bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-criteria antiphospholipid antibodies in antiphospholipid syndrome: Diagnostic value added
Authors: Liu Xiangjun , Zhu Lei , Liu Hongjiang , Cai Qingmeng , Yun Zelin , Sun Feng , Jia Yuan , Guo Jianping , Li Chun 
Published: October 2022

ObjectiveNon-criteria antiphospholipid antibodies (aPLs) increase the diagnostic value for antiphospholipid syndrome (APS) and contribute to better recognition of seronegative APS (SNAPS). However, the clinical utility and the diagnostic value of non-criteria aPLs are inconsistent. This study aimed to investigate the prevalence and clinical significance of 7 non-criteria aPLs in a large APS cohort.MethodsSeven non-criteria aPLs, including anti-phosphatidylserine/prothrombin (aPS/PT) antibodies IgG/IgA/IgM, anti-phosphatidylethanolamine antibodies (aPE) IgG/IgA/IgM, anti-Annexin V antibodies (aAnnexinV) IgG/IgA/IgM, anti-phosphatidylserine antibodies (aPS) IgM, aPS IgG, antibodies directed against a mixture of phospholipids (APhL) IgG, and APhL IgM were tested among 175 patients with APS, 122 patients with other autoimmune diseases (as disease controls), and 50 healthy controls.ResultsIn the present study, the highest prevalence of non-criteria aPLs was seen in aAnnexinV (58.86%). APhL IgG and aPS IgM showed the highest specificity (95.35%) and aPS/PT showed the highest Youden index (0.3991) for the diagnostic value of APS. The aAnnexinV also showed the highest prevalence in SNAPS (43.3%), followed by APhL IgM (21.7%), aPE (16.7%) and aPS/PT (16.7%). APhL IgG, aPS/PT, and aPS IgG showed positive association with thrombotic events in APS patients [APhL IgG: odds ratio (OR) = 2.26, 95% confidence interval (CI) 1.18-4.34, p = 0.013; aPS/PT: OR = 2.48, 95% CI: 1.32-4.69, p = 0.004; aPS IgG: OR = 1.90, 95% CI 1.01-3.60, p = 0.046; respectively). The inclusion of the non-criteria aPLs increased the accuracy of APS diagnosis from 65.7% to 87.4%.ConclusionOur data provide evidence that adding the non-criteria aPLs can improve the diagnostic accuracy in APS. APhL IgG, aPS/PT, and aPS IgG may be potential biomarkers to predict the risk of thrombosis in APS.
Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome
Authors: Sato Mami , Arakaki Rieko , Tawara Hiroaki , Nagao Ruka , Tanaka Hidetaka , Tamura Kai , Kawahito Yuhki , Otsuka Kunihiro , Ushio Aya , Tsunematsu Takaaki , Ishimaru Naozumi 
Published: October 2022

ObjectiveInnate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs). The role of NK cells among ILCs in the pathogenesis of pSS is still unclear. In this study, the characteristics and subsets of NK cells in the salivary gland (SG) tissue were analyzed using a murine model of pSS.MethodsMultiple phenotypes and cytotoxic signature of the SG NK cells in control and pSS model mice were evaluated by flow cytometric analysis. Intracellular expression of interferon-γ (IFN-γ) among T cells and NK cells from the SG tissues was compared byin vitroexperiments. In addition, pathological analysis was performed using anti-asialo-GM1 (ASGM1) antibody (Ab)-injected pSS model mice.ResultsThe number of conventional NK (cNK) cells in the SG of pSS model mice significantly increased compared with that in control mice at 6 weeks of age. The production level of IFN-γ was significantly higher in SG NK cells than in SG T cells. The depletion of NK cells by ASGM1 Ab altered the ratio of tissue resident NK (rNK) cells to cNK cells, which inhibited the injury to SG cells with the recovery of saliva secretion in pSS model mice.ConclusionThe results indicate that SG cNK cells may enhance the autoreactive response in the target organ by upregulating of IFN-γ, whereas SG rNK cells protect target cells against T cell cytotoxicity. Therefore, the activation process and multiple functions of NK cells in the target organ could be helpful to develop potential markers for determining autoimmune disease activity and target molecules for incurable immune disorders.
Bromo-protopine, a novel protopine derivative, alleviates tau pathology by activating chaperone-mediated autophagy for Alzheimer’s disease therapy
Authors: Sreenivasmurthy Sravan Gopalkrishnashetty , Iyaswamy Ashok , Krishnamoorthi Senthilkumar , Reddi Rambabu N. , Kammala Ananth Kumar , Vasudevan Karthick , Senapati Sanjib , Zhu Zhou , Su Cheng-Fu , Liu Jia , Guan Xin-Jie , Chua Ka-Kit , Cheung King-Ho , Chen Hubiao , Zhang Hong-Jie , Zhang Yuan , Song Ju-Xian , Kumar Durairajan Siva Sundara , Li Min 
Published: October 2022

