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Quantifying the combined effects of semi-closed terrain and monsoon on PM2.5 and O3 pollution aggregation in the North China Plain.

The North China Plain (NCP) and its surrounding regions represent one of the key priority areas for air pollution control. As anthropogenic emissions decline significantly, the effect of terrain and meteorology on air pollution pattern has become increasingly prominent, particularly given the NCP's unique semi-closed terrain and East Asian monsoon dynamics. However, quantitative characterization of terrain-dominated blocking effects remains unexplored. Here we quantitatively assess the blocking effects of mountains and terrain-coupled meteorological factors on air pollutant dispersion. We find the NCP on the eastern side of the Taihang Mountains showed high PM2.5 and O3 pollution levels, with winter PM2.5 and summer O3 high-value zones showing opposite north-south aggregation patterns. PM2.5 and O3 concentrations were highest in plains, followed by platforms, hills, and finally mountains. Within the 120-km buffer zones of the typical mountains in the NCP and its surrounding regions, PM2.5 and O3 concentrations increased initially with altitude but then decreased markedly above a threshold altitude. Above the threshold altitude, mountain blocking effects became dominant. The effective blocking altitudes of typical mountains in the NCP and its surrounding regions ranged between 22 and 929 m for winter PM2.5 pollution, and between 19 and 1060 m for summer O3 pollution. The Terrain-Wind Close Index indicates that the terrain-coupled East Asian monsoon showed stronger blocking effects on PM2.5 dispersion in southern NCP during winter and on O3 diffusion in northern NCP during summer, matching observed high-pollution zones. This study offers key insights for regional joint air pollution mitigation strategies, as well as regional pollution assessment.

Particulate Matter

Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has emerged as a promising gene-editing platform for genetic disorders; however, its in vivo application remains limited by low delivery efficiency and biological barriers. Many CRISPR payloads fail to reach target sites due to extracellular degradation, immune clearance, and intracellular trafficking limitations. This review examines the interplay between biological barriers and nanoparticle engineering strategies for CRISPR/Cas9 delivery. A barrier-oriented engineering approach is proposed as a central framework, encompassing ligand-based surface modification for enhanced targeting and uptake, improved circulation stability via PEGylation and biomimetic coatings, and optimized payload release through endosomal escape strategies. Stimulus-responsive nanoparticle systems further enable spatiotemporal control over payload release. Nuclear targeting strategies, including optimization of nuclear localization signals (NLS) and exploitation of endogenous trafficking pathways, are highlighted as key factors for improving genome-level editing efficiency. Despite these advances, major challenges-including limited intracellular delivery efficiency, insufficient targeting precision, and safety concerns-continue to hinder clinical translation. Future directions highlight artificial intelligence-driven nanoparticle design, personalized delivery systems, and next-generation CRISPR platforms. Overall, an integrated, barrier-oriented engineering strategy is essential for advancing CRISPR/Cas9 delivery toward clinical applications, ultimately advancing global good health and well-being.

CRISPR/Cas9

Timing of carbetocin administration in vaginal deliveries: a double-blind, randomized controlled trial.

OBJECTIVES: This study aimed to compare the efficacy of administering carbetocin before vs. after placental delivery in preventing postpartum hemorrhage (PPH) in low-risk vaginal deliveries. METHODS: The randomized controlled trial was conducted at Kartal City Hospital, Istanbul, Turkey. A total of 160 primiparous women with uncomplicated pregnancies who underwent vaginal delivery were enrolled. Participants were randomly assigned to receive 100&#x202f;&#x3bc;g of carbetocin either before or after placental delivery. The primary outcome was the incidence of PPH. Secondary outcomes included the need for additional uterotonics, manual removal of the placenta with consequent antibiotic administration, blood transfusions, maternal adverse events, and changes in hemoglobin levels at baseline and 24&#x202f;h postpartum. RESULTS: The incidence of PPH was significantly lower in the carbetocin-before group than in the carbetocin-after group (p=0.015). The carbetocin-before group had a significantly lower mean hemoglobin drop compared to the carbetocin-after group (p<0.001). The need for additional uterotonics was significantly higher in the carbetocin-after group (p<0.001). Manual placenta removal and the need for antibiotics were more frequent in the carbetocin-before group (p=0.017). No significant differences in adverse maternal events were observed between the groups. CONCLUSIONS: Administering carbetocin before placental delivery significantly reduces the incidence of PPH, blood loss, and the need for additional uterotonics. However, the increased rate of manual placenta removal necessitates individualized risk-benefit assessment; pre-placental administration may be most advantageous in women at elevated risk for PPH, in whom the hemorrhagic benefit outweighs the risks associated with manual extraction.

