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Feasibility of the Italian version of the Teen Online Problem Solving Program (I-TOPS) in a sample of adolescents with acquired brain injury: Results from a randomized controlled trial
Numerous neurocognitive and behavioral deficits in adolescents with acquired brain injury have been associated with impairments in executive functions. Nevertheless, many adolescents do not receive targeted rehabilitation. One of the most validated interventions addressing executive dysfunction in this population is the web-based Teen Online Problem Solving (TOPS) program, developed in the United States in the early 2000s. This study aimed to evaluate the feasibility of the Italian version of TOPS (I-TOPS) in its first implementation in Italy, compared with an active control wellness intervention in adolescents aged 11–19 years. Data on the feasibility of both the training and the study design and procedures are reported from the randomized controlled trial conducted to assess feasibility prior to a full evaluation of efficacy. Forty-two adolescents participated, 21 allocated to I-TOPS and 21 to the wellness intervention. Overall willingness to participate in the study, assessed before randomization across the full sample, was moderate (61.73%). The I-TOPS group, but not the wellness group, demonstrated adequate training adherence, training satisfaction and participation rates. No technological issues hindering program completion, accessibility difficulties with the web-based platform or significant loss to follow-up among participants who completed the training were reported in either group. However, challenges in collecting outcome measures on parent functioning due to refusal were observed in both groups. Adherence to the planned assessment timeline was satisfactory but not fully met. In sum, the findings suggest that I-TOPS represents a feasible approach that is subjectively perceived as useful and engaging by adolescents with acquired brain injury and their families. Nevertheless, the moderate acceptance rate in the study and the potential stigma associated with reporting mental health concerns among some parents may limit the generalizability of the findings. These factors should be taken into account when planning efficacy studies. This study was registered at ClinicalTrials.gov (NCT05169788).
GATA2-LHCGR regulatory network promotes follicle development by enhancing granulosa cell proliferation and ovarian steroidogenesis in Wanxi white geese
Peroxisomal ether lipid synthesis regulates cortical neurogenesis and maintains mitochondrial energy homeostasis in radial glial cells
Neurogenesis is characterized by dynamic structural changes and functional remodeling of multiple organelles, which interact to form an intricate network that precisely modulates processes including neural progenitor cell self-renewal, neurogenesis, and terminal neuronal development. However, the spatiotemporal dynamics of peroxisomes and their functional contributions within this regulatory network remain incompletely defined during mammalian cortical development. Here, we found that radial glial cells (RGCs) exhibit enriched peroxisome abundance, whereas neural differentiation is associated with reduced peroxisome numbers and increased pexophagy, accompanied by the remodeling of lipid metabolic programs. Acute disruption of peroxisomes by PLAAT3-PEX11 impaired neural differentiation in the embryonic mouse cortex, while PEX7 knockout compromised neurogenic progression in human cortical organoids, supporting a conserved requirement for peroxisomal function during cortical development. Lipidomic and imaging analyses revealed that peroxisome-derived ether lipids were essential for driving neural differentiation and were specifically enriched in mitochondria. Consistently, knockdown of Gnpat , which catalyzes the initial step of ether lipid biosynthesis, reduced neural differentiation, and disrupted mitochondrial structure and function, while batyl alcohol supplementation partially restored these defects. Mechanistically, the ether lipids maintain the structural integrity of mitochondrial cristae and thereby support respiratory chain activity, which in turn promotes oxidative phosphorylation and activates the NAD + associated signaling. Collectively, this work highlights the precise spatiotemporal regulation of neurogenesis through peroxisomal dynamics and interorganelle crosstalk and identifies ether lipids as a potential therapeutic target for neurodevelopmental disorders.
