bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of COL4A4 variants in Chinese patients with familial hematuria
Authors: Gao Yanan , Yuan Lamei , Yuan Jinzhong , Yang Yan , Wang Jiangang , Chen Yong , Zhang Hao , Ai Yinze , Deng Hao 
Published: January 2023

Background: Benign familial hematuria and Alport syndrome are common causes of familial hematuria among children and young adults, which are attributable to variants in the collagen type IV alpha chain genes, COL4A3, COL4A4, or COL4A5. The study was conducted to identify the underlying genetic causes in patients with familial hematuria.Methods: Two unrelated Han-Chinese pedigrees with familial hematuria were recruited for this study. Whole exome sequencing was combined with in silico analysis to identify potential genetic variants, followed by variant confirmation by Sanger sequencing. Reverse transcription, PCR, and Sanger sequencing were performed to evaluate the effect of the detected splicing variant on mRNA splicing.Results: A novel heterozygous splicing c.595-1G&gt;A variant and a known heterozygous c.1715G&gt;C variant in the collagen type IV alpha 4 chain gene (COL4A4) were identified and confirmed in patients of pedigree 1 and pedigree 2, respectively. Complementary DNA analysis indicated this splicing variant could abolish the canonical splice acceptor site and cause a single nucleotide deletion of exon 10, which was predicted to produce a truncated protein.Conclusions: The two COL4A4 variants, c.595-1G&gt;A variant and c.1715G&gt;C (p.Gly572Ala) variant, were identified as the genetic etiologies of two families with familial hematuria, respectively. Our study broadened the variant spectrum of the COL4A4 gene and explained the possible pathogenesis, which will benefit clinical management and genetic counseling.
Single-cell RNA sequencing reveals intratumoral heterogeneity and potential mechanisms of malignant progression in prostate cancer with perineural invasion
Authors: Zhang Bao , Wang Shenghan , Fu Zhichao , Gao Qiang , Yang Lin , Lei Zhentao , Shi Yuqiang , Le Kai , Xiong Jie , Liu Siyao , Zhang Jiali , Su Junyan , Chen Jing , Liu Mengyuan , Niu Beifang 
Published: January 2023

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition of tumor tissues. The differently expressed genes among each cluster were identified by EdgeR. GO enrichment analysis was used to understand the roles of genes within the clusters. Pseudotime cell trajectory was used to reveal the molecular pathways underlying cell fate decisions and identify genes whose expression changed as the cells underwent transition. We applied CellPhoneDB to identify cell-cell interactions among the epithelial and neural cells in PNI-PCa.Results: Analysis of the ∼17,000 single-cell transcriptomes in three PNI prostate cancer tissues, we identified 12 major cell clusters, including neural cells and two epithelial subtypes with different expression profiles. We found that basal/intermediate epithelial cell subtypes highly expressed PCa progression-related genes, including PIGR, MMP7, and AGR2. Pseudotime trajectory analysis showed that luminal epithelial cells could be the initiating cells and transition to based/intermediate cells. Gene ontology (GO) enrichment analysis showed that pathways related to cancer progressions, such as lipid catabolic and fatty acid metabolic processes, were significantly enriched in basal/intermediate cells. Our analysis also suggested that basal/intermediate cells communicate closely with neural cells played a potential role in PNI-PCa progression.Conclusion: These results provide our understanding of PNI-PCa cellular heterogeneity and characterize the potential role of basal/intermediate cells in the PNI-PCa progression.
Global trends in research of immune cells associated with hypertensive disorders of pregnancy: A 20-year bibliometric analyses (from 2001 to 2021)
Authors: Wang Yue , Li Baoxuan , Tong Fei 
Published: January 2023

