Suture anchors are frequently used for repairing torn rotator cuffs. However, post-operative anchor loosening is a common complication often caused by low bone density. The purpose of this study was to evaluate if a novel UHMWPE cortex locking sleeve could improve the anchor pullout strength after revision in synthetic bone. The initial failed anchor fixation was simulated by inserting a 4.5 mm anchor and pulling it out of the bone, which created an enlarged insertion hole for the revision anchor. After revision, two loosening conditions were simulated; (i) intra-operative anchor loosening where the revision anchor was directly pulled out from the block after insertion, and (ii) post-operative anchor loosening where the revision anchor was first subjected to cyclic loading and then pulled out. For both loosening conditions, the pullout strength and energy absorbed was recorded for the following configurations: (i) Group A, same-diameter anchor (SDA; 4.5 mm × 10 mm); (ii) Group B, larger-diameter anchor (LDA; 5.5 mm × 10 mm; ); and (iii) Group C, same-diameter anchor combined with the novel sleeve (SDA + NS). For intra-operative anchor loosening, the highest pullout strength was recorded in the SDA + NS group, with a mean value of 370.077 ± 32.699 N, which was significantly greater than both SDA and LDA groups (p < 0.05). Similarly with post-operative anchor loosening, the SDAP + NS group had a significantly higher pullout strength (311.114 ± 28.239 N) than the other groups. Using the UHMWPE sleeve with same diameter anchor as the initial insertion produced a significantly greater pullout strength than the revision with a larger diameter anchor but no sleeve.
Active assembly of matter is a defining trait of living systems, enabling the creation of far-from-equilibrium materials essential for the functionality of life. This is achieved through energy-dissipative, multi-step processes facilitated by biomolecular nanomachines performing bottom-up chemical and mechanical assembly of matter. Mimicking such active assembly synthetically remains a challenge. Here, a bio-inspired bottom-up strategy for energy-dissipative material assembly, driven by biomolecular nanomachines and overcoming thermodynamic and diffusive constraints, is demonstrated. Specifically, two chemically-fueled biomolecular nanomachines-DNA polymerase and kinesin-are used to demonstrate a multi-step chemical synthesis and mechanical manipulation process. This results in a DNA biopolymer network with complex hierarchical morphologies unattainable by self-assembly alone. DNA polymerase generates DNA, which forms a fibrous 2D-network when actively connected and pulled between kinesin-powered motile microtubules. Experimental data and simulations show that both DNA-DNA interactions and active mechanical forces from molecular motors are essential to this process. Furthermore, key factors for network formation are investigated by systematically investigating DNA polymerase incubation time and microtubule density. The present work provides a key step toward bottom-up fabrication of complex and dynamic materials by mimicking the sophisticated assembly strategies of living systems, potentially providing a framework for future materials assembled by nanomachines.
We describe a simple securing suture designed to prevent the accidental dislodgement of long-term, Dacron-cuffed tunneled central venous catheters during the interval before fibrous ingrowth fixes the cuff. A 3-0 nylon suture is placed at the exit site around the plastic shaft of the tunneler before the catheter is pulled through the subcutaneous tunnel; after the catheter is positioned and the Dacron cuff is seated cranial to the suture loop, the suture is tied around the catheter. The technique was applied in 207 consecutive patients (108 men, 99 women; mean age 42.4 years) over a 15-month period, with a 100% technical success rate, no procedure-related catheter injury, and no dislodgement on follow-up chest radiography at 1 to 2 weeks. The suture is performed before catheter insertion, requires no additional incision, and can be removed at the bedside, providing a safe and efficient adjunct for catheter fixation.
