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Clinical data of 3 patients with refractory systemic lupus erythematosus (rSLE) who received chimeric antigen receptor T-cell (CAR-T) therapy at the Department of Rheumatology and Immunology, the First Affiliated Hospital of University of Science and Technology of China, from June to September 2024 was prospectively enrolled. After lymphodepleting preconditioning with cyclophosphamide combined with fludarabine, 2 patients received a low dose (0.5×10⁶/kg) and 1 patient received a medium dose (1.0×10⁶/kg) of a 4th-generation CAR-T cells (SCAR02) targeting cluster of differentiation 19 (CD19) and B-cell maturation antigen (BCMA) and secreting interleukin-6 (IL-6) antibodies. Follow-up was conducted at day 14 and months 1, 2, 3, 6, 9, and 12 post-infusion to systematically evaluate safety (including treatment-related adverse events, cytokines, and immunoglobulin levels) and efficacy (including cellular kinetics, clinical efficacy, and serological markers). All 3 patients were females, aged 37, 25, and 41 years, respectively. During the follow-up period, no cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or other serious adverse events occurred. CAR-T cells expanded well in all patients; peripheral blood CD19⁺ B cells were completely depleted on days 9-13 and gradually recovered over 3-5 months. By month 12, the SLE Disease Activity Index 2000 (SLEDAI-2K) scores of patients 1 to 3 decreased from 8, 8, and 9 at baseline to 0, 4, and 0, respectively; anti-double-stranded DNA antibodies all turned negative, and complement levels returned to normal. Two patients achieved drug-free complete remission based on the Definitions of Remission in SLE (DORIS) criteria, and 1 patient achieved an SLE Responder Index-4 (SRI-4) response. This study demonstrates that SCAR02 exhibits a good safety profile and preliminary efficacy in rSLE patients, and its function of secreting IL-6 antibodies may help alleviate CRS. 前瞻性收集2024年6—9月在中国科学技术大学附属第一医院风湿免疫科接受嵌合抗原受体T细胞（CAR-T）治疗的3例难治性系统性红斑狼疮（rSLE）患者的临床资料。所有患者经环磷酰胺联合氟达拉滨清淋预处理后，2例患者接受低剂量（0.5×106/kg）、1例接受中剂量（1.0×106/kg）靶向白细胞分化抗原19（CD19）和B细胞成熟抗原并分泌白细胞介素6（IL-6）抗体的第4代CAR-T细胞（SCAR02）输注。分别于回输后第14天及第1、2、3、6、9、12个月进行随访，系统评估安全性（包括治疗相关不良事件、细胞因子及免疫球蛋白水平）与疗效（包括细胞动力学、临床疗效及血清学指标）。3例患者均为女性，年龄分别为37、25和41岁。随访期内未出现细胞因子释放综合征（CRS）、免疫效应细胞相关神经毒性综合征或其他严重不良事件。CAR-T细胞在患者体内均扩增良好，第9~13天实现外周血CD19+B细胞完全清除，3~5个月逐步恢复。至第12个月，3例患者的SLE疾病活动指数2000评分由基线的8、8、9分分别降至0、4、0分；抗双链DNA抗体均转为阴性，补体水平恢复正常；2例患者达到SLE缓解定义标准的停药完全缓解，1例患者达到SLE应答指数4应答。该研究表明，SCAR02在rSLE患者中显示出良好的安全性与初步疗效，分泌IL-6抗体的功能或有助于减轻CRS。.
