Since real-world data lack information on treatment assignment (usually the only information available is treatment prescription/administration) and early outcomes can happen in advanced cancer, some design choices may introduce immortal time due to selection or due to treatment strategy misclassification. To illustrate design choices that would biassedly introduce immortal time and propose unbiased alternatives, using as a case study the estimation of the effects of different monoclonal antibody (mAb) sequencing strategies on overall survival in colorectal cancer patients. We specified a target trial to estimate the effect on overall survival of initiating mAb within 8 weeks of starting first line chemotherapy versus initiating mAb with second line chemotherapy. The first biased design choice would be requiring the initiation of second line chemotherapy for eligibility. This was avoided by aligning eligibility with the initiation of first line chemotherapy. The second biased design choice would be excluding from the first line mAb strategy those who die during the grace period without starting mAb. This was avoided separately via cloning, censoring and weighting and by sequential emulation. There were 1014 eligible patients in GEMCAD 1401. The CCW approach estimated a 4-year survival difference (second-first line mAb) of 4.3% (95% CI) (-3.3%; 10.0%) and a risk ratio (RR) of 0.95 (0.88; 1.04). Sequential trial emulation estimated a survival difference of -2.8% (-7.5%; 1.2%) and a RR of 1.04 (0.98; 1.10). Biased analyses that introduced immortal time estimated an implausible early survival benefit for mAb initiation with second-line (6-month RR of 0.13 (0.03; 0.28)). Our results are compatible with no effect on survival by mAb sequencing. Misalignment of time zero, treatment assignment, and eligibility introduced immortal time.
A persistent challenge in implementation science is the gap between the pace and priorities of academic research and the needs of decision-makers. While traditional research emphasizes methodological rigor, policymakers often require timely, relevant, and stakeholder-engaged evidence to inform decisions. We conducted a real-time discrete choice experiment (DCE) with participants at an implementation science conference in Washington, D.C. during a 75-minute session on rapid implementation science. At the midpoint of the panel, the audience were invited to participate in a 10-minute DCE based on a vignette describing a hypothetical study on implementing a new vaccine facing public hesitancy. Choice sets included six attributes: rapidity of study, study design, primary outcome, level of community engagement, leadership, and costs. We used a mixed logit model to analyze preferences in real time and presented results back to the audience at the end of the session. Ninety-four participants completed the DCE; all reported working in research and 83% reported working in program implementation. Respondents placed high value on timing of results, with strong preferences for receiving results in 6 months compared 12 months (β=-1.1, 95% CI: - 1.6- - 0.6; p < 0.001) and 18 months (β=-1.7,-2.3- - 1.0; p < 0.001). Participants preferred the primary outcome to be vaccine uptake rather than vaccine acceptability (β = 1.7, 1.1-2.2; p < 0.001) and the study to be community-engaged rather than expert-led (β = 1.6, 1.0-2.2; p < 0.001). We found no preference for randomization compared to before and after (p = 0.88), nor leadership by the ministry of health versus academic institutions (p = 0.12). Respondents were willing to wait 11.3 (95% CI 7.0-15.5) additional months for a program developed with engaged stakeholders compared to expert-driven (p < 0.001) and 11.9 months (95% CI 8.1-15.8) for results on vaccine uptake rather than acceptability (p < 0.001). This real-time DCE demonstrated that with adequate preparation, it is feasible-to generate robust, interpretable, and actionable results within an hour. Findings challenge the assumption that randomization is the highest priority in research design, highlighting instead the importance of outcome and community engagement. By aligning more closely with the values of decision-makers, rapid science approaches such as real-time DCEs may help bridge the research-policy gap.