TranExamic Atomized for Pediatric post-Operative Tonsillectomy hemorrhage (TEAPOT): Study protocol for a pilot randomized controlled trial
Tonsillectomy is the second most common performed surgical procedure in children in the United States. Unfortunately, up to five percent of children return to emergency departments (ED) for post-tonsillectomy hemorrhage (PTH). To control PTH, most pediatric otolaryngologists return to the operating room (OR) for cauterization of the bleeding source. Retrospective studies suggest that nebulized tranexamic acid (TXA), an antifibrinolytic agent, can reduce the severity of post-tonsillectomy hemorrhage (PTH), however, its efficacy and safety have not yet been tested in randomized controlled trials. We designed the TranExamic Atomized for Pediatric post-Operative Tonsillectomy hemorrhage (TEAPOT) trial protocol to evaluate the feasibility of conducting a confirmatory clinical trial to evaluate the effects of TXA in children with PTH. We will randomize children presenting to the ED with secondary PTH to receive three 5-mL nebulized doses of either TXA (TXA 100 mg/ml) or placebo (normal saline). The following outcomes will be measured: feasibility (number of enrolled patients per site per year); protocol adherence (receipt of at least two nebulization doses); return to the operating room; pain reported on the FACES scale; parent and child anxiety assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety measure; systemic and local (pharmacokinetic model derived) concentrations of nebulized TXA; coagulation biomarkers; and adverse events, including bleeding, thrombosis, and seizures. Our multicenter trial will provide important preliminary data on the feasibility and pharmacokinetics of nebulized TXA in preparation for a definitive clinical trial of children with secondary post-tonsillectomy hemorrhage. Registered at ClinicalTrials.gov ID# (NCT07565753) on May 4 th , 2026, https://clinicaltrials.gov/study/NCT07565753?term=teapot&viewType=Card&rank=1
Rockburst mechanism and control of staggered roadways beneath upper-slice residual coal pillars in extra-thick coal seams: a case study
Abstract Upper-slice residual coal pillars in extra-thick coal seams can form local high-stress structures and strongly affect lower-slice staggered roadways. To clarify the rockburst mechanism beneath such a pillar, this study investigated the 250101-2 lower-slice working face by integrating field damage investigation, microseismic monitoring, coal-pillar mechanical analysis, FLAC3D simulation, and destressing verification. During retreat, 5737 microseismic events (MS) were recorded, including 56 high-energy events with energy not lower than $$\:1.0\times\:{10}^{4}$$ J. These events were mainly distributed within approximately 200 m ahead of the working face and concentrated on the haulage roadway side. The 20 m residual-pillar zone accounted for 41% of the high-energy event frequency and 37% of the total high-energy release, consistent with repeated field manifestations such as rib deformation, support damage, mesh failure, coal-rock collapse, and floor heave. Mechanical analysis shows that the residual pillar may behave as a narrow pillar with peak-stress superposition or evolve into a wider composite bearing structure after goaf recompaction. Numerical simulation further indicates that, during lower-slice mining, the original 20 m pillar and adjacent compacted coal-rock mass formed an effective bearing zone of approximately 54 m, enhancing stress accumulation and downward transfer. The LW250101-2 haulage roadway was located near the boundary between the high-stress zone and the stress-relieved zone, where a sharp stress gradient promoted asymmetric deformation and dynamic instability. Coordinated destressing by roof deep-hole blasting, rib deep-hole blasting, and ultra-deep large-diameter boreholes transformed microseismic activity from concentrated high-energy release to more dispersed low-energy release, reducing rockburst risk in the residual-pillar-affected roadway.
Wireless, skin-attachable patch with 3D liquid metal electrodes for vagus nerve stimulation in depression
Current nonsurgical vagus nerve stimulation (VNS) approaches often suffer from broad current spread, high electrode-skin impedance, and unintended stimulation of surrounding tissues, which can reduce efficacy and cause side effects. Here, we present a wirelessly operable, skin-attachable VNS patch with three-dimensional liquid-metal electrodes that mimic the low modulus of biological tissues, developed as a minimally invasive platform for investigating the biological mechanisms underlying VNS in a mouse model of depression. The soft, low-modulus three-dimensional liquid metal electrodes gently penetrate the skin, bypass the stratum corneum, and improve electrode–tissue coupling while minimizing tissue damage compared with conventional planar or rigid electrodes. To comprehensively assess therapeutic effects, we conducted behavioral tests, neural probe-based brain signal analysis, dendritic spine density measurements, and blood and inguinal lymph node profiling in depression model mice. VNS increased plasma serotonin levels and increased dendritic spine density, indicating improved neuroplasticity. Corticosterone-induced depressive mice exhibited elevated CD4+ and B220+ cells, which normalized with VNS. These results establish an animal-level proof-of-concept that minimally invasive VNS can engage key neural and immunological pathways relevant to depression, providing a foundation for future neuromodulation strategies.
