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Highly pathogenic avian influenza clade 2.3.4.4b virus continues to circulate in North America and has caused severe human disease. That clade includes genotype D1.1, which became dominant in birds in late 2024. Recent phylodynamic reconstructions place D1.1 emergence in mid-2024 but differ on its inferred origin and early dissemination pathways. We combined targeted surveillance of wild birds in Arizona with publicly available US clade 2.3.4.4b hemagglutinin sequences to estimate when D1.1 genotype emerged and to infer its diffusion among the 4 major US flyways. Phylodynamic analyses showed transitions concentrated among adjacent flyways regions, consistent with stepwise dissemination during fall 2024 and limited support for long-distance Pacific-Atlantic exchange. The Pacific Flyway showed patterns consistent with an early source and the Central Flyway with a secondary hub linked to onward spread. Our findings support coordinated genomic surveillance across adjacent flyways to reduce detection delays and improve situational awareness during rapid viral expansion.
Negative circumferential resection margins (CRM) have been demonstrated to confer improved survival in patients with locally-advanced rectal cancer (LARC). Multiple clinical trials have recently demonstrated non-inferior short-term outcomes for robotic-assisted surgical resection (RR) compared to laparoscopic resection (LR) for LARC. We assessed CRM and long-term survival outcomes in LARC patients undergoing RR versus LR using the National Cancer Database (NCDB). NCDB retrospective analysis was performed in clinical stage II or stage III LARC patients who underwent RR or LR following total neoadjuvant therapy (TNT) between 2006 and 2021. We analyzed short- and long-term outcomes, including CRM status and overall survival (OS). 14,744 patients were included. 6187 patients underwent RR and 8557 underwent LR. There was no difference in mean age, race, or comorbidity index scores between study groups. From 2006-2014 to 2015-2021, there was a significant increase in the proportion of LARC patients undergoing RR (31.8 to 53.0%). There was no significant difference in rate of positive CRM between the two groups (RR 5.7% vs. LR: 5.5%), however, the rate significantly decreased in the RR from Time Period 1 to Time Period 2 (6.3 to 4.8%). LR patients had a slightly higher risk of death compared to RR patients (HR 1.08, 95% CI 1.02-1.14). There was an increased risk of death in those in those with negative CRM who underwent LR compared to those with negative CRM who had undergone RR (HR 1.08, 95% CI 1.02-1.15). In those undergoing surgical resection for LARC after TNT, RR had equivalent rates of positive CRM with slightly superior long-term OS compared to those who underwent LR. This large volume, national database study demonstrates that RR for LARC continues to offer a suitable alternative to LR with non-inferior operative, short-term, as well as long-term surgical outcomes, which have not previously been demonstrated.
Chirality, a central concept across many scientific disciplines, continues to inspire the discovery of novel physical phenomena. In condensed matter physics, structural chirality-defined by the absence of mirror plane symmetries-has primarily been explored in bulk materials. However, new chiral phenomena can emerge uniquely at the interface, distinct from their bulk counterparts, when a chiral material forms a heterostructure. Here, we demonstrate that all van-der-Waals (vdW) heterostructure composed of the chiral Co1/3TaS2 and the achiral vdW ferromagnet Fe3GeTe2 exhibits two distinct and unconventional spin-orbit torques originating from the interfacial chirality. These torques enable magnetic-field-free switching of perpendicular magnetization with ultralow current density ~106A/cm2 and minimal power dissipation <1015W/m3. Moreover, by replacing Fe3GeTe2 with a similar vdW ferromagnet, Fe3GaTe2, but of higher Curie temperature, we achieved the magnetic-field-free switching at room temperature in the Fe3GaTe2/Co1/3TaS2 vdW heterostructure. Our findings establish interfacial chirality as a powerful new handle for spintronic control, opening a new pathway to explore chirality-induced phenomena beyond the bulk symmetry constraints - and paving the way toward highly efficient, low-power spintronic devices based on all-vdW heterostructures.