Humans

Response-optimised training improves learning of a complex motor task and closely related motor tasks.

Regular physical exercise is essential for promoting healthy aging and longevity. In older adults with varying physical and cognitive decline, optimising exercise interventions is crucial to maximise benefits. A promising approach to achieve this goal is by adjusting task demands to individual abilities in turn preventing over- or underloading their abilities. In the field of motor learning, it is currently unclear whether such an optimised training improves not only performance on the trained task but also transfers to untrained motor and cognitive tasks. We conducted a randomized, single-blinded, 6-week dynamic balance training (DBT) with healthy older adults (n&#xa0;=&#xa0;30). Training was tailored to individual balance ability. Participants were assigned to either suboptimal (high or low difficulty) or optimal (moderate difficulty) training groups. Transfer effects were assessed via cognitive tasks (memory and executive) and motor tasks (untrained DBT variations and other balance tasks) measured pre-, mid- and post-intervention. Multivariate longitudinal statistical analysis showed higher performance gains in the optimal training group in three out of six sessions compared to the suboptimal groups, especially under testing conditions with high task demands. The optimal group also showed greater improvements in near motor transfer tasks mid- and post-intervention, while no significant differences were observed in the cognitive tasks. Within-group DBT learning positively correlated with transfer gains, highlighting the role of training response in achieving transfer. In conclusion, optimised task difficulty in balance training enhances both task-specific performance and related motor skills, supporting the use of personalised interventions to maintain function and independence in older adults.

Humans

Adherence and effectiveness of multicomponent exercise fall prevention programmes across delivery formats in community-dwelling older adults: a systematic review and multilevel meta-analysis.

BACKGROUND: Multicomponent exercise is widely implemented for fall prevention in older adults, but the role of exercise adherence and delivery format in determining intervention effectiveness remains inadequately understood, particularly in analyses that account for within-study outcome dependence. METHODS: We searched five databases to 23 November 2025 for RCTs of multicomponent exercise in adults aged &#x2265;60 years. Fall outcomes were synthesised using three-level random-effects meta-analysis and meta-regression, with adherence evaluated as continuous/categorical factors and as moderator alongside delivery format, accounting for within-study effect-size dependence. RESULTS: Forty-one publications were included, comprising 36 distinct cohorts and involving 20,202 participants. Multicomponent exercise programmes significantly reduced fall incidence (IRR = 0.776, 95% CI 0.641-0.939), risk of experiencing at least one fall (RR = 0.914, 95% CI 0.858-0.974), and fall-related injury incidence (IRR = 0.754, 95% CI 0.663-0.858). Programmes achieving adherence &#x2265;75% were independently associated with greater reductions in fall incidence (IRR = 0.501, 95% CI 0.336-0.747) and fall risk (RR = 0.821, 95% CI 0.697-0.967). Mean adherence was highest in combined individual and group delivery, lower in single-format programmes, though including a group component may enhance adherence. CONCLUSIONS: Multicomponent exercise fall prevention programmes are effective for fall prevention in community-dwelling older adults, whereas evidence for their protective effects on fall-related injury outcomes remains limited. Adherence is an important factor influencing programme implementation and intervention effectiveness.

Aged

The present and future of nonviral delivery-based genome editing for hereditary hearing loss.

PURPOSE OF REVIEW: This review summarizes nonviral genome-editing delivery platforms for hereditary hearing loss, focusing on lipid nanoparticles (LNPs) and engineered virus-like particles (eVLPs), and discusses their advantages over adeno-associated virus-based delivery, as well as the barriers to clinical translation. RECENT FINDINGS: Recent advances have established LNPs as a clinically advanced nonviral platform, although challenges related to inner ear biodistribution, cell type specificity, endosomal escape, and immunogenicity remain to be addressed. In parallel, eVLPs have undergone substantial technical evolution, progressing from early low efficiency systems to advanced base editor- and prime editor-eVLP architectures that enhance cargo loading and editing efficiency. Extracellular vesicle-based genome editing has also emerged as an additional platform, although issues related to reproducibility, loading efficiency, and scalability remain major hurdles. SUMMARY: Nonviral genome editing platforms expand the therapeutic toolkit for hereditary hearing loss by enabling transient delivery of genome editors with potential safety advantages. Future efforts should focus on characterizing biodistribution and immunogenicity, refining cell type-specific tropism, and establishing scalable manufacturing processes to enable successful clinical translation.