The main demographic and psychological correlates of Well-Being (WB) are well-established, but have not yet been assessed in the Swedish population-regularly ranked among the world's top five ranked WB nations-based on large, nationally representative data. Using 2023 Global Flourishing Study data (N = 15,068), this paper analyzes Swedish WB across three domains: demography (e.g., gender, age, and income), individual personality traits (e.g., Big Five neuroticism and extraversion), and social relationship qualities (e.g., loneliness and relationship satisfaction). Using machine learning regression models based on these three domains, we regressed a composite 13-item WB measure-i.e., a general factor consisting of positive markers (e.g., happiness, life balance) and negative markers (e.g., depression, anxiety)--with an accuracy of r = .79 (cross-validated training) that generalized well to a holdout set (r = .79). Age was the strongest demographic marker of Swedish WB among the 65 predictors (lasso β = .10; bivariate r = .32), only surpassed by the classically strong WB predictors of neuroticism (β = -.33), loneliness (β = -.24), relationship satisfaction, (β = .17), and friendship contentment (β = .17). We replicated the age-WB relationship with complementary Gallup World Poll data; spanning 2006 to 2024, and the data suggested that older Swedes have indeed pulled ahead of young Swedes in WB, albeit only in the last five years. Further, with this paper's focus on the demographics of WB in Sweden, it offers an unprecedented set of political identity graphs for the benefit of researchers, policymakers, and the common public. The overall conclusion is that while personality and social relationship quality are stronger markers than demography for Swedish WB, age is the strongest demographic predictor, and has grown in significance recently. The findings will ideally inform and guide Swedish public policy and politics, particularly in addressing the declining WB of young Swedes.
Major laparoscopic hepatectomy along the major hepatic veins requires accurate orientation to the transection plane and safe management of the hepatic venous branches. We developed an extracorporeal ventral traction (EVT) method combined with a 3-step dorsal approach (3SDA) to standardize laparoscopic hemihepatectomy. In EVT, a traction suture secured on the caudal edge of the transection line is brought out through the epigastrium and pulled extracorporeally, elevating the liver parenchyma ventrally and allowing dorsal access under the caudal laparoscopic view. In 3SDA, the transection plane containing the major hepatic vein is divided into three areas: Area A, caudal to the hilum; Area B, dorsal to the hepatic vein; and Area C, ventral to the hepatic vein. These areas are approached sequentially to open the caudal view, maintain anatomical landmarks, and reduce venous injury. EVT and 3SDA provide a reproducible framework for laparoscopic hemihepatectomy.
Short-time Fourier transform (STFT)-based Brillouin optical time-domain reflectometry (BOTDR) utilizes a sliding window to estimate the Brillouin frequency shift (BFS). When the window spans the interface between a background region and an event region, the measured Brillouin gain spectrum (BGS) is manifested as a weighted superposition of two spectral components. For small BFS differences, the two components merged into a single distorted peak, and the extracted peak frequency was pulled, leading to a systematic bias in the estimated BFS. This bias dilated the boundary transition in the BFS profile, displaced the inferred start and end positions, and consequently overestimated the event length. In this study, an analytical model for dominant peak frequency pulling was developed, enabling a boundary correction method for small BFS differences. Experimental results demonstrate that the method reduces the boundary localization error to within 0.7 m and the event length error to within 0.4 m for BFS differences ranging from 8.24 to 36.19 MHz. Furthermore, across a broad FWHM range of 58-140 MHz, the event length error remained consistently below 0.2 m. By effectively mitigating boundary-induced BFS bias, this approach enhanced both boundary localization and event length estimation in cost-effective STFT-BOTDR systems for engineering applications.
