bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foot Assessment Clinical Scales in Charcot-Marie-Tooth Patients: A Scoping Review
Authors: Rambelli Chiara , Mazzoli Davide , Galletti Martina , Basini Giacomo , Zerbinati Paolo , Prati Paolo , Mascioli Francesca , Masiero Stefano , Merlo Andrea 
Published: June 2022

IntroductionCharcot-Marie-Tooth disease (CMT) is a slow and progressive peripheral motor sensory neuropathy frequently associated with the cavo-varus foot deformity. We conducted a scoping review on the clinical scales used to assess foot deviations in CMT patients and analyzed their metric properties.Evidence AcquisitionA first search was conducted to retrieve all scales used to assess foot characteristics in CMT patients from the Medline, Web of Science, Google Scholar, Cochrane, and PEDro databases. A second search was conducted to include all studies that evaluated the metric properties of such identified scales from the same databases. We followed the methodologic guidelines specific for scoping reviews and used the PICO framework to set the eligibility criteria. Two independent investigators screened all papers.Evidence SynthesisThe first search found 724 papers. Of these, 41 were included, using six different scales: “Foot Posture Index” (FPI), “Foot Function Index”, “Maryland Foot Score”, “American Orthopedic Foot &amp; Ankle Society's Hindfoot Evaluation Scale”, “Foot Health Status Questionnaire”, Wicart-Seringe grade. The second search produced 259 papers. Of these, 49 regarding the metric properties of these scales were included. We presented and analyzed the properties of all identified scales in terms of developmental history, clinical characteristics (domains, items, scores), metric characteristics (uni-dimensionality, inter- and intra-rater reliability, concurrent validity, responsiveness), and operational characteristics (normative values, manual availability, learning time and assessors' characteristics).ConclusionsOur results suggested the adoption of the six-item version of the FPI scale (FPI-6) for foot assessment in the CMT population, with scoring provided by Rasch Analysis. This scale has demonstrated high applicability in different cohorts after a short training period for clinicians, along with good psychometric properties. FPI-6 can help health professionals to assess foot deformity in CMT patients over the years.
Association of Coffee, Tea, and Caffeine Consumption With All-Cause Risk and Specific Mortality for Cardiovascular Disease Patients
Authors: Zheng Haotian , Lin Fan , Xin Ning , Yang Linxin , Zhu Pengli 
Published: June 2022

AimThe aim of the study was to examine the relationship between coffee, tea, caffeine consumption and risk of all-cause death and cardiovascular disease (CVD) death in CVD population.MethodsThis cohort study included 626 CVD participants aged ≥18 years old who derived from the National Health and Nutrition Examination Surveys (NHANES) database 2003–2006. The end time of follow-up was 2015, and with a median follow-up time of 113.5 (63, 133) months. CVD death was defined as a death caused by congestive heart failure (CHF), coronary heart disease (CHD), angina pectoris, heart attack or stroke. Cox model and competitive-risk model were used to explore the relationship of coffee, tea, caffeine, decaffeinated coffee/tea on the risk of the all-cause death and CVD death for CVD population, respectively. Additionally, we explored the effect of urinary caffeine and caffeine metabolites on all-cause death.ResultsAll patients were divided into survival group (n = 304), non-CVD death group (n = 223), and CVD death group (n = 99). The incidence of all-cause death and CVD death was ~51.44 and 15.81% in the study. After adjusting age, body mass index (BMI), cancer, estimated glomerular filtration rate (eGFR), energy, the history of CVD medications, carbohydrate and family income to poverty ratio (PIR), the results suggested coffee, caffeine, iced tea and hot tea consumption (≥4 cups per day) were associated with an increased risk of the all-cause death in CVD patients; while hot tea (1–3 cups per day), decaffeinated coffee/iced tea/hot tea could reduce the risk of the all-cause death. Likewise, coffee, caffeine, iced tea (≥4 cups per day), hot tea, decaffeinated iced tea/ hot tea (Always) could enhance the risk of the CVD death in CVD population. We also found that 1-methylxanthine showed a significant positive association on the risk of all-cause death in CVD population.ConclusionOur study indicated that higher consumption of coffee, tea and caffeine could increase the risk of all-cause and CVD death for CVD patients.
Royal Jelly Plus Coenzyme Q10 Supplementation Enhances High-Intensity Interval Exercise Performance via Alterations in Cardiac Autonomic Regulation and Blood Lactate Concentration in Runners
Authors: Ovchinnikov Aleksandr N. , Deryugina Anna V. , Paoli Antonio 
Published: June 2022