BackgroundA growing evidence suggests that immune cells play a significant role in the pathogenesis of hypertensive disorders of pregnancy (HDP).Over the past 20 years, several studies have been conducted on the role of immune cells in hypertensive disorders of pregnancy. This study used bibliometric analysis to assess research hotspots and future trends in studies on immune cells in hypertensive disorders of pregnancy.MethodsWe extracted all relevant literature on immune cells and hypertensive disorders of pregnancy from the Web of Science core collection for the period of 2001 to 2021. We used VOS Viewer, CiteSpace, R-bibliometrix and Python for bibliometric analysis.ResultsWe identified 2,388 records published in 593 journals by 9,886 authors from 2,174 universities/institutions in 91 countries/regions. The number of publications tended to increase over time, with the highest number of publications in 2021, up to 205. The USA was the country with the most publications. UNIVERSITY OF MISSISSIPPI was the most influential institution. Lamarca B, Romero R, and Saito S were the most prolific authors. Finally, three research hotspot clusters were identified based on keywords, which reflected the role of immune cells in the development of hypertensive disorders of pregnancy, the current research status,and predicted hot spots for future research.ConclusionsOur study systematically analyzed the role of immune cells in the pathogenesis of hypertensive disorders of pregnancy in the last 20 years. Our results indicated that immune cells, such as T cells, natural killer (NK) cells,and macrophages, and the cytokines released such as TNF-α, IFN-γ in the maternal circulation and at the maternal-fetal interface would influence the development of hypertensive disorders of pregnancy and we need further investigate the role of individual immune cells and translational studies to provide new therapeutic perspectives to mitigate adverse perinatal outcomes due to hypertensive disorders of pregnancy. In conclusion, bibliometric studies provide a general overview of immune cells in the study of hypertensive disorders of pregnancy.
Design, characterization and preliminary usability testing of a portable robot for unsupervised therapy of hand function
Authors: Ranzani Raffaele , Albrecht Martin , Haarman Claudia J. W. , Koh Emily , Devittori Giada , Held Jeremia P. O. , Tönis Frederik J. , Gassert Roger , Lambercy Olivier 
Published: January 2023

Introduction:There is evidence that increasing therapy dose after stroke might promote recovery. Unfortunately, in clinical practice, therapy dose is limited by financial and organizational constraints. Simple robotic devices could be used without supervision in the clinic or at home to increase dose without requiring additional resources. For this purpose, we developed HandyBot, a portable three-degrees-of-freedom end-effector haptic device to perform sensorimotor task-oriented therapy of hand function (i.e., grasping, forearm pronosupination, wrist flexion-extension) in different environments.Methods:We present the mechatronic design of the device and its technical evaluation in terms of workspace, dynamics (i.e., max end-effector velocity, acceleration and force), sensing (i.e., position, velocity and force resolution) and haptic performance (i.e., transparency, maximum stable impedance range, rigid contact rendering accuracy). In addition, its feasibility and usability (in terms of System Usability Scale (SUS)) were assessed in a single-session experiment with four subjects with chronic stroke that tested the HandyBot therapy platform (i.e., haptic device with a graphical/physical user interface and a set of therapy exercises) while simulating unsupervised use (i.e., the subject used the device independently while a therapist was only observing the session).Results:HandyBot showed hardware and control performances comparable to other less portable therapy devices for hand function (e.g., 94% accuracy in stiffness rendering, low apparent mass of 0.2 kg in transparency mode), making it a suitable platform for the implementation of sensorimotor therapy exercises. HandyBot showed good platform usability in terms of SUS (i.e., above 75 out of 100 for device and graphical user interfaces, above 65 out of 100 for the exercises) when tested in simulated unsupervised settings. These tests underlined minor design improvements that should be considered to allow using such a device in uncontrolled settings.Discussion:HandyBot is a novel robot for hand rehabilitation after stroke that revealed high-quality hardware and haptic performance. HandyBot was usable for stroke patients at first exposure for (simulated) unsupervised robot-assisted sensorimotor therapy of hand function. This therapy approach combined with this novel portable robotic device has the potential to help increase therapy dose and decrease therapy-associated costs (e.g., therapist time to therapy time ratio) in different environments.
Efficacy and safety of ciprofol for agitation and delirium in the ICU: A multicenter, single-blind, 3-arm parallel randomized controlled trial study protocol
Authors: Liu Guo Liang , Wu Guo Zhi , Ge Dong , Zhou Heng Jie , Cui Song , Gao Kai , Sun Wei Jia , Yu Dong Hai , Liu Si Bo , Liu Jin Jie 
Published: January 2023

