Function Testing Research Articles

Checks and balances: a meta-analysis on the known-groups validity of functional postural control tests in children.

Pediatric physical therapists commonly treat children with postural control deficits. Ideally, pediatric functional postural control tests should therefore be able to identify postural control deficits in children with various disorders. Despite a plethora of available tests, evidence for their validity - especially known-groups - remains scarce. This review aims to determine the known-group validity of available functional postural control tests to differentiate various pediatric pathological groups of different ages from their typically developing (TD) peers. PubMed, Web of Science and Scopus were systematically searched (last update: February 2023; PROSPERO: CRD42023408982). Forty case-control studies with a pathological pediatric sample (N.=1331) and TD peers (N.=1889) were included and selected for data-extraction and -analysis. Risk of bias was assessed using the SIGN checklist and level of evidence was scored using GRADE. Random-effect meta-analyses were performed to estimate pooled standardized mean differences (SMD) for the various test types and subclassified based on pathology and/or age. When compared with TD peers, children with underlying pathologies performed significantly worse on pediatric functional postural control test batteries (SMD=-2.21), the Timed Up and Go Test and variants (SMD=2.30), the One Leg Stance test and variants (SMD=-2.14), while the Reach tests showed a smaller difference (SMD=-1.19). Subclassification within the meta-analyses showed that pathology was an influencing factor for the test batteries and the one leg stance test and variants. Age was an influencing factor for the reach tests. None of the included functional postural control tests exceeded a low level of evidence. Pediatric functional postural control tests that assess multiple aspects of postural control (such as test batteries) seem to offer higher known-groups validity than single-task tests (e.g. reach tests). The underlying pathology has a larger impact on the validity of these tests than age. There remains an overall low level of evidence for the known-groups validity of pediatric functional postural control tests indicating the need for research with more homogenous groups and norm reference data.

Evaluation of the Effect of Botulinum Toxin A on the Lymphatic Endothelial Cells.

Botulinum toxin A (BoTA) is a neurotoxin formed by Clostridium botulinum, with a broad medical application spectrum. While the primary effect of BoTA is on the muscles, the effects of BoTA in other systems including the blood vasculature have already been examined, revealing unexpected actions. However, no studies exist to the best of our knowledge regarding the potential effects of BoTA on the lymphatic vascular system, possessing a critical role in health and disease. Isolated human lymphatic endothelial cells (LECs) were cultured in dedicated in vitro culture systems. The analysis including imaging and cell culture approaches as well as molecular biology techniques is performed to examine the LEC alterations occurring upon exposure to different concentrations of BoTA. Human LECs were cultured and expanded on collagen-coated petri dishes using endothelial basal medium and the commercial product Botox from Allergan as used for all our experiments. Harvested cells were used in various in vitro functional tests to assess the morphologic and functional properties of the BoTA-treated LECs. Gene expression analysis was performed to assess the most important lymphatic system-related genes and pathways. Concentrations of 1, 5 or 10 U of BoTA did not demonstrate a significant effect regarding the proliferation and migration capacity of the LECs versus untreated controls. Interestingly, even the smallest BoTA dose was found to significantly decrease the cord-like-structure formation capacity of the seeded LECs. Gene expression analysis was used to underpin possible molecular alterations, suggesting no significant effect of BoTA in the modification of gene expression versus the starvation medium control. LECs appear largely unaffected to BoTA treatment, with an isolated effect on the cord-like-structure formation capacity. Further work needs to assess the effect of BoTA on the smooth-muscle-cell-covered collecting lymphatic vessels and the possible aesthetic implications of such an effect, due to edema formation. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Does Concomitant Meniscectomy or Meniscus Repair Affect Muscle Strength, Lower Extremity Balance, and Functional Tests after Anterior Cruciate Ligament Reconstruction?

