Association between community walkability and hypertension: Evidence from the Wuhan Chronic Disease Cohort Study.

While community walkability is recognized as a key environmental factor for health status, evidence linking it specifically to hypertension is rather limited. To fill the knowledge gap, we concluded a cross-sectional study among 6421 eligible participants from the Wuhan Chronic Disease Cohort. A well-developed algorithm was performed to evaluate community walkability across Wuhan, quantified as Walk Score. We then calculated each participant residential Walk Score using the geographic information system. The logistic and linear regression models were conducted to determine the relationship between walkability, hypertension and blood pressure, respectively. We further performed the mediation analysis to explore potential mechanisms. After adjusting for extra confounders, we observed a higher community walk score was associated with a lower hypertension risk (OR = 0.73; 95% CI: 0.63, 0.84), a lower systolic blood pressure (ß = -3.152 mmHg; 95% CI: -4.25, -2.05), a lower diastolic blood pressure (ß = -2.237 mmHg; 95% CI: -2.95, -2.53) and a lower mean arterial pressure (ß = -2.976 mmHg; 95% CI: -3.75, -2.20). The effect of community walkability on hypertension was partially mediated by body fat rate. Our study indicates a positive correlation between high walkability and a reduced odds of hypertension in China. This highlights the potential role of urban design in hypertension prevention, emphasizes the need for walkability-focused planning strategies to foster healthier communities, and guides future interventions and research to mitigate hypertension.

A model for transcription-dependent R-loop formation at double-stranded DNA breaks: Implications for their detection and biological effects.

R-loops are structures containing an RNA-DNA duplex and an unpaired DNA strand. During R-loop formation an RNA strand invades the DNA duplex, displacing the homologous DNA strand and binding the complementary DNA strand. Here we analyze a model for transcription-dependent R-loop formation at double-stranded DNA breaks (DSBs). In this model, R-loop formation is preceded by detachment of the non-template DNA strand from the RNA polymerase (RNAP). Then, strand exchange is initiated between the nascent RNA and the non-template DNA strand. During that strand exchange the length of the R-loop could either increase, or decrease in a biased random-walk fashion, in which the bias would depend upon the DNA sequence. Eventually, the restoration of the DNA duplex would completely displace the RNA. However, as long as the RNAP remains bound to the template DNA strand it prevents that displacement. Thus, according to the model, RNAPs stalled at DSBs can increase the lifespan of R-loops, increasing their detectability in experiments, and perhaps enhancing their biological effects.

Improved GPS tropospheric path delay estimation using variable random walk process noise.

Accurate positioning using the Global Positioning System relies on accurate modeling of tropospheric delay. Estimated tropospheric delay must vary sufficiently to capture true variations; otherwise, systematic errors propagate into estimated positions, particularly the vertical. However, if the allowed delay variation is too large, the propagation of data noise into all parameters is amplified, reducing precision. Here we investigate the optimal choice of tropospheric constraints applied in the GipsyX software, which are specified by values of random walk process noise. We use the variability of 5-min estimated positions as a proxy for tropospheric error. Given that weighted mean 5-min positions closely replicate 24-h solutions, our ultimate goal is to improve 24-h positions and other daily products, such as precise orbit parameters. The commonly adopted default constraint for the zenith wet delay (ZWD) is 3 mm/√(hr) for 5-min data intervals. Using this constraint, we observe spurious wave-like patterns of 5-min vertical displacement estimates with amplitudes ~ 100 mm coincident with Winter Storm Ezekiel of November 27, 2019, across the central/eastern USA. Loosening the constraint suppresses the spurious waves and reduces 5-min vertical displacement variability while improving water vapor estimates. Further improvement can be achieved when optimizing constraints regionally, or for each station. Globally, results are typically optimized in the range of 6-12 mm/√(hr). Generally, we at least recommend loosening the constraint from the current default of 3 mm/√(hr) to 6 mm/√(hr) for ZWD every 300 s. Constraint values must be scaled by √(x/300) for alternative data intervals of x seconds. Supplementary Information: The online version contains supplementary material available at 10.1007/s00190-024-01898-3.

Functioning of post-COVID-19 patients: a cross-sectional study at the outpatient clinic for long-term effects.

