bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphorylation of insulin receptor substrates (IRS-1 and IRS-2) is attenuated following cecal ligation and puncture in mice
Authors: Mathew Deepa , Barillas-Cerritos Julia , Nedeljkovic-Kurepa Ana , Abraham Mabel , Taylor Matthew D. , Deutschman Clifford S.
Published: August 2023

Background

Sepsis is characterized as an insulin resistant state. However, the effects of sepsis on insulin’s signal transduction pathway are unknown. The molecular activity driving insulin signaling is controlled by tyrosine phosphorylation of the insulin receptor β-subunit (IRβ) and of insulin receptor substrate molecules (IRS) -1 and IRS-2.

Hypothesis

Cecal ligation and puncture (CLP) attenuates IRβ, IRS-1 and IRS-2 phosphorylation.

Methods

IACUC-approved studies conformed to ARRIVE guidelines. CLP was performed on C57BL/6 mice; separate cohorts received intraperitoneal insulin at baseline (T0) or at 23 or 47 h. post-CLP, 1 h before mice were euthanized. We measured levels of (1) glucose and insulin in serum, (2) IRβ, IRS-1 and IRS-2 in skeletal muscle and liver homogenate and (3) phospho-Irβ (pIRβ) in liver and skeletal muscle, phospho-IRS-1 (pIRS-1) in skeletal muscle and pIRS-2 in liver. Statistical significance was determined using ANOVA with Sidak’s post-hoc correction.

Results

CLP did not affect the concentrations of IRβ, IRS-1or IRS-2 in muscle or liver homogenate or of IRS-1 in liver. Muscle IRS-1 concentration at 48 h. post-CLP was higher than at T0. Post-CLP pIRS-1 levels in muscle and pIRβ and pIRS-2 levels in liver were indistinguishable from T0 levels. At 48 h. post-CLP pIRβ levels in muscle were higher than at T0. Following insulin administration, the relative abundance of pIRβ in muscle and liver at T0 and at both post-CLP time points was significantly higher than abundance in untreated controls. In T0 controls, the relative abundance of pIRS-1 in muscle and of pIRS-2 in liver following insulin administration was higher than in untreated mice. However, at both post-CLP time points, the relative abundance of pIRS-1 in muscle and of pIRS-2 in liver following insulin administration was not distinguishable from the abundance in untreated mice at the same time point. Serum glucose concentration was significantly lower than T0 at 24 h., but not 48 h., post-CLP. Glucose concentration was lower following insulin administration to T0 mice but not in post-CLP animals. Serum insulin levels were significantly higher than baseline at both post-CLP time points.

Conclusions

CLP impaired insulin-induced tyrosine phosphorylation of both IRS-1 in muscle and IRS-2 in liver. These findings suggest that the molecular mechanism underlying CLP-induced insulin resistance involves impaired IRS-1/IRS-2 phosphorylation.
Galcanezumab in patients with episodic migraine: results from the open-label period of the phase 3 PERSIST study
Authors: Zhou Jiying , Zhong Lianmei , Chowdhury Debashish , Skorobogatykh Kirill , Luo Guogang , Yang Xiaosu , Zhang Mingjie , Sun Lingli , Liu Hui , Qian Chenxi , Yu Shengyuan
Published: August 2023

Background

The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia.

Methods

Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability.

Results

Overall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event.

Conclusions

Galcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months.

Trial registration

ClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019.
The single-cell transcriptome and chromatin accessibility datasets of peripheral blood mononuclear cells in Chinese holstein cattle
Authors: Wang Xiao , Gao Yahui , Li Cong-jun , Fang Lingzhao , Liu George E. , Zhao Xiuxin , Zhang Yuanpei , Cai Gaozhan , Xue Guanghui , Liu Yan , Wang Lingling , Zhang Fan , Wang Kun , Zhang Miao , Li Rongling , Gao Yundong , Li Jianbin
Published: August 2023

Objectives

This study was performed in the frame of a more extensive study dedicated to the integrated analysis of the single-cell transcriptome and chromatin accessibility datasets of peripheral blood mononuclear cells (PBMCs) with a large-scale GWAS of 45 complex traits in Chinese Holstein cattle. Lipopolysaccharide (LPS) is a crucial mediator of chronic inflammation to modulate immune responses. PBMCs include primary T and B cells, natural killer (NK) cells, monocytes (Mono), and dendritic cells (DC). How LPS stimulates PBMCs at the single-cell level in dairy cattle remains largely unknown.

Data description

We sequenced 30,756 estimated single cells and mapped 26,141 of them (96.05%) with approximately 60,075 mapped reads per cell after quality control for four whole-blood treatments (no, 2 h, 4 h, and 8 h LPS) by single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq). Finally, 7,107 (no), 9,174 (2 h), 6,741 (4 h), and 3,119 (8 h) cells were generated with ~ 15,000 total genes in the whole population. Therefore, the single-cell transcriptome and chromatin accessibility datasets in this study enable a further understanding of the cell types and functions of PBMCs and their responses to LPS stimulation in vitro.
Identification and pathogenicity analysis of Fusarium spp. on peach in China
Authors: Dong Jingping , Shi Hengsong , Wu Yu , Yang Lina , Zhu Feng , Ji Zhaolin
Published: August 2023

Background

Vascular system is affected by diseases that can seriously damage plant health by inducing browning and death of branches. This study aimed to identify and analyze the pathogenicity of Fusarium spp. isolates obtained from diseased peach branches in several peach-producing areas of China.