Emerging evidence from Alzheimer’s disease (AD) patients suggests that reducing tau pathology can restore cognitive and memory loss. To reduce tau pathology, it is critical to find brain-permeable tau-degrading small molecules that are safe and effective. HDAC6 inhibition has long been considered a safe and effective therapy for tau pathology. Recently, we identified protopine as a dibenzazecine alkaloid with anti-HDAC6 and anti-AD activities. In this study, we synthesized and tested novel protopine derivatives for their pharmacological action against AD. Among them, bromo-protopine (PRO-Br) demonstrated a two-fold increase in anti-HDAC6 activity and improved anti-tau activities compared to the parent compound in both in vitro and in vivo AD models. Furthermore, molecular docking results showed that PRO-Br binds to HDAC6, with a ∆G value of −8.4 kcal/mol and an IC50 value of 1.51 µM. In neuronal cell lines, PRO-Br reduced pathological tau by inducing chaperone-mediated autophagy (CMA). In 3xTg-AD and P301S tau mice models, PRO-Br specifically decreased the pathogenic hyperphosphorylated tau clumps and led to the restoration of memory functions. In addition, PRO-Br treatment promoted the clearance of pathogenic tau by enhancing the expression of molecular chaperones (HSC70) and lysosomal markers (LAMP2A) via CMA in AD models. Our data strongly suggest that administration of the brain-permeable protopine derivative PRO-Br, could be a viable anti-tau therapeutic strategy for AD.
Influence of proprioceptive training based on ankle-foot robot on improving lower limbs function in patients after a stroke
Authors: Mao Yajun , Gao Zhenzhen , Yang Hang , Song Caiping 
Published: October 2022

BackgroundProprioception is important for our everyday activity, as it indicates the position, movement, and force on the body. This is important not only for ambulation but also for patients who are diagnosed with stroke.ObjectiveThis study aimed to evaluate the influence of proprioceptive training on lower limb function in patients after a stroke using an ankle-foot robot.MethodIn total, 60 adult participants who met the criteria were randomly divided into a control group and an experimental group. The control group (RG) was given regular physical activity, and the sensory training group (SG) was given proprioceptive training based on an ankle-foot robot, the rest being the same as RG. Measurements for 10-meter walking time (10MWT), the Berg Balance Scale (BBS), the Fugl-Meyer assessment of lower extremity (FMA-LE), and active range of motion (AROM), passive range of motion (PROM), and ankle joint sensitivity before and after 6 weeks of treatment (30 sessions; five times per week) were assessed.ResultsThere was a significant decrease in both 10MWT and ankle joint sensitivity in both groups (p &lt; 0.05), while there was a significant increase in BBS, FMA-LE, AROM, and PROM in both groups (p &lt; 0.05). A significant relationship was identified between the two groups, the SG group had greater degrees of improvement compared to the RG group.ConclusionThe proprioceptive training based on an ankle-foot robot could improve proprioception and effectively improve the motor function and walking ability in patients after a stroke. Proprioceptive strength training is recommended to be emphasized in the regular rehabilitation of patients after a stroke.
A time-restricted feeding intervention in children and adolescents with obesity: The TRansForm study protocol
Authors: Molina-Giraldo Paula , Murillo Serafin , Meis Laura , Sans Oscar , Amat-Bou Montse , Llobet Marina , Jimenez-Chillaron Josep C. , Ramon-Krauel Marta , Lerin Carles 
Published: October 2022