Background/Objective: The effects of concomitant meniscal tears and their associated treatment on strength, lower extremity balance, and functional status after anterior cruciate ligament reconstruction (ACLR) have not been widely investigated. This study aimed to compare the functional outcomes in patients who underwent ACLR with concomitant treatment of the medial meniscus repair versus meniscectomy when returning to unrestricted physical activity. Methods: A total of 85 patients who underwent primary ACLR with combined meniscal repair (MREP; n = 39) or meniscectomy (MRES; n = 46) were assessed. The dataset included the Functional Movement ScreenTM (FMS) outcomes and single-leg balance test (SLBT) with anterior-posterior, medial-lateral, and overall stability indexes. Isokinetic knee extension and flexion strengths were tested at velocities of 60 deg·s-1 and 180 deg·s-1. The peak torque-to-body weight ratio (PT/BW) and limb symmetry index (LSI) were calculated. Results: In the functional assessment, there was no significant inter-group difference in the composite score of the FMS (MREP: 15.08 pts vs. MRES: 15.13 pts; p > 0.05). The SLBT outcomes in inter-group and inter-extremity comparisons were irrelevant (p > 0.05), too. Significant differences emerged in the inter-group comparison of the knee extension strength in the non-operated extremity at both 60 deg·s-1 and 180 deg·s-1 (p = 0.02). Inter-extremity differences were significant in both the MREP and MRES groups for knee extension and flexion at both angular velocities (all p values < 0.05). For knee extension, the LSI values ranged from 82% to 87%, and for flexion, from 77% to 84%, with no significant inter-group differences. Conclusions: Patients undergoing ACLR with concomitant meniscal repair or resection did not exhibit differences in isokinetic muscle strength, lower extremity balance, and functional tests upon returning to activity. However, participants in both groups demonstrated significant differences between the operated and non-operated extremities as far as the knee joint extensor and flexor strengths are concerned. Therefore, rehabilitation protocols should prioritize equalizing inter-extremity strength differences after the ACLR with additional treatment procedures addressing the menisci.

Assessment of balance and risk of falls in people over 60 years old

Introduction: Falls of the elderly are a significant problem for public health and healthcare. They are also included in the geriatric giants, and the assessment of balance and risk of falls is an important part of the comprehensive geriatric assessment (CGA). It is estimated that almost one in three people over the age of 65 living independently in a community suffers one fall per year. These estimates increase with age, and in people older than 80 years, every second senior may experience at least one fall. The aim of the study was to assess the balance and risk of falls in people over 60 years of age living independently in society. Materials and methods: The study enrolled 40 seniors over the age of 60 who agreed to participate in the study and met the inclusion criteria. Three functional tests were used to assess balance and the risk of falls among seniors: the Timed Up and Go (TUG), the Four Square Step Test (FSST) and One-leg standing (OLS). Result: The study shows that as age increases, subjects perform worse on the Timed Up and Go rho = 0.38 test; p &lt; 0.05 and in the Four Square Step Test rho = 0.53; p &lt; 0.01. No statistically significant differences were observed between genders or age groups in the One Leg Standing test (OLS), although older people scored worse than younger age groups. There were no statistically significant associations between performance test results and BMI. The average results of the clinical tests show that the seniors in the study had good balance and a low risk of falling.

Functional clinical motor performance tests to assess potential fall risks in patients with haemophilia: A case-control study.

Patients with haemophilia (PwH) are at increased risk of falls due to haemophilic arthropathy. Yet, studies on clinical tests associated with the risk of falling are scarce in PwH. (1) To evaluate the feasibility of different clinical motor performance tests associated with the risk of falling in PwH; (2) to evaluate PwH's performance of these tests compared to a control group; (3) to identify possible influencing factors that affect performance. Twenty-nine severe and moderate PwH (57.0 years, IQR: 48.0-61.5) and 29 healthy age- and BMI-matched control participants (CG) performed 13 different clinical tests (SPPB, timed up and go, push and release, functional reach, single-leg stance, knee and grip strength). Haemophilia joint health score (HJHS), kinesiophobia (TSK-11), subjective physical performance (HEP-Test-Q), falls efficiency (FES-I) and falls were assessed. No adverse events occurred. PwH showed impaired performance in all clinical tests, a lower falls efficiency and a higher HJHS than CG. PwH with higher HJHS, lower HEP-Test-Q and higher TSK-11 scores showed higher deficits. Largest discrepancies were observed in the single-leg stance with eyes open and knee extensor strength, where orthopaedically majorly affected PwH showed worse performance compared to minorly affected PwH and the CG, respectively. The prevalence of ≥1 fall in the last year was 27.6% (PwH) and 10.3% (CG). These clinical tests are feasible in PwH. Impaired joint status, a high kinesiophobia and low physical performance impair performance. These tests can be used by clinicians for gaining specific information on functional motor abilities of patients.