Humans

Exploring Primary Care Clinicians' Sexual and Reproductive Health Care Delivery to Male Adolescents and Young Adults.

INTRODUCTION: Despite existing guidance for adolescent sexual and reproductive health (SRH) care, male adolescent SRH care receipt is inadequate. Limited research has explored factors affecting clinicians' provision of SRH care to male adolescents, specifically. METHODS: This mixed-method study with 12 primary care clinicians included a brief survey assessing care delivery practices and confidence, followed by an in-depth interview to explore factors affecting SRH care delivery. RESULTS: Clinicians reported high confidence delivering male adolescent SRH care (mean &#xb1; SD: 8.31 &#xb1; 1.71 out of 10), but delivered only about half the recommended services (20 items out of 38). Factors influencing care delivery included gaps in education/training, assumptions about male SRH care, and behavioral constraints at various levels. DISCUSSION: Findings underscore the need to strengthen male adolescent SRH care by enhancing provider training, increasing clinic-level supports, and addressing structural barriers. CONCLUSIONS: Findings can inform strategies to improve the quality and comprehensiveness of SRH services for male adolescents in primary care settings.

Humans

Preoperative Carbohydrate Supplementation Reduces Thirst and Improves Patient Satisfaction Before Elective Cesarean Delivery: A Randomized Controlled Trial.

BACKGROUND & AIMS: Prolonged preoperative fasting is a major source of patient discomfort, particularly thirst, before elective cesarean delivery. This study aimed to evaluate whether preoperative carbohydrate (CHO) supplementation could alleviate these discomforts and improve patient satisfaction without compromising safety. METHODS: In this single-center randomized controlled trial, 262 women scheduled for elective cesarean delivery under neuraxial anesthesia were randomly allocated to either the CHO group (Group CHO, n = 131), which received 355 mL of an oral carbohydrate solution on the night before and the morning of surgery, or the control group (Group C, n = 131), which followed conventional fasting. The primary outcome was the thirst Numeric Rating Scale (NRS, 0-10) score measured immediately before surgery. Secondary outcomes included hunger NRS, satisfaction NRS, and maternal and neonatal safety parameters. RESULTS: Baseline characteristics were comparable between groups. Despite a longer preoperative fasting duration in Group CHO (9.25 &#xb1; 1.05 vs. 8.74 &#xb1; 0.97 h, P < 0.001), this group exhibited significantly lower thirst NRS scores (1.69 &#xb1; 0.90 vs. 4.02 &#xb1; 0.99, P < 0.001) and hunger NRS scores (1.25 &#xb1; 0.94 vs. 2.09 &#xb1; 0.82, P < 0.001), as well as higher satisfaction NRS scores (7.70 &#xb1; 0.69 vs. 5.69 &#xb1; 1.17, P < 0.001). Subgroup analyses confirmed consistent benefits of CHO supplementation across most patient characteristics. Further analyses suggested that the maximum effect on thirst reduction occurred at approximately 9.2 h of solid fasting; however, the interaction between fasting duration and treatment group was not statistically significant (P = 0.187). CONCLUSION: Preoperative carbohydrate supplementation effectively reduces thirst and hunger and improves patient satisfaction before elective cesarean delivery without increasing maternal or neonatal risk. The beneficial effects were consistent across varying fasting durations, with exploratory spline analyses suggested a potential peak effect around 9.2 h, though this was not statistically significant and should be interpreted cautiously. These findings support the incorporation of carbohydrate loading into enhanced recovery protocols. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2500097956.

Humans

Reversed unidirectional transport in a Janus polyurethane/alginate dressing for directional postbiotic delivery to infected wounds.