Open surgical repair continues to be the standard of care for treating thoracic aortic aneurysms (TAA) and Type B Aortic Dissection (TBAD) in patients with connective tissue disorders (CTD). Data on the safety and durability of thoracic endovascular aortic repair (TEVAR) in this patient population remains limited. This study aims to evaluate the perioperative and midterm outcomes of TEVAR in patients with CTD. Patients with CTD who underwent TEVAR for TAA or TBAD between 2014 and 2024 were identified in the Vascular Quality Initiative. Patients with ruptured aneurysms, trauma, or those converted to open surgery were excluded. CTD were defined as any documented clinical or genetic history of Marfan syndrome, Loeys-Dietz syndrome, or Ehlers-Danlos syndrome. Patients were stratified and compared by aortic pathology (TAA versus TBAD) and CTD pathology (Marfan syndrome versus Loeys-Dietz/Ehlers-Danlos syndrome). Kaplan-Meier analysis was used to evaluate and compare the midterm event rates of survival, aortic reintervention, aneurysmal degeneration, and dissection propagation. Aneurysmal degeneration was defined as a ≥5 mm increase in aortic diameter from baseline, whereas dissection propagation included antegrade and/or retrograde dissection. 330 patients (median age 50 years [IQR, 35-61]) with CTD underwent TEVAR during the study period, of which 85% (n=281) had Marfan syndrome, 13% (n=42) had Loeys-Dietz syndrome, and 2% (n=7) had Ehlers-Danlos syndrome. TEVAR was performed for TBAD in 63% (n=208) of patients and TAA in 37% (n=122), with 8% (n=25) of procedures performed in an emergent setting. Median hospital stay was 5 days (IQR, 3-9). Perioperative mortality, spinal cord ischemia, and stroke each occurred in 2.1% (n=7) of patients, and reintervention was required in 10.9% (n=36). Patients undergoing TEVAR for TBAD had a longer hospital stay (6 days vs 5 days, p=0.017) and higher perioperative mortality (3.4% vs 0.0%, p=0.039) compared with TAA. Marfan syndrome patients had a significantly lower rate of perioperative mortality (1.4% vs 6.1%, p=0.036) than those with Leoys-Dietz syndrome or Ehlers-Danlos syndrome. At 18-month follow up, overall survival was 88.1% (95% CI, 84.2%-92.0%), with reintervention occurring in 30.8% (95% CI, 23.9%-37.7%), aneurysmal degeneration in 40.2% (95% CI, 29.8%-50.6%), and dissection propagation in 20.4% (95% CI, 10.8%-30.0%). Midterm outcomes were similar between TBAD and TAA for survival (p=0.369), reintervention (p=0.896), aneurysmal degeneration (p=0.151), and dissection propagation (p=0.810). Patients with Marfan syndrome had a higher midterm survival compared to patients with Loeys-Dietz or Ehlers-Danlos syndrome (91.0% vs 71.6%, p=0.001), with no difference observed in reintervention (p=0.190), aneurysmal degeneration (p=0.496), or dissection propagation (p=0.445). TEVAR in patients with CTD is associated with acceptable perioperative morbidity and mortality but carries a substantial risk of early and midterm aortic-related complications and reintervention. TEVAR should be used cautiously in this population and primarily reserved for emergency situations or carefully selected patients.
Olfactory stimulation may enhance respiratory drive in preterm infants without respiratory support. The aim of this study was to assess the efficacy of olfactory stimulation on apnea of prematurity (AOP) in preterm infants receiving nasal continuous positive pressure (nCPAP). This randomized, placebo-controlled, double-blind cross-over study enrolled preterm infants born between 23 0/7 and 31 6/7 weeks of gestation receiving nCPAP and treatment with caffeine citrate. Vanilla or strawberry odor, or an odorless placebo solution, was applied to the nCPAP masks with an odor pen. The primary outcome was the number of desaturation and bradycardia episodes. Secondary outcomes included physiological parameters and feeding tolerance. Eighty preterm infants completed the study. The median (interquartile range) number of events during the 12-hour study period was 10 (3-27) in the intervention group and 14 (3-29) in the control group (p = 0.82). No significant differences were observed in any secondary outcome measures with either vanilla or strawberry odor. This study did not demonstrate an effect of olfactory stimulation on the number of desaturation and bradycardia episodes in very preterm infants receiving nCPAP. Future research may focus on optimizing methods for delivering olfactory stimuli to infants on non-invasive respiratory support. Clinical trials have demonstrated that olfactory stimulation, using odors such as vanilla, may reduce the frequency of apnea and desaturation episodes in spontaneously breathing preterm infants. This study evaluates the effect of olfactory stimulation with vanilla and strawberry odor on the respiratory drive of preterm infants receiving nasal continuous positive pressure support - the population most severely affected by the apnea of prematurity. In this population, olfactory stimulation did not significantly reduce the number of desaturations and bradycardia. Future research may focus on optimizing delivery methods to ensure that olfactory stimuli are effectively perceived by infants on non-invasive respiratory support.
