The simulation of magnetic properties in strongly correlated systems remains a central challenge in electronic structure theory. The Difference-Dedicated Configuration Interaction (DDCI) method is widely regarded as a gold standard for computing magnetic exchange couplings, but its applicability is limited to small magnetic systems due to the steep growth of the configuration-interaction space with the number of correlated electrons and orbitals. Here, we introduce a stochastic formulation of DDCI based on Full Configuration Interaction Quantum Monte Carlo (FCIQMC) and the Generalized Active Space framework, which largely alleviates the computational bottleneck of conventional DDCI. The implementation is validated by comparison with conventional DDCI for the spin ladder of a trinuclear [Mn(IV)3O4]3+ cluster (Slocal = 3/2). Using a small CAS(9,9) reference, DDCI fails to reproduce the spin-state energy differences defined by a two-parameter (J = -76, J' = -11 cm-1) Heisenberg-Dirac-van Vleck Hamiltonian extracted from experimental measurements. In contrast, Stochastic-DDCI enables calculations with a much larger CAS(33,21) reference and reproduces the experimental spin ladder with remarkable accuracy, yielding deviations smaller than 33 cm-1 with respect to the spin ladder extracted from the experimental measurements. This development extends DDCI methodologies to substantially larger active spaces and opens the door to the study of more complex magnetic systems.
The objective of this work was to overcome some of the long-standing limitations of ratiometric fluorescent protein (FP)-based Ca2+ biosensors, which typically rely on Förster resonance energy transfer (FRET) between two FPs and generally exhibit only relatively modest Ca2+-dependent changes in emission ratio. To develop biosensors with substantially greater ratiometric changes, we explored an alternative biosensor design strategy in which two independently optimized intensiometric single FP-based Ca2+ biosensors were hybridized into a single protein construct such that they employed a shared calmodulin (CaM) and CaM-binding peptide (CBP). By hybridizing a direct-response red FP-based biosensor with an inverse-response green FP-based biosensor, we created SuiCa, a single-polypeptide Ca2+ biosensor that exhibits exceptionally large red-to-green ratiometric fluorescence changes as purified protein (∼60-fold) and when expressed in immortalized cell cultures (∼80-fold) and primary neurons (∼37-fold). Relative to co-expression of two spectrally distinct FP-based Ca2+ biosensors, SuiCa provides the advantages of a smaller gene size, a fixed fluorophore stoichiometry, and a ratiometric response that depends on Ca2+ binding to a single, shared, CaM plus CBP domain. With these advantages, along with its bright fluorescence and large ratiometric change, SuiCa represents a new addition to the Ca2+ imaging toolbox.
Growing evidence suggests that e-cigarettes can facilitate smoking cessation among adults who smoke (AWS). Whether these effects differ by characteristics of individuals with varying demographic or smoking related histories is unclear. This study uses data from a recently completed RCT testing e-cigarette sampling among AWS to evaluate moderators of smoking behavior outcomes. Analyses are based on a large, naturalistic RCT conducted across the US, in which AWS (N = 638) were randomized (2:1) to receive a 4-week supply of e-cigarettes, or not. Provision of e-cigarettes included minimal guidance on use and emphasized participants' self-determined decisions and patterns of use. Outcomes were tracked through week 24 follow-up. Secondary analyses focus on group-by-moderator (demographic, smoking history) interactions on three principal outcomes: 1) incidence of 24hr quit attempts, 2) incidence of reducing smoking (cigarettes per day; CPD) by ≥ 50%, and 3) 7-day point prevalence abstinence (PPA), each captured at week 4 and week 24. Among 10 + demographic and smoking history variables assessed at baseline, none of the group by moderator interactions were significant, for any outcome at either timepoint. Raw cessation outcomes were higher among AWS with higher motivation to quit (MTQ), but the relative risk (RR) for achieving ≥ 50% reduction in CPD after 4 weeks was similar across MTQ levels. The effects of e-cigarettes on smoking cessation outcomes were similar across multiple demographic and smoking history subgroups. The absence of any significant moderating variables is unlikely attributable to limited power since the vast majority of subgroup differences were < 10%.