Probiotic-derived postbiotics exhibit significant potential for infected wound control; however, their effective and localized delivery at wound sites remains a challenge. This study developed a polyurethane/alginate composite nonwoven via electrospinning to establish a postbiotic delivery platform for Bifidobacterium bifidum BD-1 (PU/Alg/BD-1). The beaded fibrous hydrophobic PU layer and hydrophilic Alg layer form a wettability gradient, enabling reversed unidirectional fluid transport toward the wound interface while inhibiting backflow. In vitro results showed that PU/Alg/BD-1 exhibited significant antibacterial activity against Staphylococcus aureus and Escherichia coli and good cytocompatibility with a hemolysis rate of <5%. Targeted metabolomic analysis revealed multiple organic acids in the BD-1 metabolites, which contributed to its antibacterial activity. In vivo microbial analysis verified that PU/Alg/BD-1 effectively reduced the relative abundance of Staphylococcus at the wound site while increasing the proportions of Corynebacterium and Psychrobacter. This microbial modulation contributed to infection control in a rat full-thickness infected wound model, accompanied by a shift in the macrophage phenotype and the downregulation of inflammatory factors including IL-6, TNF-&#x3b1;, and TGF-&#x3b2; in the PU/Alg/BD-1 group. Compared with the blank control, conventional gauze, PU/Alg, and BD-1 groups, PU/Alg/BD-1 significantly promoted wound contraction and re-epithelialization and enhanced collagen deposition. Hence, this study provides an effective material construction strategy for the application of probiotic-derived postbiotics to promote wound healing, demonstrates the potential of BD-1 to regulate the wound microenvironment and accelerate healing, and thereby offers a novel approach for the treatment of infected wounds.

Journal Article

Pregnancy diet based on ancestral patterns increases growth in subcortical fetal brain regions.

Evidence on the biological basis for maternal nutrition effects on fetal and newborn neurodevelopment remains limited. This randomized controlled trial in Ecuador tested a maternal dietary pattern-derived from empirical studies of nutrition in human evolution and adapted locally-on offspring growth and brain development. Pregnant women (n = 215) in their first trimester were randomized to: 1) control (n = 104); or 2) Mikhuna ("nourish" in Kichwa) intervention (n = 111). The intervention, from 12 wk gestation to birth, consisted of a weekly food delivery (8 eggs, 500 g fish, and a variety of sustainably sourced fruits and vegetables) and a behavior change communication strategy encouraging diet diversity and limiting highly processed foods. Longitudinal data collection occurred at 12 wk, 21 wk, 35 wk gestation, and 2 wk postpartum, and included ultrasound imaging of fetal bone and brain parameters, maternal dietary intakes, anthropometry, socioeconomic and demographic variables, and other biomarkers. At close of intervention, a significantly higher percentage of women met the minimum dietary diversity threshold in Mikhuna (74.5%) vs. control groups (55.8%) (P = 0.004). Generalized linear regression models showed significant differences in Mikhuna compared to control for: corpus callosum length 0.19 cm (95% CI [0.02, 0.35]), gangliothalamic ovoid height 0.15 cm (95% CI [0.03 to 0.26]), and femur length -0.10 cm (95% CI [-0.19, -0.02]) from 21 wk to 35 wk; and corpus callosum Z 0.56 (95% CI [0.03, 1.09]) and femur length Z -0.21 (95% CI [-0.42, 0.00]) at 35 wk. The Mikhuna intervention increased the growth of subcortical fetal brain structures, which have established roles in motor control, cognition, and signal transmission.

Female

Comparative effectiveness of torsemide vs furosemide in the management of heart failure patients: Win-ratio reanalysis of the TRANSFORM-HF trial.

BACKGROUND: Loop diuretics are widely used for managing congestion in patients with heart failure (HF). The TRANSFORM-HF trial is a multicenter randomized study that enrolled heart failure patients, comparing a strategy of torsemide vs furosemide. The time-to-event analysis demonstrated neutral effects on all-cause death at 30 months and the composite of all-cause death and first rehospitalization at 12 months. We evaluated whether a hierarchical win-ratio (WR) framework integrating mortality, recurrent hospitalization, and patient-reported health status provides additional interpretive insight. METHODS: This study is a secondary analysis of the pragmatic, multicenter, open-label, randomized TRANSFORM-HF trial, conducted across 60 US hospitals that randomized 2,859 patients hospitalized with HF to torsemide or furosemide. The primary 12-month hierarchical composite outcome was defined as (1) all-cause mortality, (2) recurrent all-cause hospitalizations, and (3) lack of improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). The primary statistical method was a WR analysis adjusting covariates via inverse probability weighting. Subgroup analyses evaluated potential heterogeneity across patient demographics and clinical characteristics. RESULTS: In the primary 12-month intention-to-treat analysis, the adjusted WR was 1.07 (95% CI, 0.98-1.16; P = .13), indicating no significant difference between torsemide and furosemide. A supplementary 30-month analysis with extended mortality follow-up yielded a similar estimate (adjusted WR, 1.06; 95% CI, 0.98-1.16; P = .14); hospitalization and KCCQ-CSS components were assessed through 12 months. As-treated sensitivity analyses were consistent with the neutral primary findings. Exploratory subgroup analyses were not adjusted for multiplicity and should be considered hypothesis-generating. CONCLUSIONS: The overall WR comparison between torsemide and furosemide showed no statistically significant difference in the primary 12-month analysis. The WR framework provided an interpretive decomposition across outcome domains but did not establish superiority of either loop diuretic strategy. All findings should be considered exploratory. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03296813, https://clinicaltrials.gov/study/NCT03296813.