This study aimed to describe and analyze the temporal structure of combat in female Para judo and to examine the influence of sport class and weight category following the classification changes introduced by the International Blind Sports Federation in 2022. An observational methodology was applied to 116 matches from the 2022 IBSA Judo World Championships using the OTSJUDO v.2 system. Temporal variables related to standing-combat sequences, pauses, and displacement times were analyzed according to sport class (J1 and J2) and weight category. Clear differences emerged between sport classes. J1 athletes exhibited longer pauses, whereas J2 athletes showed more dynamic combat, with longer total and sequential standing-combat time and shorter pauses. Weight-category effects varied by class. In J1, extra lightweight athletes (-48 kg) showed a more intermittent pattern with shorter pauses, while heavier categories presented longer pauses and displacement times. In J2, extra lightweight athletes performed shorter standing-combat sequences than other categories. Between-class comparisons within weight categories revealed differences mainly in intermediate divisions, particularly in standing-combat sequences (-57 kg) and pause duration (-70 kg). Sport class emerged as the primary determinant of temporal combat dynamics in female Para judo, with weight category acting as a secondary modulating factor.
In a previous study, retrospective predictions of human serum concentration-time profiles for three therapeutic monoclonal antibodies (mAbs) with linear pharmacokinetics were performed using allometric scaling in common marmosets and achieved favorable predictability. To generalize this method, in the present study, golimumab and ustekinumab, which exhibit linear pharmacokinetics, were repeatedly administered to marmosets. Additionally, the immunogenicity of these mAbs in common marmosets was evaluated. Golimumab and ustekinumab were administered in four repeated doses. Following the initial administration, the scaling exponents of the two mAbs were calculated, and the average scaling exponents of the five mAbs were used for the predictions. Furthermore, serum anti-ustekinumab and anti-golimumab antibodies were evaluated following the repeated-dose administration. Human serum concentration-time curves of golimumab and ustekinumab were predicted using the average scaling exponents of the five mAbs. Although the predictability of the golimumab elimination rate was slightly inferior, ustekinumab showed excellent prediction performance. Low levels of anti-ustekinumab antibodies were detected in the serum when the serum ustekinumab levels were considered to have completely diminished. Furthermore, serum anti-golimumab antibodies were negligible during the experimental period. We identified provisional optimal scaling exponents for predicting human PK and found minimal anti-drug antibody formation. As the cost of acquiring and maintaining cynomolgus monkeys is increasing, pharmacokinetic data of marmosets is expected to encourage the potential use of these small non-human primates as an alternative model.
The Viking missions showcased multiple spaceflight technologies that represented state-of-the-art capabilities: From digital line-scan imaging to the operation of complex onboard laboratories and software-controlled process autonomy. Since Viking, there have been extraordinary, and still accelerating, advancements in computing technology that impact science, society, and exploration. These developments have occurred in both hardware and software and have resulted in increasingly capable devices, advanced programming tools, and algorithmic innovations. The subset of artificial intelligence known as machine learning has emerged as one of the most transformative of these developments; it has major implications for space exploration and for improvements to the search for evidence of life beyond Earth. Those improvements include the integration of data across different scales and increased sensitivity to complex features in data, as well as the generation of adaptive strategies for sampling environments. In this article, the present and future nature of space exploration and astrobiological research is examined through the contextual lens of Viking and through the history and possible future of artificial intelligence.