Public health medical education is increasingly important in the low-resource, high-altitude Xizang Autonomous Region (Tibet). Traditional authoritative textbooks do not meet modern needs for accessibility and interactivity, whereas general large language models (LLMs) may hallucinate in specialized medical domains. Developing specialized LLMs for low-resource regions is also expensive and difficult. This study aimed to explore a novel approach to high-altitude public health medical education in the low-resource Xizang Autonomous Region that integrates modern LLMs and authoritative textbooks, using a comprehensive benchmark evaluation across multiple dimensions and retrieval-augmented generation (RAG) technology. We conducted a 2-stage cross-sectional comparative evaluation study to benchmark publicly available LLMs and evaluate the added value of textbook-augmented retrieval under standardized generation settings and blinded expert assessment. First, 4 publicly available LLMs (GPT-5.2 [OpenAI], Gemini 3.0 Pro [Google], DeepSeek R1 [DeepSeek], and Tencent HY 2.0 [Tencent]) were benchmarked using an 80-question benchmark on high-altitude public health medicine developed by authoritative medical specialists. Each question was asked 3 times, yielding 960 outputs; first responses (n=320) were scored under blinded conditions by 2 independent 8-member physician panels. A clinically weighted evaluation of multidimensional first-response scores (including comprehensiveness, accuracy, clarity, and relevance) and a composite consistency metric (including semantic similarity and algorithmic similarity) was administered. Second, 4 specific and prevalent authoritative textbooks on high-altitude public health medicine-Ward, Milledge and West's High Altitude Medicine and Physiology, High Altitude Medicine: A Case-Based Approach, High Altitude Medicine, and High Altitude Medical Protection-were deployed as the external knowledge base for the evaluation-optimized model. Statistical analyses included Spearman ρ, Cronbach α, intraclass correlation coefficients, Friedman tests with Dunn multiple comparisons, and paired Wilcoxon signed-rank tests. The significance threshold was set at α=.05. DeepSeek R1 was selected as the optimal base model for achieving the highest weighted score (5.61/10.00), followed by GPT-5.2 (5.51/10.00), Gemini 3.0 Pro (5.39/10.00), and Tencent HY 2.0 (4.71/10.00). The deployed retrieval-augmented model integrating the authoritative textbooks and the optimal LLM DeepSeek R1, HPHME-Xplus-RAG, achieved remarkable improvement in multidimensional scores compared to baseline DeepSeek R1 (median 8.00 [IQR 7.88-8.00] vs median 7.63 [IQR 7.38-7.88]; P<.001, r_rb=0.68, indicating a large effect). Integrating authoritative textbooks with an evaluation-optimized general LLM through an RAG framework showed strong performance for medical education in the low-resource Xizang Autonomous Region. Unlike prior studies that mainly evaluated general LLMs or used clinical guidelines to build RAG systems for diagnosis and treatment, this study used authoritative textbooks for the broader, guideline-scarce field of public health medical education. This work provides a replicable workflow-domain-authoritative knowledge+RAG+model optimization and evaluation-for low-resource settings, with practical implications for medical instructors and students, hospitals, and public health services seeking cost-effective, convenient, and trustworthy educational support.
