bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of abnormalities at the neuromuscular junction in the SOD1-G93A mouse model of ALS: dysfunction then disruption of postsynaptic structure precede overt motor symptoms
Authors: McIntosh Jayne , Mekrouda Imane , Dashti Maryam , Giuraniuc Claudiu V. , Banks Robert W. , Miles Gareth B. , Bewick Guy S. 
Published: May 2023

IntroductionThe ultimate deficit in amyotrophic lateral sclerosis (ALS) is neuromuscular junction (NMJ) loss, producing permanent paralysis, ultimately in respiratory muscles. However, understanding the functional and structural deficits at NMJs prior to this loss is crucial for therapeutic strategy design. Should early interventions focus on reversing denervation, or supporting largely intact NMJs that are functionally impaired? We therefore determined when functional and structural deficits appeared in diaphragmatic NMJs relative to the onset of hindlimb tremor (the first overt motor symptoms) in vivo in the SOD1-G93A mouse model of ALS.Materials and methodsWe employed electrophysiological recording of NMJ postsynaptic potentials for spontaneous and nerve stimulation-evoked responses. This was correlated with fluorescent imaging microscopy of the postsynaptic acetylcholine receptor (AChR) distribution throughout the postnatal developmental timecourse from 2 weeks to early symptomatic ages.ResultsSignificant reduction in the amplitudes of spontaneous miniature endplate potentials (mEPPs) and evoked EPPs emerged only at early symptomatic ages (in our colony, 18-22 weeks). Reductions in mEPP frequency, number of vesicles per EPP, and EPP rise time were seen earlier, at 16weeks, but this reversed by early symptomatic ages. However, the earliest and most striking impairment was an inability to maintain EPP amplitude during a 20 Hz stimulus train, which appeared 6 weeks before overt in vivo motor symptoms. Despite this, fluorescent α-bungarotoxin labelling revealed no systematic, progressive changes in 11 comprehensive NMJ morphological parameters (area, shape, compactness, number of acetylcholine receptor, AChR, regions, etc.) with disease progression. Rather, while NMJs were largely normally-shaped, from 16 weeks there was a progressive and substantial disruption in AChR concentration and distribution within the NMJ footprint.DiscussionThus, NMJ functional deficits appear at least 6 weeks before motor symptoms in vivo, while structural deficits occur 4 weeks later, and predominantly within NMJs. These data suggest initial therapies focused on rectifying suboptimal NMJ function could produce effective relief of symptoms of weakness.
The association between diet quality index-international and inflammatory markers in Iranian overweight and obese women
Authors: Shiraseb Farideh , Ebrahimi Sara , Noori Sahar , Bagheri Reza , Alvarez-Alvarado Stacey , Wong Alexei , Mirzaei Khadijeh 
Published: May 2023

ObjectivesThe present study was conducted to evaluate whether there is a link between the diet quality index (DQI) and markers of systemic inflammation in Iranian overweight and obese women.MethodsThis cross-sectional study included 200 Iranian overweight and obese women aged 18–48 years. The DQI-international (DQI-I) comprises four main components: variety, adequacy, moderation, and overall balance. Blood samples were collected in a fasted state to measure inflammatory markers.ResultsAfter adjusting for age, body mass index (BMI), physical activity, total energy intake, economic status, education, supplement intake, age of starting obesity, and history of body mass loss, a marginally significant negative association was observed between the homeostasis model assessment of insulin resistance (HOMA–IR) and the DQI–I (β: −0.015, 95% CI: −0.03, 0.000; p = 0.061). The results after adjustment showed that DQI–I has a negative association with high-sensitivity C-reactive protein (hs–CRP) concentrations (β: −0.031, 95% CI: −0.104, −0.031; p = 0.023). Furthermore, negative associations were observed between the adequacy component and levels of HOMA–IR (β: −0.025, 95% CI: −0.100, 0.047, p = 0.050) and hs-CRP (β: −0.615, 95% CI: −1.191, −0.020; p = 0.045). In addition, negative associations were found between transforming growth factor-β (TGF-β) and balance score (β: −6.270, 95% CI: −39.211, −3.661, p = 0.020), as well as HOMA–IR (β: −0.080, 95% CI: −0.202, −0.000, p = 0.041) and chemoattractant protein−1 (MCP−1) (β: −0.562, 95% CI: −11.414, −0.282, p = 0.021), with the various component. A marginally significant negative association between galectin 3 (Gal-3) and moderation score (β: −0.451, 95% CI: −1.171, 0.060, p = 0.060) was found. In addition, a marginally significant inverse association was also established between hs–CRP and variety score (β: −0.311, 95% CI: −0.970, 0.001, p = 0.052). The Receiver Operating characteristic (ROC) curve analysis demonstrated that DQI–I might better predict HOMA–IR with a cut point of 3.13 (AUC = 0.698, 0.511–0.699, p = 0.050).ConclusionThese findings showed that a higher adherence to diet quality and its components could probably be related to lowering the inflammatory markers considerably in overweight and obese women.
Comprehensive metabolic analyses provide new insights into primary and secondary metabolites in different tissues of Jianghua Kucha tea (Camellia sinensis var. assamica cv. Jianghua)
Authors: Wu Wenliang , Shi Jiang , Jin Jiqiang , Liu Zhen , Yuan Yong , Chen Zhida , Zhang Shuguang , Dai Weidong , Lin Zhi 
Published: May 2023