Impact of a modified produce prescription program on fruit and vegetable intake in an HBCU
Background Limited access to fruits and vegetables remains a significant barrier among underserved populations, particularly within Historically Black Colleges and Universities (HBCUs). Evidence from previous studies suggests that prescription programs, which provide incentives for fresh produce consumption, are effective in enhancing dietary quality and alleviating food insecurity. Objective This pilot investigation assessed the impact of a tailored produce prescription intervention on changes in fruit and vegetable consumption among students at a Historically Black College and University (HBCU). Methods Fifty-five students were assigned to an intervention (n = 28) or control group (n = 27); both received nutrition education and cooking demonstrations, while the intervention group additionally received biweekly personalized produce bags. Fruit and vegetable intake was assessed using a 10-item dietary screener, supported by 24-hour recalls and food frequency questionnaires. Changes in intake were evaluated using descriptive statistics, chi-square tests, and Wilcoxon signed-rank tests. Results Compared with the control group, the intervention group reported higher intake frequencies of cooked beans (χ 2 = 17.63, p = 0.014), while the intake of non-deep-fried vegetables approached statistical significance (χ 2 = 16.82, p = 0.052). Notably, only the intervention group experienced increases from baseline to endline in the intake of 100% fruit juice (Z = −2.199, p = 0.028), fruits (Z = −2.199, p = 0.028), green leafy vegetables (Z = −2.195, p = 0.028), cooked beans (Z = −2.776, p = 0.005), other non-deep-fried vegetables (Z = −2.292, p = 0.022), and tomato sauce (Z = −2.026, p = 0.043). Conclusion The results of a modified produce prescription program revealed favorable within-group changes in the frequency of consumption of several fruit- and vegetable-related foods. While most between-group differences at endline were not statistically significant, observed patterns suggest potential promise and support the need for larger, adequately powered studies to evaluate the impact more rigorously.
A multi-objective decision support system for zone-specific fertilizer recommendation using soil fertility prediction models
Cortical gray matter myelin cuts energy cost of spike propagation without increasing conduction velocity
Myelin is a hallmark of vertebrate nervous systems, yet its roles in central axons remain elusive. Using optical and electrical recordings from thin axons of Layer 5 pyramidal neurons in murine cortical gray matter of animals of either sex, and computational modeling, we argue that myelination halves the metabolic cost of spike propagation with little effect on conduction velocity. Modeling indicates that, although greater speed and energy efficiency are theoretically possible, these would compromise repolarization and the function of internodal voltage-gated channels and pumps. We further suggest that, in contrast to peripheral axons, cortical myelin segregates current flow within periaxonal nanodomains. High-frequency currents, key for the rising phase of the action potential, traverse the myelin sheath to facilitate propagation, whereas low-frequency currents leak through paranodal junctions, supporting repolarization and ion homeostasis. These results suggest that cortical myelin adopts a structural trade-off that favors metabolic efficiency and ionic homeostasis over maximal velocity.
“Please speak in Hindi”: Cognitive interviews to improve measurement of digital access in North India
Access to and use of mobile phones are increasingly a prerequisite for full participation in modern society. Yet, a significant digital gender gap persists in India, where women are less likely than men to own phones or access the internet. To measure and understand this gap, survey questions must be both comprehensible to the respondents and contextually appropriate. We conducted 101 cognitive interviews with men (n = 44) and women (n = 57) in rural Uttar Pradesh to test 118 draft survey questions developed for an upcoming survey on digital access and use. These draft questions were drawn primarily from validated global instruments, with some additional questions newly developed by our team, and were all translated into Hindi. Through team debriefs and systematic analysis of the interview transcripts, we identified seven categories of question problems: (1) inappropriate terminology, (2) overly complex wording, (3) low resonance of digital concepts (e.g., personal data, online tracking, privacy policies, hacking), (4) confusion when asking about permission and supervision of mobile phone use due to phone sharing and overlap with concept of help or support, (5) problematic question structures and response options (especially Likert scales), (6) self-practice bias, and (7) unclear time frames and recall expectations. Overall, we found that many draft survey questions were incomprehensible to respondents despite our research team’s efforts to develop clear and simple translations. Revisions were required for almost all questions. Our findings highlight the critical role of cognitive interviewing in improving data quality, particularly when conducting surveys across languages and sociocultural contexts, and amid rapidly changing digital landscapes.