Objective: To investigate the clinical efficacy of applying orthoplastic principle in treating Gustilo type ⅢB open ankle joint fractures. Methods: This study was a retrospective case series study. From January 2018 to August 2024, 33 patients with Gustilo type ⅢB open ankle joint fractures who met the inclusion criteria were admitted to Wuxi Ninth People's Hospital, including 25 males and 8 females, aged 25-65 (44±12) years. The area of skin and soft tissue defects ranged from 6 cm×3 cm to 27 cm×14 cm. The length of bone defect ranged from 3.0 to 9.2 cm (with mean of 3.7 cm). All patients were treated based on the orthoplastic principle. Phase Ⅰ-Stage 1: after thorough debridement was performed in emergency department, antibiotic bone cement was inserted in the tibial defect, an external fixator or an antibiotic bone cement-coated steel plate was applied for temporary stabilization. Nerves and tendons were repaired, and the remaining wound was covered with vacuum sealing drainage dressing. Phase Ⅰ-Stage 2: on days 3 to 7 after injury, the wound was debrided again, and the antibiotic bone cement was replaced. The internal fixation was adjusted or retained according to the fracture status, and an anterolateral thigh flap (with size ranging from 7 cm×3 cm to 30 cm×15 cm) was designed and harvested to repair the wound. A stepwise strategy was employed for treating the donor site wounds based on the defect size and local tension. For wounds with low tension, primary closure was performed. For wounds with high tension, the wound edges were appropriately pulled together during operation, and either direct closure or split-thickness skin grafting from the opposite thigh was carried out after the postoperative edema subsided. Phase Ⅱ-Stage 3 (the only stage): 7 to 30 weeks after injury (with mean of 15.8 weeks), the antibiotic bone cement was removed, the volume of bone defect was measured, and the iliac crest bone was harvested precisely, mixed with vancomycin, and used to fill the bone defect; the induced membrane and skin soft tissue were then sutured. Postoperative flap survival and infection-related complications at different stages were recorded. During follow-up, flap appearance and texture, scar condition at the donor and recipient sites, and bone healing were documented. At the last follow-up, the affected foot function was assessed using the foot and ankle ability measure (FAAM) scale, and the percentage of recovery in daily living ability was calculated. Patient health outcomes were assessed using the 36-item short form health survey (SF-36), and the scores of the physical component summary (PCS) and mental component summary (MCS) were calculated. Results: Complete flap survival was achieved in 30 patients after operation. Partial flap necrosis occurred in 3 patients, among whom 1 case healed by direct suture after debridement, and 2 cases healed by skin grafting after debridement. Infection-related complications occurred in 4 patients, including superficial infection in 3 cases (1 case after Stage 2 in Phase Ⅰ, 2 cases after Stage 3 in Phase Ⅱ), all of which were controlled after debridement with wound healing. Bone infection occurred in 1 case (after Stage 2 in Phase Ⅰ), which was controlled after repeated thorough debridement and antibiotic bone cement packing, and bone grafting healed. The follow-up period ranged from 12 to 57 months (with mean of 26.7 months). All flaps showed good color and texture. Scar hyperplasia at the flap donor site occurred in 3 cases, while only linear scars remained at the recipient site. At final follow-up, the FAAM scale score of the affected foot was 71±4, and the recovery of daily living ability reached (85±5)%. The PCS score on the SF-36 was 78±4, and the MCS score was 70±11. Conclusions: Applying the orthoplastic principle for treating Gustilo type ⅢB open ankle joint fractures results in low infection and other complication rates, along with satisfactory functional recovery of the ankle joint. 目的: 探讨基于骨整形理念治疗Gustilo ⅢB型踝关节开放性骨折的临床效果。 方法: 该研究为回顾性病例系列研究。2018年1月—2024年8月,无锡市第九人民医院收治33例符合入选标准的Gustilo ⅢB型踝关节开放性骨折患者,其中男25例、女8例,年龄25~65(44±12)岁,皮肤软组织缺损面积为6 cm×3 cm~27 cm×14 cm,骨缺损长度为3.0~9.2 cm(平均3.7 cm)。对所有患者均基于骨整形理念进行治疗。Ⅰ期第1阶段:急诊彻底清创后,于胫骨缺损区置入抗生素骨水泥,采用外固定支架或被覆抗生素骨水泥的钢板进行临时固定,并修复神经、肌腱,残留创面以负压封闭引流敷料覆盖;Ⅰ期第2阶段:伤后第3~7天再次清创并更换抗生素骨水泥,根据骨折情况调整或保留内固定,设计并切取股前外侧皮瓣(面积为7 cm×3 cm~30 cm×15 cm)修复创面。根据缺损大小及局部张力,对供区创面采用阶梯式处理:张力小者直接拉拢缝合;张力大者,术中先适度拉拢创缘,待术后水肿消退后,再行直接缝合或取对侧大腿刃厚皮片修复。Ⅱ期第3阶段(唯一阶段):伤后7~30周(平均15.8周)取出抗生素骨水泥,计算骨缺损体积并精确切取髂骨后与万古霉素混合填塞骨缺损,缝合诱导膜及皮肤软组织。记录术后皮瓣成活情况及不同阶段感染相关并发症发生情况。随访时记录皮瓣外观、质地,皮瓣供受区瘢痕情况,骨愈合情况。末次随访时,采用足踝功能评估量表评估患足功能并计算其日常生活能力恢复百分比,通过36项健康调查简表(SF-36)评估患者健康结局,计算患者的生理健康总评和心理健康总评得分。 结果: 术后皮瓣完全成活者30例;皮瓣部分坏死者3例,其中1例经清创后直接缝合,2例经清创植皮后愈合。发生感染相关并发症者4例,其中浅表感染者3例(Ⅰ期第2阶段后1例,Ⅱ期第3阶段后2例),经清创后感染得到控制,创面愈合;骨感染者1例(Ⅰ期第2阶段后),经再次彻底清创、抗生素骨水泥填塞后感染得到控制,植骨愈合。随访12~57个月(平均26.7个月),所有皮瓣颜色、质地良好;皮瓣供区发生瘢痕增生者3例,皮瓣受区仅遗留线性瘢痕。末次随访时,患足足踝功能评估量表评分为(71±4)分,日常生活能力恢复至(85±5)%;SF-36中的生理健康总评得分为(78±4)分,心理健康总评得分为(70±11)分。 结论: 基于骨整形理念治疗Gustilo ⅢB型踝关节开放性骨折,术后感染率及其他并发症发生率低,且踝关节功能恢复良好。.