Advance decisions are a key component of advance care planning (ACP) and support individuals in communicating their preferences for future medical care. Despite policy efforts to promote ACP, public awareness and engagement in completing advance decisions remain limited in many settings. Educational robots, which provide interactive and engaging learning experiences, may represent a novel strategy for delivering ACP education in community settings. This study aimed to examine older adults' acceptance of an educational robot designed to facilitate learning about advance decisions. Specifically, we investigated factors associated with their intention to continue using the robot to learn about advance decisions and their intention to recommend the robot to others for advance decisions education. A cross-sectional survey was conducted among older adults recruited from community centers in northern Taiwan. After providing informed consent, participants attended a 90-minute robot-assisted educational session introducing key concepts of advance decisions and ACP. Following the session, participants completed a self-administered questionnaire assessing human-computer trust, decisional balance (perceived pros and cons of advance decisions), personal involvement, satisfaction with the robot-assisted learning experience, intention to continue using the educational robot, and intention to recommend the robot to others. Partial least squares structural equation modeling (PLS-SEM) was used to test the proposed relationships among study variables. Human-computer trust significantly increased older adults' intention to continue using the educational robot, both directly and indirectly through satisfaction with the learning experience. Trust also influenced participants' intention to recommend the robot to others indirectly via satisfaction. Perceived benefits of advance decisions were positively associated with recommendation intention, whereas perceived barriers showed no significant effects. Neither the perceived benefits nor barriers of advance decisions significantly influenced the intention to continue using the robot. Overall, satisfaction emerged as a key mediator linking trust to behavioral intentions related to robot-assisted ACP education. Trust in the technology and satisfaction with the learning experience play critical roles in shaping continued engagement and willingness to recommend such interventions. Integrating interactive technologies into ACP education may help expand public awareness and promote broader engagement in advance care planning.
Primary healthcare (PHC) systems in Sub-Saharan Africa (SSA) continue to prioritise reactive, curative models of care, despite the region's pressing need for health-promotive and preventative strategies. Instead of disrupting the existing curative model, the expansion of digital health often automates old, treatment-oriented systems with a limited focus on creating new tools for preventive and health-promoting functions. While there is no shortage of reviews on digital health and telemedicine in SSA, these predominantly focus on curative care and service delivery within the walls of healthcare facilities. An understanding of how remotely provided preventive and health-promoting services can be implemented by PHC facilities to strengthen the PHC overall is currently lacking. Addressing this gap is critical for guiding research, policy and practice towards designing more preventive and proactive PHC service models. This protocol details a scoping review that will identify and establish what is currently known about the implementation and feasibility of remote preventive and digital health-promoting services as potential levers to strengthen PHC in SSA. The review will consolidate evidence on digital health initiatives for prevention and identify key opportunities, barriers and gaps in the current knowledge. Results will be analysed using quantitative summaries and qualitative thematic analysis. Ethical approval is not required as this study uses publicly available literature. The findings could guide policymakers, programme implementers and researchers in reorienting PHCs towards more preventive approaches. The findings of the proposed scoping review will be disseminated through publication in a peer-reviewed journal. The protocol is registered with the Open Science Framework (OSF: https://osf.io/8whkc/) to comply with methodological transparency and accountability.
PER: and polyfluoroalkyl substances (PFAS) have been implicated in metabolic dysregulation; however, longitudinal evidence linking PFAS to metabolic syndrome (MS) across the transition from adolescence or young adulthood into early adulthood is still lacking. We analyzed 516 participants aged 12-30 years in the Young Taiwanese Cohort (YOTA) with baseline examinations in 2006-2008 and follow-up in 2017-2019. Eleven plasma PFAS and MS components were quantified at both time points. We used joint models that simultaneously included baseline PFAS and long-term PFAS changes to evaluate associations with follow-up MS and its components. A PFAS exposure index was derived as the mean of standardized ln-PFAS. The baseline PFAS exposure index was not associated with MS or its components. Among individual baseline PFAS, linear PFOA was inversely associated with impaired fasting glucose, and both linear PFOA and PFHxS were inversely associated with elevated blood pressure. In contrast, the PFAS exposure index change was inversely associated with follow-up MS (OR 0.36, q = 0.050) and follow-up MS waist (OR 0.22, q < 0.001). Among individual PFAS changes, follow-up MS was inversely associated with changes in linear PFOA, PFHxS, and PFDoA, and MS waist was inversely associated with changes in linear PFOA, linear PFOS, PFNA, PFDA, PFUdA, and PFDoA. The associations between PFAS exposure index change with MS and MS waist were robust across sensitivity analyses, including qgcomp. Analyses of continuous metabolic traits showed concordant patterns for waist circumference and HDL-C. Exploratory backward models further suggested that adiposity change may influence measured PFAS change. In this Taiwanese cohort, higher ΔPFAS exposure index was associated with lower odds of MS and abdominal obesity, but the findings are consistent with reciprocal coupling rather than a protective effect of PFAS exposure. Studies with three or more repeated measurements are needed to clarify causal direction and underlying mechanisms.