Preterm birth (PTB) is associated with significant neonatal morbidity and mortality. Antenatal risk assessment is crucial for prevention and management. Recent evidence suggests that cervical injury during cesarean is a potential risk factor. This study aimed to evaluate the impact of intrapartum cesarean, specifically at full cervical dilatation (CSFD), on subsequent second-trimester loss and preterm birth. Women delivering by their first term cesarean in 2017 were included in this retrospective cohort study, and data on all subsequent pregnancies till 2024 were extracted. They were divided based on the type of cesarean- elective (CS-E) versus cesarean in latent labour (CS-L), cesarean in active labour (CS-A) and CSFD (± uterine extensions). Adjusted risk ratios (aRR) with 95% confidence intervals (CIs) were calculated to evaluate associations with subsequent pregnancy outcomes. Among 984 women, 267 had CS-E, 256 had CS-L, 212 had CS-A and 249 had CSFD. The incidence of spontaneous PTB < 37 weeks was 17.9% in CSFD (3-6% in others; p < 0.001). 26.7% of those who had a cesarean for failed instrumental delivery (FID) had a subsequent sPTB. 10.7% (vs. < 1%) and 12.5% (vs. < 6%) of CSFD with 3-5 cm extension had a second-trimester miscarriage and sPTB < 34 weeks, respectively. CSFD group had a 6.5 times higher risk of sPTB < 37 weeks compared to CS-E (CI 2.47-16.9; p < 0.001); the risk increased to 8.2 times in CSFD with 3-5 cm extensions (CI 2.27-29.5, p = 0.001). For every cm increase in cervical dilatation at the time of the index cesarean, the risk increased by 27% (CI 1.14-1.41;p < 0.001). Cesarean for no descent of head and FID had 5.3 times (CI 2.20-12.8; p < 0.001) and 8.7 times higher risk (CI 2.72-28.0; p < 0.001), respectively. CSFD is associated with a 6.5-fold increase in risk of spontaneous preterm birth. Uterine extension was an important predictor for second-trimester loss and sPTB. Risk assessment for sPTB should potentially include detailed cesarean history, and women with CSFD should potentially be referred to dedicated PTB clinics and offered preventive measures such as serial cervical length assessments, vaginal progesterone and cervical cerclage.
Over the past decade, the digitalization of health and telemedicine solutions has accelerated. Optimized digital infrastructure enables telemedicine as a complementary health care service, reducing organizational pressures and increasing accessibility. Tele medicine (TM) is well suited for chronic wound care, particularly diabetes-related foot ulcers, owing to its photo documentation and data exchange capabilities. This study aimed to explore health care professionals' (HCPs') cross-sectoral use of TM technology for the treatment and care of patients with diabetic foot ulcers (DFUs). The study used a realistic evaluation design. From 2023 to 2024, we conducted 68 h of participant observation of healthcare professionals in hospital and primary care during DFU treatment within a Danish cross-sectoral setting. The Standards for Reporting Qualitative Research (SRQR) were applied. We generated three key themes: (1) Time matters: navigating allocated and limited time in person-centred care and treatment. (2) Tech hurdles: adapting/aligning perceptions and mastering digital tools. (3) Building bridges: the power of relationships in sustaining telemedicine use. Our study led to a refined program theory allowing us to propose an answer to the problem of "what works, for whom, and under what circumstances": HCPs' cross-sectoral collaboration using the TM communication solution Pleje.net© enhances the treatment and care of patients with DFUs. This improvement is achieved in a cross-sectoral setting when care management addresses organizational challenges, such as managing time constraints, overcoming technological hurdles, and fostering strong relationships among HCPs. When robust relationships are present, the TM solution facilitates timely and coordinated care across different sectors, ultimately improving patient outcomes in a multidisciplinary setting. Findings are limited to a Danish cross-sectoral healthcare context and may not be directly transferable to other health systems.
Clathrin-mediated endocytosis (CME) relies on the dynamic assembly and remodeling of clathrin coats to drive membrane curvature and vesicle formation at the plasma membrane. Although live-cell fluorescence microscopy has provided critical insights into the timing and molecular composition of endocytic events, directly linking the nanoscale lateral organization of clathrin coats to their three-dimensional progression in real time has remained challenging. Structural approaches such as electron microscopy provide detailed snapshots of clathrin architecture but are inherently static, whereas axial TIRF-based methods report membrane-proximal position with limited lateral resolution. Here, we introduce variable-angle total internal reflection fluorescence structured illumination microscopy (vaTIRF-SIM), a live-cell imaging strategy that integrates lateral super-resolution with dynamic axial sensitivity near the plasma membrane. By combining TIRF-SIM with controlled variation of the evanescent field penetration depth, vaTIRF-SIM enables simultaneous visualization of clathrin coat architecture and relative axial displacement with high spatial and temporal resolution. Applying this approach to de novo clathrin-coated pits reveals coordinated lateral growth and progressive axial advancement from early stages of pit formation through maturation, consistent with early curvature generation that intensifies over time. Extending this analysis to clathrin plaques uncovers two distinct plaque-associated endocytic behaviors: slowly maturing pits that originate at plaque peripheries and progress similarly to de novo pits and rapid plaque subdomain internalization events marked by accelerated axial progression. Together, these results establish vaTIRF-SIM as an approach that, for the first time, enables direct real-time coupling of nanoscale clathrin coat organization with axial progression during CME in living cells, demonstrated here in genome-edited SUM-159 cells expressing AP2-EGFP from the endogenous locus.