Results

We obtained and confirmed nine Fusarium isolates based on morphological and molecular characteristics. Phylogenetic relationships using a combination of rDNA-internal transcribed spacer (ITS), elongation factor (EF)-1α, and mitochondrial small subunit (mtSSU) gene sequences were analyzed. GJH-Z1, GJH-6, and GJH-1 were identified as F. avenaceum; HYR-Z3, and ZLZT-6 as F. concentricum, HH-2020-G2, and HYTZ-4 as F. solani, GG-2020-1 as F. asiaticum, SYGZ-1 as F. equiseti. Through acupuncture comparison, the pathogenicity of F. equiseti (SYGZ-1) was highest amongst nine strains. Meanwhile, F. concentricum (HYR-Z3 and ZLZT-6), and F. solaini (HYTZ-4) had a higher level of pathogenicity as revealed by impregnation.

Conclusions

Our study shed light on the findings that Fusarium spp. can inflict vascular bundle browning of peach plants. Our results will extend the understanding of pathogenic diseases in China’s peach industry.
Prediction of adverse health outcomes using an electronic frailty index among nonfrail and prefrail community elders
Authors: Lin Kun-Pei , Li Hsin-Yi , Chen Jen-Hau , Lu Feng-Ping , Wen Chiung-Jung , Chou Yi-Chun , Wu Meng-Chen , Chan Ding-Cheng , Chen Yung-Ming
Published: August 2023

Background

Early recognition of older people at risk of undesirable clinical outcomes is vital in preventing future disabling conditions. Here, we report the prognostic performance of an electronic frailty index (eFI) in comparison with traditional tools among nonfrail and prefrail community-dwelling older adults. The study is to investigate the predictive utility of a deficit-accumulation eFI in community elders without overt frailty.

Methods

Participants aged 65–80 years with a Clinical Frailty Scale of 1–3 points were recruited and followed for 2 years. The eFI score and Fried’s frailty scale were determined by using a semiautomated platform of self-reported questionnaires and objective measurements which yielded cumulative deficits and physical phenotypes from 80 items of risk variables. Kaplan–Meier method and Cox proportional hazards regression were used to analyze the severity of frailty in relation to adverse outcomes of falls, emergency room (ER) visits and hospitalizations during 2 years’ follow-up.

Results

A total of 427 older adults were evaluated and dichotomized by the median FI score. Two hundred and sixty (60.9%) and 167 (39.1%) elders were stratified into the low- (eFI ≤ 0.075) and the high-risk (eFI > 0.075) groups, respectively. During the follow-up, 77 (47.0%) individuals developed adverse events in the high-risk group, compared with 79 (30.5%) in the low-risk group (x2, p = 0.0006). In multivariable models adjusted for age and sex, the increased risk of all three events combined in the high- vs. low-risk group remained significant (adjusted hazard ratio (aHR) = 3.08, 95% confidence interval (CI): 1.87–5.07). For individual adverse event, the aHRs were 2.20 (CI: 1.44–3.36) for falls; 1.67 (CI: 1.03–2.70) for ER visits; and 2.84 (CI: 1.73–4.67) for hospitalizations. Compared with the traditional tools, the eFI stratification (high- vs. low-risk) showed better predictive performance than either CFS rating (managing well vs. fit to very fit; not discriminative in hospitalizations) or Fried’s scale (prefrail to frail vs. nonfrail; not discriminative in ER visits).

Conclusion

The eFI system is a useful frailty tool which effectively predicts the risk of adverse healthcare outcomes in nonfrail and/or prefrail older adults over a period of 2 years.
Sintilimab plus nab-paclitaxel as second-line treatment for advanced biliary tract cancer: study protocol for an investigator-initiated phase 2 trial (NapaSinti trial)
Authors: Zhou Nan , Li Xiaofen , Yang Yu , Tan Sirui , Zhang Shunyu , Huang Qiyue , Gou Hongfeng
Published: August 2023

Background

Biliary tract cancer (BTC) is a relatively rare but highly aggressive malignancy. However, there is currently no satisfactory second-line regimen for patients without specific genetic mutations. Nanoparticle albumin–bound paclitaxel, also known as nab-paclitaxel (Abraxane, Bristol Myers Squibb), has shown activity in patients with BTC. Studies investigating the immunogenic features of BTC suggested that checkpoint inhibition may lead to antitumor immune responses. In recent years, improved survival has been observed in patients treated with chemotherapy combined with immunotherapy across multiple cancer types, including BTC. This clinical trial aims to evaluate the efficacy and safety of second-line sintilimab in combination with nab-paclitaxel in advanced BTC patients.

Methods

The NapaSinti trial is a prospective, nonrandomized, open-label, phase 2 study conducted at a tertiary hospital in Chengdu, China. Eligible patients are those with histologically or cytologically confirmed locally advanced non-resectable or metastatic adenocarcinoma in the biliary tract (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer), aged between 18 and 75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, who have experienced disease progression after prior gemcitabine- or fluorouracil-based chemotherapy and have not received taxane or immune checkpoint inhibitor treatment. Enrolled patients will receive intravenous administration of sintilimab 200 mg on day 1 and nab-paclitaxel 125 mg/m2 on days 1 and 8, every three weeks. The primary endpoint is the objective response rate (ORR), while the secondary endpoints include overall survival (OS), progression-free survival (PFS), and safety. Exploratory objectives aim to identify biomarkers and molecular signatures for predicting response or prognosis. Using Simon’s two-stage design, a total of 63 participants will be enrolled in the study. This trial was initiated in March 2022 in China.