BACKGROUND: After COVID-19 infection, long-term impacts on functioning may occur. We studied the functioning of patients with post-COVID-19 condition (PCC) and compared them to controls without PCC. METHODS: This cross-sectional study consisted of 442 patients with PCC referred to rehabilitation at the Helsinki University Hospital (HUS) Outpatient Clinic for the Long-Term Effects of COVID-19, and 198 controls without PCC. Functioning was assessed with a questionnaire including WHODAS 2.0. Patients underwent physical testing including a hand grip strength test (HGST) and a 6-minute walking test (6MWT). Lifestyle was assessed by questionnaire and comorbidities were collected as ICD-10 codes from the HUS Data Lake on the HUS Acamedic platform. RESULTS: The WHODAS 2.0 average total score was 34 (SD 18) (moderate functional limitation) for patients with PCC and 6 (SD 8) (normal or mild limitation) for the controls. The disability was higher in all aspects of WHODAS 2.0 in patients with PCC. Bivariate binomial and multivariable regression analyses showed that the presence of comorbidities, anxiety, depression, and smoking predicted a WHODAS 2.0 score of 24 (moderate functional limitation) or above in the PCC group. The average 6MWT distance was 435 m (SD 98 m) in patients with PCC and 627 m (SD 70 m) in controls. HGST measurements showed no significant differences from controls. CONCLUSIONS: In conclusion, patients with PCC had significantly reduced functioning based on WHODAS 2.0 scores and the 6MWT results. Comorbidities, anxiety, depression, and smoking were associated with moderate or severe limitations in functioning. Findings support that PCC is multifactorial and requires a holistic approach to rehabilitation.

The post-COVID-19 condition (PCC) has been shown to negatively impact functioning, quality of life, and mental health, with cognitive and physical impairments being prevalent.This study found that patients with PCC had significantly reduced functioning compared to controls.Key factors predicting severe disability included comorbidities, smoking, and mental health issues like anxiety and depression.The reduced functioning in patients with PCC appears to be multifactorial and not only related to COVID-19 infection.

Performance fatigability in adults with spinal muscular atrophy treated long-term with nusinersen.

INTRODUCTION/AIMS: Persons with spinal muscular atrophy (pwSMA) report progressive muscle weakness but also reduced endurance when performing repetitive tasks in daily life, referred to as "performance fatigability" (PF). Data regarding the effects of the new disease-modifying drugs on PF are scarce. Thus, our main objective was to examine PF in adult ambulatory pwSMA treated long-term with nusinersen. METHODS: Six-minute walk test (6MWT) data from 14 adult pwSMA treated with nusinersen for up to 70 months were retrospectively analyzed to determine PF. Performance fatigability was defined as the percentage change in the distance covered between the last and first minute of the 6MWT. In addition, relationships between PF and other clinical features were assessed. RESULTS: Performance fatigability was found in 12/14 pwSMA (85.7%) prior to treatment. The mean distance walked in the sixth minute (71.1 m) was shorter than the distance covered in the first minute (81.8 m), corresponding to a mean PF of 13.1% (95% confidence interval (CI): 6.5-19.6, p = .0007). During treatment with nusinersen, there was a mean reduction in PF of 5.6% (95% CI: -10.0 to -1.3, p = .0148). We found no relationship between PF and fatigue as measured by the Fatigue Severity Scale. DISCUSSION: This study demonstrates the presence of PF as an independent component of motor impairment and as a potential therapeutic target in our cohort of adult ambulatory pwSMA. Furthermore, the observations in our cohort suggest that nusinersen may have a beneficial effect on PF.

Exploring the Effect of Preamputation Employment and Income on Ambulation in Dysvascular Lower Extremity Amputees After Amputee Rehabilitation: A Retrospective Cohort Study.

Objective: To assess the relationship between 2-minute walk test (2MWT) distance, employment status, and median household income in adult dysvascular amputee patients after a 6-week rehabilitation program. Design: Retrospective cohort study. Setting: Amputation rehabilitation program. Participants: In total, 505 patients were included in the analysis. Most (71.1%) were men and had below-knee amputations (78.3%); the average age was 65.3±11.6 years. Interventions: Not applicable. Main Outcome Measures: 2MWT distance at discharge. Results: Men (68.3±32.6m) and below-knee amputation amputees (70.9±32.0m) walked significantly further than women (58.8±30.0m; P=.003) and above-knee amputees (47.2±25.7m; P<.001), respectively. A significant negative correlation was found between 2MWT distance and age (r=-.32; P<.001) as well as time from consultation to admission (r=-.23; P<.001). An unadjusted general linear model (GLM) revealed that employment status (F2,446=17.47; P<.001) but not income (F4,446=.714; P=.58) was statistically significantly associated with 2MWT distance. An adjusted (age, sex, time from consult to admission, and amputation level) GLM revealed employment status remained significant (F2,434=5.59; P=.004) and income remained insignificant (F4,434=.43; P=.784). Differences in 2MWT distance between employment and income groups did not meet clinical significance. Conclusions: Preamputation employment appears to be associated with postrehabilitation outcomes.

