bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADAM10‐ and γ‐secretase‐dependent cleavage of the transmembrane protein PTPRT attenuates neurodegeneration in the mouse model of Alzheimer's disease
Authors: Liu Siling , Zhang Zhongyu , Li Lianwei , Yao Li , Ma Zhanshan , Li Jiali 
Published: December 2022

AbstractPTPRT (receptor‐type tyrosine‐protein phosphatase T), a brain‐specific type 1 transmembrane protein, plays an important role in neurodevelopment and synapse formation. However, whether abnormal PTPRT signaling is associated with Alzheimer's disease (AD) remains elusive. Here, we report that Ptprt mRNA expression is found to be downregulated in the brains of both human and mouse models of AD. We further identified that the PTPRT intracellular domain (PICD), which is released by ADAM10‐ and γ‐secretase‐dependent cleavage of PTPRT, efficiently translocates to the nucleus via a conserved nuclear localization signal (NLS). We show that inhibition of nuclear translocation of PICD leads to an accumulation of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a substrate of PTPRT‐eventually resulting in neuronal cell death. Consistently, RNA sequencing reveals that overexpression of PICD leads to changes in the expression of genes that are functionally associated with synapse formation, cell adhesion, and protein dephosphorylation. Moreover, overexpression of PICD not only decreases the level of phospho‐STAT3Y705 and amyloid β production in the hippocampus of APP/PS1 mice but also partially improves synaptic function and behavioral deficits in this mouse model of AD. These findings suggest that a novel role of the ADAM 10‐ and γ‐secretase‐dependent cleavage of PTPRT may alleviate the AD‐like neurodegenerative processes.
Vitamin D–vitamin D receptor alleviates oxidative stress in ischemic acute kidney injury via upregulating glutathione peroxidase 3
Authors: Wu Xueqin , Tang Shiqi , Dai Qing , Yi Bin , Yang Shikun , Sun Jian , Zhong Yong , Lin Wei , Liu Jun , Liu Yan , Wang Jianwen , Liu Jishi , Liao Qin , Zhang Wei , Zhang Hao 
Published: December 2022

AbstractVitamin D receptor was previously reported to be protective in acute kidney injury (AKI) with the mechanism unclear, while the role of renal localized glutathione peroxidase 3 (GPX3) was not illustrated. The present study aims to investigate the role of GPX3 as well as its correlation with vitamin D–vitamin D receptor (VD–VDR) in ischemia–reperfusion (I/R)‐induced renal oxidative stress injury. We showed that the expression of GPX3 and VDR were consistently decreased in renal tissues of I/R‐related AKI patients and mice models. VDR agonist paricalcitol could reverse GPX3 expression and inhibit oxidative stress in I/R mice or hypoxia‐reoxygenation (H/R) insulted HK‐2 cells. VDR deficiency resulted in aggregated oxidative stress and severer renal injury accompanied by further decreased renal GPX3, while tubular‐specific VDR overexpression remarkably reduced I/R‐induced renal injury with recovered GPX3 in mice. Neither serum selenium nor selenoprotein P was affected by paricalcitol administration nor Vdr modification in vivo. In addition, inhibiting GPX3 abrogated the protective effects of VD–VDR in HK‐2 cells, while GPX3 overexpression remarkably attenuated H/R‐induced oxidative stress and apoptosis. Mechanistic probing revealed the GPX3 as a VDR transcriptional target. Our present work revealed that loss of renal GPX3 may be a hallmark that promotes renal oxidative stress injury and VD–VDR could protect against I/R‐induced renal injury via inhibition of oxidative stress partly by trans‐regulating GPX3. In addition, maintenance of renal GPX3 could be a therapeutic strategy for ischemic AKI.
Characteristic analysis of skin keratinocytes in patients with type 2 diabetes based on the single-cell levels
Authors: Liao Bingye , Ouyang Qiuyi , Song Hongqin , Wang Ziqi , Ou Jinhua , Huang Jinxin , Liu Liang 
Published: December 2022

Abstract

Background:
Keratinocytes play an important role in wound healing; however, less is known about skin keratinocytes in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aimed to search for the transcriptional characteristics of keratinocytes at the single-cell level from T2DM patients, and to provide experimental data for identifying the pathological mechanisms of keratinocytes under pathological conditions.