An adaptive fractional-order model predictive control (FO-MPC) framework of DC-DC boost converters, which incorporates the Exponential Recursive Least Squares (ERLS) identification, the use of the fractional-order dynamics, and the application of the Grey Wolf Optimization (GWO) is presented in this paper. An important discovery is that the combination creates synergistic effects: ERLS convergence is improved by 47% compared to standalone implementations, since the damping of adaptation transients is of fractional-order-damping-like-density, which previous combined methods (such as Wang et al. (2020)) or (Ghamari et al. (2025)) did not provide. The ERLS algorithm allows adaptation model free and convergence in 15 samples even without the use of exact mathematical models. An optimized α = 0.85, fractional-order operator in the noise rejection case and better stability margins is observed, which is 15dB more than the traditional MPC implementations. GWO, executed offline during commissioning, achieves 25 to 30 times faster convergence than conventional metaheuristics (GA, PSO) when tuning the controller parameters. Arduino DUE (84 MHz ARM Cortex-M3) hardware validation has shown that settling time is significantly decreased to 0.42s (83% lower than the baseline), that overshoot is kept to less than 1% (95% lower than the baseline), and that steady-state error is only 20mV (87% smaller than the baseline). The controller is stable in the 30% variations in parameter and 10 times changes in load with an execution time of 85µs, which is compatible with 10 kHz control frequency. Monte Carlo simulations (n = 1000) confirm a success rate of 98.2% in combined disturbances, and statistical significance is validated using the Wilcoxon signed-rank tests (p < 0.001, Cohen's d > 2.0). The industrial use has been tested and supported with 168 h continuous operation and IEC 61000-4-3 EMI compliance test.
To observe the effects of Tongdu Tiaoshen (unblocking the circulation of the governor vessel and regulating the mind) acupuncture on depressive-like behavior and the expression of microRNA-26a-5p (miR-26a-5p)/ enhancer of zeste homolog 2 (EZH2)/trimethylation of lysine 27 on histone H3 (H3K27me3) proteins and inflammatory factors in chronic unpredictable mild stress (CUMS) rats, and to explore its antidepressant mechanism. Thirty-two SPF-grade male SD rats were randomly divided into a normal group (8 rats) and a modeling group (24 rats). The modeling group was subjected to CUMS to establish depression model. After successful modeling, the rats were randomized into a model group, an acupuncture group and a fluoxetine group, with 8 rats in each group. In the acupuncture group, Tongdu Tiaoshen acupuncture was operated at "Baihui" (GV20), "Shenting" (GV24), "Shuigou" (GV26) and "Dazhui" (GV14), once daily for 6 consecutive days followed by one day of interval; and the completion of intervention was composed of 24 sessions of acupuncture. The gavage with fluoxetine solution (2.1 mg/kg) was administered in the fluoxetine group; and with 0.9% sodium chloride solution (10 mL/kg) in the other 3 groups, continuously for 28 days. Sucrose preference and the results of the open field test were observed. The hippocampal neuron morphology and Nissl bodies were examined using HE and Nissl staining. The protein expression of hippocampal EZH2 and H3K27me3 was detected using Western blot, and the mRNA expression of hippocampal miR-26a-5p and EZH2 was detected with RT-qPCR. ChIP-qPCR was applied to detect the enrichment levels of H3K27me3 in the promoter