Comparing the Physiological Responses to the 6-Minute Walk Test, Timed Up and Go Test, and Treadmill Cardiopulmonary Exercise Test.

Purpose: To compare physiological responses during a treadmill cardiopulmonary exercise test (CPX), 6-minute walk test (6MWT), and timed up and go test (TUGT) in individuals referred for unexplained breathlessness and symptom limited treadmill exercise testing. Methods: Heart rate (HR), oxygen consumption (V̇O2), carbon dioxide production (V̇CO2), respiratory exchange ratio (RER), minute ventilation (V̇E), systolic blood pressure (SBP), and rating of perceived exertion (RPE) were recorded throughout each test. Results: Each test demonstrated a significant increase (p < 0.01) in the cardiopulmonary (V̇O2, V̇CO2 and V̇E, RPE, SBP, and HR) and perceptual (RPE) responses from rest to end exercise. The increase in cardiopulmonary and perceptual responses was greatest for the CPX with significantly smaller responses demonstrated during the 6MWT (p < 0.01) and even smaller responses for the TUGT (p < 0.01 vs CPX and 6MWT). Conclusion: Not surprisingly, the treadmill CPX results is the greatest physiological response in our group. Despite being of short duration, the TUGT results in an increased physiological response.

Reference charts for the six-minute walk test in healthy school-aged children from the city of Zaragoza, Spain.

INTRODUCTION: The six-minute walk test is a stress test that provides information about exercise tolerance in chronic diseases. The aim of the study was to develop reference equations with normal values for the test in healthy children aged 6-12 years in our paediatric reference population. PATIENTS AND METHODS: The six-minute walk test was carried out in a sample of 236 healthy children, analyzing pre- and post-test variables, and we developed reference equations selecting variables that turned out to be significant (P < .05). RESULTS: The pre- and post-test values, respectively, were 97.82% (SD, 0.64) vs 97.82% (SD, 0.59) for oxygen saturation; 96.59 bpm (SD, 16.11) vs 131.89 bmp (SD, 22.64) for the heart rate; 0.52 (SD, 0.83) vs 3.01 (SD, 2.42) for the degree of dyspnea (Borg scale) and 0.68 (SD, 0.98) vs 2.95 (SD, 2.26) for the degree of lower extremities fatigue (Borg scale). The average distance walked was 668.03 m (SD, 87.36) (671.42 m in boys [SD, 92.2] vs 664.22 m in girls [SD, 81.81]). We fitted predictive equations that included the variables age, height and difference between baseline and final heart rate. We also generated percentile charts of the distance walked for height. CONCLUSIONS: Age, height, regular physical activity and obesity had an impact on test results. Obtaining reference values for the 6-min walk test in healthy children is necessary for its application in clinical practice.

DRADTiP: Drug repurposing for aging disease through drug-target interaction prediction.

MOTIVATION: The greatest risk factor for many non-communicable diseases is aging. Studies on model organisms have demonstrated that genetic and chemical perturbation alterations can lengthen longevity and overall health. However, finding longevity-enhancing medications and their related targets is difficult. METHOD: In this work, we designed a novel drug repurposing model by identifying the interaction between aging-related genes or targets and drugs similar to aging disease. Each disease is associated with certain specific genetic factors for the occurrence of that disease. The factors include gene expression, pathway, miRNA, and degree of genes in the protein-protein interaction network. In this paper, we aim to find the drugs that prolong the life span of humans with their aging-related targets using the above-mentioned factors. In addition, the contribution or importance of each factor may vary among drugs and targets. Therefore, we designed a novel multi-layer random walk-based network representation learning model including node and edge weight to learn the features of drugs and targets respectively. RESULT: The performance of the proposed model is demonstrated using k-fold cross-validation (k = 5). This model achieved better performance with scores of 0.93 and 0.91 for precision and recall respectively. The drugs identified by the system are evaluated to be potential candidates for aging since the degree of interaction between the potential drugs and their gene sets are high. In addition, the genes that are interacting with drugs produce the same biological functions. Hence the life span of the human will be increased or prolonged.