PurposeThis study aimed to examine whether oral royal jelly (RJ) and coenzyme Q10 (CoQ10) co-supplementation could improve high-intensity interval exercise (HIIE) performance in runners, reducing exercise-induced lactic acidosis and decreasing elevated sympathetic tone following exercise.MethodsThirty regional-level runners (age: 19 ± 1 years; height: 173 ± 2 cm; body mass: 68.9 ± 2 kg; body mass index: 23.1 ± 1 kg/m2) were randomly allocated to receive either 400 mg of RJ and 60 mg of CoQ10 (RJQ) or matching placebo (PLA) once daily for 10 days. Exercise performance expressed as time taken to complete HIIE was evaluated at baseline, and then reassessed at day 10 of intervention. HIIE protocol applied to the runners included three repetitions of 100 m distance at maximum possible speed interspersed with 45 s of recovery periods. Indices of heart rate variability and blood lactate concentration were also measured before and immediately after HIIE in each group.ResultsHIIE performance significantly improved in RJQ group (p = 0.005) compared to PLA group. Blood lactate levels and sympathetic influence on the heart were significantly lower both before and after the HIIE in athletes who received RJQ (p &lt; 0.05) compared to PLA. Regression analysis showed that oral RJQ administration for 10 days was significantly associated with reductions in HIIE-induced increases in blood lactate concentration and enhanced cardiac parasympathetic modulation following exercise compared to PLA. Principal component analysis revealed that runners treated with RJQ are grouped by the first two principal components into a separate cluster compared to PLA. Correlation analysis demonstrated that the improvements in runners’ HIIE performance were due in significant part to RJQ-induced reduction of increment in blood lactate levels in response to exercise in combination with a more rapid shift in autonomic activity toward increased parasympathetic control early at post-exercise.ConclusionThese findings suggest that RJQ supplementation for 10 days is potentially effective for enhancing HIIE performance and alleviating adverse effects of increased intramuscular acidity and prolonged sympathetic dominance following intense exercise.
Regulation of Gamma-Aminobutyric Acid Transaminase Expression and Its Clinical Significance in Hepatocellular Carcinoma
Authors: Gao Xiaoqiang , Jia Xiaodong , Xu Moyan , Xiang Jiao , Lei Jin , Li Yinyin , Lu Yinying , Zuo Shi 
Published: June 2022

BackgroundGamma-aminobutyric acid transaminase (ABAT) catalyzes the conversion of gamma-aminobutyric acid (GABA) into succinic semialdehyde. Although some evidence supports a key role of ABAT in the progression of hepatocellular carcinoma (HCC), no systematic analysis is available. Thus, this study aimed to investigate the possible mechanisms related to low ABAT expression and the prognostic value and potential functions of ABAT in HCC.MethodsWe obtained relevant datasets from the Encyclopedia of RNA Interactomes, MethSurv, cBioPortal, TISIDB and The Cancer Genome Atlas and used bioinformatic methods to analyze DNA methylation, copy number variation, gene mutation, and upstream microRNAs (miRNAs) of ABAT, exploring the potential relationship between ABAT expression and the prognosis, glycolysis, and immune infiltration in HCC.ResultsThe results indicated that ABAT expression was lower in HCC tumor tissues than in normal tissues or adjacent tissues. Low ABAT expression was related to patient age, T stage classification, pathologic stage, histological grade, and alpha-fetoprotein level of HCC. Kaplan-Meier survival analyses indicated that low ABAT expression was correlated with poor HCC prognosis. ABAT was also verified as an independent risk factor in HCC via Cox multivariate analysis. Gene set enrichment analysis showed enrichment in various signaling pathways. Furthermore, DNA methylation, copy number variation, and gene mutation potentially induced low ABAT expression; miR-135a-5p was a potential upstream miRNA of ABAT. Additionally, ABAT expression was associated with glycolysis-related genes, infiltrated immune cells, immunoinhibitors, and immunostimulators in HCC.ConclusionsOur study reveals that deficient ABAT expression is correlated with disease progression and poor prognosis in HCC because of its role in tumorigenesis and tumor immunity.
Harnessing the T Cell to Treat Multiple Myeloma: Dawn of a New Therapeutic Paradigm
Authors: Keller Alana L. , Sherbenou Daniel W. , Forsberg Peter A. , Mark Tomer M. 
Published: June 2022