regions of interleukin-4 (IL-4), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). ELISA was provided to measure the contents of IL-6, TNF-α, interleukin-1β (IL-1β), and IL-4 in the hippocampus and serum. Compared with the normal group, the model group showed the decrease in sucrose preference (P<0.01), the total distance, the numbers of uprighting and cleaning behavior in the open field test (P<0.01); hippocampal neurons exhibited partial cell dissolution, irregular arrangement, nuclear pyknosis, reduced Nissl bodies (P<0.01), and uneven distribution. The mRNA expression of hippocampal EZH2, and the protein expression of hippocampal EZH2 and H3K27me3 increased (P<0.01), while the mRNA expression of miR-26a-5p decreased (P<0.01). The enrichment levels of H3K27me3 in the promoter regions of IL-6 and TNF-α were elevated (P<0.01), whereas that in IL-4 was reduced (P<0.01). The levels of IL-6, TNF-α and IL-1β in the hippocampus and serum increased (P<0.01), and the levels of IL-4 decreased (P<0.01). Compared with the model group, the acupuncture group and the fluoxetine group showed the increase in sucrose preference (P<0.01), the total distance, the numbers of uprighting and cleaning behavior in the open field test (P<0.01); hippocampal neurons exhibited the reduced cell dissolution, regular arrangement, declined nuclear pyknosis, higher Nissl bodies (P<0.01), and even distribution. The mRNA expression of hippocampal EZH2, the protein expression of hippocampal EZH2 and H3K27me3 decreased (P<0.01), and the mRNA expression of miR-26a-5p increased (P<0.01); and the mRNA expression of miR-26a-5p was negatively correlated with that of EZH2 (P<0.001). The enrichment levels of H3K27me3 in the promoter regions of IL-6 and TNF-α were lower (P<0.01), and that of IL-4 was higher (P<0.01, P<0.05). The levels of IL-6, TNF-α and IL-1β in the hippocampus and serum decreased (P<0.01), and the levels of IL-4 increased (P<0.01). The differences of the above indexes were not statistically significant between the acupuncture group and fluoxetine group (P>0.05). Tongdu Tiaoshen acupuncture can ameliorate depression-like behavior in CUMS rats, with the mechanism potentially related to regulating the miR-26a-5p/EZH2/ H3K27me3 pathway and reducing central neuroinflammation. 目的：观察“通督调神”针刺对慢性不可预知温和刺激（CUMS）大鼠抑郁样行为及微小RNA-26a-5p（miR-26a-5p）/Zeste基因增强子同源物2（EZH2）/组蛋白H3第27位赖氨酸三甲基化（H3K27me3）蛋白和炎症因子表达的影响，探讨其抗抑郁机制。 方法：将32只SPF级雄性SD大鼠随机分为正常组（8只）、造模组（24只），造模组采用CUMS法建立抑郁模型，造模成功后随机分为模型组、针刺组、氟西汀组，每组8只。针刺组行“通督调神”针刺，穴取“百会”“神庭”“水沟”“大椎”，每日1次，干预6 d后休息1 d，共干预24次。氟西汀组灌胃氟西汀溶液（2.1 mg/kg），其余3组大鼠灌胃0.9%氯化钠溶液（10 mL/kg），连续28 d。观察大鼠蔗糖偏嗜度及旷场实验结果；HE和Nissl染色法观察海马神经元形态和尼氏小体；Western blot法检测海马EZH2、H3K27me3蛋白表达；RT-qPCR法检测海马miR-26a-5p、EZH2 mRNA表达；ChIP-qPCR法检测H3K27me3在白细胞介素（IL）-4、IL-6、肿瘤坏死因子-α（TNF-α）基因启动子区的富集水平；ELISA法检测海马及血清IL-6、TNF-α、IL-1β、IL-4含量。 结果：与正常组比较，模型组蔗糖偏嗜度降低（P<0.01），旷场实验运动总距离、直立次数及清洁行为减少（P<0.01）；海马神经元部分溶解、排列不齐、核固缩，尼氏小体减少（P<0.01），分布不均；海马EZH2 mRNA、EZH2及H3K27me3蛋白表达升高（P<0.01），miR-26a-5p mRNA表达降低（P<0.01）；IL-6、TNF-α基因启动子区H3K27me3富集水平升高（P<0.01），IL-4基因启动子区H3K27me3富集水平降低（P<0.01）；海马及血清IL-6、TNF-α、IL-1β含量升高（P<0.01），IL-4含量降低（P<0.01）。与模型组比较，针刺组和氟西汀组蔗糖偏嗜度增高（P<0.01），旷场实验运动总距离、直立次数、清洁行为增加（P<0.01）；神经元溶解减少、排列相对整齐、核固缩减少，尼氏小体增多（P<0.01），分布较为均匀；海马EZH2 mRNA、EZH2及H3K27me3蛋白表达降低 （P<0.01），miR-26a-5p mRNA表达升高（P<0.01），miR-26a-5p mRNA与EZH2 mRNA表达水平呈负相关（P<0.001）；IL-6、TNF-α基因启动子区H3K27me3富集水平降低（P<0.01），IL-4基因启动子区H3K27me3富集水平升高（P<0.01，P<0.05）；海马及血清IL-6、TNF-α、IL-1β含量降低（P<0.01），IL-4含量升高（P<0.01）。针刺组和氟西汀组各指标比较，差异无统计学意义（P>0.05）。 结论：“通督调神”针刺可改善CUMS大鼠抑郁样行为，其机制可能与调节miR-26a-5p/EZH2/H3K27me3通路，减轻中枢神经系统炎症有关。.
