bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTSB promotes sepsis-induced acute kidney injury through activating mitochondrial apoptosis pathway
Authors: Wang Yuting , Xi Wenjie , Zhang Xinyi , Bi Xinwen , Liu Boyang , Zheng Xiaoming , Chi Xinjin 
Published: January 2023

BackgroundAcute kidney injury is a common and severe complication of sepsis. Sepsis -induced acute kidney injury(S-AKI) is an independent risk factor for mortality among sepsis patients. However, the mechanisms of S-AKI are complex and poorly understand. Therefore, exploring the underlying mechanisms of S-AKI may lead to the development of therapeutic targets.MethodA model of S-AKI was established in male C57BL/6 mice using cecal ligation and puncture (CLP). The data-independent acquisition (DIA)-mass spectrometry-based proteomics was used to explore the protein expression changes and analyze the key proteomics profile in control and CLP group. The methodology was also used to identify the key proteins and pathways. S-AKI in vitro was established by treating the HK-2 cells with lipopolysaccharide (LPS). Subsequently, the effect and mechanism of Cathepsin B (CTSB) in inducing apoptosis in HK-2 cells were observed and verified.ResultsThe renal injury scores, serum creatinine, blood urea nitrogen, and kidney injury molecule 1 were higher in septic mice than in non-septic mice. The proteomic analysis identified a total of 449 differentially expressed proteins (DEPs). GO and KEGG analysis showed that DEPs were mostly enriched in lysosomal-related cell structures and pathways. CTSB and MAPK were identified as key proteins in S-AKI. Electron microscopy observed enlarged lysosomes, swelled and ruptured mitochondria, and cytoplasmic vacuolization in CLP group. TUNEL staining and CTSB activity test showed that the apoptosis and CTSB activity were higher in CLP group than in control group. In HK-2 cell injury model, the CTSB activity and mRNA expression were increased in LPS-treated cells. Acridine orange staining showed that LPS caused lysosomal membrane permeabilization (LMP). CA074 as an inhibitor of CTSB could effectively inhibit CTSB activity. CCK8 and Annexin V/PI staining results indicated that CA074 reversed LPS-induced apoptosis of HK-2 cells. The JC-1 and western blot results showed that LPS inhibited mitochondrial membrane potential and activated mitochondrial apoptosis pathway, which could be reversed by CA074.ConclusionsLMP and CTSB contribute to pathogenesis of S-AKI. LPS treatment induced HK-2 cell injury by activating mitochondrial apoptosis pathway. Inhibition of CTSB might be a new therapeutic strategy to alleviate sepsis-induced acute kidney injury.
Secondary myeloid neoplasms after CD19 CAR T therapy in patients with refractory/relapsed B-cell lymphoma: Case series and review of literature
Authors: Zhao Aiqi , Zhao Mingzhe , Qian Wenbin , Liang Aibin , Li Ping , Liu Hui 
Published: January 2023

BackgroundSeveral chimeric antigen receptor T cells (CAR T) targeting CD19 have induced profound and prolonged remission for refractory/relapsed (R/R) B-cell lymphoma. The risk of secondary malignancies, especially myeloid neoplasms, is of particular concern in the CAR T community, which still remains unclear.MethodsFour patients with R/R B-cell lymphoma after CD19 CAR T therapy diagnosed with secondary myeloid neoplasms (SMN) from 2 hospitals in eastern China were presented, including 3 with myelodysplastic syndrome (MDS) and 1 with acute myeloid leukemia (AML). Using single-cell RNA sequencing (scRNA-seq), we compared the cellular components of bone marrow (BM) samples obtained from one of these MDS patients and a health donor. We also provided a review of recently published literature concerning SMN risk of CAR T therapy.ResultsRelevant demographic, clinical, laboratory, therapeutic and outcome data were collected and presented by chart review. In our case series, the male-female ratio was 3.0 and the median age at MDS onset was 61.25 years old (range, 50-78). Median number of previous systemic therapies was 4.5 (range, 4-5), including autologous hematopoietic stem cell transplantation (auto-HSCT) in one patient. BM assessments prior to CAR T therapy confirmed normal hematopoiesis without myeloid neoplasms. Moreover, for 3 patients with SMN in our series, cytogenetic analysis predicted a relatively adverse outcome. In our experience and in the literature, treatment choices for the patients with SMN included allogeneic hematopoietic stem cell transplantation (allo-HSCT), hypomethylating agent (HMA), period filgrastim, transfusions and other supportive care. Finally, treatment responses of lymphoma, together with SMN, directly correlated with the overall survival of this community. Of note, it appeared that pathogenesis of MDS wasn’t associated with the CAR T toxicities, since all 4 patients experienced a pretty mild CRS of grade 1-2. Additionally, scRNA-seq analysis described the transcriptional alteration of CD34+ cells, identified 13 T/NK clusters, and also indicated increased cytotoxic T cells in MDS BM.ConclusionOur study illustrated the onset and progression of SMN after CD19 CAR T therapy in patients with R/R B-cell lymphoma, which provides useful information of this uncommon later event.
Diagnostic and prognostic value of STAP1 and AHNAK methylation in peripheral blood immune cells for HBV-related hepatopathy
Authors: Sun Libo , Lu Junfeng , Li Kang , Zhang Haitao , Zhao Xiaofei , Li Guangming , Li Ning 
Published: January 2023