BackgroundJianghua Kucha (JHKC) is a special tea germplasm with enriched specialized secondary metabolites, including theacrine, non-epimeric flavanols and methylated flavanols. Moreover, primary metabolites provide precursors and energy for the production of secondary metabolites. However, the accumulation patterns of primary and secondary metabolites in different tissues of JHKC are unclear.MethodsThe changes of primary and secondary metabolites and related metabolic pathways (primary and secondary metabolism) in different JHKC tissues (the bud, 1st-4th leaves, and new stem) were investigated via metabolomics analysis with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS).ResultsSignificant differences were observed in 68 primary and 51 secondary metabolites mainly related with the pathways of starch and sucrose, amino acids, caffeine, and flavanols metabolism and TCA cycle. The bud exhibited higher levels of glucose-6-phosphate, citric acid, most amino acids, theobromine, catechin-gallate, epicatechin-gallate, procyanidins, and theasinensins; the 1st leaf showed higher levels of caffeine and epigallocatechin-3-gallate; and the 4th leaf contained higher levels of most monosaccharides, theacrine, and epigallocatechin-3-O-(3”-O-methyl)-gallate. In addition, primary metabolites and important secondary metabolites had certain correlations.ConclusionThis study provides comprehensive insight into primary and secondary metabolites in JHKC and offers guidelines for efficiently utilizing specialized metabolites of JHKC in the future.
Acute radiotherapy-associated oral pain may promote tumor growth at distant sites
Authors: Meneses Constanza S. , Gidcumb Emily M. , Marcus Karen L. , Gonzalez Yarines , Lai Yen Hao , Mishra Santosh K. , Lascelles B. Duncan X. , Nolan Michael W. 
Published: May 2023

IntroductionPatients developing acute radiotherapy induced dermatitis or oral mucositis commonly experience pain. When severe, this radiotherapy-associated pain (RAP) can necessitate treatment breaks; unfortunately, in a variety of cancers, prolongation of the radiotherapy course has been associated with early cancer relapse and/or death. This is often attributed to accelerated repopulation, but it is unknown whether pain or pain signaling constituents might alter tumor behavior and hasten metastatic disease progression. We studied this by testing the hypothesis that severe acute RAP at one site can hasten tumor growth at a distant site.MethodsMice underwent single fraction tongue irradiation (27 Gy, or 0 Gy “sham” control) to induce severe glossitis. At the time of maximal oral RAP, one of three luciferase-transfected tumor cell lines were injected via tail vein (4T1, B16F10, MOC2; each paired to their syngeneic host: BALB/c or C57BL/6); tumor burden was assessed via in vivo transthoracic bioluminescence imaging and ex vivo pulmonary nodule quantification. Survival was compared using Kaplan-Meier statistics.ResultsTongue irradiation and resultant RAP promoted lung tumor growth of 4T1-Luc2 cells in BALB/c mice. This effect was not a result of off-target radiation, nor an artefact of environmental stress caused by standard (subthermoneutral) housing temperatures. RAP did not affect the growth of B16F10-Luc2 cells, however, C57BL/6 mice undergoing tail vein injection of MOC2-Luc2 cells at the time of maximal RAP experienced early lung tumor-attributable death. Lung tumor growth was normalized when RAP was reduced by treatment with resiniferatoxin (300 µg/kg, subcutaneously, once).DiscussionThis research points towards radiation-induced activation of capsaicin-responsive (TRPV1) neurons as the cause for accelerated growth of tumors at distant (unirradiated) sites.
Cutaneous malignancies in patients with Parkinson’s disease at a dermato-oncological university centre in Hungary
Authors: Tóth Veronika , Diakoumakou Stefani Christina , Kuroli Enikő , Tóth Béla , Kuzmanovszki Daniella , Szakonyi József , Lőrincz Kende Kálmán , Somlai Beáta , Kárpáti Sarolta , Holló Péter 
Published: May 2023

