Background. Stroke remains the primary source of prolonged disability worldwide since it often results in gait asymmetry. Research shows compensatory mechanisms in chronic stroke patients' non-paretic legs but lacks knowledge about these adaptations during the early post-stroke period when walking on inclines which mimic real-world mobility challenges. Objective. This study sought to clarify the compensatory strategies in the non-paretic leg of early post-stroke survivors by analyzing the changes in vertical ground reaction force (GRF) profiles and respective variabilities during level (0%) and inclined (6%) treadmill walking, relative to healthy, matched controls. Methods. The study included fourteen early post-stroke survivors who were three months post-event or less along with fourteen matched controls. Participants walked at their preferred speeds on treadmill at 0% and 6% grade incline settings. Researchers determined key vertical GRF profiles, including peak amplitudes (F1, F2, F3), impulses (J1-J4), timing to each peak, loading/unloading rates, and their respectively variabilities. Mixed two-way repeated measures Analysis of covariance (ANCOVA) were used and preferred walking speed was used as a covariate. Results. Stroke survivors demonstrated significantly slower walking speeds compared to control participants (0.6 km/hr vs. 2.15 km/hr) while both groups shared similar demographic characteristics. It is worth mentioning that this study specifically focused on the non-paretic side; therefore, only GRF components corresponding to the non-paretic leg of the stroke survivors were investigated. During weight acceptance (F1) and push-off (F3) phases, stroke survivors showed lower vertical ground reaction force (VGRF) peak amplitudes (F1- control (C): 1.11 vs. patients (P): 1.04, F3 - C: 1.09 vs. P: 1.03) and impulse magnitudes (J1- C: 25.46 vs. P: 18.74, J2 - C: 21.37 vs. P: 13.46, J3- C: 22.38 vs. P: 15.71, J4 - C: 22.16 vs. P: 18.19) in their non-paretic leg compared to control subjects regardless of inclines. Stroke survivors presented higher F2 (mid-stance, F2 - C: 0.92 vs. P: 0.98) values which might indicate a flatter vertical ground reaction force profile due to compensatory or pathological gait mechanisms. Inclined walking produced increased F1 (Grade 0%: 1.06 vs. Grade 6%: 1.10) and decreased F2 (Grade 0%: 0.97 vs. Grade 6%: 0.93) for both participant groups, but controls exhibited increased F3 (Grade 0%: 1.06 vs. Grade 6%: 1.12) while stroke survivors showed reductions in F3 (Grade 0%: 1.05 vs. Grade 6%: 1.01) which indicated impaired push-off mechanics. Conclusions. The study demonstrates that treating the non-paretic leg as a healthy limb is inadequate and shows the necessity for rehabilitation approaches that target both legs individually. Focusing on motor control and force steadiness instead of simply strength can more effectively reduce maladaptive variability and enhance safe and efficient walking patterns.

BACKGROUND:The iliotibial band (ITB), a unique musculoskeletal structure, is gaining interest in various fields such as biomechanics, orthopedics, sports medicine, and rehabilitation medicine. The pathogenesis, prevention, and treatment of ITB-related diseases are controversial. Despite an increasing number of studies, there is a lack of organized literature sorting and hotspot analysis. This study aims to comprehensively analyze publications related to the ITB and summarize the research focal points and current state in this domain. METHODS:Literature characteristics were extracted from the Web of Science Core Collection (WoSCC) database from inception to January 17, 2023. Quantitative and qualitative analyses were performed, and the data were visualized using Microsoft Excel, CiteSpace, VOSviewer, and Tableau software. RESULTS:A total of 1230 relevant articles were identified, with the majority from the United States (594 articles). Most articles were published in 2018, and the article with the highest number of citations (1013) was published in 2002. The American Journal of Sports Medicine had the most articles. Harvard University and Andrew Amis were the most prolific institution and author, respectively. Research hotspots identified through citation and keyword analysis included knee, anterior cruciate ligament, anatomy, iliotibial band syndrome, anterolateral ligament, injuries, and biomechanics. CONCLUSION:This study provides a comprehensive summary of the research hotspots and current status of ITB research, offering a fresh perspective for scholars to gain a deeper understanding. The findings suggest additional research directions relevant to this subject in the future.