Congenital lipoid adrenal hyperplasia (lipoid CAH) is caused by pathogenic variants in STAR, encoding steroidogenic acute regulatory protein (StAR). In affected 46,XX patients, progressive cholesterol ester accumulation in the ovaries during puberty leads to premature ovarian insufficiency and, in approximately one-third of cases, large ovarian cysts or ovarian torsion requiring surgical intervention. These complications may relate to elevated gonadotropin levels, yet no preventive strategy exists. We report a 46,XX female with classic form of lipoid CAH who underwent gonadotropin suppression with a gonadotropin-releasing hormone (GnRH) analog followed by estrogen and progestin administration, with longitudinal monitoring of the ovarian morphology. An 18-year-old Japanese female was diagnosed with lipoid CAH neonatally after presenting with failure to thrive, skin hyperpigmentation, hyponatremia, and hyperkalemia. Computed tomography revealed bilateral adrenal hyperplasia with low attenuation consistent with lipid accumulation. Genetic analysis identified compound heterozygous pathogenic STAR variants: p.Gln258* and p.Glu218Val. Glucocorticoid and mineralocorticoid replacement was initiated. The patient exhibited spontaneous breast development at age 10 years with pubertal gonadotropin responses and mildly elevated ovarian volume with a large ovarian cyst. After informed discussions with the guardians regarding the risks of ovarian complications, subcutaneous leuprorelin acetate was started at age 10 years 4 months and continued until age 15 years 7 months. Transdermal estradiol was introduced at at age 14 years, and oral norethindrone was added at 14 years 11 months, after which regular cycles were established. Before leuprorelin therapy, the maximum ovarian cyst diameter was 13 mm (right), exceeding the +2.0 standard deviation (SD) threshold for age; this decreased to 6 mm within 6 months of treatment and remained within the reference range thereafter. Ovarian volumes decreased from 3.1 mL (right) and 1.7 mL (left) before therapy to 1.1 mL and 1.0 mL at 12 months, respectively. At age 18 years, no large ovarian cysts, ovarian hypertrophy, or torsion had developed. This is the first reported case of lipoid CAH managed with GnRH analog-mediated gonadotropin suppression followed by estrogen and progestin administration. Despite a large ovarian cyst and mildly elevated ovarian volume at baseline, both measures improved and were maintained within the normal range over eight years of follow-up. This approach may be useful not only for preventing ovarian complications but also for improving and sustaining normal ovarian morphology, and warrants further evaluation, although its long-term effects on bone health, uterine maturation, and fertility require careful assessment.
Psychotic disorder represents a leading cause of disability worldwide, and relapse in psychosis is common. Artificial intelligence (AI) is increasingly recognized as a method that could aid clinical monitoring for individuals experiencing psychosis. This review aims to map the existing literature on AI-based approaches-including machine learning, deep learning, and natural language processing-used to detect relapse in individuals with psychotic disorders. A systematic search strategy was conducted on PubMed, PsycINFO, and Embase up to January 7, 2026. Observational studies, randomized controlled trials, and quasi-experimental studies that used AI methods to detect relapse in psychosis were eligible for inclusion. Screening and data extraction procedures were conducted by at least 2 reviewers working independently. Findings were extracted, charted, and described using narrative synthesis based on data extraction and consensus meetings with the research team. The scoping review was prospectively registered with the Open Science Framework. Relevant studies identified (N=10) included the use of digital tools such as smartphone- and smartwatch-based monitoring, ecological momentary assessment tools, social media activity, and internet searches. Digital phenotyping via smartphones and wearables emerged as the most common method for data collection. The efficacy of AI models varied with sensitivity (or recall) ranging from 0.25 to 0.77 and specificity (or precision) ranging from 0.06 to 0.88. The reported area under the receiver operating characteristic curve for models ranged from 0.63 to 0.78. AI models were heterogeneous across studies, and most study findings were not replicated. This scoping review highlights both the promise and the current limitations of AI in psychosis relapse detection. Passive digital phenotyping research in the detection of psychosis relapse has progressed, and personalized approaches with individual-level modeling show promise; however, further studies need to include larger numbers of participants and should incorporate methods such as large language models. Future studies will require large collaborations aimed at delivering AI methods for use in real-world clinical practice.
Pretest-posttest designs are widely used to estimate learning gain in studies evaluating educational interventions in medical education. The Weighted Gain Score (WGS) was proposed to reduce bias associated with differences in baseline performance. This study evaluated the statistical and inferential properties of the WGS by comparing it to Rasch Learning Gain (RLG) across 3 datasets. The WGS implements a weighting coefficient that includes the parameter µ, which linearly rescales the difference between pretest and posttest percentage scores. We examined the effect of varying µ (30, 50, and 70) on learning gain calculations and compared the results with those obtained using RLG. The following three datasets were analyzed: (1) a small illustrative dataset demonstrating the mathematical behavior of the WGS, (2) an empirical dataset from a previous educational evaluation study, and (3) a randomly generated binomial dataset designed to examine the metric under larger sample conditions. Changing the parameter µ in the WGS affected the magnitude of the calculated learning gains: lower µ-values produced larger gain estimates, whereas higher µ-values produced smaller estimates. Despite these differences in scale, the WGS and RLG correlated strongly in both the empirical dataset (r=0.93; P<.001) and the simulated dataset (r=0.92; P<.001); variation in µ did not alter the inferential results. Both methods identified the same interaction effect in the empirical dataset. The WGS produced results highly consistent with those of RLG while requiring substantially lower computational complexity. The metric can be applied to both small and large datasets and allows µ to function as an adjustment coefficient for calibrating learning gain estimates across cohorts without altering inferential conclusions.