BackgroundThe possible correlation between melanoma and Parkinson’s disease (PD) has been intensively studied. In this work, we aimed to assess the coincidence of skin malignancies and PD at a dermato-oncological university centre in Central-Eastern Europe, Hungary.MethodsFrom 2004 to 2017, a retrospective analysis of the centre’s database was performed based on International Statistical Classification of Diseases-10 codes.ResultsOut of the patients who visited the clinic during the study period, 20,658 were treated for malignant skin tumours. Over the 14 years, 205 dermatological patients had PD simultaneously, 111 (54%) of whom had at least one type of skin malignancy: melanoma (n=22), basal cell carcinoma (BCC) (n=82), or squamous cell carcinoma (SCC) (n=36) (in some patients, multiple skin tumours were identified). Compared to the age- and sex-matched control group, patients with PD had a significantly lower risk for basal cell carcinoma (OR, 0.65; 95% CI, 0.47–0.89, p=0.0076) and for all skin tumours (OR, 0.74; 95% CI, 0.56–0.98, p=0.0392) but not for melanoma.ConclusionsWe found a decreased risk of all skin tumours and basal cell carcinoma and an unchanged risk of melanoma among patients with PD. However, it should be kept in mind that some large-scale meta-analyses suggest a higher incidence of melanoma after a diagnosis of PD, indicating the importance of skin examination in this vulnerable population.
Venetoclax plus cyclophosphamide and cytarabine as induction regimen for adult acute myeloid leukemia
Authors: Zhang Baohang , Liu Qingguo , Li Junfan , Hu Yimin , Zhao Xin , Huang Pingping , Li Shangzhu , Wang Ying 
Published: May 2023

BackgroundThe efficacy of induction chemotherapy (IC) for acute myeloid leukemia (AML) has improved significantly with the application of targeting drugs. Our previous study showed that a 4-day IC regimen of cyclophosphamide (CTX) and Ara-C [CA (4 + 3)] achieved similar complete remission (CR) rate (80%) compared with the traditional 7-day regimen, and the survival rate appeared to be better.MethodsIn this pilot study, we further shortened the CA regimen to 3 days, added low-dose venetoclax (VEN, 200 mg/day) (VCA), and reported the efficacy and safety here.ResultsTwenty-five newly diagnosed adult AML patients were enrolled in this study and evaluated for the remission rate after one cycle of the VCA regimen. The CR/Cri was 92%, and all these patients had undetectable minimal residual disease (MRD−). The estimated overall survival at 12 months was 79.3%. The median time for both platelet recovery and absolute neutrophil count recovery was 16 days, faster than that of traditional IC. Compared with the previous CA (4 + 3) regimen, a higher CR rate (92% vs. 80%, P &lt; 0.01) and a deeper degree of remission (CRMRD− rate, 92% vs. 45%, P &lt; 0.01) were found in the VCA group.ConclusionsThis study showed that the 3-day CTX and Ara-C regimen is highly effective in newly diagnosed AML patients, and the addition of VEN to the CA regimen achieves higher and deeper one-course remission.
Thoracic epidural analgesia prolongs postoperative QT interval on electrocardiogram in major non-cardiac surgery: a randomized comparison and a prospective cohort analysis
Authors: Hori Kotaro , Tsujikawa Shogo , Egami Mika , Waki Sayaka , Watanabe Ryota , Hino Hideki , Matsuura Tadashi , Mori Takashi 
Published: May 2023