Obesity during childhood is of special concern as adiposity is typically tracked into adult life and it constitutes a major risk factor for future obesity and associated metabolic disorders. Recent studies indicate that time-restricted feeding (TRF) interventions may provide a promising strategy for obesity treatment. However, TRF interventions have only been tested in adult subjects. This study aims to determine both short- and long-term effects of a TRF intervention in children and adolescents with obesity. We will also investigate potential mechanisms mediating the response to the intervention, including the circadian rhythm and the gut microbiota composition. We have designed a randomized-controlled parallel-group clinical study in which children and adolescents (age range 8–18 year-old) with obesity will be subjected to time-restricted eating or no time restrictions for 2 months. Follow-up visits will allow for long-term effect assessments. We will measure anthropometric (BMI, body composition) and metabolic parameters (glucose and lipid metabolism), indicators of the circadian rhythm, and gut microbiota composition will be analyzed. This study will (1) determine safety and effectiveness of the TRF intervention in children and adolescents; (2) assess its long-term effects; and (3) evaluate potential mechanisms involved in the response to the intervention.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT05174871].
Physical fitness mediates the inverse association between fatness indicators and academic achievement, despite the school vulnerability of adolescents—The Cogni-Action Project
Authors: Gajardo-Araya Guillermo , Hernández-Jaña Sam , Olivares-Arancibia Jorge , Ferrari Gerson , Delgado-Floody Pedro , Cristi-Montero Carlos 
Published: October 2022

ObjectiveThis study aims to determine the mediating role of physical fitness in the relationship between fatness indicators and academic achievement, exploring the influence of school vulnerability.MethodsA total of 1,296 Chilean adolescents (aged 10 to 14 years; 50% girls) participated in this study. The global fitness score (GFS) was obtained by adding the three main components of the ALPHA fitness test: cardiorespiratory fitness (CRF), muscular fitness (MF), and speed/agility fitness (SAF). CRF was evaluated through the 20 m shuttle run test; MF by upper and lower limb strength tests; and SAF by the 4 × 10 shuttle run test. BMIz and WHtR were evaluated as general (unspecific) and central (specific) fatness indicators. Academic achievement was established through grades in math, language, and science and their average scores. Multiple mediation analyses were performed according to two models, adjusted for sex, maturity, and schools (model 1), and in model 2, the school vulnerability index (SVI) was added. The SVI is an important proxy of socioeconomic status at the school level, and it was categorized as high-, mid-, or low-SVI. Mediation percentages were calculated, and confidence intervals (bootstrapping) were used to establish significant findings.ResultsCRF, SAF, and GFS mediate the relationship between fatness indicators and academic achievement, both partially and totally (ranging from 12.7 to 59.2%). However, MF did not show any mediation effect. After controlling for SVI, CRF, and GFS, mediation changed from partial to total in the associations between math and science with WHtR. Although SAF contributed to GFS mediation, CRF seems to have the most significant mediation role for all academic achievements, regardless of SVI and the fat indicator studied.ConclusionA higher level of general physical fitness, especially CRF, significantly mediates the detrimental influence of fatness on the academic achievement of schoolchildren. This study suggests that physical fitness plays a relevant role in academic and public health, considering the high prevalence and detrimental influence of obesity and school vulnerability in children and adolescents.
Grape polyphenols decrease circulating branched chain amino acids in overfed adults
Authors: Bartova Simona , Madrid-Gambin Francisco , Fernández Luis , Carayol Jerome , Meugnier Emmanuelle , Segrestin Bérénice , Delage Pauline , Vionnet Nathalie , Boizot Alexia , Laville Martine , Vidal Hubert , Marco Santiago , Hager Jörg , Moco Sofia 
Published: October 2022