Methods:
We performed single-cell RNA sequencing on the skin tissue from two T2DM patients and one patient without diabetes-induced trauma using the BD Rhapsody™ Single-Cell Analysis System. With the help of bioinformatics R-based single-cell analysis software, we analyzed the results of single-cell sequencing to identify the single-cell subsets and transcriptional characteristics of keratinocytes at the single-cell level, including Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyzes.

Results:
In this study, we found specific highly expressed signature keratinocyte-related genes. We analyzed the transcriptome of keratinocytes from experimental and control groups and screened a total of 356 differential genes, which were subject to bioinformatics analysis. Enriched pathways included oxidative phosphorylation, antigen processing and presentation, prion and Huntingtons’ diseases, bacterial invasion of epithelial cells, thermogenesis, vasopressin-regulated water reabsorption, and protein processing in the endoplasmic reticulum.

Conclusions:
This study revealed the characteristics of keratinocytes at the single-cell level and screened a group of differentially expressed genes related to T2DM-associated keratinocytes, oxidative phosphorylation, cytokine receptor interactions, prion diseases, and other signaling pathways.
Inhibition of MYC suppresses programmed cell death ligand-1 expression and enhances immunotherapy in triple-negative breast cancer
Authors: Li Xintong , Tang Lin , Chen Qin , Cheng Xumin , Liu Yiqiu , Wang Cenzhu , Zhu Chengjun , Xu Kun , Gao Fangyan , Huang Jinyi , Wang Runtian , Guan Xiaoxiang 
Published: December 2022

Abstract

Background:
Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy.

Methods:
Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification.

Results:
A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1.

Conclusions:
The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.
Intrapartum and early postpartum glycemic profiles in women with gestational diabetes mellitus: an observational study
Authors: Ding Yu , Zheng Xueying , Liu Yujie , Wei Tian , Yue Tong , Wang Siqi , Chen Suyu , Weng Jianping , Luo Sihui 
Published: December 2022

Abstract

Background:
Data on the glycemic profile of pregnant women with gestational diabetes mellitus (GDM) during the perinatal period are sparse. This study described the intrapartum and early postpartum glucose profiles among pregnant women with GDM, and analyzed factors potentially affecting glycemic parameters during the period.

Methods:
This was a prospective observational study conducted from March 2020 to November 2021. Pregnant women with GDM receiving lifestyle interventions alone during pregnancy and matched women with non-diabetic pregnancies (NDPs) were enrolled from among patients admitted to the obstetrics department for childbirth. Glucose monitoring was performed via a flash glucose monitoring (FGM) system on admission, and glucose readings during labor and early postpartum were analyzed. The clinical characteristics and FGM-based parameters of participants in the two groups were compared.

Results:
A total of 124 participants (mean age: 29.5 ± 3.5 years, 92 [74.2%] primipara) were included in the final analysis. A total of 17,571 glucose readings were retrieved. There were no significant differences in clinical characteristics between the GDM (n = 60) and NDP (n = 64) groups. The average glucose level was 92.2 mg/dL, and the level was higher in the GDM group (95.5 ± 12.1 mg/dL vs. 89.1 ± 13.4 mg/dL, P = 0.008) during the intrapartum and early postpartum periods. The data were split into the intrapartum period (from the start of labor to delivery of the placenta) and the early postpartum period (within 24 h after placental delivery) for analysis. During intrapartum, women with GDM exhibited glycemic profiles and fluctuations similar to those in the NDP group. However, women with GDM had higher postpartum glucose levels (97.7 ± 13.4 mg/dL vs. 90.8 ± 15.3 mg/dL, P = 0.009), a longer time spent >140 mg/dL (8.7 ± 9.3% vs. 5.9 ± 10.3%, P = 0.011), and greater glycemic fluctuations than those with NDP. Postpartum hyperglycemia in GDM might be associated with high parity and postprandial glucose abnormalities in GDM screening tests.