Scientific publishing is changing - and it's changing fast. Digital platforms have made it easier than ever to share research across borders, open-access models have pulled down paywalls that once limited who could read or contribute to scientific discourse, and global collaboration has become the norm rather than the exception. Into this already shifting landscape, artificial intelligence (AI) has arrived - quietly at first, and now with considerable force - touching nearly every stage of how research gets done, analyzed, and communicated. The promise here is real. But so is the tension it creates. The central question facing the scientific community isn't whether to embrace these changes - that ship has largely sailed - but whether we can move this quickly without eroding the credibility that makes science worth doing in the first place. For journals, this isn't a theoretical problem. Editorial standards are the backbone of the scientific record, and right now, those standards are being stress-tested. As the Editor-in-Chief of Cureus, I think we're at a moment that calls for clarity, not hedging - a moment to say plainly what principles must hold even as everything else shifts. Cureus was built around a straightforward idea that medical publishing was too slow, too exclusive, and too gatekept to serve science well. The journal set out to change that by reducing barriers to dissemination while keeping editorial rigor intact. That core mission hasn't changed. What has changed is the environment in which we pursue it. Two issues now sit at the center of that effort: the responsible use of AI in scholarly communication and the ongoing fight to protect research integrity.
Anxiety and mood disorders in youth are prevalent and impairing, with high current and lifetime comorbidity. Untreated, these disorders lead to sustained functional impairment and increased risk for recurrent disorder and suicide. In addition, there are notable disparities in care, with both families experiencing increased social risk and youth of color significantly less likely to receive mental health services. In previous research, a primary-care-based transdiagnostic brief behavioral therapy (BBT) was developed and found to be effective for a broad population of youths with anxiety and depression. To increase dissemination potential to settings that serve low-resource families (e.g., community health centers [CHCs]), the intervention, now called "STEP-UP," has been expanded to support a digital health framework and delivery in Spanish. We describe the protocol for a hybrid type 1 randomized-effectiveness trial to test the effects of STEP-UP in a community sample of youths with anxiety and/or depression. Youths (age = 8-16, N = 220) will be randomized to (a) STEP-UP or (b) assisted referral to treatment as usual (TAU+). Clinical effectiveness will be assessed by masked independent evaluators at posttreatment (week 16) and at follow-up (week 32). Implementation data will be pulled from the following: (a) Surveys of health system leaders, (b) surveys of and interviews with STEP-UP clinicians, and (c) electronic health record (EHR) and health system administrative data. Specific aims include testing the clinical effectiveness of STEP-UP and engagement of the intervention mechanism (Aim 1), probing cost-effectiveness (Aim 2), testing social determinants of health (SDOH) predictors and moderators to evaluate robustness of effects (Aim 3), and identifying target mechanisms for future implementation trials using the Consolidated Framework for Implementation Research (CFIR, Aim 4). Results of the randomized trial may help move effective treatments for youth anxiety and depression problems into widespread community practice. NCT06273982. Registered on February 15, 2024.
Animal survival in the wild is largely dependent on their ability to locate food sources, find mates, and avoid predators - tasks which are all heavily reliant on their sense of smell. However, to be adept at these behaviours, animals must navigate a complex odour landscape where odour can be released in many forms, including odour trails and airborne odour plumes. Odour plumes result when an odour is carried by ambient wind, where its structure changes with distance from the odour source, providing potential navigational cues to searching animals. Odour plumes adopt a variety of structures depending on the odour landscape, such as pulled odour filaments that are interleaved with pockets of air in a turbulent environment. Due to advancements in fluid dynamics technology allowing for the detailed measurement of airborne odour plumes, recent studies have begun to explore how odour plume properties affect olfactory search behaviour in mammals. For example, our own studies have demonstrated that intermittency is an odour plume property that can inform olfactory search, is encoded in early stages of olfactory processing within the olfactory bulb, and is subject to changes in representation based on active sampling strategies. This review summarizes how mammalian odour-based navigation depends on and can be guided by odour plume properties.
