bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-contact physiotherapists’ perceived competency in a new model of care for low back pain patients: a mixed methods study
Authors: Kechichian Amélie , Viain Elsa , Lathière Thomas , Desmeules François , Pinsault Nicolas 
Published: September 2024

Background: A new advanced practice model of care enables French physiotherapists to perform medical acts for low back pain (LBP) patients as first-contact physiotherapists (FCPs).
Objective: The aim of this study is to determine the self-perceived competency of FCPs and to further explore factors underpinning this feeling.
Methods: A mixed-methods explanatory sequential design was conducted. A survey was used to self-assess the perceived competency of FCPs in performing medical tasks. Semi-structured interviews were then performed to explore determining factors of perceived competency. Inductive thematic analysis was performed.
Results: Nine FCPs answered the survey and were interviewed (mean age 40.1, standard deviation [SD]: ±10.0). FCPs felt very competent with making medical diagnosis (3.44/4, SD: ±0.53), analgesic prescription (3.11, SD: ±0.78) and referring onward to physiotherapy (3.78, SD: ±0.55). They did not feel competent with nonsteroidal anti-inflammatory drug prescription (2.78, SD: ±0.67) and issuing sick leave certificate (2.67, SD: ±1.0). The main identified influencing factors were previous FCPs’ experience, training, knowledge, collaboration with family physicians, high responsibility and risk management associated with decision-making.
Conclusion: French FCPs appeared to have the necessary skills to directly manage LBP patients without medical referral. Future training focusing on analgesic prescription and issuing sick leave certificate is however needed.
T-CLEARE: a pilot community-driven tissue clearing protocol repository
Authors: Weiss Kurt R. , Huisken Jan , Khanjani Neda , Bakalov Vesselina , Engle Michelle L. , Krzyzanowski Michelle C. , Madden Tom , Maiese Deborah R. , Waterfield Justin R. , Williams David N. , Wood Lauren , Wu Xin , Hamilton Carol M. , Huggins Wayne 
Published: September 2024

Selecting and implementing a tissue clearing protocol is challenging. Established more than 100 years ago, tissue clearing is still a rapidly evolving field of research. There are currently many published protocols to choose from, and each performs better or worse across a range of key evaluation factors (e.g., speed, cost, tissue stability, fluorescence quenching). Additionally, tissue clearing protocols are often optimized for specific experimental contexts, and applying an existing protocol to a new problem can require a lengthy period of adaptation by trial and error. Although the primary literature and review articles provide a useful starting point for optimization, there is growing recognition that results can vary dramatically with changes to tissue type or antibody used. To help address this issue, we have developed a novel, freely available repository of tissue clearing protocols named T-CLEARE (Tissue CLEAring protocol REpository; https://doryworkspace.org/doryviz). T-CLEARE incorporates community responses to an open survey designed to capture details not commonly found in the scientific literature, including modifications to published protocols required for specific use cases and instances when tissue clearing protocols did not perform well (negative results). The goal of T-CLEARE is to help the community share evaluations and modifications of tissue clearing protocols for various tissue types and potentially identify best-in-class methods for a given application.
Spatiotemporal regulation of MELK during mitosis
Authors: Majumdar Sreemita , Liu Song-Tao 
Published: September 2024

Maternal Embryonic Leucine Zipper Kinase (MELK) has been studied intensively in recent years due to its overexpression in multiple cancers. However, the cell biology of MELK remains less characterized despite its well-documented association with mitosis. Here we report a distinctive pattern of human MELK that translocates from the cytoplasm to cell cortex within 3 min of anaphase onset. The cortex association lasts about 30 min till telophase. The spatiotemporal specific localization of MELK depends on the interaction between its Threonine-Proline (TP) rich domain and kinase associated 1 (KA1) domain, which is regulated by CDK1 kinase and PP4 protein phosphatase. KA1 domains are known to regulate kinase activities through various intramolecular interactions. Our results revealed a new role for KA1 domain to control subcellular localization of a protein kinase.
Combination of aloe emodin, emodin, and rhein from Aloe with EDTA sensitizes the resistant Acinetobacter baumannii to polymyxins
Authors: Zhao Yue , Zhang Tingting , Liang Yinping , Xie Xiaoqing , Pan Hongwei , Cao Meng , Wang Shuhua , Wu Dalei , Wang Jing , Wang Chuandong , Hu Wei 
Published: September 2024