Uncontrolled bleeding is a major cause of life-threatening conditions in emergency situations. Due to their limited blood absorption and procoagulant capacity, current hemostatic materials often exhibit poor efficacy in treating uncontrolled bleeding. Although sunflower stem pith (SSP) has been proved to facilitate blood coagulation, its practical application is restricted by anisotropic fluid absorption and low mass transfer efficiency. In this study, a novel SSP composite hemostatic material was prepared by disrupting the anisotropic structure of SSP and reassembling it into an isotropic architecture within a chitosan network, which exhibited controlled fluid absorption, shape memory and procoagulant properties. Among all the samples, the SSP composite sponge containing 1% chitosan (SSP + 1% CS) showed the highest blood absorption capacity, with the blood absorption ratio reaching 2009.8% (w/w) and a blood absorption speed of 140.3 μg (cm3 s)-1, and a shape recovery ratio exceeding 95% in blood within 12 s. In vitro coagulation tests verified that the SSP composite sponge reduced the clotting time by more than 39% compared to gauze. The SSP composite sponge significantly shortened the hemostatic time and reduced the blood loss in four animal bleeding models. In the rabbit femoral artery injury model, the hemostatic time of the SSP composite sponge was 71.8 s, which was 32% shorter than 105.6 s of the QuikClot® group; the blood loss of the SSP group was 2.1 g, representing a 55% reduction relative to the 4.68 g in the QuikClot® group. Cytotoxicity and hemocompatibility assays confirmed the excellent biocompatibility of the SSP composite sponges. Consequently, the SSP composite sponge has turned out to be a promising material for prehospital emergency hemostasis, which provides a model of high-value applications of SSP bioresources.
In recent years, the development of sustainable animal feed has turned toward bioprocessing agricultural byproducts. White-rot fungi, known for their lignin-degrading ability, represent an efficient tool to improve lignocellulosic residues for ruminant feeding. This study investigated the conversion of date palm leaves (DPL) into a nutritive feed through solid-state fermentation using Lentinus tigrinus and Fomes fomentarius for 22 days at 28 °C. Fungal biotreatment significantly improved the chemical characteristics and ruminal fermentation dynamics of DPL. The estimated crude protein content increased by 33.5% with F. fomentarius and 16.2% with L. tigrinus, while structural fiber components (NDF, ADF, ADL) were significantly reduced (P < 0.05). In vitro gas production tests revealed increased gas output and improved utilization of the insoluble substrate fraction, particularly in samples treated with L. tigrinus. Overall, fungal fermentation effectively improved the nutritional value and digestibility of DPL, demonstrating its potential as a sustainable alternative feed for ruminants.
To expand the performance envelope of current unmanned underwater vehicles (UUVs) operating in near shore environments, researchers have increasingly turned to marine animals as models to develop bio-inspired robotic systems that leverage biological swimming strategies. In particular, California sea lions swim with great maneuverability in highly dynamic flow environments by coordinating multiple, spatially distributed control surfaces along their bodies. Despite significant progress in the development of bio-inspired robots, the individual and combined roles of different control surfaces and how their actuation affects turning of the robotic system remains under explored. In this study, a bio-inspired sea lion robot and its numerical model were used to understand how the actuation angle of control surfaces such as head, pelvis, fore flippers and hind flippers affected pitch and yaw turns. The turning performance of the bio-robotic platform was evaluated using turning radius, maximum angular velocities, and final orientation. Experimental and numerical results showed that actuating anterior control surfaces in combination with posterior control surfaces reduced turning radius and increased maximum angular velocity and final orientation relative to posterior-only actuation. Actuating fore flippers near the center of mass during pitch turns further enhanced turning performance by reducing lateral slip and producing tighter turns. Importantly, the results also revealed that maximum actuation of control surfaces did not always yield superior turning performance, as specific non-maximal head-pelvis actuation combinations produced better turns. These findings demonstrate that turning performance in bio-inspired, multi-body underwater systems depends on both the geometric location of control surfaces and their actuation angles. More broadly, the results suggest that actuation strategies should be tailored to the intended turning behavior, providing design and control guidance for future articulated underwater robots.