Mycobacteria comprise an uneven number of genes coding for biotin carboxylase (BC) and acyl-CoA carboxyl transferase (CT) activities and an ε-subunit of unknown function. To unravel the composition of acyl-CoA carboxylase (ACCase) holoenzymes under native conditions, we pulled down endogenously expressed biotinylated proteins from Mycobacterium smegmatis. The extract included an unexpected 16-subunit ACCase holoenzyme, exhibiting distinct long-chain (LC) and short-chain (SC) CT activities. It consists of a central two-layered CT (AccD4)₂/(AccD5)₄ assembly that interacts with a C-terminal AccE5 dimer within its central hole. On each CT hexamer face, an asymmetric BC AccA3 tetramer is connected through a flexible AccE5 segment. This is preceded by a folded AccE5 segment that contributes to an asymmetric nine-stranded β-barrel with contributions from all four AccA3 subunits. This barrel allows the BC assembly to rotate ~90o in the presence of acyl-CoA substrates. These data demonstrate that asymmetric, multi-substrate ACCases differ fundamentally from symmetric, single-substrate ACCases.
Accurate and efficient dose computation lies at the heart of modern radiotherapy planning, yet practitioners are still pulled in two opposing directions: high-fidelity solvers - Monte Carlo simulation and deterministic linear Boltzmann transport equation (LBTE) solvers such as Acuros XB - deliver the physical accuracy that adaptive workflows demand, but the runtime they impose remains hard to reconcile with on-couch decision-making. The present study introduces a physics-informed neural network (PINN) framework that embeds radiation-transport-derived constraints into a 3D encoder-decoder backbone for rapid voxel-wise dose prediction and verification. The network ingests preprocessed CT volumes together with plan-specific information - gantry, collimator and couch angles, projected MLC fluence maps, and per-beam monitor units - and outputs the full 3D dose distribution. We formulate a physics residual loss inspired by the LBTE under simplifying assumptions, applied as a soft regularizer rather than as a replacement for the supervised target, so that training data calculated by the Anisotropic Analytical Algorithm (AAA, Eclipse v15.6) remains the primary supervisory signal while physical plausibility is encouraged across the volume. To overcome the gradient competition between data-driven and physics-driven terms, a momentum-based adaptive weighting strategy continuously rebalances their contributions through training. An end-to-end verification pipeline integrating gamma analysis, dose-volume histogram (DVH) evaluation, and energy-conservation checks completes prediction-plus-quality assurance in under 15 s per patient. On a held-out cohort of 27 head-and-neck and thoracic patients, the proposed system achieved mean global gamma passing rates of 97.8% at 3%/3 mm and 93.7% at 2%/2 mm (10% low-dose threshold) against the AAA reference, outperforming both a conventional 3D U-Net and a static-weight PINN; cross-checking against a subset recomputed with Acuros XB and EGSnrc-based Monte Carlo confirmed the robustness of the gain. Notably, the physics-constrained model trained on only half of the available cases matched the data-only baseline using the full training corpus - an indicator of meaningful sample efficiency. Taken together, the results suggest that combining transport-inspired regularization with adaptive training dynamics offers a practical route toward clinically deployable real-time dose verification in adaptive radiotherapy.