Aged

Donor Human Milk Utilization in a Level 1 Newborn Unit of a High-Volume Delivery Hospital: A Cautionary Tale.

INTRODUCTION: Donor human milk (DHM) is an alternative to formula for supplementation of breastfed newborns and has been associated with higher in-hospital exclusive breast milk feeding rates. Its use has increased substantially, most recently among term newborns, yet there is scarce data to describe patient characteristics and volumes administered. We aimed to characterize DHM utilization in our level 1 nursery. METHODS: We conducted a retrospective cross-sectional study of newborns discharged in 2022 from the level 1 nursery. Variables included sex, gestational age, birth weight, delivery type, hypoglycemia diagnosis, DHM volume, and length of stay. DHM use was compared across preferred language, race, ethnicity, and payer type using chi-square testing. RESULTS: A total of 10,432 discharges were reviewed-those transferred to Neonatal Intensive Care Unit (NICU) or another unit were excluded. Of 9,074 newborns receiving level 1 care, 1,094 (12.1%) received DHM. Newborns born between 35 and 37 weeks gestation, delivered by cesarean section, or diagnosed with hypoglycemia or small for gestational age were more likely to receive DHM (p < 0.05). DHM was also more common among newborns whose birth parent preferred the English language, identified as White or non-Hispanic, or had non-Medicaid insurance (p < 0.05). 6,552.6 ounces were consumed, with a total median of 3.9 ounces per newborn (dose range 2-50 mL). CONCLUSIONS: DHM use in the level 1 nursery varied by clinical and sociodemographic factors, revealing inequities. In addition, some doses exceeded recommended supplemental volumes. Future efforts should focus on ensuring equitable access to DHM, standardized dosing and discontinuation guidelines, and evaluation of impacts on exclusive breastfeeding rates.

Humans

Comparison of a Modified Regimen of Prophylactic Phenylephrine Boluses Versus Variable Rate Infusion During Elective Cesarean Delivery Under Spinal Anesthesia: A Noninferiority Randomized Double-Blind Study.

BACKGROUND: Prophylactic phenylephrine boluses have been found to be as effective as variable rate infusions during elective cesarean delivery but require a higher number of physician interventions to maintain blood pressure near baseline values. Therefore, there is a need to find a feasible regimen of bolus administration that is equally efficacious to the infusion regimen while at the same time requires a comparable number of physician interventions and is thus non-inferior to the infusion regimen. METHODS: Healthy pregnant women with term, uncomplicated, singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomly divided into two groups. The Bolus group received a phenylephrine bolus 100 &#x3bc;g immediately after spinal anesthesia and then at every systolic blood pressure value <90% of the baseline. The infusion group received a prophylactic variable-rate infusion of phenylephrine beginning at 50 &#x3bc;g/min and titrated to maintain systolic blood pressure at 90-99% of baseline. The primary outcome was the number of physician interventions needed to maintain the target systolic blood pressure; the secondary outcomes included phenylephrine requirements, incidence of hypotension/hypertension/bradycardia, umbilical arterial and venous blood gas analysis, Apgar scores, and maternal complications. The primary outcome was analyzed in terms of non-inferiority using a non-inferiority margin of two interventions. RESULTS: Eighty patients were included in the study. The median (interquartile range [IQR]) number of physician interventions was 6 (5-8) in the infusion group and 3 (2-4) in the bolus group (P < .001). The difference of medians (95% confidence interval [CI]) between the two groups was -3 (-4 to -2). Phenylephrine requirements were higher in the infusion group (630 [426-765] &#x3bc;g) compared to the bolus group (300 [200-400] &#x3bc;g; P < .001). Blood pressure was higher at certain time points in the infusion group, but overall accuracy of blood pressure control was not different between the groups. Incidence of hypotension, hypertension, and bradycardia, neonatal outcomes, and maternal complications did not differ between the groups. CONCLUSIONS: The modified regimen of prophylactic boluses is non-inferior to variable rate prophylactic phenylephrine infusion in terms of physician interventions needed to maintain systolic blood pressure within the target range and maternal and neonatal outcomes.