Exploring nalbuphine loaded chitosan nanoparticles for effective pain management through intranasal administration: a comparative study.

BACKGROUND: Intranasal drug delivery shows potential for brain access via olfactory and trigeminal routes. PURPOSE: This work aimed to ensure brain availability of nalbuphine via the nasal route. METHOD: Chitosan based nanoparticles loaded with nalbuphine were successfully prepared using ionic gelation method and characterised. RESULT: SEM results revealed that the nanoparticles were spherical in shape, with an average size of 192.4 ± 11.6 nm. Zeta potential and entrapment efficiency was found 32.8 mV and 88.43 ± 7.75%, respectively. The X-ray diffractometry and DSC results unravel a profound understanding on the physical and thermal characteristics. The in-vitro release of nalbuphine from the nanoparticles was biphasic, with an initial burst release followed by a slow-release profile. In-vitro cell study on HEK-293 cells and microscopic images of brain tissue confirmed the safety profile of formulation. In-vivo efficacy studies on animal confirmed the effectiveness of developed intranasal formulation as compared to the standard therapy. The in-vivo pharmacokinetic studies showed that the prepared nanoparticles were able to efficiently deliver nalbuphine to the brain in comparison to the other body organs. Gamma scintigraphy images showed retention of the drug in the brain. Furthermore, the efficacy studies confirmed that the nanoparticles were found significantly more effective than the marketed formulation in pain management.

Associations between 6-minute walk distance and physiologic measures and clinical outcomes in myositis-associated interstitial lung disease.

OBJECTIVE: The 6-min walk test (6MWT) is a simple test widely used to assess sub-maximal exercise capacity in chronic respiratory diseases. We explored the relationship of 6-min walk distance (6MWD) with measurements of physiological, clinical, radiographic measures in patients with myositis-associated interstitial lung disease (MA-ILD). METHOD: We analyzed data from the Abatacept in Myositis Associated Interstitial lung disease (Attack My-ILD) study, a 48-week multicentre randomized trial of patients with anti-synthetase antibodies and active MA-ILD. 6MWD, forced vital capacity (FVC), diffusing capacity (DLCO), high resolution CT, and various physician/patient reported outcome measures were obtained during the trial. Spearman's correlations and repeated-measures analysis with linear mixed-effects models were used to estimate the associations between 6MWD and various physiologic, clinical and radiographic parameters both cross-sectionally and longitudinally. RESULTS: Twenty participants with a median age of 57, 55% male and 85% white were analyzed. Baseline 6MWD did not associate with baseline PFTs. Repeated-measures analysis showed 6MWD over time associated with FVC over time, but not with DLCO. 6MWD over time also correlated with UCSD dyspnea score, Borg scores, as well as global disease activity and muscle strength over time. Emotional role functioning, vitality, general health and physical functioning scores by short form 36 also correlated with 6MWD over time. CONCLUSIONS: : Exploratory work in a small cohort of MA-ILD demonstrated 6MWD over time associated with parallel changes in FVC and patient reported outcomes of dyspnea, but not with DLCO. Larger studies are needed to validate the reliability, responsiveness and utility of the 6MWT in MA-ILD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03215927.

Type and Distribution of Gross Motor Activity During Physical Therapy in Young Children With Cerebral Palsy.

OBJECTIVE: Physical therapists routinely deliver and prescribe motor practice to improve function. The ability to select optimal practice regimens is limited by a current lack of detail in the measurement of motor practice. The objective of this study was to quantify the type, amount, and timing of gross motor practice during physical therapist sessions. METHODS: A secondary video coding analysis of physical therapist sessions from the iMOVE clinical trial (NCT02340026) in young children with cerebral palsy (CP) was conducted. The 37 children who completed the treatment phase were included (mean age = 22.1 months). Children could initiate pulling to stand but were unable to walk. Videos of randomly selected therapy sessions were coded for gross motor activity (422 videos total). The 10 gross motor activity codes included lying, sitting, four point, crawling, kneeling, knee walking, standing, walking, transitions between floor postures, and transitions to/from an upright posture. Twenty percent of each video was double coded for reliability. Time per session, number of bouts, and median time per bout were calculated for each gross motor activity and for 2 aggregate measures: movement time and upright time. RESULTS: Participants spent more than half of therapy time in sitting and standing combined (60.3%). Transitions occurred more frequently than any other motor activity (49.3 total transitions per session). Movement time accounted for 16.3% of therapy time. Upright time accounted for 53.3% of therapy time. CONCLUSIONS: Critical practice time to gain motor skill is not equivalent to chronological time or time spent in therapy. Toddlers with CP spent a small amount of therapy time moving. Future work should explore the relations between motor practice and rehabilitation outcomes. IMPACT: Physical therapists are ideally suited to detail the content of motor practice and ultimately to prescribe optimal patterns of motor practice. We report the characteristics of gross motor practice during therapy in children with CP.