BackgroundThe continuous emergence and spread of polymyxin-resistant Acinetobacter baumannii pose a significant global health challenge, necessitating the development of novel therapeutic strategies. Aloe, with its long-standing history of medicinal use, has recently been the subject of substantial research for its efficacy against pathogenic infections.MethodsThis study investigates the potential application of anthraquinone components in aloe against polymyxin-resistant A. baumannii by liquid chromatography-mass spectrometry, in vitro activity assessment, and construction of animal infection models.ResultsThe findings demonstrate that aloe emodin, emodin, rhein, and their mixtures in equal mass ratios (EAR) exhibit strain-specific antibacterial activities against polymyxin-resistant A. baumannii. Co-administration of EAR with EDTA synergistically and universally enhanced the antibacterial activity and bactericidal efficacy of polymyxins against polymyxin-resistant A. baumannii, while also reducing the frequency of polymyxin-resistant mutations in polymyxinssensitive A. baumannii. Following toxicity assessment on human hepatic and renal cell lines, the combination therapy was applied to skin wounds in mice infected with polymyxin-resistant A. baumannii. Compared to monotherapy, the combination therapy significantly accelerated wound healing and reduced bacterial burden.ConclusionsThe combination of EAR and EDTA with polymyxins offers a novel therapeutic approach for managing skin infections caused by polymyxinresistant A. baumannii.
Association between serum iron status and the risk of five bone and joint-related diseases: a Mendelian randomization analysis
Authors: Wang Xiaolei , Qiu Linjing , Yang Zepei , Wu Changjiang , Xie Wenying , Zhang Jing , Li Wenhui , Li Wangyang , Gao Yanbin , Zhang Taojing 
Published: September 2024

BackgroundAccording to reports, iron status has been associated with the risk of bone and joint-related diseases. However, the exact role of iron status in the development of these conditions remains uncertain.MethodWe obtained genetic data on iron status, specifically serum iron, ferritin, transferrin saturation (TSAT), and transferrin, as well as data on five common bone and joint-related diseases (osteoarthritis, osteoporosis, rheumatoid arthritis [RA], ankylosing spondylitis [AS], and gout) from independent genome-wide association studies involving individuals of European ancestry. Our primary approach for causal estimation utilized the inverse variance weighted (IVW) method. To ensure the reliability of our findings, we applied complementary sensitivity analysis and conducted reverse causal analysis.ResultUsing the IVW method, we revealed a positive causal relationship between ferritin levels and the risk of osteoarthritis (OR [95% CI], 1.0114 [1.0021-1.0207]). Besides, we identified a protective causal relationship between serum iron levels and TSAT levels in the risk of RA (OR [95% CI] values of serum iron and TSAT were 0.9987 [0.9973-0.9999] and 0.9977 [0.9966-0.9987], respectively). Furthermore, we found a positive causal relationship between serum iron levels and the risk of AS (OR [95% CI], 1.0015 [1.0005-1.0026]). Regarding gout, both serum iron and TSAT showed a positive causal relationship (OR [95% CI] values of 1.3357 [1.0915-1.6345] and 1.2316 [1.0666-1.4221] for serum iron and TSAT, respectively), while transferrin exhibited a protective causal relationship (OR [95% CI], 0.8563 [0.7802-0.9399]). Additionally, our reverse causal analysis revealed a negative correlation between RA and ferritin and TSAT levels (OR [95% CI] values of serum iron and TSAT were 0.0407 [0.0034-0.4814] and 0.0049 [0.0002-0.1454], respectively), along with a positive correlation with transferrin (OR [95% CI], 853.7592 [20.7108-35194.4325]). To ensure the validity of our findings, we replicated the results through sensitivity analysis during the validation process.ConclusionOur study demonstrated a significant correlation between iron status and bone and joint-related diseases.
Causality between sarcopenia and diabetic neuropathy
Authors: Fang Yi , Yuan Xiaoqing , Zhang Qing , Liu Juan , Yao Qing , Ye Xinhua 
Published: September 2024