The increasing prevalence of autism has led to considerable system challenges as specialist-driven approaches have struggled to keep pace. Recent research has challenged status quo models by demonstrating that community-based pediatric clinicians can accurately diagnose autism in young children. This research provides an opportunity to further expand capacity of community systems to conduct developmentally relevant, context-specific assessments of autistic people over their lifespan. In this Commentary, we propose a personalized lifespan approach to autism assessment as a precision care and system organization framework that considers the ongoing and evolving needs of autistic people and aligns the necessary expertise and resources to provide focused assessment when it is most informative. This framework consists of three key principles: (1) assessment is not a one-time, one-size-fits-all event; instead, assessment continues across the lifespan; (2) assessments should generate information that is relevant to the individual's current needs and life stage; and (3) wherever possible, community-based expertise should be engaged to promote the right assessment at the right time in the right place. Adopting this framework can reduce system access challenges, while also addressing the ongoing assessment needs of an autistic person across their life course. Historical models of autism care have not kept up with the demand for autism diagnostic evaluations, leading to lengthy wait times. Recent research has shown that community‐based pediatric clinicians can diagnose autism with high accuracy. In this paper, we suggest expanding these findings into a personalized lifespan approach to autism assessment that takes a broader view of assessment as occurring across many points over a person's lifetime and in a person's community whenever possible. This model can help to ensure that autistic people have ongoing access to learn more about themselves, and that they can get these answers when they need them and closer to home.
To compare perioperative outcomes of robotic-assisted thoracic surgery (RATS) versus video-assisted thoracoscopic surgery (VATS) for mediastinal tumor resection in a propensity score-matched cohort. This retrospective study analyzed patients undergoing minimally invasive mediastinal tumor resection between January 2022 and November 2025. Patients were categorized into RATS and VATS groups. Propensity score matching balanced baseline characteristics including age, gender, body mass index, ASA score, Charlson Comorbidity Index, tumor size, tumor location, pathology, and prior thoracic surgery history. The primary outcome was postoperative complications of Clavien-Dindo grade ≥ II. Secondary outcomes included operative time, blood loss, chest tube duration, hospital stay, costs, and pain scores. After matching, 102 patients (51 per group) were included. RATS was associated with significantly less intraoperative blood loss [median difference - 15 mL (95% CI: - 20 to - 10), P < 0.001], shorter chest tube duration [median difference - 1 day (95% CI: - 1.7 to - 0.3), P = 0.003], and shorter hospital stay [median difference - 1 day (95% CI: - 1.7 to - 0.1), P = 0.009]. Total costs were higher in the RATS group [median difference +$4,400 (95% CI: $3,800-$5,000), P < 0.001]. Operative time, postoperative pain scores, and complication rates (grade ≥ II: 9.8% vs. 13.7%, P = 0.55) were comparable between groups. Using an alternative definition (grade ≥ III), complications occurred in 3.9% (RATS) vs. 5.9% (VATS), P = 0.65. For mediastinal tumor resection, RATS offers modest perioperative benefits including reduced blood loss and shorter recovery times compared to VATS, but at substantially higher cost and without a reduction in major complications. RATS is a feasible and safe minimally invasive alternative, but its advantages over VATS are small and must be weighed against economic considerations. Routine adoption is not supported by the current evidence; selection should be individualized.