Sarcopenia is an age-related disease characterized by loss of muscle mass and strength, and its prevalence is increasing. Exercise is an effective treatment to improve muscle mass, muscle strength, and functional activity in sarcopenic older adults. Kinesio taping (KT) and extracorporeal shock wave therapy (ESWT) are widely-used treatments for musculoskeletal disorders and can increase muscle performance and/or muscle mass. However, the potential synergistic effects of combining KT and ESWT with exercise for primary sarcopenia remain unknown. This study aims to determine whether the addition of KT and ESWT could enhance the beneficial effects of exercise on sarcopenia. Nighty-four older adults (60 to 75 years old) with sarcopenia will be recruited and assigned randomly into two groups: (1) exercise + placebo ESWT + placebo taping and (2) exercise + ESWT + KT. All participants will undergo an 8-week treatment program, and outcomes will be measured at recruitment and 1, 4, and 8 weeks after the initial treatment. The primary outcome will be skeletal muscle index, and the secondary outcomes will be knee muscle strength, muscle tone, gait speed, timed-up-and-go test, five-time chair test, Short Physical Performance Battery, and biomarkers in blood. Two-way repeated measure ANOVA will be used to analyze the differences between the two groups at each time point. This RCT will fill crucial evidence gaps by evaluating the first combined KT + ESWT + exercise protocol for sarcopenia. Our results will determine whether this novel strategy outperforms standard exercise therapy while expanding KT/ESWT indications beyond their current musculoskeletal uses. Chinese Clinical Trial Registry (http//www.chictr.org.cn) register number ChiCTR2200064269.

In the intensive care unit (ICU), patients often experience restricted mobility due to their critical condition, potentially leading to negative effects on both muscle strength and immune function. Previous research has highlighted the beneficial effects of early mobilization among patients, regardless of mechanical ventilation status. Hence, early bed cycling serves as a potential facilitator for early mobilization and is considered a feasible intervention for critically ill patients within the ICU. To mitigate this concern, we propose a randomized controlled clinical trial aiming to assess the efficacy of early bed cycling for patients undergoing mechanical ventilation and analgosedation. The study will encompass 56 participants randomly assigned to either the treatment or control group, each consisting of 28 patients. Participants in both groups will receive health education. However, the control group will not receive any therapeutic intervention throughout the study. In contrast, the experimental group will undergo passive bed cycling of their lower extremities for 20 minutes at a rate of 30 revolutions per minute. Primary outcomes will focus on changes in the rectus femoris muscle area and thickness, evaluated using ultrasound, interleukin-6 (IL-6), IL-10, and nitric oxide (NO) production function. Secondary endpoints will encompass the modified Barthel index score, Medical Research Council total score at 1, 2, and 4 weeks following the final treatment session, participants' mechanical ventilation duration, rate of extubation in the second week, 28-day survival rate, and occurrence of adverse reactions. Any encountered side effects will be duly documented. Statistical analysis will be employed to compare patient outcomes between the treatment and control groups.

Objectives The objective of this study was to investigate whether skeletal muscle cystathionine gamma-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle Cth knockout (Cth(Delta skm)) mice. Methods The Cth(Delta skm) mice and littermate Cth-floxed (Cth(f/f)) mice were fed with either HFD or chow diet for 13 weeks. Metabolomics and transcriptome analysis were used to assess the impact of CTH deficiency in skeletal muscle. Results Metabolomics coupled with transcriptome showed that Cth(Delta skm) mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in Cth(f/f) mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. Cth(Delta skm)+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to Cth(f/f)+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in Cth(Delta skm)+HFD mice. Omics analysis showed differential pathways enriched between Cth(Delta skm) mice and Cth(f/f) mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in Cth(Delta skm)+HFD mice compared to Cth(f/f)+HFD mice. Discussion Our results indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.