Conclusion:
Compared to those with normoglycemia, pregnant women with GDM receiving lifestyle interventions alone had similar intrapartum glucose profiles but higher early postpartum glucose levels and greater glucose variability, providing evidence for modification of the current perinatal glucose monitoring strategy for GDM.

Trial Registration:
ChiCTR.org.cn, ChiCTR2000030972
Physical Therapy Management of Postacute Sequelae of COVID-19 in Outpatient Settings: A Scoping Review
Authors: Scott Kylie , Ankrum Summer , Lindsey Elizabeth , Lopez Oskar , Beitner Jessica , Reck Cyndi , Kargela Mallory 
Published: December 2022

Purpose:
The devasting effects of the coronavirus disease 2019 (COVID-19) pandemic have warranted the rapid development of evidence surrounding the physical therapy (PT) management of the disease within inpatient settings. However, the medical community is still working to define the long-term effects of COVID-19, referred to as Postacute Sequalae of SARS-CoV-2 (PASC), and ways for physical therapists to manage them in outpatient settings. The primary objective of this review was to summarize the available evidence related to the PT management of PASC in outpatient settings.

Methods:
A systematic search in PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane CENTRAL, Academic Search Complete, and MedLine yielded systematic and scoping reviews and randomized controlled trials, among others. Data extraction was performed independently by 2 reviewers with 8 studies included.

Results:
Only 3 publications were specific to the outpatient setting area, with 5 more studies that focused on outpatient practice as part of a multisetting study, or the postacute setting. Although the limited number and quality of publications creates challenges applying the interventions provided across a population, each were specific to PASC.

Conclusions:
This review supports the need for further research focused on the PT management of patients who are experiencing PASC in outpatient settings.
Catatonia and Delirium
Authors: Appiani Francisco José , Duarte Juan Manuel , Sauré Marcelo , Rodríguez Cairoli Federico , Momeño Victoria , Yaryour Claudio , Sarotto Luis 
Published: December 2022

Abstract

Background
Catatonia is a cluster of motor features present in multiple psychiatric and clinical diseases. It may be confused with delirium because both entities are classified according to the type and degree of psychomotor activity. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for catatonia secondary to medical conditions exclude comorbid catatonia and delirium; besides, there have been increasing reports about a comorbid presentation. This study aimed to describe the prevalence of comorbid catatonia and delirium, the therapeutic response to lorazepam, and the clinical characteristics of patients with an earlier diagnosis of delirium.

Methods
A total of 120 consecutive patients at a university hospital with an earlier diagnosis of delirium were evaluated using the Delirium Scale (confusion assessment method for the intensive care unit) and the Bush-Francis Catatonia Rating Scale for catatonia. In cases of a positive diagnosis of catatonia or catatonia/delirium, a therapeutic trial with intramuscular lorazepam was performed.

Findings
Thirty-one patients (26%) were positive for both catatonia and delirium, and 8 patients (7%) had catatonia. Sixty-six patients (55%) were positive only for delirium, and 5 patients (4%) were negative for delirium and catatonia. Lorazepam tests were applied on 22 patients. One in 9 patients with catatonia/delirium responded positively to lorazepam. Patients with catatonia had a 60% positive response rate.

Conclusions
This is the first study on lorazepam use in catatonia-delirium patients; however, further studies are needed to determine the safety and efficacy of lorazepam in these patients. Catatonia and catatonia/delirium are underdiagnosed in inpatient wards and should be routinely assessed in patients with an altered mental status.
Early Response to Antidepressant Medications in Adults With Major Depressive Disorder
Authors: Belanger Heather G. , Lee Christine , Poliacoff Zachary , Gupta Carina T. , Winsberg Mirène 
Published: December 2022

Abstract

Purpose/Background
Early response after 2 to 4 weeks of antidepressant therapy has been shown to predict remission by 8 to 12 weeks. Most of the work to date on early response has been done using data from randomized controlled trials.