Multiple myeloma is an incurable hematologic malignancy. The typical disease course for myeloma patients is characterized by initial response to treatment followed by eventual development of resistance. Subsequent cycles of remission and relapse proceed as long as patients have new lines of therapy available to them. This reality has prompted development of many novel immunotherapeutics. Many of these drugs exploit the cytotoxic capabilities of the patients’ own T cells, effectively redirecting them to myeloma cells that are otherwise evading immune attack. Approaches including CAR T cell therapy and bispecific antibodies have displayed impressive efficacy in clinical trials for myeloma patients. This review examines the different approaches that utilize T cells in multiple myeloma therapy and investigates the benefits and risks of these exciting new strategies.
High-Throughput mRNA Sequencing Reveals Potential Therapeutic Targets of Febuxostat in Secondary Injury After Intracerebral Hemorrhage
Authors: Wang Xueyan , Zhang Chenyu , Li Yuwen , Xu Ting , Xiang Jin , Bai Yang , Zhang Ying , Wang Qi , Zhang Tiejun , Liao Linchuan 
Published: June 2022

Febuxostat is a urate-lowering medication for the treatment of patients with gout. This study was performed to elucidate the effects and underlying mechanisms of febuxostat on neuronal injury induced by intracerebral hemorrhage (ICH) in mice. The results showed that the administration of febuxostat improved neurological severity scores and blood–brain barrier (BBB) permeability. Moreover, febuxostat attenuated neuronal cell death and cytokine levels compared with the ICH group. Next, we conducted a transcriptome analysis of the neuroprotective effects of febuxostat. The overlapping significant differentially expressed genes (DEGs) were identified. Gene ontology (GO) analysis revealed that the overlapping significant DEGs were most enriched in five items. The intersecting DEGs of the aforementioned five pathways were Wisp1, Wnt7b, Frzb, and Pitx2. In addition, GO terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that DEGs were mainly involved in the wnt signaling pathway. Furthermore, the expression of Wisp1 and Wnt7b in the perihematomal region at 72 h post-ICH was observed. The results showed that both Wisp1 and Wnt7b were increased in the ICH group and were decreased by the administration of febuxostat. Taken together, the study showed that febuxostat protected against secondary brain injury after ICH and the Wnt7b-Wisp1 pathway was closely related to neuroprotective effects.
Advanced in Vitro Safety Assessment of Herbal Medicines for the Treatment of Non-Psychotic Mental Disorders in Pregnancy
Authors: Spiess Deborah , Winker Moritz , Dolder Behna Alexandra , Gründemann Carsten , Simões-Wüst Ana Paula 
Published: June 2022

When confronted with non-psychotic mental disorders, pregnant women often refrain from using synthetic drugs and resort to herbal medicines such as St. John’s wort, California poppy, valerian, lavender, and hops. Nevertheless, these herbal medicines have not yet been officially approved in pregnancy due to lack of safety data. Using a variety of in vitro methods (determination of cytotoxicity, apoptosis induction, genotoxicity, effects on metabolic properties, and inhibition/induction of differentiation) in a commonly used placental cell line (BeWo b30), we were previously able to show that extracts from these plants are likely to be safe at the usual clinical doses. In the present work, we wanted to extend our safety assessment of these herbal medicines by 1) looking for possible effects on gene expression and 2) using the same in vitro methods to characterize effects of selected phytochemicals that might conceivably lead to safety issues. Proteomics results were promising, as none of the five extracts significantly affected protein expression by up- or down-regulation. Protopine (contained in California poppy), valerenic acid (in valerian), and linalool (in lavender) were inconspicuous in all experiments and showed no adverse effects. Hyperforin and hypericin (two constituents of St. John’s wort) and valtrate (typical for valerian) were the most obvious phytochemicals with respect to cytotoxic and apoptotic effects. A decrease in cell viability was evident with hypericin (≥1 µM) and valtrate (≥10 µM), whereas hyperforin (≥3 µM), hypericin (30 µM) and valtrate (≥10 µM) induced cell apoptosis. None of the tested phytochemicals resulted in genotoxic effects at concentrations of 0.1 and 1 µM and thus are not DNA damaging. No decrease in glucose consumption or lactate production was observed under the influence of the phytochemicals, except for valtrate (at all concentrations). No compound affected cell differentiation, except for hyperforin (≥1 µM), which had an inhibitory effect. This study suggests that extracts from St. John’s wort, California poppy, valerian, lavender, and hops are likely to be safe during pregnancy. High plasma concentrations of some relevant compounds—hyperforin and hypericin from St. John’s wort and valtrate from valerian—deserve special attention, however.
D-Cysteine Ethyl Ester Reverses the Deleterious Effects of Morphine on Breathing and Arterial Blood–Gas Chemistry in Freely-Moving Rats
Authors: Getsy Paulina M. , Baby Santhosh M. , May Walter J. , Young Alex P. , Gaston Benjamin , Hodges Matthew R. , Forster Hubert V. , Bates James N. , Wilson Christopher G. , Lewis Tristan H. J. , Hsieh Yee-Hee , Lewis Stephen J. 
Published: June 2022