Coupling an ingestion orifice model with a gas turbine SAS code for integrated cycle modeling
Blm10 and PI31 comprise a failsafe mechanism for proteasome inhibition
Blm10 (PA200 in mammals) is an evolutionarily conserved regulator of the proteasome’s core particle (CP), a barrel-shaped complex that houses six individual protease subunits. Despite decades of study, Blm10’s function has remained unresolved. Here, we provide structural, biochemical, and genetic evidence that yeast Blm10 inhibits the proteasome and that it does so in cooperation with a second proteasome inhibitor, PI31 (also known as Fub1). Both proteins are highly enriched in CPs with abnormal subunit composition, suggesting that Blm10 and PI31 may function to neutralize aberrant proteasomes. We report an unexpected proteasome configuration in which Blm10’s dome-like structure completely encases PI31’s N-terminal domain, which sits outside and atop the CP, while PI31’s C-terminal domain is present inside the CP, simultaneously inhibiting all six active sites. These Blm10/PI31-bound CP are strongly deficient in degradation of both proteins and small peptides, and loss of both proteins results in strongly synergistic genetic phenotypes in vivo. These data suggest that Blm10 and PI31 constitute a partially redundant failsafe system for proteasome inhibition.
The multisensory cocktail party problem in adults: The effects of the configural talking-face template and of facial, vocal, and linguistic identity cues on its solution
Social communication often involves competing talkers and, thus, gives rise to the multisensory cocktail party problem (MCPP). To solve the MCPP, perceivers must bind, integrate, and segregate each talker’s auditory (A) and visual (V) speech streams. Audiovisual (AV) temporal synchrony is a known and powerful multisensory segregation cue and facial and vocal identity cues are known to facilitate segregation. Using eye tracking, we investigated whether perceptual segregation of multiple talking faces depends on the configural talking-face template (Experiment 1) and whether facial, vocal, and linguistic identity cues associated with different talkers can facilitate perceptual segregation (Experiment 2). Results indicated (a) that AV synchrony-based perceptual segregation of multiple talking faces does not depend on the configural talking-face template, (b) that linguistic identity cues facilitated synchrony-based segregation of upright talking faces independently of facial and vocal identity cues, (c) that perceptual segregation was driven primarily by AV speech processing as evidenced by greater selective attention to the talkers’ mouth, and (d) that, as evidenced by pupillary dilation, the type and number of AV congruence cues that had to be processed for successful segregation was associated with differential cognitive effort. Overall, these findings add to existing evidence indicating that adults’ solution of the MCPP relies on AV temporal synchrony cues and on facial, vocal, and linguistic identity congruence cues but not on the canonical configural talking-face template.
Combining forced limb use with Ninjin’yoeito prevents atrophy in fast-twitch muscles and promotes functional restoration after hemorrhagic stroke in rats
Electro-nuclear quantum phase transition in TmVO <sub>4</sub>
Hyperfine interactions couple nuclear and electronic degrees of freedom. The present work explores how hyperfine coupling within the Tm ions in TmVO 4 single crystals affects an electronic ferroquadrupole ordered ground state and its associated field-tuned quantum phase transition. As temperature is progressively reduced through the hyperfine energy scale, the nuclear moments reduce the critical field for the electronic order, resulting in a dramatic back-bending of the phase boundary delineating the ferroquadrupole order. This behavior is well described by a single-ion semiclassical mean-field model down to approximately 50 mK. Analysis of the effective Hamiltonian leads to a prediction of spontaneous nuclear magnetic order mediated by 4 f electrons, which in principle persists with the application of orthogonal antisymmetric strain, yielding a proposed electro-nuclear tetracritical point.
Joint optimization for throughput fairness maximization in laser-powered UAV communications
This paper investigates a laser-powered UAV communication system. To maximize the minimum throughput among ground nodes, we jointly optimize communication scheduling, transmit power, and UAV trajectory. The resulting non-convex problem is decomposed into three subproblems and solved via successive convex approximation and iterative techniques. The simulation results show that our algorithm has fast and stable convergence.