Achieving realistic seismic behavior of dam structures in numerical dynamic analyses relies heavily on the accurate representation of a semi-infinite foundation, which is conventionally truncated within a finite element mesh. During the forced-vibration phase, continuous seismic input complicates the isolation of inherent damping characteristics. Tracking energy decay during the free-vibration phase provides a clearer mechanism for quantitatively validating soil-structure interaction (SSI) models. Accordingly, this study introduces an alternative numerical methodology for evaluating SSI modeling strategies based on their energy discharge capacities during the free-vibration phase. Utilizing a comprehensive 3D model of a double-curvature concrete arch dam subjected to two earthquake records with contrasting frequency contents, the energy decay coefficient was derived from the total mechanical energy attenuation, and the dominant structural frequency was extracted via Fast Fourier Transform (FFT) analysis of the displacement histories. These fundamental mechanisms were then used to quantify the effective damping ratio and energy half-life across three foundation stiffness classes. The results demonstrated that incorporating viscous boundaries yielded field-consistent effective damping ratios ranging from 7.77 to 10.72% and increased the energy decay coefficient by 18% to 51% compared with the traditional massless foundation model. The findings confirm that seismic damping is not a constant material parameter but a highly dynamic response governed by foundation impedance and earthquake characteristics. Consequently, this methodology provides engineers with a robust tool for validating the true dynamic characteristics of numerical models, ensuring secure and optimized structural designs.
Dandy-Walker malformation (DWM) is a rare congenital malformation of the central nervous system (CNS). It is characterized by variable hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle, with or without an enlarged cisterna magna. Given that large-sample genetic analysis of DWM has not been conducted to date, this study aims to provide more comprehensive genetic counseling for prenatal diagnosis by summarizing the clinical features and genetic findings of DWM. Between January 2010 and May 2025, among 22,048 pregnant women, there were 487 cases of fetal DWM that underwent prenatal diagnosis. Karyotyping, copy number variation sequencing (CNV-seq), single-nucleotide polymorphism array (SNP-array) or whole-exome sequencing (WES) were employed for prenatal genetic diagnosis. The results of ultrasonography, genetic analyses, and prognoses were tabulated. Among the 487 cases, 35 (7.19%) were diagnosed with classic Dandy-Walker malformation (cDWM), 59 (12.11%) with vermian hypoplasia (VH), and 393 (80.70%) with mega cisterna magna (MCM) according to ultrasonography. A total of 245 cases (50.31%) presented with additional ultrasound abnormalities; central nervous system (CNS) abnormalities were the most prevalent (21.36%), among which ventriculomegaly constituted the primary finding. Prenatal genetic abnormalities were detected in 50 cases (10.27%). Karyotyping identified chromosomal abnormalities in 42 cases (8.62%), including numerical abnormalities, structural abnormalities, and chromosomal mosaicism, with trisomy-18 (2.26%) being the most commonly detected. There were 8 cases with normal karyotypes, but among them, 6 cases were detected with chromosomal abnormalities by CNV-seq/SNP-array, and 2 cases were detected with gene mutations by WES. Advanced maternal age was associated with an increased risk of chromosomal abnormalities, a proportion of which may present with DWM. Among the 453 cases that underwent follow-up, the cDWM and VH groups exhibited a significantly higher incidence of pregnancy terminations compared to the MCM group. Subsequent follow-up of cases with continued pregnancies revealed 1 case of neonatal death in the VH group and 5 cases in the MCM group. Additionally, there was 1 case of abnormal postnatal development in the cDWM group and 3 cases in the MCM group. Pregnant women carrying DWM fetuses should undergo prenatal diagnosis including karyotyping, CNV-seq/SNP-array and WES if necessary, especially for fetuses with cDWM or VH, as the fetuses with cDWM or VH showed higher rates of genetic abnormalities. The pregnancy outcomes of most fetuses with MCM are favorable, while fetuses with cDWM or VH are prone to adverse gestational outcomes.
Recent advances in machine learning have applied novel tools to aging research, yet the relationship between the gut microbiome and epigenetic aging remains underexplored. This proof-of-concept study investigates whether gut microbial composition is associated with biological aging pace independent of chronological age. Using paired 16S rRNA gene sequencing and DNA methylation data from 123 monocyte-enriched samples in a cohort including Native Hawaiian and Pacific Islander participants, we developed "EpiBiome" models to predict epigenetic age acceleration residuals and DunedinPACE, a DNA methylation biomarker that estimates the instantaneous pace of biological aging. Models predicting residuals of traditional clocks (Horvath, Levine, GrimAge2) showed no predictive signal at either taxonomic rank. By contrast, the EpiBiome-Accel model for DunedinPACE reached statistical significance at both the species level (R2 = 0.152, Spearman ρ = 0.408, p = 0.012; permutation p < 0.001) and the genus level (R2 = 0.099, permutation p = 0.036). Adding chronological age as a feature did not improve performance (ΔR2 =  - 0.046 at species level), indicating age-independence. SHAP analysis of the species-level ElasticNet model identified Bifidobacterium adolescentis as the dominant contributor and the strongest predictor of decelerated aging, with Succinivibrio dextrinosolvens showing the strongest association with accelerated aging. These findings reveal specific gut taxa as hypothesis-generating candidates for mechanistic follow-up, rather than as individual-level diagnostic markers.