Approximately 60% of women experience some degree of perineal laceration following vaginal delivery. Although there is evidence supporting the use of photobiomodulation (PBM) for pain relief and wound healing in various conditions, there is a lack of studies on its effect on these lacerations. Our hypothesis is that PBM aids in pain management and healing in perineal lacerations/episiotomies in hospitalized women. A randomized, controlled, double-blind clinical trial in women with grade I/II lacerations and/or episiotomy, assigned to the intervention group (660 nm; 4 J) or placebo group (device turned off). Primary outcome was perineal pain at rest and during movements, measured using the numeric rating scale. Secondary outcome was healing, measured using the REEDA (redness, edema, ecchymosis, discharge, approximation) scale. Additionally, in-hospital analgesic consumption, self-perception of perineal laceration healing, and satisfaction with the intervention were analyzed. Analysis performed pre-intervention (6-12 h postpartum), post-intervention 1 (6-12 h post-first intervention), post-intervention 2 (12-18 h post-first intervention), and follow-up (7-15 days postpartum). Analysis was performed on an intention-to-treat basis using the Mann-Whitney test. A total of 59 women participated (intervention 30; placebo 29), most of whom were primiparous. The intragroup analysis shows a reduction in perineal pain during rest and movements, with improved healing in both groups. No difference was observed in intergroup analysis. The intervention group consumed fewer analgesics and had a longer interval between doses than the placebo group. Photobiomodulation (660 nm; 4 J) applied within 24 h postpartum, did not result in clinical improvement in pain or healing in women with perineal lacerations/episiotomies.
Abdominal aortic aneurysms (AAA) occupy the first place by the incidence amongst all aortic aneurysms and are found in 0.1-1.6% of all autopsies. The natural outcome of the AAA course is rupture occurring, according to literature data, in 50-80% of patients Amongst AAAs, there are forms posing great challenges in diagnosis and surgical management due to rarity of the disease and diversity of clinical manifestations. The purpose of this study was to determine the leading clinical signs of rare forms of AAA rupture and develop optimal surgical tactics of treating them. At the Department of Vascular Surgery of the 'Institute of Emergency and Restorative Surgery named after V.K. Gusak', we operated on a total of 633 patients with AAAs, of these, 285 (45%) for a ruptured aneurysm. Amongst the latter, there were 22 (7.7%) patients presenting with rare forms of rupture defined as: chronic contained rupture in 7 (2.5%) patients, aneurysmal rupture into the gastrointestinal tract with the formation of an aortoenteric fistula in 6 (2.1%) patients, rupture into the inferior vena cava with the formation of an aortocaval fistula in 6 (2.1%) patients, and a combination of AAA rupture with abdominal aortic dissection in 3 (1%) cases. The main methods of examination included duplex and triplex scanning, Doppler ultrasonography, and in insufficient information, spiral computed tomography (SCT) and SCT-angiography. All 22 patients were operated on. Of these, 9 (40.9%) patients died. The diagnostic peculiarities were as follows: 1. Chronic contained rupture turned out to be difficult to differentiate from a retroperitoneal tumor, both before and during surgery. Two-phase nature of clinical manifestations was characteristic of the clinical course of this variant of rupture. 2. Aortoenteric fistulas were characterized by symptoms of a pulsatile mass in the abdominal cavity, relapsing gastrointestinal bleeding, with negative results of fibrogastroduodenoscopy. 3. Aortocaval fistulas were characterized by systolic-diastolic murmur above the aneurysm and acute right ventricular cardiovascular insufficiency. Diagnosis of rare forms of AAA rupture is a difficult task, the clinical course of the disease is characterized by a wide variety of symptoms, thus leading to delayed rendering of emergency specialized care. Surgical tactics in rare forms of abdominal aneurysm rupture has not yet been standardized and solving this problem requires further accumulation of experience.
Leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the leading death cause, with extramedullary disease history as an independent relapse risk factor in acute leukemia. We analyzed 10 patients with extramedullary disease history who received allo-HSCT with mitoxantrone liposome (Lipo-MIT)-containing conditioning at our center (Dec 2022-Jan 2025). Median age was 39.5 (14-63), 7 had acute myeloid leukemia (AML, including myeloid sarcoma), 2 T lymphoblastic lymphoma/leukemia, and 1 B-cell acute lymphoblastic leukemia. Pre-transplant, 4 were in complete remission (CR) (1 with minimal residual disease [MRD] positivity) and 6 had residual lesions (2 with BM blasts ≥ 5%, 2 with MRD positivity). The conditioning regimen was Lipo-MIT + total body irradiation/busulfan + cyclophosphamide ± cytarabine, with a median Lipo-MIT dose of 26.1 (18.5-28.9) mg/m2. Mucosal injury showed a high incidence (9/10) after conditioning, but most were transient and controllable with supportive care. Engraftment succeeded in 9 patients, with a median neutrophil recovery time of 16 (11-21) days and platelet recovery time of 20 (11-39) days. Only 1 patient developed grade 2 skin acute graft-versus-host disease (aGVHD). All 9 engrafted patients achieved complete remission (CR) post-transplantation; one had MRD positivity at + 177 days, which turned negative after chemotherapy combined with donor lymphocyte infusion. One patient relapsed at + 234 days and died at + 272 days. The patient with engraftment failure died at + 346 days due to disease progression, with a history of polycythemia vera complicated by myelofibrosis. Lipo-MIT conditioning shows promising efficacy/safety for allo-HSCT in extramedullary disease patients. Randomized trials are needed.
The rigid polystyrene (PS) waste could be an alternative bitumen modifier, which brings great economic and environmental efficiency. However, because of low polarity and high rigidity nature of PS, it sometimes poses some difficulties in compatibility, elasticity, and storage stability. To address these limitations, the present study proposed an alternative chemical modification method for waste polystyrene through grafting with acrylic acid followed by a reaction with diethylenetriamine to produce PS-g-AM. Functionalized groups of the polymer were confirmed by performing FT-IR and 1 H-NMR spectroscopy which approved that PS-g-AM was successfully synthesized and identified. The synthesized PS - g-AM was mixed with bitumen with percentages of 3, 5, 7 and 10wt% from total binder weight. A multi-scale correlation between microscopic mechanisms and macroscopic performance is integrated. The microscopic characterization including FTIR and AFM techniques were performed and successfully verified the good compatibility via hydrogen bonding interaction between PS-g-AM and bitumen. Also, the macroscopic characterization including storage stability, and elastic recovery test demonstrated that the prepared PS-g-AM modified binders (7wt%) showed significantly a high storage stability (≤ 0.3), and better elastic recovery (55%) compared to untreated PS modifier (2.5), and (25%) respectively. The dynamic mechanical properties are also studied and the results revealed a considerable improvement in rutting resistance (G/sin δ) PG degree increased from 70 to 76, tan δ reduction. In summary, results confirmed that chemical grafting turned PS from a hardening agent to an efficient elastic modifier into asphalt and provided great opportunity for a high-performance sustainable method of modifying the asphalt.
Point-of-care diagnostics are reshaping healthcare worldwide by enabling rapid, decentralized testing across clinical and non-clinical settings, particularly in regions with limited laboratory infrastructure. These technologies are transforming telemedicine and disease surveillance by providing timely results. However, the performance and accuracy of these devices heavily rely on the choice of the substrate material. In point-of-care diagnostics, the substrate is the base material of a device that supports sensing components and facilitates interaction between the biological sample and the detection system, as in lateral flow assays for pregnancy testing, electrochemical biosensor strips for glucose monitoring, and reagent dipsticks for urine analysis. Conventional polymeric materials are commercialized as substrates due to their low cost and ease of processing. Nevertheless, their limited biocompatibility, non-degradability, and potential to generate toxic medical waste have raised growing concerns regarding their single-time use. This push for greener materials has turned attention toward biopolymers. Biopolymers derived from plants, animals, marine sources, and microbes are increasingly being explored as point-of-care substrates. Among these, bacterial cellulose stands out as a promising candidate due to its environmentally friendly production route and interconnected nanofibrillar network with high porosity, hydrophilicity, and water-retention capacity while maintaining superior mechanical strength. The abundance of hydroxyl groups allows diverse surface functionalization, while its tunable optical characteristics and biodegradability make it suitable for scientific integration and environmentally responsible disposal. Although notable progress has been made, comprehensive studies linking the structural features of bacterial cellulose to its performance in healthcare testing remain scarce. This review bridges this gap by systematically compiling recent research, examining modification approaches, and outlining how material-driven routes can be implemented to improve the reliability of disease diagnostics. This review also discusses emerging directions where bacterial cellulose may play a broader role in future diagnostic technologies.