Methods/Procedures
This naturalistic study uses archival data from a national tele-mental health company. The positive and negative predictive values as well as sensitivity and specificity were calculated using different drops in baseline Patient Health Questionnaire 9 scores at various periods. Demographic and clinical characteristics were compared between early responders versus those lacking early response. Binary logistic regression analyses determined if early response was predictive of remission, response, and greater than minimal improvement at 14 weeks. For those who do not show early improvement, treatments were investigated using binary logistic regression to see if changes predicted later outcomes.

Findings/Results
Positive predictive values for all endpoints improved with the strength of early response but did not improve much with the time allowed for that response to occur. In contrast, negative predictive values increased substantially with time. Using a definition of 30% drop in Patient Health Questionnaire 9 score at week 4, 56.5% of patients were early responders. Early responders were ~3.2 times more likely to achieve remission than those lacking early response. Of nonresponders by week 4, those prescribed atypical antipsychotics (+SSRI) had significantly reduced odds of response at week 14, whereas those prescribed a norepinephrine and dopamine reuptake inhibitor had increased odds.

Implications/Conclusions
Early response may be associated with better outcomes at 14 weeks. In those with lack of response by week 4, patients prescribed a norepinephrine and dopamine reuptake inhibitor may achieve superior outcomes.
Chinese Immigrants’ Health Beliefs and Practices of Traditional Chinese Medicine in British Columbia of Canada
Authors: Wu Tina 
Published: December 2022

Objective:
This study is to address the health beliefs and health behavior of Chinese immigrants residing in the Greater Vancouver area of British Columbia (BC) Province in Canada. This article discussed Chinese immigrants’ traditional Chinese medicine (TCM) use, health beliefs, and health behaviors.

Methods:
Information used in this study is based on data collected in the Chinese-speaking community in the Greater Vancouver area of BC in 2020–2022. Quantitative and qualitative methods were applied to this study. The first stage recruited 314 participants for the quantitative study to cross-validate an instrument tool, followed by the 2nd stage of 20 stratified random sampling out of the 314 participants for TCM-related in-depth qualitative interviews. This study focuses on the second stage of TCM qualitative interviews.

Results:
Results indicated that TCM health beliefs have cultural and spiritual meanings tied to the Chinese-speaking participants. There are barriers for the Chinese-speaking population to access the existing healthcare services due to their TCM health beliefs and other health needs, for example, family doctors, integrated medicine for better health outcomes, and mental health services especially during the coronavirus disease 2019 (COVID-19) pandemic.

Conclusion:
Integrating TCM health beliefs and behaviors of Chinese-speaking immigrants into existing Canadian mainstream health services are strongly recommended.
Effect of resistance exercise on stress, lower extremity edema, and body composition in intensive care unit nurses
Authors: Kim Ki Yong , Kim Won Jong 
Published: December 2022

Background:
This study investigated the effects of resistance exercises using elastic bands on stress, lower extremity edema, and body composition in intensive care unit nurses.

Methods:
Twenty-three and 21 participants were classified into the experimental and control groups, respectively. Only the experimental group was subjected to a resistance exercise program using elastic bands for 8 weeks. Variables were measured before the experimental treatment and at the 4th and 8th weeks post-treatment. Stress was assessed using a numeric rating scale and stress index. Lower extremity edema was determined using a tape measure. Body composition around the calf and tibia muscle was measured using a body composition analyzer. The homogeneity of participants’ general characteristics and the dependent variable was ensured.