Pyroptosis and mitochondrial function participated in miR-654-3p-protected against myocardial infarction

Myocardial infarction (MI) is one of the leading causes of heart failure with highly complicated pathogeneses. miR-654-3p has been recognized as a pivotal regulator of controlling cell survival. However, the function of miR-654-3p in cardiomyocytes and MI has yet to be reported. This study aimed to identify the role of miR-654-3p in the regulation of myocardial infarction. To understand the contribution of miR-654-3p on heart function, we generated cardiac-specific knockdown and overexpression mice using AAV9 technology in MI injury. Mechanically, we combined cellular and molecular techniques, pharmaceutical treatment, RNA sequencing, and functional testing to elucidate the potential pathological mechanisms. We identified that mice subjected to MI decreased the expression of miR-654-3p in the border and infarcted area. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. Furthermore, we found a deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death but not other programmed cell death. Intriguingly, miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Cardiac elevating miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Using RNA sequence and molecular biological approaches, we found overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function. Our finding identified the character of miR-654-3p in protecting against MI damage by mediating pyroptosis and mitochondrial metabolism. These findings provide a new mechanism for miR-654-3p involvement in the pathogenesis of MI and reveal novel therapeutic targets.miR-654-3p expression was decreased after MI. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. The deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death. miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Overexpression of miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function.

Soqia-Advice: A Web-GIS Advisory Platform for Efficient Irrigation in Arboriculture

The determination of water requirements for crops holds a crucial role in optimizing irrigation and enhancing agricultural productivity. However, identifying these needs remains a significant challenge due to the variety of factors influencing this decision, such as meteorological conditions, soil structure, and the phenological stages of each crop. In this study, we propose the design and development of a dedicated web-based irrigation advisory platform for arboriculture named ‘Soqia-Advice’. This platform will provide services to farmers, advisors, and decision-makers. The proposed methodology is based on four main steps: (1) need assessments; (2) definition of functionalities to fulfill these needs; (3) design of the overall architecture and the conceptual data model; and (4) implementation of key features of the module dedicated to farmers. The prototype of the “Farmer” module was tested on a farm in Azrou city, Morocco, as a case study. Seven-day weather forecasts were seamlessly integrated using the Weatherbit API. Additionally, the irrigation schedule was accurately displayed, ensuring efficient water management. Functionality tests were conducted on each menu to ensure the seamless and reliable operation of all planned features. The results were rigorously assessed to ensure that each feature aligned with the identified needs.

On periodic maintenance for a protection system

This article presents a model for maintenance planning of protection systems, such as isolation valves, circuit breakers, and other safety barriers. These systems are designed to operate on demand and prevent environmental catastrophes. The proposed model is novel because: (i) inspections (functional tests) are fixed and periodic; and (ii) the replacement policy has three-phases, corrective, opportunistic-preventive, and scheduled-preventive. Thus, the system is replaced: at a positive test; at a test regardless of the outcome either if an opportunity arises or when the system reaches a critical age. The model is relevant because periodic inspections are largely the practical, engineering reality, and particularly useful for geographically distributed systems, for which there is limited time and resources for maintenance. The paper provides a web-based application as a demonstrator of the proposed model. The study extends and refines well-known policies from the literature, providing valuable insights about applicability across various parameter settings.

Cardiac Health Assessment Using a Wearable Device Before and After Transcatheter Aortic Valve Implantation: Prospective Study.