Introduction: Prolongation of QT interval on electrocardiogram can be associated with perioperative lethal arrhythmia. Epidural analgesia is a commonly used modality to relieve surgical pain by blocking sensory nerves, which also blocks the autonomic nervous system and can affect QT interval. Since patient monitoring becomes much less frequent after surgery than intraoperative period, we investigated the effects of epidural analgesia on postoperative QT interval with a randomized clinical trial and a prospective cohort study.Methods: In a randomized study, we assigned 60 patients undergoing thoracic epidural analgesia to an epidural analgesia or no-epidural analgesia group, in which 3 ml/h of 0.25% epidural levobupivacaine (7.5 mg/h) was administered only in the epidural analgesia group during surgery. The primary outcome was the postoperative heart rate-corrected QT interval. In a prospective cohort study, patients were assigned to receive 5 ml/h epidural levobupivacaine (12.5 mg/h). The plasma concentration of levobupivacaine was measured using liquid chromatography-mass spectrometry.Results: The median postoperative corrected QT interval interval with 3 ml/h epidural levobupivacaine was significantly longer than that without epidural analgesia. Using multiple regression analysis for the factors known to affect postoperative corrected QT interval interval, epidural analgesia was found to be an independent variable for prolongation, and the mean difference of the corrected QT interval interval with or without epidural analgesia was 23 ms after adjustment. The median plasma concentration of levobupivacaine at the end of surgery was 164 ng/ml with 3 ml/h epidural levobupivacaine, and the correlation coefficient to the postoperative corrected QT interval interval was 0.14, showing a not significant correlation. A prospective cohort study showed that 5 ml/h epidural levobupivacaine significantly prolonged postoperative corrected QT interval interval compared to preoperative baseline. The median plasma concentration of levobupivacaine was 166 ng/ml with 5 ml/h, the correlation coefficient of which showed no significant correlation.Conclusion: Thoracic epidural analgesia could enhance postoperative corrected QT interval prolongation after general anesthesia. The mechanism is possibly caused by blocking neighboring or part of the cardiac sympathetic nerves, rather than by systemic effects of epidurally administered levobupivacaine.Clinical trial number: UMIN000013347 for the randomized study and UMIN000041518 for the prospective cohort study, which were registered at University hospital Medical Information Network Center.
Biological sex differences in renin angiotensin system enzymes ACE and ACE2 regulate normal tissue response to radiation injury
Authors: Sharma Guru Prasad , Frei Anne , Fish Brian , Gasperetti Tracy , Veley Dana , Szalewski Nathan , Nissen Austen , Himburg Heather A. 
Published: May 2023

Introduction: In experimental animal models, biological sex-differences in the manifestation and severity of normal tissue radiation injury have been well-documented. Previously we demonstrated male and female rats have differential and highly reproducible responses to high-dose partial body irradiation (PBI) with male rats having greater susceptibility to both gastrointestinal acute radiation syndrome (GI-ARS) and radiation pneumonitis than female rats.Methods: In the current study, we have investigated whether differential expression of the renin-angiotensin system (RAS) enzymes angiotensin converting enzyme (ACE) and ACE2 contribute to the observed sex-related differences in radiation response.Results: During the period of symptomatic pneumonitis, the relative ratio of ACE to ACE2 (ACE/ACE2) protein in the whole lung was significantly increased by radiation in male rats alone. Systemic treatment with small molecule ACE2 agonist diminazene aceturate (DIZE) increased lung ACE2 activity and reduced morbidity during radiation pneumonitis in both sexes. Notably DIZE treatment also abrogated morbidity in male rats during GI-ARS. We then evaluated the contribution of the irradiated bone marrow (BM) compartment on lung immune cell infiltration and ACE imbalance during pneumonitis. Transplantation of bone marrow from irradiated donors increased both ACE-expressing myeloid cell infiltration and immune ACE activity in the lung during pneumonitis compared to non-irradiated donors.Discussion: Together, these data demonstrate radiation induces a sex-dependent imbalance in the renin-angiotensin system enzymes ACE and ACE2. Additionally, these data suggest a role for ACE-expressing myeloid cells in the pathogenesis of radiation pneumonitis. Finally, the observed sex-differences underscore the need for consideration of sex as a biological variable in the development of medical countermeasures for radiation exposure.
Effectiveness and mechanisms of the arts therapies in forensic care. A systematic review, narrative synthesis, and meta analysis
Authors: Abbing Annemarie , Haeyen Suzanne , Nyapati Sashank , Verboon Peter , Hooren Susan van 
Published: May 2023