Neurodegenerative diseases are characterised by the progressive dysfunction of neurons, and memory impairment is one of their most debilitating clinical manifestations. The etiopathogenic mechanisms are multifactorial, such as protein misfolding, oxidative stress, and mitochondrial malfunction and synaptic degeneration along with neuroinflammation. As yet, therapists still focus mainly on symptomatic treatment and no agents are found to halt or reverse the decline of cognitive, indicating what is more needed is other kinds of neuroprotective strategy. In this context, the plant-derived phytochemicals stand out as promising candidates owing to their multi-targeted mode of action, favourable safety profile and long-standing use in traditional medicine systems. These bioactive compounds modulate oxidative stress, inflammatory signalling, neurotransmitter balance, apoptotic pathways and protein aggregation to elicit neuroprotection. The attention of the research community has also turned towards using Drosophila melanogaster as a model system for neurodegenerative-related studies due to its genetic tractability, accessible behavioural learning and memory tests, and the evolutionary conservation of potentially important biological pathways. This review consolidates recent evidence regarding plant-based neuroprotective strategies against memory impairment, with a specific focus on mechanistic mechanisms elucidated from Drosophila models of neurodegenerative diseases. Integrating findings across molecular, cellular and behavioural levels, the review illustrates the therapeutic promise of phytochemicals and reaffirms Drosophila as a valuable preclinical tool. It also addresses practical translational considerations, such as bioavailability, standardisation, and clinical validation, and sets forth future directions for effectiveness of plant-based interventions to facilitate improvements out in the real world.
This article uses case studies to explore the nature and limits of accompagnement, the self-consciously "relational" care practiced by palliative care providers in Montagnac, a town in southern France. Medical anthropologists have attended to the ways that care premised on individual choice often fails as care, particularly for marginalized patient groups presumed to be incapable of making "good" decisions. This paper asks when, where, and why self-consciously relational care like accompagnement might also fail. I argue that despite a claim to "meet patients where they are," accompagnement, like choice, requires providers to project their own assumptions about the nature and telos of human beings onto their patients. When patients fail to mirror those assumptions, "relationality" quickly turns into paternalism. This argument complicates medical anthropology's embrace of relationality as an antidote to the violence associated with choice-based models of medicine.
Animals employ different strategies for relating sensory input and behavioral output to navigate sensory environments, but what strategy to use, when to switch and why remain unclear. Caenorhabditis elegans navigate by combining "steering" (small heading changes) with "turn" (large reorientations). It is unknown whether transitions between these elements are driven solely by sensory input or also by persistent internal states. It is also unclear how worms sometimes appear to exit turns such that they are already oriented toward a goal, despite their presumed lack of spatial awareness during turns. We address these questions with measurements of sensory-guided navigation and a statistical model of state-dependent control. Worm navigation is well described by a sensory-driven, two-state-switching model whose states persist for seconds and produce distinct sensorimotor mixtures: one state is steer-enriched, the other turn-enriched. This hierarchical temporal organization challenges the view that gradient-climbing strategies are static and purely stimulus-locked. Instead, sensory input causally modulates transitions between persistent states, creating the appearance of "directed turns" when exiting the turn-enriched state. Measurements using genetically perturbed animals and modeling with data-constrained reinforcement-learning both show that state switching enhances gradient-climbing performance. Together, measurement, perturbation, and modeling reveal that state switching is functionally beneficial, organizing behavior across time-a principle that may generalize across species and contexts.