Discussion

The NapaSinti trial evaluates the efficacy and safety of second-line sintilimab plus nab-paclitaxel for advanced biliary tract cancer. Additionally, the trial provides an opportunity for translational research.

Trial registration

Chinese Clinical Trial Registry ChiCTR2100052118. Registered October 19, 2021.
Re-hospitalizations within 30-days and mortality outcomes among severely visually impaired and blind patients: analysis of the National Readmission Database
Authors: Fatuyi Michael , Anibire Oladipupo , Harris Che Matthew
Published: August 2023

Background

Readmissions and in-hospital mortality among patients with severe vision impairment or blindness (SVI/B) has not been fully studied. We investigated hospital outcomes for adults with SVI/B in the United States.

Methods

Using the Nationwide Readmission Database year 2017, we analyzed primary outcomes for thirty-day readmission rates for patients with and without SVI/B. Secondary outcomes were in-hospital mortality rates for readmitted patients, in-hospital mortality rates for index patients, the five most common principal diagnoses for readmission, and resource utilization.

Results

34,558 patients had an index admission for SVI/B vs. 24,600,000 who did not. Patients with SVI/B had a 13.3% [4,383] readmission rate within 30 days compared to 8.4% [2,033,329] without SVI/B. Compared to readmitted patients without SVI/B patients, those with SVI/B were older (mean [SD] age: 64.4 [SD ± 19] vs. 61.4 [SD ± 20] years) and had more comorbidities (Charlson comorbidity score ≥ 3: 79.2% [ 3,471] vs. 60.9% [1,238,299]). The mortality rate among patients readmitted with SVI/B was 5.38% [236] vs. 4.02% [81,740] for patients without SVI/B, p-value = 0.016. Top reasons for readmissions among patients with SVI/B included sepsis 12% [526], heart failure 10.5% [460)], acute renal failure 4.4% [193], complications due to type II diabetes mellitus 4.1% [178], and pneumonia 2.7% [118]. The mean length of stay for readmitted patients with SVI/B was 6.3 days (confidence interval [CI]: 6.0-6.7 days), vs. 5.6 days for patients without SVI/B (CI: 5.5–5.8 days), p-value < 0.01. The mean hospital charges for readmitted patients with SVI/B was $57,202 (CI: $53,712–$61,292) vs. $51,582 (CI: $49,966–$53,198), p-value < 0.01.

Conclusion

Patients with SVI/B had higher readmission rates and greater mortality on readmissions than those without SVI/B. Interventional studies for optimal discharge strategies are critically needed to improve clinical and resource utilization outcomes in patients with SVI/B.
Establishment and application of cricothyrotomy in vivo
Authors: Song Fengxiang , Han Cailing , Liu Bin , Qiu Yuxue , Hou Haitao , Yan Xiaoqiong , Deng Liqin
Published: August 2023

Background

Cricothyrotomy is a procedure performed to establish an airway in critical airway events. It is performed only rarely and anesthesiologists are often unprepared when called upon to perform it. This study aimed to simulate cricothyrotomy using pig larynx and trachea models to help anesthesiologists master cricothyrotomy and improve the ability to establish cricothyrotomy quickly.

Methods

The porcine larynx and trachea were dissected and covered with pigskin to simulate the structure of the anterior neck of a human patient. An animal model of cricothyrotomy was established. Forty anesthesiologists were randomly divided into four groups. Each physician performed three rounds of cricothyrotomy, and recorded the time to accomplish each successful operation. After training the cricothyrotomy procedure, a questionnaire survey was conducted for the participating residents using a Likert scale. The participants were asked to score the utility of the training course on a scale of 1 ((minimum) to 5 ((maximum).

Results

Through repeated practice, compared with the time spent in the first round of the operation (67 ± 29 s), the time spent in the second round of the operation (47 ± 21 s) and the time spent in the third round of the operation (36 ± 11 s) were significantly shortened (P < 0.05). Results of the survey after training were quite satisfied, reflecting increased the ability of proficiency in locating the cricothyroid membrane and performing a surgical cricothyrotomy.

Conclusion

The porcine larynx and trachea model is an excellent animal model for simulating and practicing cricothyrotomy, helping anesthesiologists to master cricothyrotomy and to perform it proficiently when required.
Low alanine aminotransferase activity gene variant in a Siberian Husky with copper-associated hepatopathy
Authors: Kim Christine , Loftus John P. , Huson Heather J.
Published: August 2023

Background

Alanine aminotransferase (ALT) is commonly used as a marker of hepatocellular injury. Increased serum ALT activity due to hepatocyte injury occurs in copper-associated hepatopathy (CuCH) and other necroinflammatory liver conditions. Blood ALT concentrations are frequently used to monitor therapy in cases of CuCH. Low serum ALT activities have been associated with an allele at a CFA13 locus.