Introduction and aimsDietary polyphenols have long been associated with health benefits, including the prevention of obesity and related chronic diseases. Overfeeding was shown to rapidly induce weight gain and fat mass, associated with mild insulin resistance in humans, and thus represents a suitable model of the metabolic complications resulting from obesity. We studied the effects of a polyphenol-rich grape extract supplementation on the plasma metabolome during an overfeeding intervention in adults, in two randomized parallel controlled clinical trials.MethodsBlood plasma samples from 40 normal weight to overweight male adults, submitted to a 31-day overfeeding (additional 50% of energy requirement by a high calorie-high fructose diet), given either 2 g/day grape polyphenol extract or a placebo at 0, 15, 21, and 31 days were analyzed (Lyon study). Samples from a similarly designed trial on females (20 subjects) were collected in parallel (Lausanne study). Nuclear magnetic resonance (NMR)-based metabolomics was conducted to characterize metabolome changes induced by overfeeding and associated effects from polyphenol supplementation. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov.ResultsChanges in plasma levels of many metabolic markers, including branched chain amino acids (BCAA), ketone bodies and glucose in both placebo as well as upon polyphenol intervention were identified in the Lyon study. Polyphenol supplementation counterbalanced levels of BCAA found to be induced by overfeeding. These results were further corroborated in the Lausanne female study.ConclusionAdministration of grape polyphenol-rich extract over 1 month period was associated with a protective metabolic effect against overfeeding in adults.
Meta analysis of indocyanine green fluorescence in patients undergoing laparoscopic colorectal cancer surgery
Authors: Deng Jia , Hu Wenting , Li Yang , Xiong Kai , Yue Tinghui , Lai Xiangquan , Xiao Tianbao 
Published: October 2022

This meta-analysis intended to systematically evaluate the clinical implications of indocyanine green fluorescence (ICG) in patients undergoing laparoscopic colorectal surgery. PubMed, MEDLINE, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Medical Information System and China Biomedical Database were synthetically searched for studies published from inception to April 14, 2022. The randomized controlled trials comparing ICG-use with controls were selected. The incidence of anastomotic leakage (AL), lymph node detection, operation duration, intraoperative bleeding, postoperative morbidity, and hospitalization time were evaluated in summary analysis, and calculated the corresponding 95% confidence intervals (CI). Subsequently, in addition to subgroup analyses, studies for heterogeneity, sensitivity, and publication bias were carried out. Consequently, 3453 patients in the enrolled 15 studies were included; 1616 patients were allocated to the experimental group, and 1837 patients were assigned to the control group. The ICG group had a significantly decreased risk of AL (RR: 0.50, 95% CI: 0.37–0.67) and shorter hospitalization time (SMD: -0.31, 95% CI: -0.54–0.08) compared to the control group. Meanwhile, the ICG showed clearly better lymph node detection (SMD: 0.19, 95% CI: 0.02–0.36). However, when the content of operation duration (SMD: -0.07, 95% CI: -0.30–0.15) and intraoperative bleeding (SMD: -0.16, 95% CI: -0.35–0.04) were compared, no statistical significance was found. Furthermore, the pooled analysis of postoperative morbidity was not statistically significant (RR:0.79, 95% CI: 0.58–1.08). The results of the subgroup analysis of AL indicated that there may be regional variations in AL (RR: 0.50, 95% CI: 0.37–0.67) but not in postoperative morbidity (RR: 0.79, 95% CI: 0.58–1.08). In conclusion, the application of ICG in laparoscopic colorectal surgery can effectively reduce the AL, lymph node detection, and hospitalization time. However, more multicenter large-sample randomized controlled trials are required to further confirm its advantages. The meta-analysis was registered in PROSPERO (no. CRD42022288054).
Detection of asymptomatic recurrence following curative surgery improves survival in patients with gastric cancer: A systematic review and meta-analysis
Authors: Pang Hua-Yang , Yan Meng-Hua , Chen Li-Hui , Chen Xiu-Feng , Chen Zhi-Xiong , Zhang Shou-Ru , Sun Hao 
Published: October 2022