This study examined if characteristics of direct visibility metrics in passenger vehicles, such as large blind zones, corresponded with higher risk of turning crashes with pedestrians aged 16 years and older. It also evaluated effects of vehicle front structures on some direct visibility metrics. Single-passenger vehicle, single-pedestrian crashes in seven states were included. Direct visibility metrics included driver- and passenger-side blind zone sizes, front nearest visible point (NVP) distance, and front field of view (FOV) width; measurements were taken on 168 combinations of vehicle make, series, and redesign years. Logistic regression analyses evaluated effects of visibility metrics and other factors on the odds of a left- or right-turning pedestrian crash, relative to straight-moving. Linear regression analyses examined effects of front structures on blind zone sizes and front NVP distances. For left-turning pedestrian crashes, large (> 30%) and medium (> 20% and ≤ 30%) driver-side blind zones were, respectively, associated with a significant 75.3% and 62.4% increase in the odds, compared with a small size (≤ 20%). A narrow front FOV (≤ 85°) was associated with a significant 49.6% increase in the odds, compared with a wide FOV (> 90°). A long front NVP distance (> 9 m) was associated with a significant 35.3% increase in the odds, compared with a short distance (≤ 6 m). No significant associations were found between visibility metrics and right-turning pedestrian crashes. Larger driver-side blind zones, longer front NVP distances, and narrower front FOVs increased risk of left-turning pedestrian crashes. Effects of A-pillars, side mirrors, hoods, and windshields on blind zone sizes and front NVP distances were also validated. Findings could help automakers improve safety for road users outside vehicles with changes in vehicle design to enhance drivers' direct vision and improvements to AEB technology to address vehicle-turning conflicts.
Kalaallit Nunaat (Greenland) continues to experience a very high burden of suicide, while knowledge about culturally meaningful recovery processes remains limited. This qualitative pilot study explores how Inuit individuals with lived experience of suicide attempts describe coping, turning points, and pathways toward thriving lives. Six participants who had experienced suicide attempts in childhood, adolescence or early adulthood, took part in semi-structured interviews conducted in Kalaallisut. Data were analyzed using systematic text condensation. Findings show that recovery was not experienced as an individual trait but as a relational and culturally embedded process. Supportive relationships, cultural grounding, connections to nature and land based practices, language-accessible services, and opportunities for belonging and contribution functioned as key protective resources. Inuit worldviews, including understandings of Sila and Inua, and engagement with land-based practices supported emotional regulation, meaning-making, and hope.