Case presentation

A 9-year-old female spayed Siberian Husky was diagnosed with CuCH (hepatic copper dry weight 2680 µg/g [normal, 120–400 µg/g; toxic, > 1500 µg/g]) and a normal ALT (78 U/L; reference range, 10–125 U/L). Mild hepatocellular necrosis was evident histologically. Genetic testing (Embark) revealed that the dog was heterozygous for the low ALT activity gene allele.

Conclusions

This case report illustrates the clinical implications for diagnosing and managing necroinflammatory liver disease such as CuCH in dogs with a low ALT activity genotype.
HIF-1α increases the osteogenic capacity of ADSCs by coupling angiogenesis and osteogenesis via the HIF-1α/VEGF/AKT/mTOR signaling pathway
Authors: Song Shuang , Zhang Guanhua , Chen Xutao , Zheng Jian , Liu Xiangdong , Wang Yiqing , Chen Zijun , Wang Yuxi , Song Yingliang , Zhou Qin
Published: August 2023

Background

Stabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) can directly increase cancellous bone formation and play an essential role in bone modeling and remodeling. However, whether an increased HIF-1α expression in adipose-derived stem cells (ADSCs) increases osteogenic capacity and promotes bone regeneration is not known.

Results

In this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression plasmid were established to investigate the proliferation, migration, adhesion, and osteogenic capacity of ADSCs and the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Overexpression of HIF-1α could promote the biological functions of ADSCs, and the angiogenic ability of HUVECs. Western blotting showed that the protein levels of osteogenesis-related factors were increased when HIF-1α was overexpressed. Furthermore, the influence of upregulation of HIF-1α in ADSC sheets on osseointegration was evaluated using a Sprague–Dawley (SD) rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The overexpression of HIF-1α in ADSCs enhanced bone remodeling and osseointegration around titanium implants. However, transfecting the small interfering RNA (siRNA) of HIF-1α in ADSCs attenuated their osteogenic and angiogenic capacity. Finally, it was confirmed in vitro that HIF-1α promotes osteogenic differentiation and the biological functions in ADSCs via the VEGF/AKT/mTOR pathway.

Conclusions

This study demonstrates that HIF-1α has a critical ability to promote osteogenic differentiation in ADSCs by coupling osteogenesis and angiogenesis via the VEGF/AKT/mTOR signaling pathway, which in turn increases osteointegration and bone formation around titanium implants.

Graphical Abstract
3D organization of regulatory elements for transcriptional regulation in Arabidopsis
Authors: Deng Li , Zhou Qiangwei , Zhou Jie , Zhang Qing , Jia Zhibo , Zhu Guangfeng , Cheng Sheng , Cheng Lulu , Yin Caijun , Yang Chao , Shen Jinxiong , Nie Junwei , Zhu Jian-Kang , Li Guoliang , Zhao Lun
Published: August 2023

Background

Although spatial organization of compartments and topologically associating domains at large scale is relatively well studied, the spatial organization of regulatory elements at fine scale is poorly understood in plants.

Results

Here we perform high-resolution chromatin interaction analysis using paired-end tag sequencing approach. We map chromatin interactions tethered with RNA polymerase II and associated with heterochromatic, transcriptionally active, and Polycomb-repressive histone modifications in Arabidopsis. Analysis of the regulatory repertoire shows that distal active cis-regulatory elements are linked to their target genes through long-range chromatin interactions with increased expression of the target genes, while poised cis-regulatory elements are linked to their target genes through long-range chromatin interactions with depressed expression of the target genes. Furthermore, we demonstrate that transcription factor MYC2 is critical for chromatin spatial organization, and propose that MYC2 occupancy and MYC2-mediated chromatin interactions coordinately facilitate transcription within the framework of 3D chromatin architecture. Analysis of functionally related gene-defined chromatin connectivity networks reveals that genes implicated in flowering-time control are functionally compartmentalized into separate subdomains via their spatial activity in the leaf or shoot apical meristem, linking active mark- or Polycomb-repressive mark-associated chromatin conformation to coordinated gene expression.

Conclusion

The results reveal that the regulation of gene transcription in Arabidopsis is not only by linear juxtaposition, but also by long-range chromatin interactions. Our study uncovers the fine scale genome organization of Arabidopsis and the potential roles of such organization in orchestrating transcription and development.
Effects of remote ischemic conditioning on conditioned pain modulation and cardiac autonomic modulation in women with knee osteoarthritis: placebo-controlled randomized clinical trial protocol
Authors: Biral Taíse Mendes , de Souza Cavina Allysiê Priscilla , Junior Eduardo Pizzo , Filho Carlos Alberto Toledo Teixeira , Vanderlei Franciele Marques
Published: August 2023

Background

It is estimated that over 240 million people worldwide have osteoarthritis, which is a major contributor to chronic pain and central changes in pain processing, including endogenous pain modulation. The autonomic nervous system plays a crucial role in the pain regulatory process. One of the main mechanisms of remote ischemic conditioning is neuronal signaling from the preconditioned extremity to the heart. This study aims to analyze the acute effect of remote ischemic conditioning on local pain, conditioned pain modulation, and cardiac autonomic control in women with knee osteoarthritis and to see if there is a correlation between them.