Humans

Quantification of appetite-regulating hormones in children with hypothalamic and common obesity.

CONTEXT: The pathophysiology of hypothalamic obesity (HyOb) remains incompletely understood with no effective treatments. OBJECTIVE: We examined differences in appetite-regulating hormone concentrations between patients with HyOb, common obesity, and lean controls. DESIGN: Multiway cross-sectional case-control study of patients aged 2 through 19 years. SETTING: Two tertiary pediatric endocrinology centers. PATIENTS: Cases were obese (body mass index [BMI] > +2 SD score [SDS], "HyOb") and lean ("HyLean") patients with congenital (septo-optic dysplasia) or acquired (suprasellar brain tumor) hypothalamic disorders. Controls had common obesity ("Ob") or nonhypothalamic disorders and normal BMI ("Lean"). MAIN OUTCOME MEASURES: Relationships between the Dykens' Hyperphagia Questionnaire Score (DHQS), plasma or serum concentrations of leptin, insulin, &#x3b1;-melanocyte stimulating hormone (&#x3b1;MSH), brain-derived neurotrophic factor, oxytocin, acylated ghrelin, agouti-related peptide and copeptin, and BMI SDS. RESULTS: Dykens' Hyperphagia Questionnaire Score did not differ between HyOb and Ob patients (24 [17-34] vs 24 [18-31]) but correlated with BMI SDS in patients with hypothalamic disorders (P = 0.02). HyOb and Ob patients exhibited similarly increased anorexigens (insulin, leptin) and decreased orexigens (ghrelin, agouti-related peptide) compared to HyLean and Lean patients. The rate of BMI increase was independently associated with lower &#x3b1;MSH (&#x3b2; = -0.23 [-0.36 to -0.11], P = .0007) and ghrelin (&#x3b2;=-0.004 [-0.01 to 0.00], P = .001) concentrations, suggesting that &#x3b1;MSH replacement may be a therapeutic target for HyOb. HyLean patients demonstrated intermediate insulin responses to glucose compared to other subcohorts. CONCLUSION: In our cohort, patients with HyOb appeared indistinguishable from Ob in terms of their appetite and appetite-regulating neuroendocrine circuitry. Higher &#x3b1;MSH concentrations are associated with reduced weight gain and may be a target for therapeutic intervention.

alpha-MSH

Beyond risk factors: A capacity framework for cancer survivorship research.

Cancer survivorship research has identified numerous biological, behavioral, psychosocial, health care, and structural factors that influence recovery. However, these factors are typically studied as separate determinants rather than interacting influences. This commentary proposes available survivorship capacity as a unifying framework that explains how these diverse determinants collectively shape recovery and survivorship outcomes. Concepts from geroscience, health care delivery, rehabilitation, occupational therapy, and human factors science were synthesized to develop a conceptual framework of available survivorship capacity. The framework conceptualizes recovery as a function of the capacity remaining after competing health care and life demands draw upon survivors' finite physical, cognitive, emotional, social, financial, temporal, and health care resources. It generates testable propositions for measurement, intervention research, health care delivery, and implementation science while positioning available survivorship capacity as a common mechanism linking diverse determinants of recovery and identifying actionable targets for intervention. Available capacity offers a unifying conceptual framework for understanding heterogeneity in survivorship outcomes and intervention effectiveness while generating a research agenda for future survivorship science. Measuring and strengthening survivors' available capacity, while reducing unnecessary demands, may improve engagement in care, health behaviors, and long-term recovery.

Humans

Phase 1 Study Evaluating Gefurulimab Pharmacokinetics and Safety Following Delivery Via Autoinjector or Prefilled Syringe With Needle Safety Device in Healthy Adults.