Construction digital twins aim to maintain an up-to-date, BIM-consistent as-built state from streaming multi-line LiDAR to enable progress verification, dimensional compliance control, and proactive safety management on construction sites. However, converting sequential LiDAR observations into a temporally stable, element-centric BIM state is difficult in realistic AEC environments. Existing approaches mainly fall into geometry-driven Scan-to-BIM registration frameworks and learning-based point cloud perception models, with some system-level digital-twin frameworks built on BIM-centric reasoning. Purely geometric alignment is brittle under occlusion, clutter, and repetitive structures, and registration uncertainty can propagate to downstream progress and deviation conclusions. Meanwhile, generic perception networks are often trained on static frames, lack temporal stabilization, and do not explicitly optimize BIM-consistent element association or geometry-aware alignment cues. In addition, many digital-twin systems expose limited, loosely coupled state representations that hinder causal, reliable site updates. To address these gaps, we propose LiBiDT (LiDAR-BIM Digital Twin), a causal LiDAR-BIM digital-twin model-where "causal" refers to computational online updating in which only past observations enter the current state-that integrates spatio-temporal mapping, geometric-semantic perception, and scan-to-BIM association for consistent state evolution. LiBiDT consists of Spatio-Temporal Global Registration (STGR) with LiDAR-IMU-GNSS priors, Multi-task Perception (MTP) using a PointNet++ backbone with semantic/instance/normal heads, and Scan-to-BIM Association and State Updating (S2B) via normal-guided point-to-plane refinement, bipartite matching with fused overlap/deviation/semantic evidence, and exponential moving average (EMA) stabilization. The Decision and Risk Analytics (DRA) layer turns the BIM-aligned state into auditable construction-management indicators-weighted completion, deviation summaries, and three forward-evaluable safety/compliance hazard flags. Experiments on three public benchmarks (Hilti SLAM, CV4AEC 2024 Scan-to-BIM, and S3DIS Area-5) cover trajectory, perception, and association evaluation. On CV4AEC 2024 Scan-to-BIM, LiBiDT reaches association F1 = 0.837 and Chamfer Distance (CD) / surface Root Mean Square Error (RMSE) of 3.2/3.5 cm; relative to the perception-replacement baseline (PointNet++ + S2B, F1 = 0.758) the gain is large, while relative to the strongest competing baseline-CoFiNet (Reg) + S2B at F1 = 0.822-the absolute association gain narrows to 0.015 F1 points, with the bigger gains coming from temporal identity consistency (IDF1 0.854 → 0.861) and ID-switch reduction. A held-out tile-stream case study visualises BIM-element state evolution, alignment refinement, EMA-stabilised evidence streams, and hazard-flag firing as the scan progressively covers the floor; a strict temporal validation under active construction will require time-stamped multi-acquisition data and is left to future work. Ablation results confirm that evidence stabilization and multi-cue matching contribute complementary gains in accuracy and temporal consistency, yielding a favorable efficiency-accuracy trade-off.
Postural instability and gait dysfunction (PIGD) subtype of PD has been associated with a more rapid progression of cognitive and motor dysfunction while tremor dominant (TD) subtype is associated with more severe tremors and slower disease progression. The purpose of this study was to examine longitudinal differences in walking and cognition in pwPD between subtypes. This was a five-year observational longitudinal study. Participants underwent motor and non-motor assessments every six months.TD and PIGD clinical subtypes were determined at the initial visit. Primary outcomes were gait speed, double support time, turning velocity, Timed up and Go Cognitive (TUGc) duration, and MoCA. Forty people living with PD were included in this study [TD (n = 24), PIGD (n = 16)]. PIGD subtype had longer disease duration (p = 0.018) than the TD subtype and worse overall disease severity with higher scores on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 2 (p = 0.001), Part 3 (p = 0.026), and total score (p = 0.003) at baseline. Gait speed showed similar rates of change between the TD and PIGD subtypes, with no significant subtype-by-time interactions. Double support time and TUG cognitive duration changed significantly over time across both subtypes, while turning velocity did not; for all outcomes the rate of change did not differ between the TD and PIGD subtypes. Cognition did not significantly decrease across time. While baseline differences between TD and PIGD groups were evident, the similar rates of change over time suggest that subtype identification alone may not be sufficient for predicting individual trajectories.