BackgroundAgitation is very common in the intensive care unit (ICU). The causes include pain, delirium, underlying disease, withdrawal syndrome, and some drug treatments. The practical goal of ICU treatment is to find an appropriate sedation regimen to reduce pain, restlessness, and delirium. Previous trials have examined the use of dexmedetomidine, but no trials have evaluated the efficacy and safety of ciprofol, a new sedative drug.MethodsThis study was a multicenter, single-blind, 3-arm parallel randomized controlled trial. ICU patients aged ≥ 18 years with agitation and delirium who met the eligibility criteria were included. The main outcome was the proportion of patients who needed additional study medication or midazolam due to agitation within 4 h after the first intravenous injection of the study medication. The secondary outcomes included the pass rate as indicated by a Richmond Agitation-Sedation Scale (RASS) score &lt; +1, the effectiveness rate of improving delirium symptoms, the number of recurrences of agitation within 24 h, the incidence of rescue treatment, the dose and cost of analgesic and sedative drugs, the length and cost of ICU stay, and the 30-day survival period. The safety evaluation included the incidence of adverse events (hypotension, bradycardia, hypoxia, etc.) and the rate of endotracheal intubation. The subjects were randomly assigned to receive ciprofol, dexmedetomidine, or normal saline at a ratio of 1:1:1. The rates of additional drug administration within 4 h after the first injection of the study drug in the three groups were 40, 50, and 90%, respectively. A total sample size of 81 subjects was required to reach 90% power and an α of 0.05. Considering a 20% loss rate, 102 patients were enrolled and randomly assigned to the three groups in equal proportions.Ethics and communicationThis trial was approved by the Ethics Committee of Dalian Municipal Central Hospital. The communication plan includes presentations at scientific conferences, scientific publications, and presentations to the public through non-professional media.Clinical trial registrationwww.ClinicalTrials.gov, identifier ChiCTR220006 2799.
Novel models for early prediction and prevention of acute respiratory distress syndrome in patients following hepatectomy: A clinical translational study based on 1,032 patients
Authors: Wang Xiaoqiang , Zhang Hongyan , Zong Ruiqing , Yu Weifeng , Wu Feixiang , Li Yiran 
Published: January 2023

BackgroundAcute respiratory distress syndrome (ARDS) is a serious organ failure and postoperative complication. However, the incidence rate, early prediction and prevention of postoperative ARDS in patients undergoing hepatectomy remain unidentified.MethodsA total of 1,032 patients undergoing hepatectomy between 2019 and 2020, at the Eastern Hepatobiliary Surgery Hospital were included. Patients in 2019 and 2020 were used as the development and validation cohorts, respectively. The incidence rate of ARDS was assessed. A logistic regression model and a least absolute shrinkage and selection operator (LASSO) regression model were used for constructing ARDS prediction models.ResultsThe incidence of ARDS was 8.8% (43/490) in the development cohort and 5.7% (31/542) in the validation cohort. Operation time, postoperative aspartate aminotransferase (AST), and postoperative hemoglobin (Hb) were all critical predictors identified by the logistic regression model, with an area under the curve (AUC) of 0.804 in the development cohort and 0.752 in the validation cohort. Additionally, nine predictors were identified by the LASSO regression model, with an AUC of 0.848 in the development cohort and 0.786 in the validation cohort.ConclusionWe reported the incidence of ARDS in patients undergoing hepatectomy and developed two simple and practical prediction models for early predicting postoperative ARDS in patients undergoing hepatectomy. These tools may improve clinicians’ ability to early estimate the risk of postoperative ARDS and timely prevent its emergence.
Patterns and factors associated with pneumococcal vaccination in a prospective cohort of 1,697 patients with rheumatoid arthritis
Authors: Thomas Konstantinos , Lazarini Argyro , Kaltsonoudis Evripidis , Voulgari Paraskevi V. , Drosos Alexandros A. , Repa Argyro , Sali Ainour Molla Ismail , Sidiropoulos Prodromos , Tsatsani Panagiota , Gazi Sousana , Fragkiadaki Kalliopi , Tektonidou Maria G. , Sfikakis Petros P. , Katsimbri Pelagia , Boumpas Dimitrios , Argyriou Evangelia , Boki Kyriaki A. , Karagianni Konstantina , Katsiari Christina , Evangelatos Gerasimos , Iliopoulos Alexios , Grika Eleftheria P. , Vlachoyiannopoulos Panagiotis G. , Dimitroulas Theodoros , Garyfallos Alexandros , Melissaropoulos Konstantinos , Georgiou Panagiotis , Georganas Constantinos , Vounotrypidis Periklis , Ntelis Konstantinos , Areti Maria , Kitas George D. , Vassilopoulos Dimitrios 
Published: January 2023