The ankle-brachial index, gastrocnemius mitochondrial respirometry, and walking performance in people with and without peripheral artery disease.

Background: Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle-brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. Objective: To describe associations of the ABI with mitochondrial respiratory function in gastrocnemius muscle biopsies and associations of gastrocnemius mitochondrial respirometry with 6-minute walk distance in people with and without PAD. Methods: People with (ABI ⩽ 0.90) and without (ABI 1.00-1.40) PAD were enrolled. ABI and 6-minute walk distance were measured. Mitochondrial function of permeabilized myofibers from gastrocnemius biopsies was measured with high-resolution respirometry. Results: A total of 30 people with PAD (71.7 years, mean ABI: 0.64) and 68 without PAD (71.8 years, ABI: 1.17) participated. In non-PAD participants, higher ABI values were associated significantly with better mitochondrial respiration (Pearson correlation for maximal oxidative phosphorylation PCI+II: +0.29, p = 0.016). In PAD, the ABI correlated negatively and not significantly with mitochondrial respiration (Pearson correlation for PCI+II: -0.17, p = 0.38). In people without PAD, better mitochondrial respiration was associated with better 6-minute walk distance (Pearson correlation: +0.51, p < 0.001), but this association was not present in PAD (Pearson correlation: +0.10, p = 0.59). Conclusions: Major differences exist between people with and without PAD in the association of gastrocnemius mitochondrial respiration with ABI and 6-minute walk distance. Among people without PAD, ABI and walking performance were positively associated with mitochondrial respiratory function. These associations were not observed in PAD.

Prognostic Value of Borg Scale Following Six-minute Walk Test in Hospitalized Older Patients with Heart Failure.

AIMS: The six-minute walk test (6MWT) is a widely accepted tool for evaluating exercise tolerance and physical capacity, and the six-minute walk distance (6MWD) is an established prognostic factor in patients with heart failure (HF). However, the prognostic implications of post-6MWT dyspnoea remain unknown. We aimed to investigate the prognostic value of Borg scores after the 6MWT in patients with HF. METHODS: Patients hospitalized for HF who underwent the 6MWT before discharge were included. Post-test dyspnoea was assessed using the Borg scale. Patients were stratified into low and high Borg score groups based on the median Borg score. The primary outcome was 2-year mortality. RESULTS: Among 1,185 patients analysed, the median Borg score was 12. The 6MWD was significantly shorter in the high Borg score group than in the low Borg score group. The 2-year mortality rate was 20.2%. In the Kaplan-Meier analysis, the high Borg score group demonstrated an association with 2-year mortality, which remained significant even after adjustment for conventional risk factors, including the 6MWD. Furthermore, Borg scale provided significant net reclassification improvement to the conventional risk model incorporating 6MWD. CONCLUSION: In hospitalized patients with HF, post-6MWT Borg scores were associated with 2-year mortality independent of the 6MWD, providing incremental prognostic value to the 6MWD. Even if patients are able to walk long distances for 6 minutes, it is essential to closely observe dyspnoea immediately thereafter.

Our study investigated the significance of breathlessness after a walking test in patients with heart failure and found that this provides important information about their prognosis. Key findings: Patients with heart failure who felt more breathless after the six-minute walk test (6MWT) were at a higher risk of mortality within two years.The level of breathlessness after the 6MWT provided additional information about prognosis beyond just how far patients could walk during the test.

Mobility trajectories in multiple sclerosis: A comparative study of timed 25-foot walk and a patient-reported outcome measure.