Metabotropic glutamate receptor 6 (mGluR6) is a synaptic receptor expressed predominantly in retinal ON-bipolar cells. The N-terminal extracellular domain (ECD) of mGluR6 engages in ligand binding and also participates in mGluR6 cell-surface localization and trans-synaptic cell-adhesion complex formation. We herein investigated whether N-glycosylation in the mGluR6 ECD is involved in modulating receptor cell-surface transport, G-protein coupling, and interactions with Elfn1 and Lrit1 using 293T cells expressing ECD mutants with the asparagine-to-glutamine (N-to-Q) substitution in N-glycosylation sequons. The results obtained showed that mGluR6 underwent N-glycosylation at the asparagine residues N290, N445, N473, and N561 in the ECD, and the simultaneous blockage of N-glycosylation at these sites reduced cellular mGluR6 levels. Furthermore, mGluR6 cell-surface levels were decreased by N290Q and N445Q, but unaffected by N473Q and N561Q, while each N-to-Q substitution at the respective sites consistently impaired glutamate-induced G-protein-mediated responses. We also showed that mGluR6 was pulled down with Elfn1 in vitro, and coimmunoprecipitated with Lrit1 in co-transfected cells. The mGluR6-Elfn1 interaction was inhibited by N445Q and facilitated by N473Q and N561Q, whereas the mGluR6-Lrit1 interaction was promoted by N290Q and suppressed by N561Q. Collectively, these results indicate that each of the N-glycosylation sites contributed to efficient G-protein coupling, while the respective sites were involved in the modulation of receptor cell-surface transport and adhesion complex formation with Elfn1 and also with Lrit1 in distinct directions. Therefore, the N-glycosylation of synaptic receptors may have roles in modulating trans-synaptic bridge formation, potentially influencing the tuning of signal transmission.
Childhood maltreatment has lasting adverse effects across multiple domains, contributing to cumulative disadvantage and accelerated aging. These outcomes may reflect not only individual vulnerability, but also ethnoracial-related differences in lived experience, highlighting how sociocultural contexts shape long-term risk. The effect of childhood maltreatment on cognitive functioning later in life varies, raising questions about the mechanisms that drive this association. Data were drawn from the Midlife in the United States (MIDUS) study. Participants were categorized into two racial groups for analysis; non-Hispanic white and ethnoracial minority. Physiological and psychosocial variables were pulled from wave II and cognitive variables were extracted from waves II and III. At wave II, the analytic sample included 692 adults (56% female, 19.5% ethnoracial minority, age: 53.43 ± 10.72 years). Serial mediation models evaluated whether depression and perceived stress linked childhood maltreatment to later cognitive decline, predicting wave III cognitive functioning while controlling for wave II cognitive decline, in the overall sample and by ethnoracial subsamples. In the full sample, the relationship between childhood maltreatment and cognitive decline was fully mediated via the indirect pathway from depression to perceived stress. Ethnoracial minority status significantly moderated the association between depression and perceived stress, yet, the subgroups estimates of the indirect pathway were not significantly different from each other. In the non-Hispanic white group, the total effect of childhood maltreatment on cognitive functioning was not significant (b = - 0.0014, p = 0.283), but a significant indirect pathway existed through depression to stress (b = - 0.0012, 95%CI [- 0.0023, - 0.0003]). However, in the ethnoracial minority group, the total and direct effects of childhood maltreatment on cognitive performance were significant (b = - 0.0079, p = 0.001, and b = - 0.0066, p = 0.013, respectively) with no significant indirect pathways. These findings highlight distinct psychosocial pathways that link childhood maltreatment to cognitive aging and underscore the importance of contextually relevant prevention and intervention strategies.
In the past few decades, it was assumed that high testosterone levels were associated with increased risk of prostate cancer (CAP) while low testosterone was protective. However, more recent studies reported an association between low serum testosterone and high-grade CAP. These studies were largely done in the Western world, thus leaving a knowledge gap as regards such a relationship in Africans. Therefore, the aim of this study was to bridge this gap in knowledge by assessing the nature of the relationship between serum testosterone and tumor grade in a black African population of men with hormone naïve CAP. This was a prospective study carried out in Enugu, Southeast Nigeria. The study population was drawn from men with histologically diagnosed CAP who subsequently had bilateral total orchidectomy (BTO) as a form of androgen deprivation therapy. Data were pulled from three referral centers for urological services in the city center with a study period extending from April 2022 to May 2025. Serum total testosterone and prostate-specific antigen (PSA) were assayed for each subject before undergoing BTO. A total of 147 subjects that met the inclusion criteria were included in this study. The mean age of the subjects was 70.2 ± 8.3 years, while the median Gleason score was 8.0 (IQR: 7.0-9.0). Majority of the subjects had Gleason scores of 7 (31.4%) or 9 (33.6%). The median PSA was 80.0 ng/ml (IQR: 40.0-103.0) while the median testosterone level was 3.7 ng/ml (IQR: 1.5-6.9). There was a very weak, statistically insignificant correlation