IntroductionPatients with rheumatoid arthritis (RA) are at increased risk for serious infections. Pneumococcal vaccination is among the most important preventive measures, however, vaccine uptake is suboptimal. We explored the rate and factors associated with pneumococcal vaccination in a contemporary RA cohort.Materials and methodsMulti-center, prospective, RA cohort study in Greece. Patient and disease characteristics and influenza and pneumococcal vaccinations were documented at baseline and 3 years later.ResultsOne thousand six hundred and ninety-seven patients were included and 34.5% had already received at least one pneumococcal vaccine at baseline. Among 1,111 non-vaccinated patients, 40.1% received pneumococcal vaccination during follow-up, increasing the vaccine coverage to 60.8%. By multivariate analysis, positive predictors for pneumococcal vaccination included prescription of influenza vaccine (OR = 33.35, 95% CI: 18.58–59.85), history of cancer (OR = 2.35, 95% CI: 1.09–5.06), bDMARD use (OR = 1.85, 95% CI: 1.29–2.65), seropositivity (OR = 1.47, 95% CI: 1.05–2.05), and high disease activity (DAS28-ESR, OR = 1.33, 95% CI: 1.17–1.51). Male sex (OR = 0.65, 95% CI: 0.43–0.99) was a negative predictor for pneumococcal vaccination during follow-up.DiscussionDespite increasing rates of pneumococcal vaccine coverage, 40% of RA patients remain unvaccinated. Severe disease, bDMARD use, comorbidities, and more importantly flu vaccination were the most significant factors associated with pneumococcal vaccination, emphasizing the currently unmet need for cultivating a “vaccination culture” in RA patients.
Comparative effectiveness of acupuncture in sham-controlled trials for knee osteoarthritis: A systematic review and network meta-analysis
Authors: Lee Boram , Kim Tae-Hun , Birch Stephen , Alraek Terje , Lee Hye Won , Nielsen Arya , Wieland L. Susan , Lee Myeong Soo 
Published: January 2023

ObjectivesAlthough many trials have assessed the effect of acupuncture on knee osteoarthritis (KOA), its efficacy remains controversial. Sham acupuncture techniques are regarded as representative control interventions in acupuncture trials and sometimes incorporate the use of sham devices (base units) to support a non-penetrating needle. To achieve successful blinding, these trials also use acupuncture base units in the verum acupuncture group. Base units are not used in real-world clinical settings. We aimed to assess the effect sizes of verum and sham acupuncture for KOA in sham-controlled trials with or without base units.MethodsA total of 10 electronic databases for randomized controlled trials (RCTs) comparing the efficacy of verum manual acupuncture and sham acupuncture for the treatment of KOA were searched for articles published before April 12, 2022. The primary outcome was pain intensity, and the secondary outcomes included physical function. The first assessment after the end of treatment was chosen for analysis. Effect sizes are reported as standardized mean differences (SMDs) with 95% confidence intervals (95% CIs). The risk of bias was assessed using the Cochrane risk of bias tool, and publication bias was evaluated using a funnel plot and Egger’s test. The quality of evidence for estimates was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.ResultsFifteen RCTs were included. There was generally a low risk of bias except for the difficulty in blinding acupuncture therapists (performance bias). Compared to verum acupuncture in sham-controlled trials using base units, verum acupuncture in sham-controlled trials without base units was more effective for improving pain (SMD −0.56, 95% CI −1.09 to −0.03) and function (SMD −0.73, 95% CI −1.36 to −0.10) in KOA. The quality of evidence for network estimates was moderate to low due to the risk of bias and imprecision.ConclusionThese findings suggest that verum acupuncture in different types of sham-controlled trials has different effect sizes for KOA. Because base units are not used in clinical settings, the results of verum acupuncture in sham-controlled trials with base units need to be interpreted carefully.Systematic review registrationhttps://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/registryofsystematicreviewsmeta-analysesdetails/6269f962606c5e001fd8790c/, identifier reviewregistry1351.
Clinical characteristics and outcomes of critically ill coronavirus disease 2019 patients in Malaysia during the first wave: A multi-center observational study (COVIDICU-MY)
Authors: Ab Rahman Noor Iftitah , Yunos Nor’azim Mohd , Atan Rafidah , Mariapun Jeevitha , Ab Rahman Mohd Ali‘Imran , Ismail Abdul Jabbar , Deva Shanti Rudra 
Published: January 2023