BACKGROUND: Loss of mobility is common in persons with multiple sclerosis (PwMS), but little is known about this impairment from the patient's perspective. OBJECTIVE: The aim is to model longitudinal variation in a mobility patient-reported outcome (PRO) and compare trajectories to those observed for Timed 25-Foot Walk (T25FW) in a retrospective cohort. METHODS: Latent-class growth analysis was applied to 47,508 measures of Performance Scales© Mobility PRO (PS-Mobility) over ~4 years for 8524 PwMS. For 7347 PwMS, there were 41,988 T25FW measures during this period. Repeated measures correlation and concordance of trajectory assignment were evaluated. RESULTS: At the group level, PS-Mobility and T25FW linearly worsened and repeated-measures correlation was moderate. Eight latent classes with varying shapes that worsened described PS-Mobility variation, compared to six latent classes for T25FW that differed by intercept. The agreement between PS-Mobility and T25FW cluster assignment was modest. A higher proportion of individuals who were Black/African American, older, Medicaid beneficiaries, living in deprived neighborhoods, had longer disease duration, had progressive disease, and ever smokers were assigned to more impaired clusters. DISCUSSION: Cross-sectionally, PS-Mobility and T25FW were highly correlated, but longitudinally correlation was modest to moderate, underscoring the importance of considering both objective and subjective perspectives in evaluating mobility changes in PwMS.

Where is the heat threat in a city? Different perspectives on people-oriented and remote sensing methods: The case of Prague.

Extreme heat in urban areas has a severe impact on urban populations worldwide. In light of the threats posed by climate change, it is clear that more holistic and people-oriented approaches to reducing heat stress in urban areas are needed. From this perspective we aim to identify and compare thermal hotspots and places with favourable thermal conditions, based on three different methods - thermal walk, participatory-based cognitive mapping, and remote sensing in a Central European city. Although major hotspots in large low-rise development zones were identified by all three methods, the overall agreement between on-site thermal sensation votes, cognitive maps and surface temperatures is low. In the urban canyon of compact mid-rise and open mid-rise development, the thermal walk method proved to be useful in the identification of the specific (parts of) streets and public spaces where citizens can expect thermal discomfort and experience heat stress, e.g. crossroads, arterial streets with a lack of greenery, north facing unshaded parts of streets, and streets with inappropriate tree spacing. Cognitive maps on an urban neighbourhood scale are not specific enough on a street level; however, as a supplementary method they can help identify discrepancies between on-site sensations and thermal conditions. For further research on effective and cost-efficient urban heat mitigation, we suggest combining thermal walks with numerical model simulations.

Physiotherapeutic Interventions for Patients With Rare Genetic Muscle-Wasting Disorders: A Systematic Review and Meta-Analysis.

Patients with rare genetic muscle-wasting disorders (MWDs) often experience significant motor function impairments, making effective management strategies crucial for improving their quality of life. This systematic review and meta-analysis aimed to evaluate the impact of physiotherapeutic interventions on motor outcomes in this patient population.  A comprehensive literature search was conducted to identify randomized controlled trials (RCTs) and cohort-based studies that assessed physiotherapeutic interventions in patients with rare genetic MWDs. The primary outcome measure was the 6-minute walk test (6MWT). A random effects model was employed to calculate the mean difference (MD) and 95% confidence interval (CI).  Nine studies were selected for inclusion, and most demonstrated observable improvement in different facets of individuals with MWDs using physiotherapy. The meta-analysis of RCTs showed that physiotherapy statistically improved 6MWT performance (MD: -35.25 meters; 95% CI: -54.14 to -16.37) with low heterogeneity (Tau² = 0.00; Chi² = 0.48, df = 2, P = 0.79; I² = 0%). Similarly, the cohort-based studies demonstrated an overall MD (MD: -10.00; 95% CI: -11.07 to -8.93), with low heterogeneity (Tau² = 0.00; Chi² = 0.01, df = 1, P = 0.94; I² = 0%). Both analyses indicated significant improvements in 6MWT performance (RCTs: Z = 3.66, P = 0.0003; cohort-based: Z = 18.26, P < 0.00001). Physiotherapeutic interventions significantly enhanced motor function in patients with rare genetic MWDs, as evidenced by improved 6MWT performance. Exercise and intensive physiotherapy programs were particularly effective, although the benefits varied depending on the specific intervention and patient population. These findings support incorporating tailored physiotherapeutic strategies in MWD management to improve motor outcomes and overall quality of life.

Evaluation of Five Screening Tools in Detecting Physical Frailty in Cirrhosis and Their Prognostic Role.