Anterior cruciate ligament (ACL) injury is one of the common sports injuries. Anterior cruciate ligament reconstruction (ACLR) is the mainstream treatment for ACL injury, aiming to regain normal anatomical structure and stability of the knee joint and promote the patient's return to sports. Under the guidance of the concept of enhanced recovery after surgery, early weight-bearing rehabilitation (EWB) is an important factor affecting patient function and quality of life. However, there is no consensus on whether EWB rehabilitation can be performed after ACL surgery. This study aims to explore the safety and feasibility of EWB after ACL surgery. The study implemented a gradual EWB rehabilitation program in the experimental group, including weight-shifting training, balance training, and gait training on the affected lower limb, and assessed wound healing and stability of the knee joint. The study found that EWB after ACLR is safe and feasible. EWB rehabilitation not only does not pose a negative effect on the patient's knee pain, swelling, wound healing, and stability, but also helps to improve knee active flexion and quality of life faster and better. The EWB program in this study is simple, safe, and effective, and it provides strong theoretical guidance and practical demonstration for accelerated rehabilitation after ACLR.

BACKGROUND:Whole-body vibration (WBV) is a commonly used physical exercise for disease prevention and rehabilitation. Recent studies indicated the beneficial mechanism of WBV may be associated with its anti-inflammatory potential, however, its regulatory roles on different inflammatory mediators remained controversial. The aim of this study was to perform a meta-analysis to re-confirm the effects of WBV exercise on various inflammatory factors. METHODS:The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 to collect all articles comparing WBV with control (or post-pre trials). The effect size was expressed as the standardized mean difference (SMD) and 95% confidence intervals (CI). RESULTS:A total of 31 eligible studies were included, including 14 pre-clinical and 17 clinical studies. The meta-analysis of pre-clinical studies showed that compared with the control group, WBV exercise could significantly reduce the level of IL-6 (SMD: -1.03, 95% CI: -1.93, -0.13), TNF-α (SMD: -1.36, 95% CI: -2.54, -0.17) (for disease subgroup), IL-1β (SMD: -2.20, 95% CI: -3.24, -1.15), IFN-γ (SMD: -1.91, 95% CI: -2.71, -1.12), IL-4 (SMD: -0.71, 95% CI: -1.39, -0.03) and IL-17 (SMD: -1.32, 95% CI: -2.05, -0.59) overall. Pooling of clinical studies revealed WBV exercise significantly reduced the level of TNF-α (WBV vs control: SMD: -1.11, 95% CI: -2.16, -0.06; post vs pre: SMD: -1.29, 95% CI: -1.91, -0.67), CRP (SMD: -3.59, 95% CI: -6.36, -0.82, P = 0.011) and enhanced the level of IL-10 (WBV vs control: SMD: 2.90, 95% CI: 1.10, 4.71; post vs pre: SMD: 1.75, 95% CI: 0.64, 2.87) and IL-6 (SMD: 0.91, 95% CI: 0.31, 1.52) (healthy subgroup). CONCLUSION:WBV may be an effective prevention and rehabilitation tool for inflammatory diseases.

OBJECTIVE:This randomized controlled trial aims to compare the effects of high versus low dose extracorporeal shockwave therapy (ESWT) on immune system activation and regulation in elderly patients with osteoarthritis.METHODS:120 patients aged 65 years and older with knee osteoarthritis will be randomly allocated to receive either high dose (0.25 mJ/mm2) or low dose (0.10 mJ/mm2) ESWT administered weekly for 4 weeks. Serum cytokines, stimulated immune cell subsets, and T regulatory cells will be measured at baseline, 4 weeks after intervention and at 1-month follow-up.RESULTS:High dose ESWT will increase pro-inflammatory cytokines and decrease immunosuppressive T regulatory cells compared to low dose ESWT in elderly osteoarthritis patients may be the outcome mainly.CONCLUSION:This study will provide evidence on ESWT dosing protocols and their differential immunomodulatory effects, which can guide optimal use for musculoskeletal conditions in geriatric populations.

