly after an initial ESBL-E. colibacteriuria episode (OR 2.27, 95% CI 1.82, 2.83, p < 0.001).ConclusionWe found spatial clusters of ESBL-E. colibacteriuria episodes. However, this was partly explained by clustering within individuals more than between individuals, as having an ESBL-E. colibacteriuria was associated with recurrence with ESBL-E. coli. These findings may help better tailor clinical treatment of patients with recurrent urinary tract infections after an initial episode caused by ESBL-E. coli.
Change-point models for identifying behavioral transitions in wild animals
Authors: Gundermann Kathleen P. , Diefenbach D. R. , Walter W. D. , Corondi A. M. , Banfield J. E. , Wallingford B. D. , Stainbrook D. P. , Rosenberry C. S. , Buderman F. E. 
Published: October 2023

AbstractAnimal behavior can be difficult, time-consuming, and costly to observe in the field directly. Innovative modeling methods, such as hidden Markov models (HMMs), allow researchers to infer unobserved animal behaviors from movement data, and implementations often assume that transitions between states occur multiple times. However, some behavioral shifts of interest, such as parturition, migration initiation, and juvenile dispersal, may only occur once during an observation period, and HMMs may not be the best approach to identify these changes. We present two change-point models for identifying single transitions in movement behavior: a location-based change-point model and a movement metric-based change-point model. We first conducted a simulation study to determine the ability of these models to detect a behavioral transition given different amounts of data and the degree of behavioral shifts. We then applied our models to two ungulate species in central Pennsylvania that were fitted with global positioning system collars and vaginal implant transmitters to test hypotheses related to parturition behavior. We fit these models in a Bayesian framework and directly compared the ability of each model to describe the parturition behavior across species. Our simulation study demonstrated that successful change point estimation using either model was possible given at least 12 h of post-change observations and 15 min fix interval. However, our models received mixed support among deer and elk in Pennsylvania due to behavioral variation between species and among individuals. Our results demonstrate that when the behavior follows the dynamics proposed by the two models, researchers can identify the timing of a behavioral change. Although we refer to detecting parturition events, our results can be applied to any behavior that results in a single change in time.
Earthworms facilitated pepper (Capsicum annuum L.) growth via enhancing the population and function of arbuscular mycorrhizal fungi in a low-density polyethylene-contaminated soil
Authors: Liu Yifan , He Baiping , Xiao Qingqing , Wang Xin , Lin Xiangui , Hu Junli 
Published: October 2023

AbstractMicroplastics (MPs) produced by the decomposition of plastics exist persistently, interfering with soil fertility and plant nutrition. Both arbuscular mycorrhizal (AM) fungi and earthworms are beneficial in terrestrial ecosystems, but their interactions under MPs contamination are unclear so far. Here, the influences of inoculating earthworms (Eisenia fetida) on indigenous AM fungi and pepper (Capsicum annuumL.) growth were investigated in a vegetable soil treated with 0.1% low-density polyethylene (LDPE), while the specific interactions of earthworm and AM fungus (Funneliformis caledonium) under LDPE contamination were further resolved in another experiment using sterilized soil. Inoculation of earthworms shifted soil AM fungal community structure, replacing the predominant genusGlomusbyParaglomus, and increased the abundance, diversity (i.e., Shannon) index, and root colonization rate of AM fungi by 108, 34.6 and 45.0%, respectively. Earthworms also significantly decreased soil pH, and significantly increased soil alkaline phosphatase (ALP) activity, shoot biomass and fruit yield of pepper by 394, 82.8 and 188%, respectively. In the sterilized soil, bothE. fetidaandF. caledoniumimproved pepper growth, while the latter noticeably increased phosphorus (P) translocation efficiency from root to shoot, and the combination induced the highest soil ALP activity and pepper fruit yield. Furthermore, the significantly interactive effects between earthworm and AM fungus were observed in soil pH and available P concentration, as well as in shoot P concentration and fruit yield of pepper. This study revealed the interaction between earthworms and AM fungi under MPs contamination conditions for the first time, indicating that earthworms could facilitate vegetable growth via enhancing the propagation and P-promoting function of AM fungi in LDPE-contaminated soils.Graphical Abstract