Exertional heat illness encompasses a continuum from heat exhaustion (EHE) to heat stroke (EHS), yet the molecular mechanisms remain poorly understood. DNA methylation offers a stable epigenetic signature linking environmental stress to gene regulation and long-term physiological outcomes. We profiled genome-wide DNA methylation in blood from active-duty service members hospitalized for EHE (n = 36), heat injury (EHI; n = 18), or EHS (n = 50). Blood was collected longitudinally and analyzed using the Illumina 850 K array, with normalization and time-course clustering (TCseq) to identify co-regulated CpG networks. Ingenuity Pathway Analysis was applied differentially methylated probes (p < 0.01, Δβ > 0.04). At diagnosis, both EHI and EHS shared hypomethylation in pathways regulating heat sensing, oxidative defense, and vascular tone. Over time, EHI exhibited adaptive methylation changes supporting neuronal repair, glucocorticoid regulation, and cytoskeletal stability. In contrast, EHS demonstrated sustained downregulation of metabolic and cardiovascular regulators, persistent inflammasome activation, and oxidative imbalance. Early patterns were shared between EHI and EHS, reflecting a common acute stress response, but later responses diverged: EHI showed partial epigenetic recovery, while EHS exhibited sustained metabolic suppression and inflammasome activation. These time-dependent methylation signatures identify potential molecular targets for promoting recovery and preventing long-term complications of heat illnesses.
Consistent with WHO guidance Zimbabwe is transitioning from annual single visit screen-and-treat using visual inspection with acetic acid and cervicography (VIAC) to HPV testing every three years to screen women living with HIV (WLHIV) for cervical cancer. We administered a questionnaire at three public-sector facilities in Zimbabwe to understand reasons why WLHIV accept or decline VIAC and preferences for implementation of HPV testing. A total of 451 WLHIV completed the questionnaire, of whom 414 (91.8%) accepted VIAC screening and 37 (8.2%) declined screening. Close to 50% of the 37 women who declined screening indicated a preference for HPV testing. The majority of WLHIV (76.3%) had known their HIV positive status for ≥ 5 years and nearly all (99.8%) were on antiretroviral therapy. Among the 414 WLHIV accepting VIAC screening, 323 (78.0%) were re-screening, and 91 (22.2%) were screening for the first time. WLHIV accepting VIAC re-screening were motivated by healthcare workers helping them feel secure about their health (45.8%), compliance with annual screening recommendations (39.6%), and encouragement from a healthcare worker (8.0%). Those accepting VIAC screening for the first time were motivated by encouragement from a healthcare worker (39.6%), compliance with annual screening recommendations (38.5%), and helping them feel secure about their health (17.6%). When asked what screening approach they would prefer in the future, the majority of women accepting re-screening (70.3%) and first-time screeners (89%) indicated a preference for continuing with VIAC screening. The 93 WLHIV with a screening history who indicated a preference for HPV testing were evenly split between preferring provider-collected sampling (13.9%) and self-collected sampling at the health facility (13.6%). Fear of physical discomfort of a pelvic exam (54.1%), worry about the screening result (13.5%), and perceived side effects of VIAC (10.8%) were the most common reasons given by the 37 WLHIV who declined VIAC. Facilities transitioning to HPV testing will need to incorporate client-centered education that acknowledges existing individual commitment to VIAC, explains the benefits of HPV testing, and offers HPV self-sampling for WLHIV who are hesitant to undergo a pelvic exam.