Alcoholic liver disease (ALD) is characterized by gut dysbiosis, yet the functional contribution of specific commensals remains largely unexplored. Here, we identify a significant reduction of Lactobacillus reuteri in both ALD patients and mouse models compared with their respective healthy controls. Using fecal microbiota transplantation (FMT), we first establish a causative role of the dysbiotic gut microbiota in driving ALD pathophysiology. In line with this finding, oral supplementation with L. reuteri ameliorates ALD phenotypes. Mechanistically, L. reuteri activates the farnesoid X receptor (FXR) signaling pathway, thereby restoring bile acid homeostasis, as evidenced by reduced levels of cholic acid (CA) and deoxycholic acid (DCA). The functional importance of FXR is further validated in Fxr-/- mice, where the protective effects of L. reuteri on both ALD and bile acid metabolism are largely abrogated. Moreover, both in vitro and in vivo experiments confirm that CA and DCA directly compromise hepatocyte viability and exacerbate liver injury, reinforcing their roles as pathogenic effectors downstream of FXR dysregulation. Expanding upon these mechanistic insights, we identify the natural compound echinacoside as a gut microbiota-targeting intervention that not only enriches L. reuteri but also potentiates FXR signaling, leading to significant improvement of ALD. Collectively, our findings define a microbiota-host metabolic axis centered on L. reuteri and FXR-dependent bile acid homeostasis, offering a conceptual framework for targeting host-microbe interactions in alcoholic liver disease.
Ferrocene (Fc) derivatives are classically used as redox reporters in electrochemical DNA biosensors; it is therefore critical to understand how tethering to DNA strands alters their intrinsic electrochemical behavior. Here, we investigate the electron transfer energetics of soluble ferrocenedimethanol at a mercaptohexanol-coated gold electrode to establish a reference model for DNA-bound labels. Using high-scan-rate and convolutive cyclic voltammetry analyzed via the Marcus-Hush-Levich-Chidsey formalism, we determine the heterogeneous rate constant and reorganization energy across varying temperatures and viscosities. We report a relatively low reorganization energy (0.4 eV), driven by a large, positive activation entropy attributable to reporter desolvation. Comparing these results with literature data reveals how electron transfer energetics fundamentally change between the free reporter in solution, rigid Fc-alkyl monolayers, and sensing Fc-DNA layers on electrodes. We suggest that the unique kinetic behavior of Fc-DNA, characterized by a large suppression of the reorganization energy, reflects a transition from a purely ergodic, solvation-dominated mechanism for the free reporter to a non-ergodic regime dictated by the restricted conformational sampling of the DNA tether.
Sexual harassment persists in academic workplaces despite extensive policy frameworks. This study explored how employees at a large Swedish university perceive and articulate the organisational culture and everyday norms that shape sexual harassment. Ten focus group discussions were held with forty staff members, separated by managerial role and conducted in Swedish or English. Transcripts were analysed using qualitative content analysis to identify shared meanings, latent themes and interpretive patterns. Analysis generated one overarching theme, perceiving sexual harassment through the lens of organisational silence, power relations, and negotiated boundaries, supported by four sub-themes. Participants described boundary-setting as a collective, situational process: definitions of harassment shifted in real time, with women often seeking peer confirmation while men framed the same conduct as innocuous. Formal and informal hierarchies amplified this ambiguity: senior researchers with grant-generating prestige were deemed 'untouchable', and managers reported uncertainty about how to act without clear procedural guidance. Silence emerged as a strategic response to protect careers and collegial relationships, normalising borderline behaviours through humour and rationalisation. Yet employees also engaged in discrete forms of peer solidarity, staying with vulnerable colleagues after meetings, quietly redirecting collaborations, which signalled a sense of collective responsibility even in the absence of robust institutional support. These findings show that policy compliance alone cannot shift workplace culture when interpretive authority rests with peer groups and incentive structures reward silence. Universities therefore need to focus on organisational level responses that equip leaders with emotional competence and procedural clarity and support the creation of a work environment that can identify, prevent, and respond to sexual harassment. Embedding such measures can transform informal solidarity into a shared, institutionally endorsed standard of respect.