IntroductionAlthough we had identified that the methylation of AHNAK was a good diagnostic marker for hepatopathy, here we speculate that there was also another marker, STAP1, whose methylation also involved in the detection of hepatopathy.MethodsWe investigated the methylation levels of the AHNAK and STAP1 in peripheral blood mononuclear cells of chronic hepatitis B (CHB) patients, compensatory liver cirrhosis (CLC) patients, decompensated liver cirrhosis (DCLC) patients, hepatocellular carcinoma (HCC) patients and healthy controls by methylation-specific PCR. We also evaluated the differences and changes of methylation and expression of AHNAK and STAP1 at different stages of liver disease using the TCGA and GEO public datasets.ResultsMethylation level of STAP1 in PBMC was positively correlated with the course of liver cancer. The combination of AHNAK and STAP1 methylation was able to predict differrent HBV related hepatopathy. The GEO datasets also supported that the methylation of AHNAK and STAP1 was associated with different types of hepatopathy. The TCGA data showed that the levels of methylation and expression of STAP1 were down-regulated in HCC. We also found the STAP1 methylation level in PBMC and T cells was associated with age, gender, alcohol drinking and anti-HBe. Hyper-methylation of STAP1 was correlated with the poor prognosis of patients but its expression had no association.ConclusionWe concluded that combination of AHNAK and STAP1 methylation in peripheral blood immune cells can be used as a diagnostic marker for HBV related hepatopathy and STAP1 methylation may be a potential prognostic marker for HBV related HCC. Our clinical study registration number was ChiCTR2000039860.
Pre-clinical efficacy evaluation of human umbilical cord mesenchymal stem cells for ischemic stroke
Authors: Shen Danpeng , Wang Hongwei , Zhu Hongyan , Jiang Cuibao , Xie Fan , Zhang Hongpeng , Lv Qian , Liu Qi , Wang Zhiqiang , Qi Nianmin , Wang Hao 
Published: January 2023

ObjectiveThis study explored the underlying therapeutic mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) for ischemic stroke (IS), and determined the optimal administration time windows and dose-effect relationship.MethodsThe levels of SDF-1α, IL-10, IL-6, TNF-α, BDNF, IL-1β, and VEGF-A factors in serum and brain tissue lysate were measured by ELISA. The pathological status of brain tissues was evaluated by Hematoxylin-Eosin (HE) staining, and apoptosis of nerve cells was detected by tunel. The protein expression of CXCR-4, NeuN, and Nestin in the brain tissues was assessed through immunofluorescence. The balance beam, forelimb muscle strength, and limb placement were tested on MCAO rats at different time points and doses. The infarct area of the rat brain tissues was measured at the end of the experiment.ResultsThe hUCMSC treatment during the acute phase of MCAO significantly reduced the secretion of IL-6, TNF-α, IL-1β but increased IL-10 in serum, and the levels of SDF-α and BDNF in serum and brain tissues lysate were also increased. The pathological results showed that there were more neurons in the treatment group compared to the model group. Immunofluorescence assays showed that the expression of CXCR4、Nestin、NeuN was relatively higher than that in the model group. The d4 and d7 treatment significantly improves the motor function, promotes the recovery of forelimb muscle strength, increases the forelimb placement rate and reduces the scope of cerebral infarction, but the d14 treatment group has less therapeutic effect compared to the d4 and d7 treatment. The 2×107/kg treatment showed the best therapeutic effect, followed by the 1×107/kg treatment, and the worst is 0.5×107/kg treatment from the test of balance beam, forelimb muscle strength, limb placement and the infarct area of the rat brain tissues.ConclusionThe hUCMSCs can inhibit the infiltration of inflammatory cells in the brain tissue, and promote the repair of brain tissue structure and function. Early intervention by injecting high-dose of hUCMSCs can significantly improve the recovery of neurological/motor function and reduce the size of cerebral infarction in rats.
Effectiveness of a brief motivational intervention in the management of risky alcohol use in primary care: ALCO-AP20 study protocol
Authors: Romero-Rodríguez Esperanza , Pérula-Jiménez Celia , Fernández-López Sara , Cabello-Gracia Gregorio , Fernández-García José Ángel , Pérula-de Torres Luis Ángel , Roldán-Villalobos Ana , Leiva-Cepas Fernando , Fernández-Márquez Rodrigo , Parras-Rejano Juan Manuel ,   ALCO-AP-20 Collaborative Study Group
Published: January 2023