PURPOSE: Gefurulimab, a novel dual-binding nanobody targeting complement component 5 (C5), is in clinical development for anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. Gefurulimab has a low molecular weight, enabling subcutaneous (SC) self-administration by autoinjector (AI) or prefilled syringe with needle safety device (PFS-SD). We compared gefurulimab pharmacokinetic (PK) exposure and safety in healthy adults following a single SC dose administered by AI versus PFS-SD. METHODS: In this phase 1, open-label, randomized, parallel-group study (NCT06208488), healthy participants aged 18 to 65 years were stratified by weight and randomized equally to 1 of 6 combination groups of device and injection site (abdomen/thigh/upper arm). Participants received a single SC dose of gefurulimab on day 1 and were assessed throughout the 92-day evaluation period. Primary endpoints were PK parameters for each device: maximum observed concentration (Cmax) and area under the serum concentration-time curve (AUCinf, AUClast). PK across injection sites, pharmacodynamics, safety, immunogenicity, and device performance were also assessed. FINDINGS: Overall, 175 participants were randomized: AI (n = 87), PFS-SD (n = 88). Geometric least squares mean ratios (90% CI) comparing AI/PFS-SD for Cmax, AUCinf, and AUClast were 97.6% (94.5-100.8), 99.6% (96.1-103.3), and 98.8% (95.2&#x2012;102.6), respectively. Secondary analyses found no meaningful differences in PK parameters across injection sites. Serum-free C5 concentrations over time, treatment-emergent adverse event (TEAE) profiles, and antidrug antibody responses were similar between cohorts. Most TEAEs were mild; none led to study discontinuation. IMPLICATIONS: SC administration of gefurulimab by AI and PFS-SD was well tolerated with comparable exposure, meeting bioequivalence criteria.

Humans

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems

Vitamin D Deficiency During Pregnancy Is Associated With Greater LDL-C Increase, Elevated &#x3b2;-Hydroxybutyrate and Altered Neonatal Metabolic Markers-A Secondary, Pooled Analysis of the Randomized, Controlled Vitamin D and Lifestyle for Gestational Diabetes Prevention Trial (DALI).

INTRODUCTION: Vitamin D (vitD) plays a role in metabolic regulation, including lipid metabolism and insulin sensitivity. During pregnancy, profound physiological changes in lipid handling and ketogenesis occur to support fetal development. However, the extent to which maternal vitamin D status influences these metabolic adaptations and fetal metabolic markers remains unclear. METHODS: In this secondary analysis, we examined lipid distribution throughout pregnancy-from before 20&#x2009;weeks' gestation to delivery-in women with overweight or obesity, stratified by vitamin D status (deficiency, insufficiency, or sufficiency), assessing both maternal and cord blood. Main inclusion criteria were: age&#x2009;>&#x2009;=18&#x2009;years, singleton pregnancy, <&#x2009;20&#x2009;weeks' gestation, BMI &#x2265;&#x2009;29&#x2009;kg/m2. Women with GDM <&#x2009;20&#x2009;weeks' gestation were excluded. In total, 962 pregnant women were divided into vitD deficient (<&#x2009;30&#x2009;nmol/L, n&#x2009;=&#x2009;102), insufficient (30-50&#x2009;nmol/L, n&#x2009;=&#x2009;222) and sufficient (>&#x2009;50&#x2009;nmol/L, n&#x2009;=&#x2009;638) groups. VitD levels and lipid concentrations were assessed at <&#x2009;20, 24-28 and 35-37&#x2009;weeks' gestation and in cord blood. RESULTS: Compared with vitD sufficient women, women with vitD deficiency had significantly larger increases in LDL-C throughout pregnancy and &#xdf;-OH-butyrate at 24-28&#x2009;weeks' gestation, in adjusted analysis. VitD in cord blood was highest in offspring of mothers with vitD sufficiency. In cord blood, significantly higher &#xdf;-OH-butyrate was observed with vitD deficiency; lipid concentrations were similar between groups. CONCLUSIONS: Early vitamin D deficiency before 20&#x2009;weeks of gestation was associated with altered metabolic trajectories during pregnancy, including greater increases in LDL cholesterol and ketone body concentrations in women with overweight or obesity, as well as higher cord blood ketone levels in their offspring. These findings suggest that early maternal vitamin D status may influence maternal and fetal metabolic adaptations, although causal relationships and clinical implications require further investigation. TRIAL REGISTRATION: Trial registered at ISRCTN registry (https://doi.org/10.1186/ISRCTN70595832) trial number ISRCTN70595832. Registration date 02/12/2011.

Humans