IntroductionMental health care provided to offenders with psychiatric problems in forensic settings mainly consists of verbal oriented treatments. In addition, experience-based therapies are used such as (creative) arts therapies: (visual) art therapy, music therapy, drama therapy and dance (movement) therapy. There are indications for effectiveness of arts therapies, but a systematic overview of effect studies of all arts therapies in forensic care is lacking.MethodsFirst, we performed a systematic review. Second, Thematic Analysis was used to synthesize the qualitative narrative results and define the hypothesized mechanisms of change. Third, we performed a meta-analysis to investigate the effects of arts therapies in reducing psychosocial problems of offenders. Twenty-three studies were included in the review. Quality and risk of bias was assessed using EPHPP (Effective Public Health Practice Project).ResultsThe included studies were heterogeneous in type of outcome measures and intervention characteristics. Synthesis of mechanisms of change involved in the methodical use of the arts in arts therapies resulted in a description of regulatory processes which are stimulated in arts therapies: perceptive awareness (interoceptive and exteroceptive), the regulation of emotions, stress, impulses, cognitions, social regulation, and self-expression. These processes play a role in developing prevention, coping and self-management skills. Eighteen studies were included in the meta-analyses (11 RCTs/CCTs; 7 pre-post studies). The meta-analyses indicated significant effects on both risk factors (psychiatric symptoms and addiction) and protective factors for criminal behavior (social functioning and psychological functioning). Effects on criminal and/or antisocial behavior were not significant, but this outcome measure was scarcely used among the studies.DiscussionThe analyses in this study should be considered explorative. More research is needed to gain more solid conclusions about effectiveness and mechanisms of change of arts therapies in forensic institutions. However, the results of this first systematic review, synthesis of mechanisms and meta-analysis in this field are promising and show effects of arts therapies on risk and protective factors in individuals in forensic institutions.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020217884, identifier: CRD42020217884.
Cigarette smoking and risk of suicide in bipolar disorder: a systematic review
Authors: García-Jiménez Jesús , Gómez-Sierra Francisco José , Martínez-Hortelano Alicia , Moreno-Merino Paula , Girela-Serrano Braulio , Molero Patricio , Gutiérrez-Rojas Luis 
Published: May 2023

ObjectiveBipolar disorder (BD) is a highly prevalent, chronic and recurrent mental illness. The smoking rates in patients with BD are much higher than those of the general population, and BD is associated with an increased risk of suicide. An association between smoking and suicidal behavior has been found in the general population, this systematic review examines whether there is evidence of an association between smoking and suicide behavior in patients with BD.MethodA database search was carried out in Medline, Embase, The Cochrane Library, Scopus, and Web of Science, updated until December 31st, 2021, according to the 2020 PRISMA guidelines. We identified prospective and retrospective studies that included patients diagnosed with BD types I, II, and not otherwise specified, and in which smoking and suicidal behavior were correlated. Articles that focused exclusively on other mental disorders were excluded. The Ottawa-Newcastle scale was used to assess the methodological quality of the included articles.ResultsFifteen articles (n = 7,395) met all the inclusion criteria. In nine of these articles, the authors found an association between smoking and suicidal behavior in BD, while in the remaining six articles, this association was not found. A great deal of variability was observed between articles, particularly in the measurement of suicidal behavior and tobacco consumption. The risk of bias, as assessed by the NOS, was high for most of the included articles, except for two papers, whose risk was low.ConclusionIt was not possible to establish a clear relationship between tobacco use and the risk of suicide in BD patients due to the heterogeneity of the articles included in this systematic review, which had different sample sizes and methodological issues. However, both conditions are highly prevalent and have a negative impact on the prognosis of BD. Therefore, a systematic approach is needed, based on accurate measurement of a patient’s smoking habits and their risk of suicidal behavior, in order to establish an appropriate therapeutic plan.Additional informationThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors and was registered on PROSPERO with the CRD42022301570 on January 21th 2022.