BackgroundMotivational interviewing (MI) could be a method for minimizing alcohol-related harm. The study aims to assess the effectiveness of a brief intervention, based on a MI, in patients with risky alcohol use attended in Primary Care (PC).Materials and methodsA cluster-randomized, two-arm parallel, multicenter, open-label, controlled clinical trial. Fifty PC healthcare professionals from the province of Córdoba (Spain) will be randomized to one of the two study groups: (1) Experimental Group (EG): MI-based approach; (2) Control Group (CG): Usual care based on health advice. EG intervention: Professionals will receive a training program focused on MI, consisting of a training workshop and the use of pre- and post-workshop questionnaires to measure knowledge and skills acquired, as well as the degree of empathy, with a videotape of the health professionals with standardized patients, before and after the workshop, and subsequent training feedback. CG intervention: Workshop on the management of risky alcohol use based on health advice; participants will also complete the pre-and post-workshop questionnaires and be videotaped. Study population: Patients ≥ 14 years old with risky alcohol consumption (28 Standard Drink Units-SDU-/week in men and 17 SDU/week in women) or excessive alcohol use (≥ 6 SDU in men or ≥ 4 SDU in women, in less than 2 h). It would be necessary to include 110 subjects/group to find a difference of 20% between the percentage of patients in abstinence between EG (37%) and CG (20%), alpha error of 5%, and statistical power of 80%. Assuming a loss rate of 5% and the cluster design effect, the number of subjects to be recruited is estimated at 197/group. The follow-up period will be 12 months. The primary outcome variables will be the self-reported alcohol use level and the Alcohol Use Disorders Identification Test (AUDIT) questionnaire score.DiscussionThe study aims to demonstrate the effectiveness of the motivational approach in the comprehensive treatment of the patient with risky alcohol use, improving the empathy of the healthcare professionals and strengthening the healthcare professional-patient relationship to achieve the behavioral change of the patients with this problem in primary care consultations.Clinical trial registrationClinicalTrials.gov.
Tool design for low-frequency vibration cutting on surface property
Authors: Nakamura Shogo , Nakanishi Kenichi , Ohara Kenji , Nakamura Yoshikatsu , Ren Zongwei , Kizaki Toru , Sugita Naohiko 
Published: January 2023

Low-frequency vibration cutting is a machining technology in which chips are broken by applying periodic vibrations along a specific axis. Periodic vibration deteriorates the surface roughness and roundness of the workpiece when compared to without vibration cutting. In this study, the properties of a machined surface under low-frequency vibration were simulated. Based on the simulation results, a tool was designed to reduce the effects of periodic vibration on the surface properties. Actual machining experiments were conducted using the proposed tool to clarify the relationship between tool shape, surface roughness, and roundness under low-frequency vibration. Using the proposed tool on low-frequency vibration cutting, the surface roughness was reduced (from 5.74 µm to .94 µm in Ra and 23.09 µm–6.66 µm in Rz), average roundness improved (from 4.73 µm to 2.95 µm), and maximum roundness decreased (from 15.34 µm to 3.61 µm) compared with those of the conventional tool.
On-device synaptic memory consolidation using Fowler-Nordheim quantum-tunneling
Authors: Rahman Mustafizur , Bose Subhankar , Chakrabartty Shantanu 
Published: January 2023