Land subsidence and rebound have emerged as critical geological hazards threatening urban safety in economically developed and densely populated coastal plains and river deltas. However, conventional surface monitoring methods struggle to reveal the stratified deformation characteristics of deep Quaternary deposits and their differential responses to groundwater fluctuations, historical abstraction, and engineering disturbances. To address this, we integrated persistent scatterer interferometric synthetic aperture radar (PS-InSAR), distributed fiber optic sensing (DFOS), and fiber Bragg grating (FBG) piezometers to systematically analyze strata deformation processes under multiple driving forces in the Shengze area. PS-InSAR was initially applied to characterize the overall regional deformation field, which revealed a distinct spatial heterogeneity in land subsidence with rates ranging from -20 to -14 mm/yr in the central area. DFOS technology was then employed to investigate the depth-resolved deformation behaviour of the subsurface, enabling the identification of three distinct deformation processes: First, DFOS reveals that deformation between 2012 and 2015 was predominantly driven by delayed consolidation of deep aquitards (approximately 60-100 m), which continued to compact and contributed a cumulative displacement of 13.39 mm. Second, during 2016-2020, the primary driver shifted to seasonal groundwater fluctuations. The aquitard layers at comparable depths exhibited a synchronous periodic response, with deformation amplitudes cycling between 0 and 5 mm in accordance with seasonal hydraulic patterns. Finally, a short-term unloading effect dominated the total deformation in July 2020. DFOS captured a full-depth (0-196 m) synchronous uplift triggered by building demolition, characterized by a peak tensile strain of approximately 100 με and a surface rebound of approximately 21 mm, and this uplift signal is independently confirmed by PS-InSAR observations. This study demonstrates that strata deformation in soft soil regions is a composite result of long-term delayed consolidation, seasonal hydraulic fluctuations, and rapid engineering unloading, providing a crucial basis for assessing subsidence and rebound risks in the context of urban renewal.
Synaptic pruning refines neural circuits during development, but altered trajectories are implicated in neurodevelopmental disorders. Here, we use a task-gated neural network to show that the timing and quantity of pruning critically determine functional outcomes. Networks subjected to aggressive pruning only after an initial period of high connectivity develop enhanced resistance to interfering inputs, yet exhibit marked fragility to internal noise. In contrast, moderate pruning preserves robustness but allows greater interference. Cue-utilization diagnostics showed that apparent ambiguity tolerance in the sparsest networks was largely artifactual: at 10% early density, the network partly ignored the task cue, whereas from 20% density onward cue-dependent switching was intact. A continuous late-pruning sweep further showed that the selectivity benefit of aggressive pruning was conditional and non-monotonic, emerging most reliably when early density was high. These trade-offs emerge prominently when late pruning follows early overgrowth, providing a buffer for refinement into highly selective circuits. The findings reveal developmental phasing as a key driver of circuit specialization versus resilience, offering a computational account of one ASD-relevant trajectory in which focused selectivity coexists with fragility to perturbation, while also highlighting principles relevant to efficient sparse neural networks.
Clonal cancer cells show heterogeneous responses to cytotoxic drugs, raising the question of whether this variability reflects discrete phenotypes or a continuum of underlying cell states. We address this by quantifying single-cell caspase-8 activation dynamics after TRAIL treatment and developing an extended mechanistic model of the extrinsic apoptosis pathway that incorporates c-FLIP-mediated control of initiator caspase activation. Fitting this model to individual trajectories across multiple doses recovers cell-specific procaspase-8 and c-FLIP abundances, together with three kinetic parameters, and reproduces the full diversity of observed responses. Embedding these inferred parameters into a shared state space reveals that sensitive and tolerant outcomes do not correspond to discrete subpopulations. Instead, a single biochemical pathway generates a continuous distribution of cell states whose position at treatment determines fate. Linking each trajectory to its early activation rate identifies a dose-dependent hyperplane that partitions this landscape into apoptotic and tolerant regions. Increasing drug dose translates this decision surface predictably, altering the outcome only for cells positioned near the boundary. This geometric perspective explains fractional killing in clonal populations and shows how drug-tolerant persister cells can arise from reversible variation in cell state. It further suggests that shifting state-space distributions relative to the decision surface may offer new strategies to limit persistence.