Due to aging of the population, the prevalence of aortic valve stenosis will increase drastically in upcoming years. Consequently, transcatheter aortic valve implantation (TAVI) procedures will also expand worldwide. Optimal selection of patients who benefit with improved symptoms and prognoses is key, since TAVI is not without its risks. Currently, we are not able to adequately predict functional outcomes after TAVI. Quality of life measurement tools and traditional functional assessment tests do not always agree and can depend on factors unrelated to heart disease. Activity tracking using wearable devices might provide a more comprehensive assessment. This study aimed to identify objective parameters (eg, change in heart rate) associated with improvement after TAVI for severe aortic stenosis from a wearable device. In total, 100 patients undergoing routine TAVI wore a Philips Health Watch device for 1 week before and after the procedure. Watch data were analyzed offline-before TAVI for 97 patients and after TAVI for 75 patients. Parameters such as the total number of steps and activity time did not change, in contrast to improvements in the 6-minute walking test (6MWT) and physical limitation domain of the transformed WHOQOL-BREF questionnaire. These findings, in an older TAVI population, show that watch-based parameters, such as the number of steps, do not change after TAVI, unlike traditional 6MWT and QoL assessments. Basic wearable device parameters might be less appropriate for measuring treatment effects from TAVI.

Significance of Selected Posturographic Methods in Diagnosis of Balance Disorders in Patients with Early-Stage Gonarthrosis.

Degenerative joint disease is a dynamic pathological process characterised by a destabilisation of the degradation and synthesis processes of articular cartilage and subchondral bone layer. Studies suggest that individuals with gonarthrosis experience deficits in proprioception, in addition to changes within their joints, which directly affects their ability to maintain posture and increases their risk of falling. Objectives: The aim of this study was to assess the functional status of patients with gonarthrosis through a posturographic examination conducted on a stabilometric platform (force plate) and a functional clinical examination. Methods: Participants were divided into two groups-a control group (n = 125) and a study group (n = 125). During the qualification process, subjective and objective examinations were conducted, including a functional assessment by means of such tests as the "Up and Go" Test, Functional Reach Test, Five Time Sit to Stand Test, and the Step Test. Subsequently, an assessment was conducted on the force plate by means of a posturographic test-the Romberg test performed with open and closed eyes in a standing position-and balance was evaluated using the Berg Balance Scale. The obtained data were analysed with the use of the IBM SPSS Statistics software version 27.0, by means of the Mann-Whitney test, and correlations were determined by means of Spearman's test. A significance level of p = 0.05 was adopted. Results: Statistically significant differences were observed among the assessed groups as a result of both functional and posturographic examinations, along with positive correlations for disease duration, age, and BMI index. Conclusions: Patients with gonarthrosis exhibited disturbances in balance, functionality, and posture compared to healthy individuals in the control group.

Which reference equation should we use for interpreting spirometry values for First Nations Australians? A cross-sectional study.

To evaluate the suitability of the Global Lung Function Initiative (GLI)-2012 other/mixed and GLI-2022 global reference equations for evaluating the respiratory capacity of First Nations Australians. Cross-sectional study; analysis of spirometry data collected by three prospective studies in Queensland, the Northern Territory, and Western Australia between March 2015 and December 2022. Opportunistically recruited First Nations participants in the Indigenous Respiratory Reference Values study (Queensland, Northern Territory; age, 3-25 years; 18 March 2015 - 24 November 2017), the Healthy Indigenous Lung Function Testing in Adults study (Queensland, Northern Territory; 18 years or older; 14August 2019 - 15 December 2022) and the Many Healthy Lungs study (Western Australia; five years or older; 10 October 2018 - 7November 2021). Goodness of fit to spirometry data for each GLI reference equation, based on mean Z-score and its standard deviation, and proportions of participants with respiratory parameter values within 1.64 Z-scores of the mean value. Acceptable and repeatable forced expiratory volume in the first second (FEV1) values were available for 2700 First Nations participants in the three trials; 1467 were classified as healthy and included in our analysis (1062 children, 405 adults). Their median age was 12 years (interquartile range, 9-19 years; range, 3-91 years), 768 (52%) were female, and 1013 were tested in rural or remote areas (69%). Acceptable and repeatable forced vital capacity (FVC) values were available for 1294 of the healthy participants (88%). The GLI-2012 other/mixed and GLI-2022 global equations provided good fits to the spirometry data; the race-neutral GLI-2022 global equation better accounted for the influence of ageing on FEV1 and FVC, and of height on FVC. Using the GLI-2012 other/mixed reference equation and after adjusting for age, sex, and height, mean FEV1 (estimated difference, -0.34; 95% confidence interval [CI], -0.46 to -0.22) and FVC Z-scores (estimated difference, -0.45; 95% CI, -0.59 to -0.32) were lower for rural or remote than for urban participants, but their mean FEV1/FVC Z-score was higher (estimated difference, 0.14; 95% CI, 0.03-0.25). The normal spirometry values of healthy First Nations Australians may be substantially higher than previously reported. Until more spirometry data are available for people in urban areas, the race-neutral GLI-2022 global or the GLI-2012 other/mixed reference equations can be used when assessing the respiratory function of First Nations Australians.