IntroductionFor artificial synapses whose strengths are assumed to be bounded and can only be updated with finite precision, achieving optimal memory consolidation using primitives from classical physics leads to synaptic models that are too complex to be scaled in-silico. Here we report that a relatively simple differential device that operates using the physics of Fowler-Nordheim (FN) quantum-mechanical tunneling can achieve tunable memory consolidation characteristics with different plasticity-stability trade-offs.MethodsA prototype FN-synapse array was fabricated in a standard silicon process and was used to verify the optimal memory consolidation characteristics and used for estimating the parameters of an FN-synapse analytical model. The analytical model was then used for large-scale memory consolidation and continual learning experiments.ResultsWe show that compared to other physical implementations of synapses for memory consolidation, the operation of the FN-synapse is near-optimal in terms of the synaptic lifetime and the consolidation properties. We also demonstrate that a network comprising FN-synapses outperforms a comparable elastic weight consolidation (EWC) network for some benchmark continual learning tasks.DiscussionsWith an energy footprint of femtojoules per synaptic update, we believe that the proposed FN-synapse provides an ultra-energy-efficient approach for implementing both synaptic memory consolidation and continual learning on a physical device.
Evaluating the local expression pattern of IGF-1R in tumor tissues and the circulating levels of IGF-1, IGFBP-1, and IGFBP-3 in the blood of patients with different primary bone tumors
Authors: Vaezi Mohammad Amin , Eghtedari Amir Reza , Safizadeh Banafsheh , Babaheidarian Pegah , Salimi Vahid , Adjaminezhad-Fard Fatemeh , Yarahmadi Sahar , Mirzaei Alireza , Rahbar Mahtab , Tavakoli-Yaraki Masoumeh 
Published: January 2023

IntroductionThe present study tried to provide insights into the expression pattern and diagnostic significance of the IGF-1 axis main mediators in three main primary bone tumor types with different degrees of severity.MethodsThe real-time qRT-PCR (to analyze IGF-1R gene expression), the immunohistochemistry (to measure IGF-1R protein), and the ELISA assay (to assess the circulating level of IGF-1, IGFBP-1, and IGFBP-3) were applied to confirm this hypothesis. A total number of 180 bone tissues (90 tumors and 90 noncancerous adjacent tissues) and 120 blood samples drained from 90 patients with bone tumors and 30 healthy controls were enrolled in the study. The association of insulin-like growth factor (IGF)-1 axis expression pattern with the patient’s clinical pathological characteristics and tumor aggressive features, the diagnostic and predictive values were assessed for all tumor groups.ResultsA significantly elevated level of IGF-1R gene and protein was detected in bone tumors compared to the noncancerous bone tissues that were prominent in osteosarcoma and Ewing sarcoma compared to the GCT group. The positive association of the IGF-1R gene and protein level with tumor grade, metastasis, and recurrence was detected in the osteosarcoma and Ewing sarcoma groups. The circulating level of IGF-1, IGFPB-1, and IGFBP-3 were increased in osteosarcoma and Ewing sarcoma and GCT groups that were correlated significantly to the tumor severity. The ability of the IGF-1 axis to discriminate between bone tumors also malignant and benign tumors was considerable.DiscussionIn summary, our data suggested that IGF-1R, IGF-1, IGFBP-1, and IGFBP-3 levels are associated with bone tumor malignancy, metastasis, and recurrence that might serve as biomarkers for osteosarcoma and Ewing sarcoma recurrence.
Hemorrhagic schwannoma of the trochlear nerve: Case report and a review of the literature
Authors: Lei Jin , Li Yu , Wan Xueyan , Wang Junwen , You Chao , Zhao Kai , Niu Hongquan 
Published: January 2023

BackgroundSchwannomas of the trochlear nerve with the absence of systemic neurofibromatosis are considerably uncommon, especially complicated by intra-tumoral hemorrhage. Due to the lack of typical clinical manifestations and imaging findings, a definite diagnosis of trochlear schwannomas before surgery is particularly difficult.Case presentationWe report the case of a 64-year-old female patient who presented with a unilaterally intermittent headache of 2-month duration and without a remarkable neurological deficit at admission. Imaging studies revealed a well-demarcated cystic-solid lesion with mixed signals beside the brainstem and suprasellar cisterna. The patient underwent a surgical operation with total resection of the tumor by a subtemporal surgical approach. The tumor was intraoperatively found to originate from the trochlear nerve and was pathologically confirmed as a hemorrhagic schwannoma with cystic degeneration.ConclusionsWe describe this case in detail and conduct a concomitant survey of the literature, summarizing the clinical presentations, radiological features, surgical treatment, and the possible mechanisms of hemorrhage in relevance to trochlear nerve schwannoma.
Survival and predictors of mortality among preterm neonates in Northern Ethiopia: A retrospective follow-up study
Authors: Girma Bekahegn , Berhe Hailemariam , Mekonnen Furtuna , Nigussie Jemberu 
Published: January 2023