Everyday listening ability is essential for individual health and well-being. Age-related hearing loss (ARHL) is associated with reduced communication engagement, social isolation, loneliness, cognitive decline, and increased dementia risk. Interventions that simultaneously target auditory processing and cognitive function, particularly within engaging and ecologically valid contexts, may offer greater benefits than unimodal approaches. However, culturally adapted, web-based, gamified auditory-cognitive dual-task training (ACDT) tailored for older adults with ARHL remains underexplored. At the time of this writing, few auditory or auditory-cognitive training programs are available in Chinese languages, creating linguistic and cultural barriers for older adults. This study aimed to (1) assess the feasibility and acceptability of home-based ACDT among older Chinese adults with ARHL and (2) examine its preliminary effects on global cognition, hearing, social engagement, and loneliness. It was hypothesized that the intervention group would demonstrate greater improvements in global cognition, hearing, and social engagement than the control group. Sixty community-dwelling older adults with mild-to-moderate ARHL were randomized 1:1 to either the ACDT group or a waitlist control group in a single-blinded pilot randomized controlled trial. Demographic data and outcome measures were collected at baseline, week 6, and week 12. Postintervention interviews were conducted to assess the feasibility and acceptability of ACDT. A total of 60 participants were randomized (mean age 67.65, SD 4.78 years; 45/60, 75% male). ACDT demonstrated high feasibility and acceptability. The ACDT group showed significant improvements in focused attention (mean change=-0.15; P=.02; d=-0.46) and divided attention (mean change=-0.21; P=.002; d=-0.63). Significant cognitive improvements on the Hong Kong-Montreal Cognitive Assessment were identified in naming (r=0.37; P=.05) and visual cognition (r=0.44; P=.02) in the intervention group, while no significant improvements were found in the control group. Both groups reported significant decreases in emotional hearing handicap, with slightly greater improvement in the intervention group (r=0.39; P=.03) than in the control group (r=0.37; P=.04). Linear mixed model analysis revealed a small to moderate group effect (Cohen d=0.38) for 5-minute delayed recall on the Auditory Verbal Learning Test, with the fixed effects explaining 69% of the variance (marginal R²=0.69). A significant time×group interaction was observed for left-ear thresholds (P=.01). Qualitative analysis identified three key themes: (1) intervention coherence and participants' affective attitude toward ACDT; (2) perceived benefits in cognition, information acquisition, and self-awareness from ACDT; and (3) perceiving ACDT as less burdensome with enhanced self-efficacy. Future iterations should incorporate artificial intelligence-enhanced personalization. Large-scale randomized controlled trials involving diverse samples and active control conditions are needed to confirm sustained effects on auditory and cognitive health, dual-task listening-cognitive abilities, and real-world functioning.