We evaluated the safety, acceptability, and cost-effectiveness of all published studies on fluoroquinolone (FQ)-based TB preventive treatment (TPT) regimens in all settings and populations. We searched for studies published between February 2014 and September 2023 using PubMed, Embase, Turning Research Into Practice (TRIP), Global Health Library, and the Cochrane Central Register of Controlled Trials. Meta-analysis was conducted using random effects models. Twenty-two observational and modelling studies evaluating FQ-based TPT were included, assessing outcomes of safety (n = 16), acceptability (n = 9), and cost-effectiveness (n = 2). Only 2% (95% confidence interval [CI]: 0%-4%) of children and adolescents and 8% (95% CI: 2%-14%) of adults discontinued FQ monotherapy due to drug-related adverse events (AEs). Compared to FQ monotherapy, rates of drug-related AEs of any severity were non-significantly higher with multidrug FQ regimens without pyrazinamide (PZA). Pooled discontinuation rates were 50% (95% CI: 34%-67%) among children and 57% (95% CI: 16%-98%) among adult contacts treated with PZA-containing FQ-based regimens. Pooled acceptance rates exceeded 80% among all groups. FQ-based TPT was cost-effective to avert TB-related deaths and loss of quality-adjusted life-years. These results complement the evidence from two recent randomised trials. FQ monotherapy is a safe, acceptable, and cost-effective TPT regimen for contacts exposed to multidrug-resistant or rifampicin-resistant TB disease.
Falls constitute a significant public health burden across the adult lifespan, affecting both working-age and older populations and compromising functional independence and quality of life through physical and psychological consequences. Current interventions typically address these dimensions in isolation, emphasizing fall avoidance rather than equipping individuals to manage and recover from falls when they occur. This exploratory study evaluated the feasibility, acceptability, and safety of the Floor-Hugging Intervention (Floor-HI), a novel multicomponent program that combines controlled exposure to fall-risk environments with systematic training in post-fall recovery skills, including floor-to-standing transitions, fall imagination, and role-playing scenarios. Eight community-dwelling, middle-aged adults (3 males, 5 females; aged 31-55 years) completed a 3-week program. Outcomes including concern of falling, postural control, floor-rise ability, turning ability, and health-related quality of life were assessed at four time points (Weeks 0, 3, 6, and 9). Recruitment, retention, and adherence rates were 100%, 89%, and 100%, respectively. Significant improvements over time were observed in postural stability (Mini-BESTest, p = .011), floor-rise ability (Sitting Rising Test, p = .011), and turning capacity (360° Turn Test duration, p = .012-.017). Concern of falling (Falls Efficacy Scale-International, p = .145) and health-related quality of life (RAND-36, p > .05) remained unchanged. Intervention acceptability was high across all domains of the Theoretical Framework of Acceptability questionnaire. Only a small number of mild, transient adverse events were reported, all resolving without medical intervention, and no serious adverse events occurred. Despite being limited by the absence of a control group and a small sample size, this study demonstrates that Floor-HI is feasible, acceptable, and safe in community-dwelling middle-aged adults. These findings provide a foundation for future feasibility and controlled trials to establish efficacy and applicability in populations with elevated fall risk.
Dry turning of AISI D2 steel requires a balance between productivity, surface integrity, thermal loading, and energy demand. This study compares the machinability of a chamfered Xcel insert and a conventional carbide insert during dry turning of AISI D2 steel using a 24 full-factorial design with cutting speed (VCS: 100-150 m/min), feed rate (FR: 0.2-0.3 mm/rev), and depth of cut (DOC: 0.5-1.0 mm). Volumetric material removal rate (VMR), microhardness (MH), turning-zone temperature (TTZ), and power consumption (PC) were measured and analysed using ANOVA, ANN modelling, and NSGA-II optimization. The results showed that the Xcel insert consistently outperformed the conventional carbide insert within the investigated range. The highest measured VMR and MH were 1341.57 cm3 and 177.78 HV, respectively, whereas the lowest TTZ and PC were 272 °C and 420.28 W under conservative cutting conditions. ANOVA showed that FR was the dominant factor for VMR (27.69%), while VCS dominated MH (74.51%) and TTZ (49.36%); DOC was the strongest contributor to PC (29.55%). Artificial neural network (ANN) models were used as local-response surrogates, and Non-dominated sorting genetic algorithm (NSGA-II) identified an optimum at 149.84 m/min, 0.3 mm/rev, 0.997 mm, and Xcel insert. The study shows that the Xcel geometry is beneficial for increasing productivity in dry turning of AISI D2 without a disproportionate increase in thermal and energy penalties.