IntroductionThe adverse effects of neuromuscular junction dysfunctions caused by immune checkpoint inhibitor (ICI) drugs have not been thoroughly assessed in the clinics. ObjectiveTo assess the neuromuscular junction dysfunctions in cancer patients with adverse events caused by ICI therapy by searching the Food and Drug Administration Adverse Event Reporting System (FAERS) database. MethodsThe FAERS data from January 2004 to December 2020 were collected to analyze the association between neuromuscular connection dysfunction and ICI use. Disproportionate analysis and Bayesian analysis were used to quantify the association between the neuromuscular junction dysfunctions and ICIs. The onset time and outcome of neuromuscular junction dysfunctions in different ICI regimens were also compared. ResultsOut of 88,617 adverse event reports, 557 neuromuscular junction dysfunction reports (0.63%) were analyzed. Marketed ICI drugs, including ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, cemiplimab, avelumab, as well as their combinations, showed positive associations with four detection methods. Most of the adverse event reports were associated with the use of nivolumab (53.32%) and pembrolizumab (31.96%). However, nivolumab-related neuromuscular junction dysfunctions were similar with pembrolizumab (33.33% vs 33.14%, p > 0.05). The onset time of neuromuscular junction dysfunctions showed no significant difference among different ICIs (p > 0.05). ConclusionsAnalysis of FAERS data identified that over 30% (32.85%) of reports of neuromuscular junction dysfunctions resulted in death. Ongoing monitoring, risk evaluations, and further comparative studies of ICIs should be considered.

Background Kinesio Taping (KT) is proved useful to many musculoskeletal disorders. But the mechanism remains unclear. The kinesio tape works by sticking to the skin surface. So exploring the interaction between the tape and the skin and analyzing its biomechanical influence may be an effective way to explore the mechanism of the tape. Objectives This study aimed to investigate the effect of Kinesio taping and taping methods on skin deformation during knee joint flexion and extension motion and further explore its possible functional mechanisms. Methods Ten healthy and pain-free subjects (4 males, 6 females) were recruited in this study. The skin observation area on the anterior side of the right thigh of the subjects was divided into 11 segments by 12 reflective marker points for distance measurement, from the distal knee to the proximal knee, the length of the interval was L1 to L11, and the total length was L0. Subjects were treated with no KT (NT), resting positive taping (RPT), resting negative taping (RNT), stretching positive taping (SPT), and stretching negative taping (SNT). A Qualisys infrared high-speed three-dimensional spatial coordinate capture system was used to observe changes in the length of the observed skin surface on the right anterior thigh during right knee flexion and extension in the sitting position. Results During right knee flexion and extension in the seated position in 10 subjects, all skin segment deformations produced significant differences between intervention groups ( P < 0.05), except for L1 during flexion ( P = 0.07). During right knee flexion and extension, total length, L0, and spacing lengths, L1, L6, and L11, were longer in the NT group than in all other groups. L0 and L1 were both longer in the stretched position than in the rest position; L11 also showed this trend. Conclusions The usage of the KT had an effect on the biomechanical changes of the skin, resulting in changes in skin deformation. I-tape, natural tension taping can shorten the skin distance between the two ends of the tape. Limb position during taping may influence the KT’s effects. However, the change in taping direction showed no significant effects on skin deformation during exercise. KT may apply a pre-stress in the biomechanics of the skin.

This study was aimed to investigate the influence of miR-33-5p on the M1/M2 polarization of microglia and the underlying mechanism. Transcriptome sequencing was performed using microglia from miR-33-5p mimic and control groups. In total, 507 differentially expressed genes, including 314 upregulated genes and 193 downregulated genes, were identified. The subnetwork of module A, which was extracted from the protein-protein interaction networks, mainly contained the downregulated genes. Cdk1,Ccnb,and Cdc20, the members of module-A networks with the highest degrees, possess the potential of being biomarkers of ischemic stroke due to their function in the cell cycle. NFY, a transcription factor, was predicted to have the regulatory relation with nine downregulated genes. Overall, our findings will provide a valuable foundation for genetic mechanisms and treatment studies of ischemic stroke.