Results:
Following experimental treatment, subjective (F = 11.674, P < .001) and objective stresses (F = 6.965, P < .001) decreased. No difference was detected in calf and ankle circumference between the groups, while differences in muscle thickness (left, F = 31.708, P < .001; right, F = 18.630, P < .001) and fat thickness (left, F = 19.984, P < .001; right, F = 24.640, P < .001) were observed. Muscle thickness increased, and fat thickness decreased in the body composition around the lower extremities.

Conclusion:
Resistance exercises using the TheraBand can be an intervention to decrease stress and improve lower extremity body composition in intensive care unit nurses.
The efficacy of tolvaptan for heart failure in chronic kidney disease: A protocol for systematic review and meta-analysis
Authors: Zhu Zhi-Yong , Cui Meng , Zhao Jie , Wang Hong-Yun 
Published: December 2022

Background:
Approximately half of people with heart failure have chronic kidney disease (CKD). Tolvaptan is reported to be effective in treating heart failure. However, the safety and efficacy of its use in patients with CKD is uncertain. In this study, we conducted a protocol for systematic review and meta-analysis to investigate the efficacy and safety of tolvaptan on patients with heart failure and CKD.

Methods:
This study protocol has been registered in the PROSPERO and the registration number is CRD42022368148. The consent of this protocol report is based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement guidelines. We will include randomized controlled trials related to tolvaptan in patients with heart failure and CKD. Two research members will electronically and independently search 4 English databases (EMBASE, PubMed, National Guideline Clearinghouse, and Cochrane Central Register of Controlled Trials) and 4 Chinese databases (Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Wanfang Database, and VIP Database) from their inception to November 2022. The risk of bias in each included study will be assessed utilizing the Cochrane Collaboration’s risk of bias tool. All statistical analyses will be conducted using the software program Review Manager version 5.3.

Results:
The results of this systematic review will be published in a peer-reviewed journal.

Conclusion:
This review can provide convincing evidence to help clinicians make decisions when dealing with heart failure and CKD.
Comparison of multiple acupoints combination in the treatment of post-stroke cognitive impairment: A network meta-analysis
Authors: Li Ruo-Yang , Chen Ke-Yu , Zheng Hong-Yi , Tian Yang , Yu Qian , Xu Li 
Published: December 2022

Background:
To evaluate the efficacy of multiple acupoint combinations for the treatment of post-stroke cognitive impairment (PSCI) using a network meta-analysis method.

Methods:
Searches for clinical randomized controlled trials (RCTs) of various types of acupuncture treatments for post-stroke cognitive dysfunction were conducted, data were extracted from studies selected according to the inclusion criteria, and the RCTs included in the analysis were assessed separately for risk of literature bias. Network meta-analysis was performed using Stata 14.0.

Results:
Sixteen RCTs involving 1257 patients were included, which involved 9 groups of acupoint treatment plans. The best treatment plan for improving the mini-mental state examination score of PSCI was a cephalic plexus spur (99.7%). The best treatment option for improving the montreal cognitive assessment score for PSCI was Zishen Yisui acupuncture therapy (ZSYSA) (77.3%). The best option for improving the barthel index score of PSCI was ZSYSA (99.2%). In terms of improving the overall clinical outcomes of PSCI, the best treatment option for improving the overall clinical effectiveness of PSCI is ZSYSA Therapy (92.2%).

Conclusion:
The analysis of all results shows that ZSYSA can significantly improve PSCI compared to other acupuncture therapies.

Strengths and limitations of this study:
This is the 1st study on the treatment of PSCI with different acupoint combinations based on a network meta-analysis method, which provides a reference for clinical rehabilitation workers; all included studies were randomized controlled trials, which increased the reliability of this study. Limitations; The number of relevant clinical studies retrieved was too small, and all included clinical trials were located in China; therefore, there is a great possibility of publication bias; Most of the included studies did not clearly explain the random distribution mode, follow-up, distribution concealment, or other experimental conditions. Therefore, selection and reporting biases cannot be excluded, suggesting that the quality of the literature is not high; Because of the strict inclusion criteria, the number of studies was limited, and subgroup analysis could not be performed according to the time of onset and the length of the disease course.