Methods

Women more than 50 years with knee osteoarthritis diagnosed according to the American College of Rheumatology criteria in the postmenopausal period will be considered eligible. The study will have blind randomization, be placebo-controlled, and be balanced in a 1:1 ratio. The total of 44 participants will be divided into two groups (22 participants per group): (i) remote ischemic conditioning and (ii) placebo remote ischemic conditioning. Protocol consisting of four cycles of total ischemia, followed immediately by four cycles of 5 min of vascular reperfusion, totaling 40 min. The primary outcomes in the protocol are conditioned pain modulation, which has the pressure pain threshold (kgf/cm2) as its primary outcome measure, and cardiac autonomic modulation, which has the indices found in heart rate variability as its primary outcome measure. Comparisons will be performed using generalized linear mixed models fitted to the data. For correlation, the Pearson or Spearman test will be used depending on the normality of the data. All analyses will assume a significance level of p < 0.05.

Discussion

It is believed that the results of this study will present a new perspective on the interaction between the pain processing system and the cardiovascular system; they will provide the professional and the patient with a greater guarantee of cardiovascular safety in the use of the intervention; it will provide knowledge about acute responses and this will allow future chronic intervention strategies that aim to be used in the clinical environment, inserted in the multimodal approach, for the treatment of osteoarthritis of the knee.

Trial registration

ClinicalTrials.gov NCT05059652. Registered on 30 August 2021. Last update on 28 March 2023.
Unraveling the serotonin saga: from discovery to weight regulation and beyond - a comprehensive scientific review
Authors: Conde Kristine , Fang Shuzheng , Xu Yong
Published: August 2023

The prevalence of obesity is rapidly increasing worldwide, while the development of effective obesity therapies lags behind. Although new therapeutic targets to alleviate obesity are identified every day, and drug efficacy is improving, adverse side effects and increased health risks remain serious issues facing the weight-loss industry. Serotonin, also known as 5-HT, has been extensively studied in relation to appetite reduction and weight loss. As a result, dozens of upstream and downstream neural targets of 5-HT have been identified, revealing a multitude of neural circuits involved in mediating the anorexigenic effect of 5-HT. Despite the rise and fall of several 5-HT therapeutics in recent decades, the future of 5-HT as a therapeutic target for weight-loss therapy looks promising. This review focuses on the history of serotonin, the state of current central serotonin research, previous serotonergic therapies, and the future of serotonin for treating individuals with obesity.
The impact of COVID-19 on clinical outcomes in people undergoing neurosurgery: a systematic review and meta-analysis
Authors: Teng Haiying , Wang Zilan , Yang Xingyu , Wu Xiaoxiao , Chen Zhouqing , Wang Zhong , Chen Gang
Published: August 2023

Background

The coronavirus disease-2019 (COVID-19) pandemic has created a global crisis unique to the healthcare system around the world. It also had a profound impact on the management of neurosurgical patients. In our research, we investigated the effect of the COVID-19 pandemic on clinical outcomes in people undergoing neurosurgery, particularly vascular and oncological neurosurgery.

Method

Two investigators independently and systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrail.Gov, and Web of Science to identify relevant studies respecting the criteria for inclusion and exclusion published up to June 30, 2022. The outcomes of our research included mortality rate, length of stay, modified Rankin Score, delay in care, Glasgow outcome scale, and major complications. The risk of bias was assessed using the Methodological Index for Non-randomized Studies (MINORS) checklist.

Results

Two investigators independently and systematically searched 1378 results from MEDLINE, EMBASE, Cochrane database, ClinicalTrail.Gov, and Web of Science and extracted the detailed data from 13 studies that met the review’s eligibility criteria. Two articles reported on patients with intracerebral hemorrhages, five on patients with subarachnoid hemorrhages, four on patients undergoing surgery for neuro-oncology, and in two studies the patients’ conditions were unspecified. A total of 26,831 patients were included in our research. The number who died was significantly increased in the COVID-19 pandemic group (OR 1.52, 95% CI 1.36–1.69, P < 0.001). No significant difference was found between the two groups in terms of length of stay (SMD − 0.88, 95% CI − 0.18–0.02, P = 0.111), but it differed between regions, according to our subgroup analysis.

Conclusion

Compared to the pre-pandemic group, the number who died was significantly increased in the COVID-19 pandemic group. Meanwhile, the effect of the pandemic on clinical outcomes in people undergoing neurosurgery might differ in different regions, according to our subgroup analysis.
Common coincidence points for Nadler’s type hybrid fuzzy contractions
Authors: Kanwal Shazia , Maham Shumaila , Shagari Mohammed Shehu , Mohamed OM Kalthum S. K. , Mustafa Arafa O. , Bakery Awad A.
Published: August 2023

In the framework of complete metric spaces, the major objective of this paper is to investigate if a common coincidence point exists for more than two fuzzy mappings meeting the criteria of hybrid fuzzy contractions of Nadler’s type in connection with the Hausdorff metric. Fascinating examples are also provided to show how the strategy can be used. For the presence of a common α-fuzzy fixed point of three and four fuzzy mappings, we have derived sufficient requirements. Further prior observations are offered as corollaries from the relevant literature. Some implications that are clear in this mode and widely covered in literature are expanded upon and included in our study.
The efficacy and safety of vonoprazan–amoxicillin dual therapy in eradicating Helicobacter pylori: a systematic review and meta-analysis
Authors: Feng Jia-Hui , Cheng Jie , Lao Yao-Jia , Huang Kai , Mou Juan-Li , Hu Fan , Lin Meng-Lu , Lin Jun
Published: August 2023

Aim

To evaluate the efficacy and safety of vonoprazan–amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori).