To estimate longitudinal predictive relationships between team resilience and team stress among low-stability clinical nursing teams, identifying core driving factors and bridging mechanisms using cross-lagged panel network analysis. Chronic instability in clinical nursing teams disrupts workflows and triggers systemic team stress, which is further exacerbated by digital health technology burdens and moral distress. Understanding how specific dimensions of team resilience interact with these facets of team stress over time is essential for developing precise organizational interventions. A two-wave longitudinal panel study. Data from the Nurse Team Health Management Research Cohort across two waves (October 2024 and December 2025) included 5164 clinical nurses aggregated into 285 low-stability nurse teams. Team resilience and team stress were assessed using the Analyzing and Developing Adaptability and Performance in Teams to Enhance Resilience Scale and a customized Nursing Job Stressor Inventory. A cross-lagged panel network was estimated to identify influential nodes and network conduits. Digital health technology burden exhibited the highest predictive power, driving team stress and significantly predicting subsequent moral distress. Moral distress emerged as a potentially destructive bridge, which may negatively predict multiple resilience dimensions over time. Conversely, cooperation with other departments appeared to serve as a protective bridge, mitigating subsequent subjective work stress and digital technology burden. Monitoring exhibited a potentially paradoxical effect, positively predicting subsequent subjective work stress. Digital health technology burden drives occupational stress in low-stability nursing teams. Moral distress may erode team resilience, whereas cross-departmental cooperation acts as a potential protective shield. This study shifts the focus of occupational stress management from the individual to the team level. To stabilize nursing teams facing chronic instability and high turnover, healthcare administrators should move beyond generic stress reduction. Targeted interventions must focus on alleviating digital workflow burdens, instituting routine ethical debriefings to resolve moral distress, and formalizing boundary-spanning cooperation protocols.
Nontraumatic low back pain is highly prevalent in Australia, affecting 79.2% of adults and accounting for up to 4% of emergency department (ED) presentations. This study examines the postdischarge outcomes of ED patients admitted to a short stay unit (SSU) for low back pain management. A cross-sectional observational study design was employed, comprising retrospective observational data and a follow-up cross-sectional survey. Data were collected between June 2023 and February 2024. Functional status was measured with the Modified Oswestry Low Back Pain Disability Questionnaire. Of the 422 participants invited, 21% (n = 89) completed questionnaires. Respondents were 58% female and 42% male, aged 20.3-96.1 years (mean 63.4, SD 19.4). Most respondents (71.2%) reported moderate-to-severe disability, with 19.1% reporting complete disability. Over 50% were still taking opioid analgesics at the time of survey completion. In the multivariable regression model, pharmacological treatments were significantly associated with disability scores (F (4, 84) = 5.34, p < 0.001). Use of short-acting opioids was associated with an average increase of 7.5 units in disability score and use of long-acting opioids with an average increase of 8.1 units, reflecting ongoing pain or greater disability among participants receiving opioid medications. Time spent in the SSU was associated with the severity of disability. Patients who later developed moderate or severe disability spent a mean of 31 h in SSU, compared to 17.5 h among those with no or mild disability (p = 0.012). Only 45% of patients sought ongoing physiotherapy care in the month following discharge. At one month postdischarge, most participants reported considerable ongoing disability and pain. A substantial proportion continued to use opioids, while physiotherapy services remained underutilised. Findings from this study informed a local business case to establish physiotherapy 'virtual hot clinics' for patients within 1 week of discharge.
Assess in vitro efficacy of a device emitting 265 nm UVC light against bacteria isolated from veterinary infectious keratitis. Twenty-seven clinically-derived bacterial isolates: Staphylococcus pseudintermedius (n = 10; including n = 2 methicillin-resistant Staphylococcus pseudintermedius [MRSP]), Staphylococcus aureus (n = 1), Streptococcus canis (n = 4), Escherichia coli (n = 4, including n = 2 multidrug-resistant isolates), Pseudomonas aeruginosa (n = 7) and Serratia marcescens. (n = 1), and three type culture strains (n = 1 E. coli, S. aureus, S. pseudintermedius) were lawn cultured. Prototype UVC device (2.50 mW/cm2 intensity, 23 mm diameter beam) provided triplicate exposures at 1, 2, 3, and 5 s, and plates incubated (37°C, 16-20 h). All experiments were performed in duplicate (n = 6 treatment zones per timepoint, per isolate). Absence of growth in all exposed areas at any time demonstrated complete UVC inhibition; presence of growth was categorized as < 10 or ≥ 10 colonies. UVC inhibition was complete in 11/30 isolates at ≤ 5 s exposure. Partial efficacy was seen in 18/19 remaining isolates at 5 s; ≥ 33% zones demonstrated absence of bacterial growth. Efficacy against MDR-MRSP and MDR-E. coli was comparable to susceptible counterparts. All P. aeruginosa were completely inhibited at ≤ 5 s; the S. marcescens isolate was least susceptible with ≥ 10 bacterial colonies within 50% zones after 5 s. Five seconds of UVC exposure is sufficient to markedly reduce growth of most bacterial species, including MDR-isolates and completely inhibit P. aeruginosa in vitro. These findings support further controlled in vivo safety and efficacy studies of UVC as an adjunct to topical antibiotics in companion animal infectious keratitis.