Associations Between Fat and Lean Mass Indexes and Physical Performance in Prefrail and Frail Older Women.

Age-related changes in body composition have been associated with reduced physical performance. However, the relationship of fat and lean mass indexes with physical performance in the setting of frailty is yet to be clearly established. We investigated the association between fat and lean mass indexes and physical performance in prefrail and frail older women. Fifty-one community-dwelling women 65 years and older (mean age 76 years) were classified as prefrail or frail according to a modified frailty phenotype. Body composition was estimated by dual-energy X-ray absorptiometry, while physical performance was assessed via the following tests: Berg balance scale, timed-stands, timed up-and-go test, 6-minute walk test, and the short performance physical battery. Correlation coefficients were determined to assess the association between body composition and physical performance parameters. Associations between continuous variables with a p-value <0.05 were included in a linear regression analysis. All fat mass indexes predicted a reduced performance in at least one functional test. Among the lean mass indexes, only leg lean mass adjusted by body fat mass was directly associated with better physical performance. Our findings indicate that fat mass indexes may have a greater impact on physical performance than lean mass in frail and prefrail older women.

Operative Repair of Hamstring Injuries From the Jackling Position in Rugby.

The jackling position within rugby has not been previously described as a mechanism for proximal hamstring injuries. Acute surgical repair of proximal hamstring avulsion injuries sustained from the jackling contact position enables a return to a previous level of sporting activity with low risk of recurrence. Case series; Level of evidence, 4. This study included 54 professional rugby players (mean age, 26 ± 4.8 years) who underwent acute primary surgical repair of complete, proximal hamstring avulsion injuries. The mean follow-up time was 17 months (range, 12-24 months). Mean isometric hamstring strength and function testing was performed at 3 months and 1 year after repair. Of the 54 players, 51 (94.4%) returned to their preinjury level of sporting activity. The mean time from surgical repair to full sporting activity was 7 months (range, 4-12 months). No patients had recurrence of the primary injury. At 1 year postoperatively, patients had significantly restored mean isometric hamstring muscle strength when compared with the uninjured leg at 0° (98.4% ± 2.8%), 15° (95.9% ± 2.9%), and 45° (92.9% ± 4.1%); improved Lower Extremity Functional Score (78.0 ± 2.0); and improved Marx activity rating score (14.3 ± 1.5) (P < .001 for all). Acute surgical repair of proximal hamstring avulsion injuries caused by the contact jackling position produced a high return to preinjury level of sporting activity, increased muscle strength, and improved functional outcome scores, with a low risk of recurrence at short-term follow-up.