between Gleason score and serum testosterone (r =-0.066, P = 0.442). The correlation between serum testosterone and tumor aggressiveness (as determined by Gleason score) is weak. Hence, by extrapolation, there may not be a need to include serum testosterone as part of preoperative workup investigations for CAP patients in our environment. Résumé Contexte:Au cours des dernières décennies, il a été supposé que les niveaux de testostérone élevés étaient associés à un risque accru de cancer de la prostate (CAP), tandis que la faible testostérone était protectrice. Cependant, des études plus récentes ont signalé une association entre testostérone sérique faible et capuchon de haute qualité. Ces études ont été largement faites dans le monde occidental, laissant ainsi un déficit de connaissances en ce qui concerne une telle relation chez les Africains. Par conséquent, le but de cette étude était de combler cette lacune en matière de connaissances en évaluant la nature de la relation entre la testostérone sérique et la nuance de la tumeur dans une population d’hommes africaines noires d’hommes naïfs hormones.Méthodes:Il s’agissait d’une étude prospective réalisée à Enugu, au sud-est du Nigeria. La population de l’étude a été tirée d’hommes avec un plafond histologiquement diagnostiqué qui a ensuite eu une orchidectomie totale bilatérale (BTO) comme une forme de thérapie de privation d’androgène. Les données ont été tirées de trois centres de référence pour des services urologiques dans le centre-ville avec une période d’étude s’étendant du 2022 au mai 2025. Le sérum Total Total de testostérone et d’antigène spécifique à la prostate (PSA) a été analysé pour chaque sujet avant de subir une enquête.Résultats:Au total, 147 sujets répondant aux critères d’inclusion ont été inclus dans cette étude. L’âge moyen des sujets était de 70,2 ± 8,3 ans, tandis que le score de Gleason médian était de 8,0 (IQR: 7.0-9.0). La majorité des sujets avaient des scores de Gleason de 7 (31,4%) ou de 9 (33,6%). Le PSA médian était de 80,0 ng / ml (IQR: 40.0-103.0) tandis que le niveau de testostérone médian était de 3,7 ng / ml (IQR: 1.5-6.9). Il y avait une corrélation très faible et insignifiante entre la score de Gleason et la testostérone sérique (R = -0.066, P = 0,442).Conclusion:La corrélation entre la testostérone sérique et l’agressivité tumorale (comme déterminé par la score de Gleason) est faible. Par conséquent, par extrapolation, il peut non être nécessaire d’inclure la testostérone sérique dans le cadre d’enquêtes de travail préopératoires pour les patients capucheux de notre environnement.
This article extends on a previously published scoping review by describing the what and the how of a specialised, culturally responsive, joint early falls response service practice between occupational therapy and paramedics that could enhance falls management and prevention for older adults in Aotearoa New Zealand. The research replicated a previous literature search, with critical refinements in search terms and criteria, to identify new or previously overlooked research. Research included was pulled apart to describe an overall model that could be utilised for a local context. Fourteen studies focussing on how occupational therapists and paramedics work together were used. Articles discussed rapid response, early response and hybrid models of service to assess patients and effectively prevent recurrent falls. Articles also included studies on effective falls management and prevention involving occupational therapists following a fall. Grey literature sourced included government reports and healthcare evaluations. These sources informed key considerations for developing a falls response service in Aotearoa New Zealand. Investing in a rapid response, interprofessional service would enhance quality of life while easing pressure on emergency and long-term care. Cost-effective, community-based solutions present opportunities to support independence, dignity and wellbeing for an ageing population.
Spatial transcriptomics (ST) technologies capture transcriptomics of genens with spatial context, enabling systematic exploration of micro-environment of tissues that is highly associated with spatial domains. And, noise of ST data poses a great challenge on designing algorithms for identifying spatial domains, whereas available methods remove noise by employing pre-processing procedure, resulting in the undesirable performance. To overcome this limitation, we propose a robust and joint framework, called jNFACL (joint Network-based Feature-Affinity Contrastive Learning), for identifying spatial domains of noised ST data, where deniosing of ST data and identifying spatial domains are simultaneously integrated. Specifically, jNFACL first constructs expression and spatial graphs with transcriptomics and spatial coordinates of spots, which removes heterogeneity of ST data. And, jNFACL separates noise of ST data by jointly projecting these constructed graphs into the shared subspace, where noise of ST data is separated from feature level with nonnegative matrix factorization. To further enhance quality of features of spots, contrastive learning is adopted to leverages spatial neighborhoods by pulling similar spots together and pushing dissimilar spots apart, where self-supervision information is incorporated, thereby improving the characterization and identification of spatial domains. Experiments on various datasets with different noise levels from multiple platforms and species demonstrate that jNFACL is much more accurate and robust than state-of-the-art methods, providing alternatives for analyzing noised ST data.