BackgroundPast studies have demonstrated that diabetic neuropathy is related to sarcopenia, but the further causal relation is still unclear. We sought to investigate the causal relationship by combining data from cross-sectional and Mendelian randomization (MR) studies.MethodsThe genome-wide association studies data were collected from the UK Biobank and the European Working Group on Sarcopenia to conduct a bi-directional two-sample MR study to explore the causality between diabetic neuropathy and relevant clinical traits of sarcopenia, including appendicular lean mass (ALM), walking speed and low hand grip strength. The inverse-variance weighted and various sensitivity analyses were used to obtain MR estimates. We also enrolled a total of 196 Type 2 diabetes patients from April 2021 to April 2024 and divided them into the Distal peripheral neuropathy (DPN) group (n=51) and non-DPN group (n=145) via vibration perception threshold (VPT) and neuropathy deficit score. Logistic regression and ROC curve analysis were used to investigate the relationship between DPN and relevant sarcopenia clinical features.ResultsAccording to a forward MR analysis, decreased walking speed (OR: 0.04, 95% confidence interval (CI): 0.01-0.16; P&lt;0.001) and increased ALM (1.25 [1.05-1.50], P=0.012) had a causal effect on developing diabetic neuropathy. According to reverse MR results, developing diabetic neuropathy had a causal effect on decreased walking speed (0.99 [0.99-1.00], P=0.007) and low grip strength (1.05 [1.02-1.08], P&lt;0.001). The cross-sectional study showed that 5-time stand time (P=0.002) and 6-meter walking speed (P=0.009) had an inverse association with DPN. Additionally, we discovered that ASMI (P=0.030) and 5-time stand time (P=0.013) were separate risk factors for DPN.ConclusionThe MR study suggested that diabetic neuropathy may have a causality with relevant clinical traits of sarcopenia, and our cross-sectional study further proved that sarcopenia indexes are predictors of diabetic neuropathy.
Association between metabolic score for insulin resistance and cardiovascular disease mortality in patients with rheumatoid arthritis: evidence from the NHANES 1999-2018
Authors: Zhou Yan , Gao Jie 
Published: September 2024

AimTo explore the association between Metabolic Score for Insulin Resistance (METS-IR) and the risk of cardiovascular disease (CVD) death in patients with rheumatoid arthritis (RA).MethodsThis retrospective cohort study extracted data on 1,218 RA patients from the National Health and Nutrition Examination Survey. The weighted univariate and multivariate Cox regression model was established to explore the association between METS-IR and CVD mortality. Subgroup analysis was performed in terms of age, gender, body mass index, diabetes, and CVD. Hazard ratios (HRs) and 95% confidence levels (CIs) were presented.ResultsIncreased METS-IR was associated with a significantly higher risk of CVD mortality (HR=4.59, 95%CI: 1.98-10.67), and METS-IR&gt;2.48 was associated with higher odds of CVD mortality compared with METS-IR ≤ 2.25 (HR=3.57, 95%CI: 2.04-6.24). METS-IR was positively associated with the risk of CVD mortality (HR=3.83, 95%CI: 1.62-9.08), and METS-IR&gt;2.48 was associated with a significantly higher risk of CVD mortality in contrast to METS-IR ≤ 2.25 (HR=3.38, 95%CI: 1.87-6.09).ConclusionIncreased METS-IR was associated with a significantly higher risk of CVD mortality in RA patients. Clinicians could consider incorporating the METS-IR score into routine assessment of the prognosis of RA patients.
Exhausted signature and regulatory network of NK cells in myasthenia gravis
Authors: Zhang Qing , Han Xingyu , Bi Zhuajin , Yang Mengge , Lin Jing , Li Zhijun , Zhang Min , Bu Bitao 
Published: September 2024