BackgroundTo date, there is no evidence that intensive follow-up provides survival benefit in gastric cancer patients undergoing curative gastrectomy. The aim of this study is to investigate the efficacy of detection of asymptomatic recurrence using intensive surveillance strategy in long-term survival after curative gastric cancer surgery.MethodsA systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library and China National Knowledge Infrastructure, Clinical Trials Registry and Google Scholar was performed up to April 2022. The primary outcomes were survival outcomes: overall survival, recurrence-free survival and post-recurrence survival. The secondary endpoints were clinicopathological features, recurrence patterns and treatment after recurrence. The registration number of this protocol is PROSPERO CRD42022327370.ResultsA total of 11 studies including 1898 participants were included. In the pooled analysis, the detection of asymptomatic recurrence was significantly associated with an improved overall survival compared to patients showing symptoms of recurrence (HR=0.67; 95%CI: 0.57-0.79; P&lt;0.001), which was primarily driven by the prolongation of post-recurrence survival (HR=0.51; 95%CI: 0.42-0.61; P&lt;0.001), since there was no significant difference observed in recurrence-free survival (HR=1.12; 95%CI: 0.81-1.55; P=0.48) between the two groups. Meanwhile, male sex and advanced T stage were more frequently observed in the symptomatic recurrence group. Furthermore, patients in the symptomatic recurrence group had a higher proportion of peritoneal relapse but lower proportion of distant lymph node metastasis. Additionally, patients in the symptomatic recurrence group were less likely to receive surgery treatment and post-recurrence chemotherapy.ConclusionThe detection of asymptomatic recurrence using intensive follow-up was associated with an appreciable improvement in overall survival. However, more robust data from high-quality studies are still required to verify this issue.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=327370, identifier CRD42022327370.
Novel small 99mTc-labeled affibody molecular probe for PD-L1 receptor imaging
Authors: Liang Zhigang , Hu Xianwen , Hu Hongyu , Wang Pan , Cai Jiong 
Published: October 2022

ObjectiveThe in vivo imaging of programmed death ligand 1 (PD-L1) can monitor changes in PD-L1 expression and guide programmed death 1 (PD-1) or PD-L1-targeted immune checkpoint therapy. A 99mTc-labeled affibody molecular probe targeting the PD-L1 receptor was prepared and evaluated its tracing effect in PD-L1-overexpressing colon cancer.MethodsThe PD-L1 affibody was prepared by genetic recombineering. The 99mTc labeling of the affibody was achieved by sodium glucoheptonate and an SnCl2 labeling system. The labeling rate, radiochemical purity, and stability in vitro were determined by instant thin-layer chromatography; MC38-B7H1 (PD-L1-positive) and MC38 (PD-L1-negative) colon cancer cells were used to evaluate its affinity to PD-L1 by cell-binding experiments. The biodistribution of the 99mTc-labeled affibody molecular probe was then determined in C57BL/6J mice bearing MC38-B7H1 tumors, and tumor targeting was assessed in C57BL/6J mice with MC38-B7H1, MC38 double xenografts.ResultThe nondecayed corrected yield of the 99mTc-PD-L1 affibody molecular probe was 95.95% ± 1.26%, and showed good stability both in phosphate-buffered saline (PBS) and fetal bovine serum within 6 h. The affinity of the 99mTc-PD-L1 affibody molecular probe for cell-binding assays was 10.02 nmol/L. Single photon emission–computed tomography imaging showed a rapid uptake of the tracer in PD-L1-positive tumors and very little tracer retention in PD-L1-negative control tumors. The tracer was significantly retained in the kidneys and bladder, suggesting that it is mainly excreted through the urinary system. Heart, liver, lung, and muscle tissue showed no significant radioactive retention. The biodistribution in vitro also showed significant renal retention, a small amount of uptake in the thyroid and gastrointestinal tract, and rapid blood clearance, and the tumor-to-blood radioactivity uptake ratio peaked 120 min after drug injection.ConclusionThe 99mTc-PD-L1 affibody molecular probe that we prepared can effectively target to PD-L1-positive tumors imaging in vivo, and clear in blood quickly, with no obvious toxic side effects, which is expected to become a new type of tracer for detecting PD-L1 expression in tumors.