Rapid diagnosis is critical for the early detection and control of transboundary animal diseases such as African Swine Fever (ASF) and Avian Influenza (AI), particularly because it enables timely containment measures at the farm level. In low-resource settings where sample transport, cold chain maintenance, and access to centralized laboratories are challenging, portable qPCR systems offer a clear operational advantage by enabling on-site or near-site testing thus reducing diagnostic turnaround and response time. This study evaluated three qPCR platforms for detecting African Swine Fever Virus (ASFV) and Avian Influenza Virus (AIV): two laboratory-based systems, CFX96 Touch (Bio-Rad) and MIC (BioMolecular Systems), and the portable qPCR platform Franklin by Biomemex. Seventy-two ASF virus samples representing genotypes I, II, IX, XIV, XXIII, and a genotype I/II recombinant from eleven countries were tested on two laboratory platforms (CFX96, MIC) and one rapid platform (Franklin) alongside 50 AI virus samples (H5N1, H9N2) from seven countries. Both laboratory platforms achieved consistent results. Franklin required protocol optimization when the WOAH-recommended protocol produced predominantly false-negative results, but adapted amplification conditions restored performance. Limits of detection per reaction calculated by probit analysis were: CFX96 21.28 (14.85-68.67), MIC 32.76 (21.12-96.11), Franklin with lyophilized reagents 4.12 (2.71-14.97), and Franklin with adapted protocol 6.85 (4.33-20.11). After adaptation, all platforms exhibited high diagnostic sensitivity and specificity for ASFV detection. For the AIV detection protocol, false negative results were observed on MIC and Franklin platforms compared to the CFX96. The laboratory platforms tested in this study (CFX96 and MIC) provided robust high-throughput capabilities, while the portable system (Franklin) offered superior sensitivity but required protocol adaptation of established WOAH-recommended procedures.
Brief inhalation of carbon dioxide (CO2) has been proposed to counteract transient hypocapnia by enhancing oxygen unloading, vasodilation, and sympathetic modulation. Despite these potential ergogenic mechanisms, CO2 has rarely been investigated in the exercise context. The present study investigated whether brief CO2 inhalation (iCO2) influences performance and recovery during high-intensity interval exercise. Nine healthy adults completed two randomized, single-blinded crossover trials of repeated cycling intervals at 85% peak work rate until volitional exhaustion or cadence dropped below 60 rpm, with a minimum 2-min interval duration required and 3-min active recovery between bouts. Participants inhaled 5% CO2 or room air (15 breaths) before and after each exercise bout. Gas exchange, cardiovascular responses, and perceived exertion were assessed. Total exercise time was similar between trials; however, participants completed more intervals with iCO2. During the first interval, iCO2 increased exercise duration and VO2. At matched exercise time, perceived exertion and dyspnea were lower with iCO2. During recovery, systolic blood pressure was lower and heart rate was higher following iCO2. Brief iCO2 improved first-interval performance, altered cardiovascular recovery, and reduced perceptual strain but did not extend overall exercise duration. These findings suggest iCO2 may transiently modulate tolerance and autonomic-vascular responses during high-intensity interval exercise.