Utility and Validity of the HFA-PEFF andH2FPEF Scores in Patients With Symptomatic Atrial Fibrillation.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with atrial fibrillation (AF) represents a significant clinical challenge. Two diagnostic scoring tools have been developed to aid the noninvasive diagnosis of HFpEF: the HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology) and the H2FPEF scoring systems. The purpose of this study was to evaluate the performance of these 2 scoring tools for the diagnosis of HFpEF against a gold standard of invasive evaluation in a cohort of patients with AF. The authors recruited consecutive patients with symptomatic AF and preserved ejection fraction who were scheduled for an AF ablation procedure. Gold-standard invasive diagnosis of HFpEF was performed at the AF ablation procedure using mean left atrial pressure at rest and following infusion of 500mL fluid. Each participant was scored according to the noninvasive HFA-PEFF and H2FPEF scoring systems. Sensitivity and specificity analyses were performed to assess the accuracy of these scoring systems in diagnosing HFpEF. In total, 120 participants were recruited. HFpEF was diagnosed invasively in 88 (73.3%) participants, whereas 32 (26.7%) had no HFpEF. Using the HFA-PEFF score, 38 (31.7%) participants had a high probability of HFpEF and 82(68.3%) had low/intermediate probability of HFpEF. Using the H2FPEF tool, 72 (60%) participants had a high probability of HFpEF and 48 (40%) had intermediate probability. A high HFA-PEFF (≥5 points) score could diagnose HFpEF with a sensitivity of 40% and a specificity of 91%, and a high H2FPEF score (≥6 points) could diagnose HFpEFwith a sensitivity of 69% and specificity of 66%. Overall diagnostic accuracy was similar using both tools (AUC:0.663 vs 0.707, respectively; P = 0.636). Against a gold standard of invasively diagnosed HFpEF, the HFA-PEFF and H2FPEF scores demonstrate only moderate accuracy in patients with AF and should be utilized with caution in this cohort of patients. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921).

Clinical validation of image-based AI predictive biomarkers for precision neoadjuvant triple-negative breast cancer treatment (PEAR-TNBC).

TPS627 Background: Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancer subtypes, with a 5-year recurrence rate of 30% in patients with localized disease. Pathological Complete Response (pCR) strongly predicts the risk of recurrence and death, which are reduced by approximately 80% in patients who achieve a pCR following neoadjuvant treatment. There are multiple treatment regimens available for TNBC patients in the neoadjuvant setting but no biomarkers to match patients to treatments. Giving ineffective treatment leads to worse outcomes for patients and additional burden on healthcare systems. Pear Bio has developed a functional precision medicine test coupling an organ-on-a-chip with a computer vision (CV) pipeline through which an individual patient’s response to different treatments can be monitored simultaneously ex vivo. Each microtumor’s response is monitored using time-lapse 3D microscopy. A proprietary CV pipeline quantifies the responses (e.g. tumor cell viability, culture size). Lab test responses are correlated to the clinical outcomes of the patients to identify biomarkers with high predictive accuracy. This generates multiple CV-based biomarkers with potential predictive value. PEAR-TNBC (NCT05435352) is a prospective, observational UK-wide trial aimed at assessing the test’s accuracy in predicting pCR in TNBC patients in the neoadjuvant setting. The study recruits patients with early TNBC (N=54) who are willing to undergo an additional core needle biopsy prior to starting neoadjuvant therapy. The assay is run in parallel with the patient’s treatment and the treating oncologist is blind to the results of the Pear Bio test. Methods: The study has 2 cohorts (A and B), each recruiting at least 20 evaluable patients. To be eligible, patients need to have ≥10mm tumor, stage I-III, TNBC, with planned neoadjuvant treatment followed by surgery and be willing to undergo a study-specific core needle biopsy procedure. Cohort B also requires a 40mL blood sample. To be evaluable, eligible patients’ samples must be successfully cultured in the 3D ex vivo assay and they must complete at least 4 cycles of neoadjuvant chemotherapy prior to surgery. Cohort A recruitment began on 05/27/22 and has recruited 20 evaluable patients, through 5 sites. Cohort B accrual will begin upon completion of Cohort A. The primary endpoint is the accuracy of the Pear test in predicting pCR, defined as specificity, with secondary outcomes as sensitivity, and positive and negative predictive values. Novel aspects include a focus on specificity (i.e. accurately predicting patients who will not achieve pCR) combined with the use of Receiver-operating characteristic curves to define optimal cutoffs for the CV biomarkers. Future trials will aim to run the test prior to therapy selection, guiding the choice of regimen to assess the test’s ability to increase pCR rates. Clinical trial information: NCT05435352 .