Methods

The PubMed, Cochrane Library, Embase, China National Knowledge  Infrastructure (CNKI) and Wanfang databases were searched up to July 7, 2022, to identify clinical trials comparing the efficacy of VA dual therapy and triple therapy for H. pylori eradication. After evaluating the quality of the included studies, random effects models were conducted, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to estimate the efficacy and safety of each approach.

Results

Six publications (including four randomized controlled trials) involving 2019 patients were included in this meta-analysis. Overall, the eradication rate for VA dual therapy was 89.9%, while it was 85.2% for triple therapy based on other acid inhibitors. The eradication rate of H. pylori in the VA dual regimen group was higher than that in the PPI-based (omeprazole or lansoprazole) triple therapy group (RR = 1.15, 95% CI 1.07–1.23, p < 0.0001). However, the efficacy of VA dual therapy was comparable with VA–Clarithromycin (VAC) triple therapy (RR = 0.97, 95% CI 0.93–1.02). Besides, the incidence of adverse reactions in VA dual therapy was also lower than that in triple therapy (RR = 0.80, 95% CI 0.70–0.91, p = 0.0009).

Conclusion

Compared with PPI-based triple therapy, VA dual therapy showed a better therapeutic effect, safety and patient compliance rate for eradicating H. pylori, which should be used as a novel curative strategy in the future.
The relationship between exercise addiction, eating disorders, and insecure attachment styles among recreational exercisers
Authors: Lev Arey Dalit , Sagi Adi , Blatt Asaf
Published: August 2023

Background

Exercise addiction (EA) and eating disorders (ED) frequently co-occur in both professional and amateur athletes, with up to 48% of individuals with EA also exhibiting symptoms of ED. Furthermore, pathological attachment styles have been linked to both EA and ED. The current study aimed to explore the unique association between types of insecure attachment styles (i.e., anxiety or avoidance) and EA and ED.

Method

Four hundred and five Israelis (199 women, 206 men) who were recreational exercisers (i.e., exercised at least four hours a week for at least one year) with ages ranging from 18 to 78 (M = 38, SD = 12.31) completed a set of questionnaires, including the Eating Attitudes Test (EAT-26), Exercise Addiction Inventory, and the Experiences in Close Relationship Scale. Path analysis was used to simultaneously examine the associations of attachment anxiety and avoidance with EA and ED symptoms. Attachment anxiety and avoidance were specified as independent variables predicting ED and EA symptoms and were entered into the analysis as two parallel dependent variables.

Results

The results of the study indicate that attachment anxiety is positively associated with symptoms of EDs, while the association between attachment anxiety and symptoms of EA is not significant. On the other hand, attachment avoidance shows a positive association with symptoms of exercise addiction, but no significant association with symptoms of EDs is found.

Conclusions

These results imply that the anxious attachment regulation strategy is highly associated with body image concerns. Furthermore, individuals characterized by avoidance attachment manifest regulation strategies through excessive exercise. Scholars and practitioners could use these results to examine dispositional risk factors for insecure attachment styles and to assess specific pathologies among the population of recreational exercisers. The study also discusses limitations, future directions, and implications in detail.
Psychometric properties of the Coronavirus Anxiety Scale based on Classical Test Theory (CTT) and Item Response Theory (IRT) models among Chinese front-line healthcare workers
Authors: Zhang Dongmei , Wang Congzhi , Yuan Ting , Li Xiaoping , Yang Liu , Huang Anle , Li Jing , Liu Mingming , Lei Yunxiao , Sun Lu , Zhang Jing , Zhang Lin
Published: August 2023

Background

Since March 2022, the COVID-19 epidemic has rebounded widely and frequently in China. Healthcare workers have faced grand challenges such as soaring COVID-19 patients, being busy with the nucleic acid screening of all the populations in the epidemic areas every day, and testing positive for COVID-19, all of which contributed to anxiety easily according to the Conservation of Resources theory. However, anxiety among healthcare workers is not only associated with personal health but also adversely affects the quality of health services. Therefore, it is crucial to search for suitable tools to monitor the anxiety related to COVID-19 among healthcare workers. The current study aimed to test the Coronavirus Anxiety Scale (CAS) in Chinese healthcare workers.

Methods

The current study employed a cross-sectional design. The CAS was translated into Chinese. Then, according to Classical Test Theory (CTT) and Item Response Theory (IRT) models, the psychometric properties of the Chinese version were measured among 811 healthcare workers.

Results

The split‐half reliability was 0.855. The Cronbach’s α coefficient was 0.895. The retest coefficient was 0.901 with 10 days as the retest interval. The content validity index was 0.920. In exploratory factor analysis, one common factor was extracted and explained 72.559% of the total variance. All item load values on the common factor ranged from 0.790 to 0.885, and the communality of each item ranged from 0.625 to 0.784. With confirmatory factor analysis, the single factor model showed an excellent goodness-of-fit, chi-square/degree of freedom (χ2/df) = 3.339, goodness of fit index (GFI) = 0.992, adjusted goodness of fit index (AGFI) = 0.975, root-mean-square error of approximation (RMSEA) = 0.054, root mean square residual (RMR) = 0.005, incremental fit index (IFI) = 0.967, Tucker-Lewis index (TLI) = 0.932, and comparative fit index (CFI) = 0.966. The multiple-group confirmatory factor analysis revealed the invariance measuring anxiety of COVID-19 was in similar ways across ages, hospital degrees, and professional titles. With convergent validity, the CAS was positively correlated with post-traumatic stress disorder (r = 0.619, P < 0.001), fear of COVID (r = 0.550, P < 0.001), and depression (r = 0.367, P < 0.001). According to IRT models, the results showed that all item discrimination parameters were higher than 1.70 and difficulty parameters ranged from 1.13 to 2.83.