BackgroundIn the year 2015, more than one-third of neonatal deaths caused by prematurity was recorded worldwide. Despite different kinds of efforts taken at the global and local levels to reduce neonatal mortality, it remains high with low reduction rates, especially in low- and middle-income countries like sub-Saharan Africa and South Asia. Therefore, this study aims to assess the survival status and predictors of mortality among preterm neonates.MethodsA retrospective follow-up study was conducted on randomly selected 561 preterm neonates. Data were extracted from patient records using a pretested checklist. Data entry and analysis were done using Epi-Data Version 4.4.2.1 and Stata version 14, respectively. The Cox proportional hazard regression model was fitted to identify the predictors of mortality. A hazard ratio with a 95% confidence interval (CI) was estimated and p-values &lt; 0.05 were considered statistically significant.ResultThe proportion of preterm neonatal deaths was 32.1% (180) with an incidence of 36.6 (95% CI: 31.6–42.4) per 1,000 person days. The mean survival time was 18.7 (95% CI: 17.7–19.9) days. Significant predictors for time to death of preterm neonates were respiratory distress syndrome [adjusted hazard ratio (AHR): 2.04; 95% CI: 1.48–2.82], perinatal asphyxia (AHR: 2.13; 95% CI: 1.32–3.47), kangaroo mother care (AHR: 0.14; 95% CI: 0.08–0.24), and gestational age (AHR: 0.85; 95% CI: 0.80–0.90).ConclusionPreterm neonatal death is still a major public health concern. Respiratory distress syndrome, perinatal asphyxia, kangaroo mother care, and gestational age were independent significant predictors for time to death, as found in this study. Hence, priority must be given to neonates with the above illnesses and strengthen the management and care of preterm neonates.
Adverse drug reactions in an ageing PopulaTion (ADAPT) study: Prevalence and risk factors associated with adverse drug reaction-related hospital admissions in older patients
Authors: Cahir Caitriona , Curran Carmel , Walsh Caroline , Hickey Anne , Brannigan Ross , Kirke Ciara , Williams David J. , Bennett Kathleen 
Published: January 2023

Background: Older people experience greater morbidity with a corresponding increase in medication use resulting in a potentially higher risk of adverse drug reactions (ADRs).Objectives: The aim of this study was to; 1) determine the prevalence and characteristics of ADR-related hospital admissions among older patients (≥65 years) in Ireland; and 2) identify the risk factors associated with ADR-related hospital admissions.Methods: A cross-sectional study of ADR prevalence in patients aged ≥65 years admitted acutely to hospital in Ireland over a 8 month period (November 2016- June 2017). A multifaceted review of each hospital admission was undertaken to assess the likelihood of an ADR being a reason for admission (cause of admission or contributing to admission) in the context of the patient’s medication, clinical conditions, comorbidities and investigations. A number of decision aids were applied by two independent reviewers to assess ADR causality, avoidability and severity. A random sample of patients, determined not to have a suspected ADR on screening, were assigned to a non-ADR control group. Multivariable logistic regression was used to assess the association between potential risk factors for ADR-related admissions compared with non-ADR-related admissions.Results: In total, 3,760 hospital admission episodes (in 3,091 patients) were screened and 377 admissions were considered ADR-related (10.0%, 95% CI 9.1%, 11.0%). 219 (58.1%) ADR-related admissions were caused by an ADR, while ADRs contributed to 158 (41.9%) admissions. 268 (71.1%) of all ADR-related admissions were deemed definitely or possibly preventable/avoidable. 350 (92.8%) ADRs were classified as being of moderate severity, with 27 (7.2%) classified as severe. Antithrombotic agents, mainly aspirin and warfarin, were the drugs most frequently associated with ADR-related admissions (gastrointestinal and vascular haemorrhagic disorders). In multivariable analysis, immobility, frailty, having delirium or ulcer disease and taking anticoagulant and antiplatelet medication on admission were significantly associated with an ADR-related hospital admission.Conclusion: One in ten hospital admissions, among those aged 65 + years, were considered ADR-related, with approximately 70% potentially avoidable. Reliable and validated ADR detection and prediction tools are needed to develop prevention strategies.