Development of Arduino-based high heat detector temperature control prototype for household appliances

&lt;span lang="EN-US"&gt;In the Philippines, fires are a widespread concern, with plenty of incidents attributed to electrical appliances. These incidents are a leading cause of non-open flame fires in the country, highlighting the urgent need for preventative measures. Existing devices could only trigger an alarm at 100 °C without shutting off the appliance automatically. To address these limitations, the researchers aimed to develop a high heat detector with 95% detection accuracy and less than 5% error in detecting high heat. This device used an Arduino Uno Board and relay to trigger an automated power-off mechanism in appliances experiencing high heat. Temperature changes were detected, and alarms were activated using an LM35 temperature sensor and buzzer. The accuracy of the LM35 sensor was assessed through hot bath tests, which included 12 trials at each temperature level between 80 °C and 150 °C with 10 °C intervals. The prototype’s performance revealed an average error rate of 1.13% and an average standard deviation of 0.9403. The computed F1 Score of 98% indicated that the prototype fulfilled the objectives. Functionality tests confirmed that the prototype successfully achieved its intended goal by shutting off the appliance when the threshold temperature was reached and enabling its operation otherwise.&lt;/span&gt;

A comprehensive two-dimensional scoring system to assess the single-leg squat task in football players

BackgroundThe single-leg squat (SLS) is a safe and widespread functional test commonly performed in the mid-stages of rehabilitation after severe knee injuries. The use of reliable objective measures has been advocated to improve the quality of SLS assessment. The aim of this study was to describe a qualitative whole-body scoring system based on two-dimensional (2D) video analysis during SLS test and validate it against three-dimensional (3D) kinetics and kinematics. MethodsThirty-four competitive football (soccer) players performed a series of SLS tasks. 3D kinematics and kinetics were collected through infrared cameras, and 2D video analysis was performed through a scoring system with sub-scores ranging from 0/2 (non-adequate movement) to 2/2 (adequate movement) based on frontal and lateral planes objective measurements. 3D kinematics and kinetics were grouped according to the results of the 2D evaluation and compared through the analysis of variance (P < 0.05). ResultsHigher hip adduction, hip internalrotation, and knee valgus collapse were found in trials rated 0/2 or 1/2 compared with theone rated 2/2 in the limb stability score. Hip flexion and hip/knee moment ratio were lower in those scoring 0/2 comparedwith those scoring 2/2 in the movement strategy criterion. A low total score was associated with higherknee valgus collapse and lower hip/knee extensor moment ratio. Compensatory strategieswere found in frontal plane scores. ConclusionsThe 2D scoring system described was strongly associated with kinematics and kinetics from gold-standard 3D motion capture and might represent a valid tool to describe the movement quality of an SLS task.

Cosmic Whirl: Navigating the Comet Trail in DNA: H2AX Phosphorylation and the Enigma of Uncertain Significance Variants.

Pathogenic variations in the BRCA2 gene have been detected with the development of next-generation sequencing (NGS)-based hereditary cancer panel testing technology. It also reveals an increasing number of variants of uncertain significance (VUSs). Well-established functional tests are crucial to accurately reclassifying VUSs for effective diagnosis and treatment. We retrospectively analyzed the multi-gene cancer panel results of 922 individuals and performed in silico analysis following ClinVar classification. Then, we selected five breast cancer-diagnosed patients' missense BRCA2 VUSs (T1011R, T1104P/M1168K, R2027K, G2044A, and D2819) for reclassification. The effects of VUSs on BRCA2 function were analyzed using comet and H2AX phosphorylation (γH2AX) assays before and after the treatment of peripheral blood mononuclear cells (PBMCs) of subjects with the double-strand break (DSB) agent doxorubicin (Dox). Before and after Dox-induction, the amount of DNA in the comet tails was similar in VUS carriers; however, notable variations in γH2AX were observed, and according to combined computational and functional analyses, we reclassified T1001R as VUS-intermediate, T1104P/M1168K and D2819V as VUS (+), and R2027K and G2044A as likely benign. These findings highlight the importance of the variability of VUSs in response to DNA damage before and after Dox-induction and suggest that further investigation is needed to understand the underlying mechanisms.