Conclusion

The Chinese version of CAS has good psychometric properties in healthcare workers after China adjusted the COVID-19 management measures during the COVID-19 Omicron epidemic, and can be used for assessing the anxiety associated with COVID-19 in Chinese healthcare workers.
Geochemical and H–O–Sr–B isotope signatures of Yangyi geothermal fields: implications for the evolution of thermal fluids in fracture-controlled type geothermal system, Tibet, China
Authors: Cao Rui , Dor Ji , Cai YongQiang , Chen XiaoLin , Mao Xiang , Meng Hui-ren
Published: August 2023

High-temperature hydrothermal systems are mainly distributed in the north–south graben systems of southern Tibet as an important part of the Mediterranean–Tethys Himalayan geothermal belt in mainland China. As the largest unit capacity and second stable operating geothermal power station in China, Yangyi is the fracture-controlled type geothermal field in the center of Yadong–Gulu Graben. In this paper, hydrogeological and hydrochemical characteristics, isotope composition (δD and δ18O, 87Sr/86Sr and δ11B) of borehole water, hot springs, and surface river samples were analyzed. From the conservative elements (such as Cl− and Li+) and δD and δ18O values, the geothermal water of the Yangyi high-temperature geothermal field is estimated to be of meteoric origin with the contributions of chemical components of the magmatic fluid, which is provided by partially molten granite as a shallow magmatic heat source. According to logging data, the geothermal gradient and terrestrial heat flow value of the Yangyi high-temperature geothermal field are 6.48 ℃/100 m and 158.37 mW m−2, respectively. Combining the hydrothermal tracer experiment, 87Sr/86Sr and δ11B ratios obtained with gradually decreasing reservoir temperatures from the Bujiemu stream geothermal zone to Qialagai stream geothermal zone, we suggested the deep geothermal waters were mixed with local cold groundwater and then flow northeastward, forming the shallow reservoir within the crushed zone and intersect spot of faults in the Himalayan granitoid. Furthermore, in the process of ascent, the geothermal water is enriched in K+, Na+, and HCO3− during the interaction with underlying Himalayan granitoid and pyroclastic rocks that occur as wall rocks. The detailed description and extensive discussion are of great significance for the further exploitation and utilization of north–south trending geothermal belts in Tibet.
Pediatric firearm injury epidemiology at a level 1 trauma center from 2019 to 2021: including time of the COVID-19 pandemic
Authors: Orantes Cynthia , Chan Hei Kit , Walter Daniel , Chavez Summer , Ugalde Irma T.
Published: August 2023

Background

Firearms are a leading cause of death in children. The demand for firearms increased following COVID-19 “stay-at home orders” in March 2020, resulting in record-breaking firearm sales and background checks. We aim to describe the changes in pediatric firearm-related injuries, demographics, and associated risk factors at a Level 1 trauma center in Houston before and during the COVID 19 pandemic.

Results

The total number of pediatric firearm-related injury cases increased during March 15th to December 31st, 2020 and 2021 compared to the same time period in 2019 (104 verses 89 verses 78). The demographic group most affected across years were males (87% in 2019 vs 82% in 2020 and 87% in 2021) between 14 and 17 years old (83% in 2019 vs 81% in 2020 and 76% in 2021). There was an increase in firearm injuries among black youth across all years (28% in 2019 vs 41% in 2020 vs 49% in 2021). Injuries in those with mental illness (10% in 2019 vs 24% in 2020 vs 17% in 2021), and injuries where the shooter was a known family member or friend (14% in 2019 vs 18% in 2020 vs. 15% in 2021), increased from 2019 to 2020.

Conclusion

The total number of pediatric firearm-related injuries increased during the COVID-19 pandemic compared to the previous year despite a decline in overall pediatric emergency department visits. Increases in pediatric firearm-related injuries in already vulnerable populations should prompt further hospital initiatives including counseling on safe firearm storage, implementation of processes to identify children at risk for firearm injuries, and continued research to mitigate the risk of injury and death associated with firearms in our community.
Study on synthesis of ursodeoxycholic acid by reduction of 7-ketolithocholic acid in double aprotic solvents and molecular simulations
Authors: Dai Mohan , Xu Binpeng , Guo Qing , Wan Junfen , Cao Xuejun
Published: August 2023