Congenital hyperinsulinism (CHI) is a rare but severe genetic disorder characterized by inappropriate insulin secretion, leading to recurrent and persistent hypoglycemia in neonates and children. If not promptly diagnosed and adequately treated, CHI may result in irreversible neurological damage. The disease shows marked clinical heterogeneity, largely driven by underlying genetic mutations, which also influence response to medical therapy and the need for surgical intervention. Data on genotype-treatment correlations remain limited, particularly in Middle Eastern populations. This cross-sectional observational study was conducted at a tertiary pediatric referral center between September 2023 and September 2024. Thirty-three neonates and children (aged 1 week to 18 years) with biochemically confirmed congenital hyperinsulinism were enrolled. All patients underwent genetic testing using next-generation sequencing. Treatment response was assessed based on glycemic stability achieved with diazoxide alone, combination medical therapy, or the requirement for pancreatectomy. Associations between genetic mutations and treatment response were analyzed using chi-square tests or Fisher's exact test where appropriate, with a p-value <0.05 considered statistically significant. The mean age of participants was 13.7 ± 18.1 months. Pathogenic or likely pathogenic variants were most frequently identified in the ABCC8 and HK1 genes. Diazoxide monotherapy was effective in 60.6% (20/33) of patients, while 18.2% (6/33) required combination therapy with diazoxide and octreotide. Approximately 21.2% (7/33) of patients were refractory to medical treatment and required surgical intervention. A statistically significant association was observed between genotype and treatment response (p = 0.026). Mutations in KCNJ11 and ABCC8 were significantly associated with poor response to diazoxide and increased likelihood of pancreatectomy, whereas HK1 mutations were predominantly associated with diazoxide responsiveness. Our findings demonstrate a significant correlation between genetic etiology and treatment response in children with congenital hyperinsulinism. Early genetic diagnosis may play a critical role in predicting therapeutic outcomes, guiding individualized treatment strategies, and avoiding unnecessary delays in definitive management. These results should be interpreted with caution given the small sample size and the rarity of certain genotypes.
The goal of antiretroviral therapy is to achieve and sustain the suppression of human immunodeficiency virus (HIV) viral load. In this study, we aimed to identify risk factors for low-level viremia (LLV) and examine their association with clinical outcomes in South Korea. We retrospectively reviewed the medical records of patients with human immunodeficiency virus infection registered at Seoul Medical Center and Hallym University Sacred Heart Hospital between 2014 and 2023. LLV was defined as at least two consecutive HIV RNA measurements of 40-199 copies/mL taken more than 4 weeks apart. Patients with LLV were compared with those who maintained virological suppression (viral load < 40 copies/mL). Of the 381 patients included in the analysis, 15 (3.94%) experienced LLV. Compared with patients who maintained virological suppression, patients with LLV more frequently had an initial viral load ≥ 500,000 copies/mL (P < 0.01). No significant differences were observed between the groups in the rates of virological rebound, new-onset acquired immune deficiency syndrome-defining conditions, or mortality. Multivariable logistic regression identified an initial viral load ≥ 500,000 copies/mL as an independent risk factor for LLV (adjusted odds ratio, 4.735; 95% confidence interval, 1.505-14.897). A high viral load was a significant risk factor for LLV. Large multicenter studies are required to further investigate risk factors and clinical implications of LLV in people living with HIV.
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a crucial therapy for chronic kidney disease (CKD), yet concerns persist regarding their impact on bone metabolism. This systematic review evaluates the skeletal safety and metabolic effects of SGLT2i in patients with CKD. A systematic review of randomized controlled trials (RCTs) and observational cohort studies was conducted. Data on study design, population characteristics, baseline kidney function, bone-related comorbidities, and outcomes (osteoporosis, fractures, falls, amputations, and bone mineral markers) were summarized. Risk of bias was evaluated according to the included category. The analysis revealed that while one RCT and a cohort study reported a significantly increased risk of bone fracture and amputation, this finding was not replicated in other subsequent cohort studies and other RCTs, which generally showed non-significant differences. Of note, the reporting of bone-related outcomes was inconsistent throughout the literature, and a substantial proportion of the evidence derives from studies primarily designed for patients with type 2 diabetes, largely involving early-stage CKD subgroups. One study suggests that SGLT2i may favorably modulate markers of CKD-mineral bone disease (MBD), reporting reduced risk of hyperphosphatemia, hypocalcemia, high parathyroid hormone, and low vitamin D levels. The reviewed literature primarily included data on empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin. Mostly, SGLT2i demonstrated a possible reassuring skeletal safety profile in CKD. Initial safety concerns regarding fractures have not been consistently supported, although evidence in moderate-to-advanced CKD remains limited. Long-term, prospectively defined skeletal outcomes are needed to confirm these findings and clarify class effects.