Background: Physical frailty (PF) is a syndrome of decreased physical function and reserves, preventing patients from coping with stressful events. PF screening tools in patients with liver cirrhosis (LC) can help evaluate the risk of complications and death. The aim of this study was to assess the performance of five screening tools in detecting PF and their ability to predict 18-month mortality in LC. Methods: The Short Physical Performance Battery (SPPB), Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and 6-Minute Walk Test (6MWT) were compared with the Liver Frailty Index (LFI) as the method of reference. Patients with an LFI ≥ 4.5, SPPB ≤ 8, FFP ≥ 3, CFS ≥ 6 points, and those walking <250 m, were considered frail. Results: A total of 109 consecutive patients with stable LC were included [63.3% male, median age 62 years, (IQR 52-70), MELD 9 (7-14.5), 46.8% with decompensated LC (DC)]. PF was present in 23.9%, 27.5%, 41.3%, 13.8%, and 28.4% as assessed by the LFI, SPPB, FFP, CFS, and 6MWT, respectively. Cohen's kappa measurement of agreement of four of the tools with LFI was 0.568, 0.334, 0.439, and 0.502, respectively (p < 0.001 for each). Kaplan-Meier survival curves at 18 months showed higher mortality in frail patients compared to non-frail patients by any method (log rank p < 0.05). In the multivariate models, PF defined by any method emerged as an independent prognostic factor of 18-month mortality after adjustment for age, gender, and MELD-score. Conclusions: Patients characterized as frail by five screening tools were not identical. However, PF defined by either method was proven to be an independent poor prognostic factor for long-term mortality after adjustment for covariates.

Percent Predicted vs. Absolute Six-Minute Walk Distance as Predictors of Lung Transplant-Free Survival in Fibrosing Interstitial Lung Diseases.

INTRODUCTION: Fibrosing interstitial lung diseases (ILDs) often progress despite treatment and become life-threatening, with lung transplant (LTx) remaining the only curative option. Six-minute walk distance (6MWD) is increasingly recognized as reliable predictor of clinical course, especially when longitudinally considered. The use of reference equations to express 6MWD as percent predicted (6MWD%) has not been previously studied in fibrosing ILDs. We sought to investigate whether the prognostic power of 6MWD% is superior to that of 6MWD expressed in meters (6MWD-m). METHODS: A retrospective, multicenter cohort analysis was conducted on both idiopathic pulmonary (IPF) and non-IPF fibrosing ILD patients. Patients were divided into a discovery (n = 211) and a validation (n = 260) cohort. Longitudinal changes of 6MWD% and lung function parameters were simultaneously considered. LTx-free survival at 3 years from baseline was the endpoint. Competing risks of death and LTx were considered. RESULTS: Baseline 6MWD% and its longitudinal changes were significant predictors of LTx-free survival and independent from lung function variables. In both cohorts, on multivariate cox proportional hazard regression analysis, receiver operating characteristics analysis and Kaplan-Meier estimates, 6MWD% was consistently, but only slightly superior to 6MWD-m as a predictor of LTx-free survival. CONCLUSION: 6MWD% has only a slight, yet detectable advantage over 6MWD-m as a predictor of survival in fibrosing ILDs. Utilizing 6MWD% may aid in risk stratification, treatment monitoring, and LTx timing optimization. However, available reference equations do have predicting limitations. Refined predictive equations and standardizing reporting practices are therefore needed to further enhance the clinical utility of 6MWD% in fibrosing ILDs.

Imputing Metagenomic Hi-C Contacts Facilitates the Integrative Contig Binning Through Constrained Random Walk with Restart.

Metagenomic Hi-C (metaHi-C) has shown remarkable potential for retrieving high-quality metagenome-assembled genomes from complex microbial communities. Nevertheless, existing metaHi-C-based contig binning methods solely rely on Hi-C interactions between contigs, disregarding crucial biological information such as the presence of single-copy marker genes. To overcome this limitation, we introduce ImputeCC, an integrative contig binning tool optimized for metaHi-C datasets. ImputeCC integrates both Hi-C interactions and the discriminative power of single-copy marker genes to group marker-gene-containing contigs into preliminary bins. It also introduces a novel constrained random walk with restart algorithm to enhance Hi-C connectivity among contigs. Comprehensive assessments using both mock and real metaHi-C datasets from diverse environments demonstrate that ImputeCC consistently outperforms other Hi-C-based contig binning tools. A genus-level analysis of the sheep gut microbiota reconstructed by ImputeCC underlines its capability to recover key species from dominant genera and identify previously unknown genera.