Effect of SLAMF8 on the phagocytosis of tumor-associated macrophages in colorectal cancer.

e14571 Background: Phagocytosis plays an essential role in innate immunity and is key in bridging innate immunity and adaptive immunity. Phagocytosis checkpoints promote tumor immune escape by inhibiting phagocytosis by tumor-associated macrophages (TAMs). SLAMF8, which is mainly expressed on the surface of TAMs, may be involved in regulating the tumor immune microenvironment. However, its regulation of the phagocytosis of TAMs remains unclear. The present study aims to investigate the effect of SLAMF8 on the phagocytosis of TAMs and to provide a new target for tumor immunotherapy. Methods: The dataset including 458 colorectal cancer (CRC) tissues from the TCGA database was used to analyze the correlation between the expression of SLAMF8 and several classical phagocytosis checkpoint molecules, and the above correlation was further verified by the RNA-sequencing data of 20 CRC tissues in our center. In vitro, the effects of SLAMF8 expression level on tumor cell proliferation and macrophage phagocytosis were also evaluated. RNA sequencing was used to analyze the effect of SLAMF8 on the expression of genes related to promoting macrophage phagocytosis. The effect of SLAMF8 on the expression levels of proteins related to FcR-mediated phagocytosis was detected by flow cytometry. Results: The results from the TCGA dataset and our validation dataset both showed that the SLAMF8 expression was significantly positively correlated with the expression levels of classical phagocytosis checkpoint molecules such as SIGLEC11, SIGLEC10, SIGLEC9, CD274and LILRB1. In vitro, functional tests showed that the phagocytosis of CT26 CRC cells by macrophages was significantly enhanced after SLAMF8 knockdown. RNA sequencing results suggested that the expression levels of molecules related to FcR-mediated phagocytosis were significantly upregulated after the decreased expression of SLAMF8.Flow cytometry analysis confirmed that SLAMF8 inhibited the expression levels of FcR-mediated phagocytosis related proteins such as CD16/32, CD64, and CD11b. Conclusions: SLAMF8 may release the “don’t-eat me” signal to inhibit FcR-mediated phagocytosis of tumor cells by macrophage. Further studies are needed to investigate the underlying mechanism of SLAMF8 on the regulation of macrophage phagocytosis and to test its possibility as a new immunotherapy target.

The association between six-minute walk test and one minute sit to stand test in patients with acute exacerbations of COPD

ABSTRACT Aim: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major complication of COPD and a leading cause of hospitalization, detrimentally affecting functional exercise capacity. The 6-minute walk test (6MWT) is a reliable measure of exercise capacity in chronic lung diseases. Conversely, the 1-minute sit-to-stand test (1STST) offers a simpler assessment of physical function. The aim was to demonstrate the association of functional exercise capacity assessed by 1STST and 6MWT in COPD patients with acute exacerbation. Materials and Methods: In this study, 37 hospitalized patients with acute exacerbation COPD (mean age:66 years) underwent assessments including pulmonary function testing, 6MWT, 1STST and modified Medical Research Council (MMRC). Parameters such as heart rate, oxygen saturation, and perceived dyspnea (via the modified Borg scale) were monitored during tests. Results: The results showed a significant correlation between 6MWT and 1STST performance (r=0.656, p&amp;lt;0.001). Notably, end-tidal oxygen saturation differed between tests, with the 6MWT showing higher end-tidal dyspnea scores. During recovery, 1STST induced increased heart rate and decreased oxygen saturation. Both 6MWT and 1STST were negatively associated with age and MMRC. Positive correlations were observed between 6MWT and FEV1(L) and PEF(L). Conclusions: Similar to the 6MWT, the 1STS test may be used to evaluate how well patients with AECOPD perform during functional exercise. We propose that the 1STST is a suitable alternative to the 6MWT for the assessment of functional exercise performance during hospitalization in AECOPD patients.