IntroductionNK cells are dysfunctional in myasthenia gravis (MG), but the mechanism is unclear. This study aims to measure associations and underlying mechanisms between the NK cells and the development of MG.MethodsTwenty healthy controls (HCs) and 53 MG patients who did not receive glucocorticoids and immunosuppressants were collected. According to the Myasthenia Gravis Foundation of America (MGFA) classification, MG patients were categorized into MGFA I group (n = 18) and MGFA II-IV group (n = 35). Flow cytometry, cell sorting, ELISA, mRNA-sequencing, RT-qPCR, western blot, and cell culture experiments were performed to evaluate the regulatory mechanism of exhausted NK cells.ResultsPeripheral NK cells in MGFA II-IV patients exhibit exhausted phenotypes than HCs, marked by the dramatic loss of total NK cells, CD56dimCD16− NK cells, elevated PD1 expression, reduced NKG2D expression, impaired cytotoxic activity (perforin, granzyme B, CD107a) and cytokine secretion (IFN-γ). Plasma IL-6 and IL-21 are elevated in MG patients and mainly derived from the aberrant expansion of monocytes and Tfh cells, respectively. IL-6/IL-21 cooperatively induced NK-cell exhausted signature via upregulating SOCS2 and inhibiting the phosphorylation of STAT5. SOCS2 siRNA and IL-2 supplement attenuated the IL-6/IL-21-mediated alteration of NK-cell phenotypes and function.DiscussionInhibition of IL-6/IL-21/SOCS2/STAT5 pathway and recovery of NK-cell ability to inhibit autoimmunity may be a new direction in the treatment of MG.
Supplementation with Lactobacillus helveticus NS8 alleviated behavioral, neural, endocrine, and microbiota abnormalities in an endogenous rat model of depression
Authors: Alatan Husile , Liang Shan , Shimodaira Yosuke , Wu Xiaoli , Hu Xu , Wang Tao , Luo Jia , Iijima Katsunori , Jin Feng 
Published: September 2024

IntroductionMajor depressive disorder is a condition involving microbiota–gut–brain axis dysfunction. Increasing research aims to improve depression through gut microbiota regulation, including interventions such as probiotics, prebiotics, and fecal microbiota transplants. However, most research focuses on exogenous depression induced by chronic stress or drugs, with less attention given to endogenous depression. Additionally, research on gut mycobiota in depression is significantly less than that on gut bacteria.MethodsIn the present study, Wistar–Kyoto rats were used as an endogenous depression and treatment-resistant depression model, while Wistar rats served as controls. Differences between the two rat strains in behavior, gut bacteria, gut mycobiota, nervous system, endocrine system, immune system, and gut barrier were evaluated. Additionally, the effects of Lactobacillus helveticus NS8 supplementation were investigated.ResultsWistar–Kyoto rats demonstrated increased depressive-like behaviors in the forced swimming test, reduced sucrose preference in the sucrose preference test, and decreased locomotor activity in the open field test. They also exhibited abnormal gut bacteria and mycobiota, characterized by higher bacterial α-diversity but lower fungal α-diversity, along with increased butyrate, L-tyrosine, and L-phenylalanine biosynthesis from bacteria. Furthermore, these rats showed dysfunction in the microbiota–gut–brain axis, evidenced by a hypo-serotonergic system, hyper-noradrenergic system, defective hypothalamic–pituitary–adrenal axis, compromised gut barrier integrity, heightened serum inflammation, and diminished gut immunity. A 1-month L. helveticus NS8 intervention increased the fecal abundance of L. helveticus; reduced the abundance of Bilophila and Debaryomycetaceae; decreased immobility time but increased climbing time in the forced swimming test; reduced hippocampal corticotropin-releasing hormone levels; decreased hypothalamic norepinephrine levels; increased hippocampal glucocorticoid receptor, brain-derived neurotrophic factor dopamine, and 5-hydroxyindoleacetic acid content; and improved the gut microbiota, serotonergic, and noradrenergic system.ConclusionThe depressive phenotype of Wistar–Kyoto rats is not only attributed to their genetic context but also closely related to their gut microbiota. Abnormal gut microbiota and a dysfunctional microbiota–gut–brain axis play important roles in endogenous depression, just as they do in exogenous depression. Supplementing with probiotics such as L. helveticus NS8 is likely a promising approach to improve endogenous depression and treatment-resistant depression.
Association between dietary vitamin C intake and gout among American adults
Authors: Zou Yadan , Liu Yongyu , Li Shengguang 
Published: September 2024