Cell-penetrant thiol esters including the disulfides, D-cystine diethyl ester and D-cystine dimethyl ester, and the monosulfide, L-glutathione ethyl ester, prevent and/or reverse the deleterious effects of opioids, such as morphine and fentanyl, on breathing and gas exchange within the lungs of unanesthetized/unrestrained rats without diminishing the antinociceptive or sedative effects of opioids. We describe here the effects of the monosulfide thiol ester, D-cysteine ethyl ester (D-CYSee), on intravenous morphine-induced changes in ventilatory parameters, arterial blood–gas chemistry, alveolar–arterial (A-a) gradient (i.e., index of gas exchange in the lungs), and sedation and antinociception in freely-moving rats. The bolus injection of morphine (10 mg/kg, IV) elicited deleterious effects on breathing, including depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive. Subsequent injections of D-CYSee (2 × 500 μmol/kg, IV, given 15 min apart) elicited an immediate and sustained reversal of these effects of morphine. Morphine (10 mg/kg, IV) also A-a gradient, which caused a mismatch in ventilation perfusion within the lungs, and elicited pronounced changes in arterial blood–gas chemistry, including pronounced decreases in arterial blood pH, pO2 and sO2, and equally pronounced increases in pCO2 (all responses indicative of decreased ventilatory drive). These deleterious effects of morphine were immediately reversed by the injection of a single dose of D-CYSee (500 μmol/kg, IV). Importantly, the sedation and antinociception elicited by morphine (10 mg/kg, IV) were minimally affected by D-CYSee (500 μmol/kg, IV). In contrast, none of the effects of morphine were affected by administration of the parent thiol, D-cysteine (1 or 2 doses of 500 μmol/kg, IV). Taken together, these data suggest that D-CYSee may exert its beneficial effects via entry into cells that mediate the deleterious effects of opioids on breathing and gas exchange. Whether D-CYSee acts as a respiratory stimulant or counteracts the inhibitory actions of µ-opioid receptor activation remains to be determined. In conclusion, D-CYSee and related thiol esters may have clinical potential for the reversal of the adverse effects of opioids on breathing and gas exchange, while largely sparing antinociception and sedation.
Toward Therapeutic Drug Monitoring of Lenalidomide in Hematological Malignancy? Results of an Observational Study of the Exposure-Safety Relationship
Authors: Song Zaiwei , Ma Lan , Bao Li , Ma Yi , Yang Ping , Jiang Dan , Liu Aijun , Zhang Lu , Li Yan , Cheng Yinchu , Dong Fei , Zhao Rongsheng , Jing Hongmei 
Published: June 2022