Ursodeoxycholic acid (UDCA) is not only safer than chenodeoxycholic acid in the treatment of hepatobiliary diseases, but also has a wide range of applications in Acute Kidney Injury and Parkinson’s Disease. The purpose of this experiment is to improve the conversion rate of 7-ketocholic acid (7K-LCA) and the yield of ursodeoxycholic acid in aprotic solvents during electrochemical reduction process. Three aprotic solvents were investigated as electrolytes. 1,3-Dimethyl-2-imidazolidinone (DMI) has a stable five-membered ring structure, and 7K-LCA has undergone two nucleophilic reactions and “Walden” inversion, the 7K-LCK was stereoselectively reduced to UDCA. Hexamethylphosphoramide (HMPA) and 1,3-methyl-3,4,5,6-Tetrahydro-2(1H)-pyrimidinone (DMPU) can be attacked by chloride ions to produce by-products. Molecular orbital theory-based simulations were conducted to study the reducibility of three aprotic solvents [hexamethylphosphoramide (HMPA), 1,3-methyl-3,4,5,6-Tetrahydro-2(1H)-pyrimidinone (DMPU), and 1,3-Dimethyl-2-imidazolidinone (DMI)] in combination with experiments. Choose the best solvent based on the simulation results, the electrolysis reaction can be carried out by applying current and voltage when lithium chloride is used as electrolytes. Calculations using Materials Studio showed that Cu, Pb, Hg–Cu, and Ni exhibited the highest binding energies to the substrate in this system. Using Cu as the electrode when the solvent is a 1:1 mix of DMI and HMPA, the conversion rate of 7-ketocholic acid (could reach 98%, the yield of ursodeoxycholic acid was up to 80%. Under the same conditions, linear voltammetry was performed on the electrochemical workstation to study the electrolysis behavior, and the obtained results were consistent with the experiment.

Graphical Abstract
Prehabilitation for frail patients undergoing total hip or knee replacement: protocol for the Joint PREP feasibility randomised controlled trial
Authors: Khalid Tanzeela , Ben-Shlomo Yoav , Bertram Wendy , Culliford Lucy , England Clare , Henderson Emily , Jameson Catherine , Jepson Marcus , Palmer Shea , Whitehouse Michael R. , Wylde Vikki
Published: August 2023

Background

Approximately, 8% of community-based adults aged ≥ 50 years in England are frail. Frailty has been found to be associated with poorer outcomes after joint replacement. Targeting frailty preoperatively via exercise and protein supplementation has the potential to improve outcomes for people undergoing joint replacement. Prior to proceeding with a randomised controlled trial (RCT), a feasibility study is necessary to address key uncertainties and explore how to optimise trial design and delivery.

Methods

The Joint PRehabilitation with Exercise and Protein (Joint PREP) study is a feasibility study for a multicentre, two-arm, parallel group, pragmatic, RCT to evaluate the clinical and cost-effectiveness of prehabilitation for frail patients undergoing total hip or knee replacement. Sixty people who are ≥ 65 years of age, frail according to the self-reported Groningen Frailty Indicator, and scheduled to undergo total hip or knee replacement at 2–3 hospitals in England and Wales will be recruited and randomly allocated on a 1:1 ratio to the intervention or usual care group. The usual care group will receive the standard care at their hospital. The intervention group will be given a daily protein supplement and will be asked to follow a home-based, tailored daily exercise programme for 12 weeks before their operation, in addition to usual care. Participants will be supported through six follow-up calls from a physiotherapist during the 12-week intervention period. Study questionnaires will be administered at baseline and 12 weeks after randomisation. Embedded qualitative research with patients will explore their experiences of participating, reasons for nonparticipation, and/or reasons for withdrawal or treatment discontinuation. Primary feasibility outcomes will be eligibility and recruitment rates, adherence to the intervention, and acceptability of the trial and the intervention.

Discussion

This study will generate important data regarding the feasibility of a RCT to evaluate a prehabilitation intervention for frail patients undergoing total hip and knee replacement. A future phase-3 RCT will determine if preoperative exercise and protein supplementation improve the recovery of frail patients after primary joint replacement.

Trial registration

ISRCTN11121506, registered 29 September 2022.
Bioequivalence clinical trial simulation: a case study of apalutamide administered in applesauce versus whole tablets
Authors: Yu Alex , Ackaert Oliver
Published: August 2023

Patients who have difficulty swallowing apalutamide tablets may benefit from administration in a food vehicle that is easier to swallow. In a previous single-dose study conducted in healthy male volunteers (n = 12) a larger peak exposure was observed (+ 27.6%) for apalutamide in applesauce compared with whole tablets, despite a comparable extent of exposure (+ 5%). However, because apalutamide is taken daily which results in a 3–5 fold accumulation ratio, the observed 27.6% difference in peak exposure with single-dose administration may be reduced with multiple doses. To evaluate the difference in peak exposure under daily administration of apalutamide, bioequivalence trial simulations assessing the probability of success in demonstrating bioequivalence between the two administration methods after repeat dose and single-dose administration were conducted. Simulated pharmacokinetic (PK) profiles for the reference treatment were based on an established population PK model for apalutamide. Simulated profiles for test treatment were based on the same model but with a treatment covariate fitted to the PK observations of the single-dose study. The present analysis found that > 85% of simulated steady-state bioequivalence trials with 10 subjects or more comparing daily apalutamide administration in applesauce versus whole tablets met the 80–125% criteria for bioequivalence for both maximum concentration (Cmax,ss) and area under the concentration curve at steady state (AUC0–24 h,ss). Results of these clinical trial simulations suggest that the daily administration of 240 mg apalutamide in applesauce is bioequivalent to whole tablet administration.