IntroductionGout is a common type of inflammatory arthritis. Vitamin C is a potent antioxidant that neutralizes reactive oxygen species. However, the association between dietary vitamin C levels and gout remains unclear. This study evaluated the relationship between dietary vitamin C intake and gout.MethodsCross-sectional data from individuals aged &gt; 20 years who participated in the National Health and Nutrition Examination Survey between 2013 and 2018 were collected. Details on gout, dietary vitamin C intake, and several other essential variables were recorded.ResultsThere were 12589 participants, 5% (652/12589) of whom experienced gout. Compared with individuals with lower vitamin C consumption in the Q1 group (≤19.9 mg/day), the adjusted odds ratio(OR)values for dietary vitamin C intake and gout in the Q2 group (19.9–49.7 mg/day), Q3 group (49.7–110.375 mg/day), and Q4 group (≥110.375 mg/day) were 0.87 (95% confidence interval (CI): 0.69–1.1, P = 0.237), 0.81 (95% CI: 0.64–1.02, P = 0.076), and 0.77 (95% CI: 0.6–0.99, P= 0.042), respectively. Accordingly, the association between dietary vitamin C intake and gout exhibited an L-shaped curve (nonlinear, P = 0.245) in a restricted cubic spline. Subgroup analysis revealed significant interactions between vitamin C levels and gout according to sex (P &lt; 0.05). When we used data on dietary vitamin C from the second survey, we observed a similar inverse association between vitamin C intake and gout. The vitamin C was also negatively associated with hyperuricemia (OR, 0.94; 95% CI, 0.9–0.98, P=0.005). Compared with Q1, the adjusted OR values for dietary vitamin C and hyperuricemia in Q2, Q3, and Q4 were 0.77 (95% CI: 0.69–0.86, P = 0.65), 0.81 (95% CI: 0.72–0.91, P = 0.014), and 0.72 (95% CI: 0.64–0.81, P &lt; 0.001), respectively. No association was observed between vitamin C supplementation and gout.ConclusionThe population-based data indicate that dietary vitamin C intake is inversely associated with gout. These findings support the potential role of vitamin C in preventing gout.
Multivalent MVA-vectored vaccine elicits EBV neutralizing antibodies in rhesus macaques that reduce EBV infection in humanized mice
Authors: Escalante Gabriela M. , Reidel Ivana G. , Mutsvunguma Lorraine Z. , Cua Simeon , Tello Brenda A. , Rodriguez Esther , Farelo Mafalda A. , Zimmerman Cloe , Muniraju Murali , Li He , Govindan Aparna N. , Axthelm Michael K. , Wong Scott W. , Ogembo Javier Gordon 
Published: September 2024

IntroductionEpstein-Barr virus (EBV) is an oncogenic human herpesvirus associated with ~350,000 cases of lymphoid and epithelial malignancies every year, and is etiologically linked to infectious mononucleosis and multiple sclerosis. Despite four decades of research, no EBV vaccine candidate has yet reached licensure. Most previous vaccine attempts focused on a single viral entry glycoprotein, gp350, but recent data from clinical and pre-clinical studies, and the elucidation of viral entry mechanisms, support the inclusion of multiple entry glycoproteins in EBV vaccine design.MethodsHere we generated a modified vaccinia Ankara (MVA)-vectored EBV vaccine, MVA-EBV5-2, that targets five EBV entry glycoproteins, gp350, gB, and the gp42gHgL complex. We characterized the genetic and translational stability of the vaccine, followed by immunogenicity assessment in BALB/c mice and rhesus lymphocryptovirus-negative rhesus macaques as compared to a gp350-based MVA vaccine. Finally, we assessed the efficacy of MVA-EBV5-2-immune rhesus serum at preventing EBV infection in human CD34+ hematopoietic stem cell-reconstituted NSG mice, under two EBV challenge doses.ResultsThe MVA-EBV5-2 vaccine was genetically and translationally stable over 10 viral passages as shown by genetic and protein expression analysis, and when administered to female and male BALB/c mice, elicited serum EBV-specific IgG of both IgG1 and IgG2a subtypes with neutralizing activity in vitro. In Raji B cells, this neutralizing activity outperformed that of serum from mice immunized with a monovalent MVA-vectored gp350 vaccine. Similarly, MVA-EBV5-2 elicited EBV-specific IgG in rhesus macaques that were detected in both serum and saliva of immunized animals, with serum antibodies demonstrating neutralizing activity in vitro that outperformed serum from MVA-gp350-immunized macaques. Finally, pre-treatment with serum from MVA-EBV5-2-immunized macaques resulted in fewer EBV-infected mice in the two challenge experiments than pretreatment with serum from pre-immune macaques or macaques immunized with the monovalent gp350-based vaccine.DiscussionThese results support the inclusion of multiple entry glycoproteins in EBV vaccine design and position our vaccine as a strong candidate for clinical translation.