High-speed atomic force microscopy (HS-AFM) enables direct visualization of protein dynamics under near-physiological conditions, yet its intrinsic limitation to surface topography prevents atomic-level structural characterization. We present AFM-Fold, a generative AI-based framework that reconstructs three-dimensional protein conformations directly from AFM images. AFM-Fold combines a group-equivariant convolutional neural network, which extracts low-dimensional collective variables (CVs) from AFM images, with a guided diffusion process that generates conformations consistent with the inferred CVs. Using pseudo-AFM images of Adenylate kinase, AFM-Fold accurately reproduced not only the open and closed conformations, but also a continuous range of intermediate conformations spanning the open-closed transition. Application to 159 experimental HS-AFM frames of the flagellar protein FlhAC further demonstrated that AFM-Fold yields conformations more consistent with experimental images than rigid-body fitting of the crystal structure, and captures time-correlated domain motions that reflect underlying conformational dynamics. AFM-Fold enables rapid, physically plausible structure estimation from individual AFM images, typically within one minute per frame, without relying on molecular dynamics simulations. This unified and computationally efficient pipeline opens a route to high-throughput structural analysis of HS-AFM movies.
Peripheral vascular interventions (PVIs) are less invasive alternatives to surgical bypass. However, the impact of PVIs on the post-procedural quality of life of patients and workload of nurses remains unclear. Therefore, we conducted a questionnaire-based survey including patients and nurses. The patient questionnaire consisted of eight items, including intra-procedure access site pain, post-procedure access site pain, discomfort during rest time, difficulty eating, bathroom difficulties, difficulty sleeping, difficulty walking the following day, and overall procedure satisfaction. The nurses' workload questionnaire comprised seven items, including bathroom care, eating care, pain care, access-site care, post-procedure nurse call support, handling postoperative complications, and overall workload. Patients who underwent PVIs using the transradial approach expressed significantly less discomfort during the post-procedure rest time, difficulty eating, bathroom difficulties, difficulty sleeping, and difficulty walking the following day than those who underwent the transfemoral approach. Nurses found the post-procedural management of the transradial approach easier than that of the transfemoral approach, with significant differences in bathroom care, eating care, access-site care, and handling postoperative complications. Notably, the overall workload was significantly lower for the transradial approach than that for the transfemoral approach. Thus, the transradial arterial approach for PVI had advantages over the transfemoral approach in this study, including improved patient comfort and decreased nursing workload.
Soft tissue grafts are commonly used in periodontal surgery around teeth and implants. However, few studies have examined donor-site pain through patient-reported outcomes following soft tissue grafting. This study aimed to minimize donor-site pain during autologous gingival grafting using a three-dimensionally (3D)-printed stent and evaluate its effectiveness from a patient-centered perspective. In this randomized controlled trial, 32 patients requiring autogenous gingival grafts were equally allocated to the control group (Omnivac stent) or the test group (3D-printed stent). Patient-reported outcomes were assessed using a visual analog scale (VAS) and the Oral Health Impact Profile-14 (OHIP-14) questionnaire on the day of surgery and at 1, 7, and 14 days postoperatively. Data from 16 control and 14 test patients were analyzed (two patients were lost to follow-up). The test group reported significantly lower VAS scores than the control group. Despite a lack of statistically significant temporal differences, marked reduction was observed on the day of surgery and on postoperative day 7. OHIP-14 scores were significantly lower in the test group than in the control group across all time points. Analysis of the individual OHIP-14 items at different intervals revealed significant reductions in discomfort-specifically in pronunciation, taste, mastication, and daily activities-when using 3D-printed stents. This study applied 3D-printed stents to reduce donor-site discomfort after autogenous soft tissue grafting and evaluated their effectiveness using patient-reported outcomes. Although 3D-printed stents may not directly reduce postoperative pain, they help alleviate discomfort during routine oral functions and daily activities. This study focuses on the free gingival graft, one of the most frequently employed soft tissue grafts in periodontal practice. While autogenous gingival grafting on the palatal side is currently considered the gold standard, it causes additional pain and discomfort in patients. This study demonstrates that three-dimensional technology can be used to improve stent design to reduce patient pain and discomfort. This randomized controlled trial demonstrates that compared with a conventional stent, a customized 3D-printed palatal stent significantly improves patient-reported comfort and oral function after autologous gingival grafting, thereby enhancing postoperative quality of life.