Objective: Continuous lenalidomide (LEN) therapy is important to achieve a therapeutic effect in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). However, despite dose adjustment according to kidney function, many patients discontinue LEN therapy because of hematological toxicity. To date, therapeutic drug monitoring (TDM) of LEN has not been performed in oncology, and no target concentration level has been yet defined. The aim of this study was to evaluate the exposure-safety relationship of LEN and determine the target concentration for toxicity.Materials and Methods: A prospective observational study was designed and implemented. Blood samples were collected at 0.5 h (trough concentration, Cmin) before oral administration and 1 h (C1h) thereafter on the day. Clinical data were gathered from patients’ medical records and laboratory reports. Outcome measures of hematological toxicity were defined by the Common Terminology Criteria for Adverse Events. The concentration values were dichotomized by receiver operating characteristic (ROC) curve analysis, and the association between exposure and outcome was determined using the logistic regression model.Results: Out of the 61 patients enrolled in this study, 40 (65.57%) had MM, and 21 (34.43%) had NHL. Hematological toxicity was reported in 15 (24.59%) patients. The LEN Cmin showed remarkable differences (p = 0.031) among patients with or without hematological toxicity, while no association between C1h values and toxicity was noted (p&gt;0.05). By ROC analysis, a Cmin threshold of 10.95 ng/mL was associated with the best sensitivity/specificity for toxicity events (AUC = 0.687; sensitivity = 0.40; specificity = 0.935). By multivariate logistic regression, an LEN Cmin below 10.95 ng/mL was associated with a markedly decreased risk of hematological toxicity (&lt;10.95 ng/mL vs. &gt;10.95 ng/mL: OR = 0.023, 95% CI = 0.002–0.269; p = 0.003).Conclusions: We demonstrate that the LEN trough concentration correlates with hematological toxicity, and the Cmin threshold for hematological toxicity (10.95 ng/mL) is proposed. Altogether, LEN TDM appears to be a new approach to improve medication safety and achieve continuous treatment for patients with NHL or MM in routine clinical care.
An Ionization-Driven Air Plasma Jet
Authors: Jin Shaohui , Nie Lanlan , Zhou Rusen , Luo Jingyi , Lu Xinpei 
Published: June 2022

Non-thermal atmospheric pressure plasma jets (NAPPJs) using ambient air as the inducer are of particular and desirable interest but with significant challenges. In this study, we report an air APPJ driven by ionization in the afterglow region, resembling noble gas APPJs. A pin-to-nozzle electrode is used for the air plasma jet with a nanosecond-pulsed DC high voltage as the power supply. Results show that the nozzle diameter plays an essential role in forming the air plasma jet. When the nozzle diameter is 3 mm, the air APPJ is driven by ionization in the afterglow region which is proved by the following three phenomena. First, with an exposure time of 0.1 s, an obvious shiny line (the narrow channel plasma) formed by electron accumulation is observed in the jet. The narrow channel becomes much brighter with a grounding pin approaching the nozzle vertically. In comparison, there is no such phenomenon with a 1-mm diameter nozzle. Second, the afterglow region discharge current of the ionization-driven processes is hundreds of mA distinguished from airflow-driven processes, the afterglow region current of which is typically zero. By using E-FISH to measure the electric field in the afterglow region, it can detect the electric field which has a maximum value of 10.5 kV/cm. Third, the intensity of the N2+ band is much stronger with a 3-mm diameter nozzle than with a 1-mm diameter nozzle, indicating that the local electric field plays an important role in the discharge. We expect this study can offer useful guidelines on the design and understanding of ionization-driven air plasma jets.
Workplace Support for Mental Health Workers Who Are Parents: A Feasibility Study
Authors: Dunn Abby , Dixon Clare , Thomson Abi , Cartwright-Hatton Samantha 
Published: June 2022

BackgroundMental health workers are subject to high levels of occupational stress which is associated with poorer health and wellbeing and impaired patient outcomes. For individuals operating in high stress environments, reducing challenge at home, in particular around parenting, has been found to generalize into improvements in the professional domain. The present study sought to investigate the effectiveness and feasibility of brief targeted workplace intervention to support workers in terms of their parental role.Design/MethodologyAn uncontrolled evaluation of a series of three-session parenting-focused courses delivered to employees of a large Mental Health Trust. A pre-post-follow-up design was used to investigate effects on outcomes including parenting practice and experience, wellbeing, stress, and occupational self-efficacy. Intervention feasibility and acceptably was also evaluated.FindingsData from 15 participants who completed measures pre-post indicates the courses were associated with improved parenting practice and experience at a p &lt; 0.005 level. Improvements were reported at 6-month follow up. Participant satisfaction and course acceptability was highly rated by 100% of participants.