ISO 14644-1 defines ISO-8 cleanrooms, often found in pharmaceutical manufacturing facilities, by maximum allowable concentrations of airborne particles at specified threshold sizes (commonly ≥0.5 μm and ≥5.0 μm) within a classification particle size range of 0.1-5 μm. For ISO Class 8, though ISO 14644- 1 lists sizes from 0.1 to 5.0 μm, classification commonly uses the operationally relevant limits of ≥0.5 μm and ≥5.0 μm. While ISO classification establishes a compliance boundary, it does not fully leverage modern optical particle counter (OPC) time series data to detect early environmental degradation driven by controllable operational factors in non-sterile areas (traffic, door cycling, material handling, and housekeeping drift). FDA's Process Analytical Technology (PAT) guidance combined with Quality by Design (QbD) principles, promotes timely measurement, enhanced process understanding, and multivariate/statistical approaches to manage variability proactively. This paper proposes a PAT aligned framework for installing and operating particle counting systems in ISO-8 non-sterile controlled areas to detect pre-limit particle size distribution (PSD) shifts. The approach integrates (i) risk-based monitoring network design, (ii) PSD-shift features (coarse to fine ratios, event rate, recovery time, persistence) that translate raw counts into actionable change signals, and (iii) statistical change detection (EWMA/CUSUM) to distinguish transient events from sustained shifts. One thing which is often overlooked is physical collection issues, especially when pulling samples through long tubes or curved lines. Particles at 5 microns or more tend to drop out under those conditions, skewing results noticeably. So this guidance covers considerations for choosing particle counters and where to place ports for truer readings. Instead of waiting until thresholds breach, the system proposed in this article acts earlier using feedback loops tied directly to control actions there by providing a robust continuous monitoring system.
Quadrupedal animals employ diverse galloping strategies to optimize speed, stability and energy efficiency. However, the biomechanical mechanisms that enable adaptive gait transitions during high-speed locomotion under load remain poorly understood. In this study, we present new empirical and modelling insights into the biomechanics of load-pulling quadrupeds, using sprint sled dogs as a model system. High-speed video and force recordings reveal that sled dogs often switch between rotary and transverse galloping gaits within just a few strides and with minimal changes in speed and stride duration, suggestive of locomotor multi-stability during high-speed load pulling. To investigate the mechanical basis of these transitions, a physics-based quadrupedal spring-loaded inverted pendulum (SLIP) model with hybrid dynamics and prescribed footfall sequences was used to reproduce the asymmetric galloping patterns observed in racing sled dogs. Through trajectory optimization, we replicate experimentally observed gait sequences and identify swing-leg stiffness modulation as a key control mechanism for inducing transitions. This work provides a much-needed biomechanical perspective on high-speed animal draft and establishes a modelling framework for studying locomotion in pulling quadrupeds, with implications for both biological understanding and the design of adaptive legged systems.
Protein nanopores have evolved into a powerful biophysical tool, from direct DNA sequencing to versatile molecular sensors that detect RNA, proteins, aptamers, and low-molecular-weight analytes. This review summarizes the current state of nanopore technologies for biopolymer sequencing and metabolite detection and discusses prospects for developing universal sensors based on engineered protein channels. We trace the evolution of nanopore applications from reading genomic DNA to direct detection of diverse molecules, including RNA, proteins with post-translational modifications, and metabolites. We analyze key physicochemical parameters of the pore that determine selectivity and sensitivity and outline engineering strategies to optimize constriction geometry, charge patterning, signal-to-noise ratio, and stability. Mechanisms for controlled molecular translocation are considered, including enzyme-driven pulling, electroosmotic capture, and other motor-free approaches. Different membrane systems, from lipid bilayers to polymer and hybrid matrices, are compared in terms of protein compatibility, noise, and lifetime. We also describe advances in electronic readout, including parallel recording, integrated analog-to-digital conversion, adaptive sampling, and embedded real-time processing. Finally, we highlight emerging applications, from protein sequencing with modification mapping to multiplexed biomarker assays and hybrid nanopore devices, and discuss how modelling, de novo design, and directed evolution can accelerate the development of universal nanopore biosensors for biomedical diagnostics.