Crystalline lens geometry from a clinical OCT-based biometer in pre-cataract surgery patients
Abstract Understanding relationships between crystalline lens geometry, eye’s refractive error and aging will be insightful to inspire new intraocular lenses (IOLs) and improve selection methods of the IOLs implanted in refractive lens exchange and cataract surgery. In this study we evaluated the relationships between the full geometry of the crystalline lens and age, axial length (AL), and refractive error in patients scheduled for cataract surgery. Optical Coherence Tomography (IOLMaster700, Zeiss) combined with custom-developed full crystalline lens shape reconstruction algorithms were applied to image 327 eyes from 327 participants and quantify lens geometrical parameters, including thickness (LT), radii of curvature of the anterior and posterior lens surfaces (RAL, RPL), volume (LV), surface area (LSA), diameter (DIA) and equatorial plane position (EPP). Correlation and partial correlation analysis (controlling for age, AL, and refractive error) were performed. Multiple linear regression models evaluated whether age and AL predicted LT, DIA, LV and LSA. Age was significantly correlated with LT, LV, LSA, DIA, EPP, and these associations persisted after controlling for AL or refractive error. AL was correlated with RAL, RPL, DIA and refractive error, and with RAL, RPL, LV, LSA, DIA, and refractive error after adjusting for age. Overall, the lens expands axially and meridionally with age, increasing in thickness, diameter, volume and surface area, accompanied by a hyperopic shift. Longer eyes exhibited lenses with larger diameters and flatter anterior and posterior surfaces, partially offsetting myopia. These findings suggest that age- and growth-related lens remodeling contributes to refractive shifts.
<i>SHOOT GRAVITROPISM 9</i> links sensory timing to the initial lateral root growth angle
Plants strategically respond to gravity and actively set defined growth angles. These gravitropic set-point angles (GSAs) shape the width and depth of the root system, determining soil exploration for water and nutrient uptake. Despite its physiological importance, the concept by which lateral roots establish their growth angle has remained largely unclear. Here, we show that temporal regulation of gravity responsiveness within a defined developmental phase sets the initial GSA in lateral roots. Stage-specific transcriptome profiling revealed that SHOOT GRAVITROPISM 9 ( SGR9 ) is upregulated in emerged lateral roots as they first respond to gravity. Loss of SGR9 slows amyloplast sedimentation and delays the PIN3-dependent establishment of asymmetric auxin distribution. Notably, the delay in the gravity response alters, rather than merely postpones, the initial stable growth angle. Our findings reveal that a developmental time window enables transient sensory dynamics to be translated into stable initial root growth angles, illustrating how developmental timing can convert short-lived signals into lasting form.
Plasmodium falciparum non-synonymous Kelch13 mutations mediating artemisinin resistance in East Africa: A systematic review and meta-analysis: 2014–2024
Background Resistance to antimalarial drugs has posed a significant challenge to global efforts to control and eliminate malaria. Partial artemisinin resistance has been observed in East Africa, a region that has been a historical hotspot for antimalarial drug resistance across the continent. Consequently, this review assesses the extent of non-synonymous mutations mediating artemisinin resistance, the varieties of these mutations, and their effects on treatment outcomes in East Africa. Methods Studies reporting artemisinin resistance (samples collected between 2014 and 2024), particularly the Pf-Kelch13 mutation among malaria patients in East Africa, were searched through the Medline, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, and EMBASE online databases. The protocol for the review was registered at PROSPERO (Reference number: CRD42024602752). Two independent reviewers extracted data. Potential publication bias was assessed using a funnel plot. Pooled proportion estimates were calculated using a random-effects model, and heterogeneity was assessed using I 2 statistics. Results Twenty-four (24) studies were deemed eligible for data extraction. The heterogeneity among the studies included in the meta-analysis was high (I 2 > 95% and p < 0.01). The overall estimated pooled proportions of non-synonymous Pf-Kelch13 mutations, using the random effects model, were 5.0% (95% CI 3.0%–7.0%), with the pooled proportion estimates being higher in Rwanda and Uganda (10.0%, 95% CI 4.0%–16.0%) and (10.0%, 95% CI 6.0%–14.0%), respectively. Subgroup analysis (per mutation type) revealed that R561H and A675V were the most prevalent non-synonymous mutations (9.0%, 95% CI 5.0%–15.0% and 7.0%, 95% CI 4.0%–10.0%, respectively). Patients harbouring parasites with Pf-Kelch13 non-synonymous mutations were significantly more likely to experience treatment failure than those harbouring wild P. falciparum parasites (Log OR: −2.06, 95% CI, −2.71–1.41). Conclusion The prevalence of Pf-Kelch13 non-synonymous mutations known to be associated with artemisinin resistance was significant. The most common mutations identified were R561H and A675V. Continued molecular surveillance and coordinated efforts are essential to contain the partial artemisinin resistance in the East African region and prevent its spread across the continent.