Healthcare workers (HCWs) faced a range of stressors during the coronavirus (COVID-19) pandemic, contributing to psychological stress. We use a psychological trauma framework to characterize the mental health burden for clinical and non-clinical healthcare worker occupations during the COVID-19 pandemic. The objective was to measure and characterize risk factors for trauma and anxiety-related mental health problems among HCWs at a public hospital in the epicenter of the COVID-19 pandemic in New York City (NYC). This study reports findings from a cross-sectional survey of NYC HCWs shortly after the initial 2020 infection surge. Over 800 hospital employees completed the survey that assessed professional quality of life indicators (compassion satisfaction [CS], burnout [BO], secondary traumatic stress [STS]), Coronavirus Anxiety (CS), Obsession with Coronavirus (OC), and PTSD symptoms. The survey also assessed pandemic-related work and life circumstances such as “do you have a family member or friend who tested positive for COVID”. Relatively small percentages of HCWs endorsed probable Coronavirus Anxiety (6%), PTSD (13%), and Coronavirus Obsession (21%). We observed higher proportions of Burnout (29%), Moderate or High Secondary Traumatic Stress (45%), and High Compassion Satisfaction (52%). Adjusted regression models showed important implications for prior behavioral/emotional health concerns among HCWs, providing care for a patient that died from COVID-19, and other characteristics. This study supports prior studies documenting the mental health consequences for the healthcare workforce during the COVID-19 pandemic. This study builds on that base by including non-clinical staff in the sample and assessing pandemic life-stressors such as caring for sick family members.

Purpose: The development of treatment-related adverse events (trAE) correlates favorably with clinical outcomes in multiple studies of patients receiving immune checkpoint inhibitors (ICI); however, this relationship is undefined in patients with hepatocellular carcinoma (HCC). Patients and methods: We derived a cohort of 406 patients with unresectable/advanced HCC receiving ICI therapy as part of international clinical trials submitted to the US Food and Drug Administration (FDA) in support of marketing applications. We tested whether the development of clinically significant trAE (i.e. graded >2, trAE2) predicted improved overall survival (OS), progression-free survival (PFS), and objective response rates (ORR) following ICI. We established an international consortium of 10 tertiary-care referral centres located in Europe (n = 67), United States (US, n = 248) and Asia (n = 42) to validate this association. Results: In the FDA dataset of 406 patients, 325 (80%) with Barcelona Clinic Liver Cancer (BCLC) stage C HCC mostly treated with ICI monotherapy (n = 258, 64%), trAE2 were reported in 228 patients (56.1%). Development of trAE2 was associated with longer OS (16.7 versus 11.2 months) and PFS (5.5 versus 2.2 months) and persisted as an independent predictor of outcome after adjusting for viral aetiology, gender, Child-Pugh class, BCLC stage, AFP levels, ECOG-PS, ICI regimen (mono/combination therapy) and receipt of corticosteroid therapy. In a multi-institutional cohort of 357 patients with similar characteristics mostly treated with ICI monotherapy (n = 304, 85%), the development of trAE2 was associated with longer OS (23.3 versus 12.1 months) and PFS (9.6 versus 3.9 months). TrAE2 were confirmed predictors of improved OS (HR 0.43; 95% CI:0.25-0.75) and PFS (HR 0.48; 95% CI: 0.31-0.75), with multivariable analyses confirming their association with outcome independent of clinicopathologic features of interest. Additional time-varying multivariable analyses also indicated that trAEs were associated with a decreased risk of progression (HR 0.56, 95% CI: 0.46-0.67) in the FDA dataset and death (HR 0.55; 95% CI: 0.32-0.95) in the multi-institutional dataset. Conclusion: Development of trAE2 correlates with improved outcomes in patients with HCC receiving ICI in clinical trials and in routine practice. Prospective studies aimed at understanding the underlying immunologic foundations of such relationships are warranted to identify predictive biomarkers of toxicity and response. 2021 Elsevier Ltd. All rights reserved.

ObjectiveDynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggest an initial decay of antibody followed by subsequent stabilisation. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCWs).DesignA prospective longitudinal study.SettingThis study was conducted in a New York City public hospital in the South Bronx, New York.ParticipantsHCWs participated in phase 1 (N=500) and were followed up 4 months later in phase 2 (N=178) of the study. They underwent SARS-CoV-2 PCR and serology testing for N and S protein antibodies, in addition to completion of an online survey in both phases. Analysis was performed on the 178 participants who participated in both phases of the study.Primary outcome measureEvaluate longitudinal humoral responses to viral N (qualitative serology testing) and S protein (quantitative Mount Sinai Health System ELISA to detect receptor-binding domain and full-length S reactive antibodies) by measuring rate of decay.ResultsAnti-N antibody positivity was 27% and anti-S positivity was 28% in phase 1. In phase 1, anti-S titres were higher in symptomatic (6754 (5177–8812)) than in asymptomatic positive subjects (5803 (2825–11 920)). Marginally higher titres (2382 (1494–3797)) were seen in asymptomatic compared with the symptomatic positive subgroup (2198 (1753–2755)) in phase 2. A positive correlation was noted between age (R=0.269, p<0.01), number (R=0.310, p<0.01) and duration of symptoms (R=0.434, p<0.01), and phase 1 anti-S antibody titre. A strong correlation (R=0.898, p<0.001) was observed between phase 1 titres and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever (R=0.428, p<0.001), gastrointestinal symptoms (R=0.340, p<0.05), and total number (R=0.357, p<0.01) and duration of COVID-19 symptoms (R=0.469, p<0.001).ConclusionsHigher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as a faster decay between the two time points.

It has been shown that circular RNA XPO1 (circXPO1) is involved in cancer (e.g., lung adenocarcinoma and osteosarcoma) progression by sponging microRNAs. Nevertheless, the role of circXPO1 and its interaction with microRNAs in prostate cancer remains unknown. In this study, the results of quantitative real-time PCR showed that circXPO1 levels were dramatically increased in human prostate cancer tissue and cell lines compared with those in normal tissue and cell line. Furthermore, cell proliferation, colony formation, and cell invasion assays showed that circXPO1 promoted the malignant behavior of pancreatic cells in vitro . Mechanistically, bioinformatics prediction, a dual-luciferase reporter assay, and pull-down assay suggested that circXPO1 physically targets miR-23a and negatively regulates its expression in pancreatic cancer cells. miR-23a mimics and inhibitors effectively reversed the effects of circXPO1 on the malignant behavior of prostate cancer cells in vitro . Consistent results were observed in the xenograft tumor model. In conclusion, circXPO1 promotes prostate cancer progression via targeting miR-23a, thus suggesting the circXPO1/miR-23a axis can be used as a potential therapeutic target for prostate cancer treatment.

Introduction This study investigated the relationships between differentially co-expressed gene pairs or links (DCLs) and transcription factors (TFs) in the gene transcription regulatory network (GTRN) to clarify the molecular mechanisms underlying the pathogenesis of Parkinson’s disease (PD). Material and methods Microarray dataset GSE7621 from Gene Expression Omnibus (GEO) was used to identify differentially expressed genes (DEGs) and perform Gene Ontology (GO) enrichment analysis. Differentially co-expressed genes (DCGs) and DCLs were identified by the DCGL package in R soft-ware. DCLs that were potentially related to the regulation mechanisms, and corresponding TFs, were identified using the DR sort function in the DCGL V2.0 package. The GTRN was constructed with these DCLs-TFs, and visualized with Cytoscape software. Results A total of 131 DEGs, including 77 up-regulated DEGs and 54 down-regulated DEGs, were identified, which were mainly enriched for plasma membrane, cell activities, and metabolism. We found that ICAM1-LTBP and CTHRC1-UTP3 might alter gene regulation relationships in PD. The GTRN was constructed with DCLs-TFs, including 348 nodes (118 TFs and 230 DCGs) and 1045 DCLs. These TFs (AHR, SP1, PAX5, etc.) could regulate many target genes (e.g. ICAM1 and LTBP) in the GTRN of PD. Conclusions ICAM1 and LTBP may play a role in PD symptom development and pathology, and might be regulated by important TFs (AHR, SP1, PAX5, etc.) identified in the GTRN of PD. These findings may help elucidate the molecular mechanisms underlying PD and find a novel drug target for this disease.