We study life-expectancy loss (LEL) from the COVID-19 pandemic in the U.S. from March 2020 through April 2023. We use individual-level death-certificate data and the cohort-based approach to life expectancy. We also examine how LEL varies with age, gender, race/ethnicity, county-level socio-economic status (county-SES). The U.S. recorded 983 000 COVID-19 deaths. The COVID-19 Mortality Rate (COVID-MR, the fraction of the population who died of COVID-19) was 0.30%. An upper bound estimate of years of life lost per person (YLL) is 14.6 years (thus population loss of 14.32 million life-years). Estimated LEL based on this YLL estimate was 0.043 years (16 days). However, LEL rose rapidly with age averaging 8 weeks for ages 75+. LEL was substantially higher for Native Americans, Blacks, and Hispanics than for Whites at all ages. LEL also increased as county-SES decreased. Our cohort-based LEL estimates are a small fraction of period-based estimates during the pandemic, which were based on mortality in a particular year and assumed the pandemic would continue indefinitely with no change in severity. Using current life expectancies, cohort-based LEL for the COVI|D-19 pandemic was a fraction of LEL for the 1918 influenza pandemic (14 weeks), but well above three recent, severe influenza seasons (average of 0.12 weeks).
Proteinuria is a standard predictor for kidney prognosis in patients with diabetic nephropathy (DN). Even among patients with similar levels of proteinuria, the protein load per functioning nephron can vary substantially depending on the total number of functioning nephrons. We examined whether fractional excretion of total protein (FETP), which reflects the protein load per single functioning nephron, provides superior prognostic value for kidney outcomes compared with conventional proteinuria in DN. This observational study included patients with biopsy-proven DN at our institution between June 1981 and December 2014. The primary focus was the incremental prognostic value of adding FETP, compared with proteinuria, to a baseline clinical model for predicting kidney failure requiring replacement therapy (KFRT). Improvements in model discrimination and risk reclassification were quantified using the concordance index (C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). This study included 376 patients with biopsy-proven DN (median age: 59 years; 62.5% male; median estimated glomerular filtration rate, 58.1 mL/min/1.73 m2). Over a median follow-up period of 6.7 years, 97 patients developed KFRT. Compared with the proteinuria-based model, the FETP-based model showed a significantly higher discrimination ability (ΔC-index: 0.021 [95% confidence interval (CI): 0.002-0.039]) and improved IDI (0.089 [95% CI: 0.001-0.207]). In contrast, the continuous NRI was not statistically significant. FETP was independently associated with KFRT in patients with DN and may provide additional prognostic information beyond conventional proteinuria for risk stratification. UMIN000031121 (University Hospital Medical Information Network).
Artificial intelligence (AI) has rapidly evolved into a transformative adjunct to gastrointestinal (GI) endoscopy, particularly through deep-learning-based computer-aided detection (CADe) and diagnosis (CADx) systems. Early randomized controlled trials demonstrated substantial improvements in adenoma and polyp detection, fueling high expectations for AI-enhanced screening performance. However, real-world evidence has since revealed more modest and heterogeneous benefits, underscoring the challenges of generalizability, algorithmic transparency, workflow integration, and user engagement. This review synthesizes the current state of AI in colorectal cancer screening and polyp assessment, outlining both its strengths-including improved lesion recognition, enhanced quality assurance, and potential for real-time optical diagnosis and its limitations, such as false positives, variable clinical impact, medicolegal uncertainties, and the risk of cognitive offloading. Positioned along the "slope of enlightenment" of the Gartner Hype Cycle, AI in endoscopy is entering a phase of maturation characterized by pragmatic adoption, refined human-AI interaction and development of multimodal, explainable systems. Continued multicenter validation, standardized reporting, and responsible integration are essential to assess the technology's long-term value and achieving sustainable improvements in endoscopic quality and future colorectal cancer prevention.
Antibiotic misuse is a major global health concern that contributes to antimicrobial resistance (AMR), particularly among young adults who have easy access to medications. This study assessed the knowledge, attitudes, and misuse of antibiotics among Yarmouk University students in Jordan following the COVID-19 pandemic. A cross-sectional online survey was conducted using a self-administered questionnaire distributed to Yarmouk University students. A total of 1,070 participants completed a structured questionnaire addressing demographics, knowledge, attitudes and practices related to antibiotic use, including perceptions and practices related to antibiotic use during the post-COVID-19 period. Descriptive statistics were generated and 95% confidence intervals (CIs) were computed for key estimates using the standard normal (Wald) approximation. More than half of the students (53.2%, 95% CI: 50.2-56.2%) continue to use antibiotics for common cold and influenzae and 53% (95% CI: 50.0-56.0%) expected healthcare providers to prescribe antibiotics for these conditions. Although most students were aware that antibiotic overuse leads to resistance (79.0%, 95% CI:76.5-81.4%), many misunderstood its broader community impact. Antibiotic resistance remains an underestimated public health issue. There is still much work needed to raise more awareness regarding safety and proper antibiotic usage in Jordan among different group of the population starting with young adults and university students who will have a major role in bridging the gap for action on antibiotic resistance.