BackgroundCoronavirus disease 2019 (COVID-19) emerged with a wide range of clinical presentations; Malaysia was not spared from its impact. This study describes the clinical characteristics of COVID-19 patients admitted to intensive care unit, their clinical course, management, and hospital outcomes.MethodsCOVIDICU-MY is a retrospective analysis of COVID-19 patients from 19 intensive care units (ICU) across Malaysia from 1 March 2020 to 31 May 2020. We collected epidemiological history, demographics, clinical comorbidities, laboratory investigations, respiratory and hemodynamic values, management, length of stay and survival status. We compared these variables between survival and non-survival groups.ResultsA total of 170 critically ill patients were included, with 77% above 50 years of age [median age 60, IQR (51–66)] and 75.3% male. Hypertension, diabetes mellitus, hyperlipidemia, chronic cardiac disease, and chronic kidney disease were most common among patients. A high Simplified Acute Physiology Score (SAPS) II score [median 45, IQR (34–49)] and Sequential Organ Failure Assessment (SOFA) score [median 8, IQR (6–11)] were associated with mortality. Patients were profoundly hypoxic with a median lowest PaO2/FiO2 ratio of 150 (IQR 99–220) at admission. 91 patients (53.5%) required intubation on their first day of admission, out of which 38 died (73.1% of the hospital non-survivors). Our sample had more patients with moderate Acute Respiratory Distress Syndrome (ARDS), 58 patients (43.9%), compared to severe ARDS, 33 patients (25%); with both ARDS classification groups contributing to 25 patients (54.4%) and 11 patients (23.9%) of the non-survival group, respectively. Cumulative fluid balance over 24 h was higher in the non-survival group with significant differences on Day 3 (1,953 vs. 622 ml, p &lt; 0.05) and Day 7 of ICU (3,485 vs. 830 ml, p &lt; 0.05). Patients with high serum creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and low lymphocyte count throughout the stay also had a higher risk of mortality. The hospital mortality rate was 30.6% in our sample.ConclusionWe report high mortality amongst critically ill patients in intensive care units in Malaysia, at 30.6%, during the March to May 2020 period. High admission SAPS II and SOFA, and severe hypoxemia and high cumulative fluid balance were associated with mortality. Higher creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and lymphopenia were observed in the non-survival group.
Clinical efficacy of acupuncture for pain relief from renal colic: A meta-analysis and trial sequence analysis
Authors: Chen Hsiao-Tien , Kuo Cheng-Feng , Hsu Chin-Chia , Lai Li-Chun , Cheng Ai-Chin , Sun Cheuk-Kwan , Hung Kuo-Chuan 
Published: January 2023

BackgroundThis meta-analysis aimed at investigating the efficacy of acupuncture for relieving renal colic and reducing the risk of analgesic-related complications.MethodsRandomized controlled trials (RCTs) comparing the efficacy of acupuncture (acupuncture group) with conventional interventions (control group) were screened from MEDLINE, EMBASE, Cochrane library databases, China Knowledge Network (CNKI), and Airiti Library till July 15, 2022. The primary outcome was the rate of effective pain relief (response rate), while secondary outcomes included the time of onset of pain relief, visual analog scale (VAS) at 30–60 min and risk of side effects.ResultsThirteen eligible studies involving 1,212 participants published between 1992 and 2021 were analyzed. Compared with the control group, patients receiving acupuncture had a higher overall response rate [risk ratio (RR) = 1.12, 95% CI: 1.05–1.19, p = 0.0002, I2 = 41%, 1,136 patients] (primary outcome) and a faster pain relief [MD = −10.74 min, 95% CI: −12.65 to −8.82, p &lt; 0.00001, I2 = 87%, 839 patients]. Patients receiving acupuncture had a lower pain score [MD = −0.65, 95% CI: −1.09 to −0.21, p = 0.21, I2 = 55%, 327 patients] and risk of side effects (RR = 0.11, 95% CI: 0.04–0.26, p &lt; 0.00001, I2 = 0, 314 patients) compared to those receiving conventional interventions. Results from trial sequence analysis revealed sufficient evidence supporting the beneficial effects of acupuncture on response rate, time to pain relief, and pain score at 30–60 min.ConclusionCompared with conventional analgesic-based interventions, acupuncture can more efficiently relieve renal colic with fewer adverse effects. The limited number and quality of included studies warrant more clinical RCTs to support our findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022346714.