We aimed to provide the first national study of out-of-hospital cardiac arrests (OHCA) witnessed by emergency medical services (EMS) during interfacility transport (IFT). We used a nationwide prehospital patient care report dataset from 2023 to complete a cross-sectional observational study of EMS encounters for IFT during which OHCA occurred. Descriptive statistics were computed, stratified by level of EMS care provided. Multivariable logistic regression analysis was completed to evaluate factors associated with return of spontaneous circulation (ROSC) at the end of the IFT encounter upon transfer of care to the receiving facility. Finally, we completed a similar multivariable logistic regression analysis restricted to the subgroup of patients with an unshockable initial rhythm. A total of 1,466 OHCA incidents occurred during an IFT with EMS: 7.5% with basic life support (BLS), 53.6% with advanced life support (ALS), and 38.9% with critical care transport (CCT). Among these incidents 11.8% were associated with trauma, 9.2% involved cardiopulmonary resuscitation (CPR) prior to EMS unit arrival, 14.7% involved a mechanical device to perform CPR, 22.2% had a shockable initial rhythm, and 58.1% were transported via ground as opposed to air. At the conclusion of the IFT EMS encounter, 50.3% had sustained ROSC. Geriatric age (aOR 0.64, 95%CI 0.44-0.94), BLS care (aOR 0.45, 95%CI 0.22-0.90), and ground transport (aOR 0.58, 95%CI 0.38-0.89) were associated with worse outcomes on adjusted analysis, whereas shockable initial rhythm (aOR 3.86, 95%CI 2.42-6.36) and CCT care (aOR 2.21, 95%CI 1.42-3.48) were associated with better outcomes. The sub-analysis for OHCA during IFT with an unshockable initial rhythm also showed greater odds of ROSC when managed by CCT relative to ALS (aOR 2.65, 95%CI 1.64-4.33) while adjusting for other key factors. Using a large nationwide sample of OHCA incidents that occurred during IFT, we found that higher level of EMS care was associated with superior short-term outcomes while controlling for other key factors. These findings underscore the importance of accurate patient triage at sending facilities and the value of CCT for high-risk patients.
Modern individual first aid kits (IFAKs) were designed to stabilize a single casualty during short evacuation timelines, an increasingly invalid assumption in large-scale combat operations. Sustained exposure to artillery, mortars, and dronedelivered munitions produces multiple simultaneous casualties with complex polytrauma and prolonged evacuation delays. This article uses a firsthand account from a trench engagement in Ukraine to examine how contemporary injury patterns rapidly overwhelm standard IFAK contents. Through structured interviews with a combat-experienced Soldier, the narrative illustrates repeated depletion and physical destruction of individual medical kits during ongoing contact, despite appropriate hemorrhage control techniques. Adaptations in medical loadouts observed in this environment emphasize distributed supplies, redundancy, and forward shifting of traditionally medic-held equipment to individual Soldiers. These observations highlight a critical mismatch between currently issued IFAKs and the realities of modern high-intensity conflict, underscoring the need to reassess individual medical loadout doctrine for future battlefields.
Astrocytes play an essential role in the control of gonadotropin-releasing hormone (GnRH) neurons. However, limited information is available in non-conventional animal models. This study aimed to explore hypothalamic astrocyte distribution in the plains vizcacha (Lagostomus maximus), a South American hystricomorph rodent with distinctive reproductive physiology, and to analyze their spatial relationship with GnRH neurons throughout the life cycle. Female plains vizcachas were evaluated during non-pregnancy (ovulating and non-ovulating) and pregnancy (early-, mid-, and late-pregnant). Plasma levels of estradiol (E2), progesterone (P4), and luteinizing hormone (LH) were determined. Astrocytes were assessed by glial fibrillary acidic protein (GFAP) immunohistochemistry in hypothalamic regions involved in reproductive control, including the medial preoptic area (mPOA), arcuate nucleus (ARC), and median eminence (ME). Their spatial relationship with GnRH-immunoreactive neurons and fibers was also analyzed. Pregnancy was associated with marked hormonal changes, including significantly elevated E2 levels and dynamic variations in P4 and LH (p<0.01). Astrocyte distribution was largely conserved across life stages in the mPOA and ME, whereas a significant reduction in GFAP-immunoreactive area was detected in the ARC during early pregnancy. Close appositions between astrocytic processes and GnRH-neurons were observed in ovulating non-pregnant and pseudo-ovulating mid-pregnant animals. In the ME, very intimate contacts between astrocytic processes and GnRH-fibers in the palisade layer were detected exclusively during pregnancy. In conclusion, these findings reveal a steroid-dependent plasticity of hypothalamic astrocytes and support a key role for astrocyte-GnRH neuron interactions in the regulation of reproductive neuroendocrine function during gestation in the plains vizcacha.