The socially vulnerable have been most affected due to the COVID-19 pandemic, similar to the aftermath of any major disaster. Racial and social minorities are experiencing a disproportionate burden of morbidity and mortality. The aim of this study was to evaluate the impact of residential location/community and race/ethnicity on outcomes of COVID-19 infection among hospitalized patients within the Bronx. This was a single center retrospective observational cohort study that included SARS-CoV2 positive adult residents of the Bronx (stratified as residents of South Bronx vs Rest of Bronx) hospitalized between March-May 2020. Data extracted from hospital electronic medical records included residential addresses, race, comorbidities, and insurance details. Comorbidity burden other clinical and laboratory details were also assessed to determine their correlation to COVID-19 severity of illness and outcomes of mortality and length of stay. As expected, the COVID-19 pandemic differentially affected outcomes in those in the more socially disadvantaged area of the South Bronx versus the rest of the Bronx borough. Residents of the South Bronx had a significantly higher comorbidity burden and had public insurance to access medical care in comparison to the remainder of the Bronx. Interestingly, for the patient population studied there was no observed difference in 30-day mortality by race/ethnicity among those infected with COVID-19 in spite of the increased disease burden observed. This adds an interesting perspective to the current literature, and highlights the need to address the social/economic factors contributing to health access disparity to reduce the adverse impact of COVID-19 in these communities.

Background and Rationale: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC. Methods: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within −30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. Results: Our study comprised mostly cirrhotic (329, 73.3%) males (355, 79.1%) with a Child-Turcotte Pugh class of A (332, 73.9%), receiving ICI after 1 therapy line (251, 55.9%) for HCC of Barcelona clinic liver cancer stage C (325, 72.4%). EIOP (n = 170, 37.9%) was independent of baseline clinicopathologic features of HCC and correlated with longer PFS (6.1 vs. 3.7 months, log-rank p = 0.0135). EIOP+ patients had similar OS, overall response, and disease control rates (DCRs) compared to EIOP. The effect of EIOP persisted in landmark time analyses and in multivariable models, confirming the independent predictive role of EIOP in influencing PFS following adjustment for covariates reflective of tumor burden, liver function, and ICI regimen administered. In patients receiving programmed cell death-1 receptor/ligand inhibitors monotherapy, EIOP was also associated with higher DCRs (61.4% vs. 50.9%, p = 0.0494). Conclusions: Unlike other oncological indications, ATB in the 30 days before or after ICI initiation is associated with improved benefit from immunotherapy, independent of disease and treatment-related features. Evaluation of the immune microbiologic determinants of response to ICI in HCC warrants further investigation.

目的 探究全身振动训练对痉挛型脑瘫患儿步行及粗大运动能力的影响.方法 选取2019年1月至2019年12月在上海市第一人民医院康复医学科门诊行康复治疗的痉挛型脑瘫患儿40例,随机(抛硬币法)分为试验组(全身振动训练结合常规康复治疗)20例,对照组(常规康复训练)20例.分别于干预前、干预12周后评估粗大运动功能评定(GMFM-88)中D区(站立)、E区(走、跑、跳)评分;Peabody运动发育量表(PDMS-2)中姿势项、移动项和实物操作项评分;10m步行测试(1OMWT),分析比较步行及粗大运动能力改善情况.结果 两组患儿干预前粗大运动功能分类系统(GMFCS)等级;GMFM-88中D区(站立)、E区(走、跑、跳)评分;PDMS-2中姿势项、移动项和实物操作项评分;1OMWT差异均无统计学意义(P＞0.05).治疗后,GMFM-88中的D区(站立)、E区(走、跑、跳)评分两组均有改善且试验组较对照组评分改善更为显著(P＜0.01);PDMS-2中姿势项、移动项评分两组均有改善且试验组较对照组改善更为显著(P＜0.01),实物操作项评分比较两组组内、组间差异均无统计学意义(P＞0.05);10MWT两组均有提高且试验组较对照组提高更明显(P＜0.01).结论 全身振动训练结合常规康复治疗可促进痉挛型脑瘫患儿步行及运动功能改善.