Mechanically guided 3D assembly has emerged as a powerful approach for constructing complex mesostructures, but conventional strategies rely on selective chemical bonding between 2D precursors and elastomeric substrates, restricting material compatibility and scalability. Here, we introduce a physical anchoring-based, buckling-guided assembly platform that decouples 3D structure formation from chemical adhesion. The platform employs an elastomeric substrate patterned with an array of rods to achieve robust mechanical fixation, enabling the integration of diverse functional materials, including polymers, metals, water-soluble polymers, and stimuli-responsive systems, independent of their interfacial or mechanical properties. Oxygen plasma surface treatment further reduces adhesion, allowing reliable assembly of freestanding and large-area architectures. As a proof-of-concept, we integrate liquid crystalline networks (LCNs) to demonstrate light-responsive soft robotic systems capable of remote actuation. This physically anchored assembly strategy establishes a general and scalable framework for mesoscale fabrication, expanding material and geometric design freedom for applications in soft robotics, bioelectronics, and multi-material integration.
Statistical and culture-based models propose that environmental disturbances reshape competitive interactions among functionally redundant microbial taxa. However, the mechanisms driving these changes and their impact on biogeochemical processes remain largely untested in soil, owing to the challenge of linking functions to specific taxa in highly diverse and functionally complex soil microbiomes. Here, we simulated environmental disturbance in microcosms containing organic carbon-rich or sandy soils. Using bacterial and archaeal nitrifiers, a functionally tractable microbial guild, we examined how disturbance restructures competition among diverse microbial taxa within this guild. In both soils ammonia-oxidizing archaea (AOA) predominated numerically and functionally under steady climax conditions. Following disturbance, ammonia-oxidizing bacteria (AOB) and complete ammonia oxidizers (comammox) rapidly gained a growth-related competitive advantage, likely due to increased per-cell ammonium availability supporting their intrinsic high growth rates. AOB recolonization was essential for full post-disturbance nitrogen turnover, resulting in elevated nitrification rates and increased nitrous oxide emissions. Nitrification rate did not fully recover when AOB were inhibited. In contrast, AOA and comammox played a dispensable role in recovering post-disturbance nitrification, limited by slower growth and lower per-cell activity, respectively. Competitive regrowth ability of microbial species showed a tradeoff with pre-disturbance abundance, highlighting the enhanced post-disturbance role of rare-abundance AOA, in addition to AOB phylotypes. Our findings demonstrate that bacterial and archaeal nitrifiers constitute a continuous spectrum between r- and K-strategists. Disturbance reshapes competition through differential growth and activity traits among functionally redundant taxa, favoring AOB and thereby transforming community assembly while intensifying nutrient cycling and greenhouse gas fluxes.
Rice responds to salt stress by modulating a vast array of genes integrated into a sophisticated regulatory network. This complexity makes it challenging to identify the key genes and the specific alleles that confer tolerance. We used time-course expression analysis to profile gene and miRNA expression associated with salt tolerance in Pokkali, a salt-tolerant rice variety. We established a framework for studying transcription factor-target(mRNA/miRNA) interactions using gene co-expression and machine-learning models. Moreover, we developed a hypergeometric distribution-based method to elucidate the interactions of salt stress-related miRNA-targets. Using these approaches, we established co-expression (GCN) and gene regulatory networks (GRN) based on co-expression and TF/miRNA-target interactions. Hub genes with high connectivity in our networks were enriched for previously reported salt tolerance genes, a finding largely supported by subsequent haplotype analysis of 374 rice accessions. Finally, we functionally validated three crucial hub genes, OsCAF1B, OsADR3 and Ospdr9, by demonstrating their roles in salt tolerance using their knockout mutants. The crucial genes, haplotypes and networks for salt tolerance identified in this study (resource available at https://cbi.njau.edu.cn/RiceSALTnet) provide a foundation for breeding rice cultivars with enhanced salt tolerance.