Browse Articles

Validating the 2-minute walk test MCID for subacute stroke patients: A Pakistani multicenter cohort analysis

Background The 2-Minute Walk Test (2MWT) is a simple and reliable test used by clinicians to evaluate mobility gains in stroke populations. Objective To determine the minimally clinically important difference (MCID) for the 2-Minute Walk Test (2MWT) in subacute stroke populations. Design This was a prospective cohort study. Setting The study was carried out across seven rehabilitation centers in Pakistan. Participants 150 adults (<180 days post-stroke),with a confirmed ischemic or hemorrhagic stroke, able to walk at least 10 meters, and Mini-Mental State Examination score ≥24. Interventions Participants underwent 6–8 weeks of standard rehabilitation, including physical therapy (gait and balance training) and, in some centers, robotic gait training. Interventions varied by center but followed standardized gait and balance goals. Main outcome measures The 2MWT was the primary outcome measure whereas, the Activities-specific Balance Confidence gait subscale (ABC_Gait), Global Perceived Effect (GPE) scale, and Modified Barthel Index (MBI) were the secondary outcome measures. The MCID was estimated using an anchor-based approach (ABC_Gait ≥10% improvement), validated by distribution-based methods. Results The 2MWT MCID was 33 meters (95% CI: 30–36 meters), with 87% sensitivity and 82% specificity. A strong correlation was observed between 2MWT and ABC_Gait change scores (r = 0.68, p < 0.001). The mean 2MWT distance improved from 62.5 ± 38.4 meters to 98.7 ± 42.1 meters (p < 0.001). Subgroup analyses showed that MCID was consistent across age groups, stroke types, and intervention modalities. Conclusion The 33 meters MCID for the 2MWT is a reliable and patient-centered benchmark for assessing mobility gains in subacute stroke populations. Validation in chronic stroke populations and exploration of emerging interventions like virtual reality (VR) is needed to extend the 2MWT MCID’s applicability.

Chiral Pyridoxals Enabled Efficient Enantioselective Synthesis of α-Substituted Tryptophan Derivatives

Meta-encoder: a unified integration framework for multiple pathological foundation models in cancer detection

An algorithm to identify less invasive surfactant administration using a real-world database of preterm infants

Background Surfactant replacement therapy is central to respiratory distress syndrome (RDS) management in preterm infants, which can be delivered using a variety of methods. Less invasive surfactant administration (LISA) has been increasingly adopted due to its association with improved neonatal outcomes. However, there are no procedure codes to identify LISA in large real-world data (RWD), limiting the ability to evaluate its use and effectiveness on a large scale. This study aimed to develop an algorithm to identify LISA procedures using administrative data. Methods We conducted a retrospective study using chart reviews as the gold standard to identify preterm infants receiving surfactant via LISA or non-LISA procedures across Kaiser Permanente Northern California (KPNC) facilities. We selected 82 candidate variables from administrative data between birth and date of first surfactant administration. The algorithm was developed using births between 2019 and 2023, which were randomly split into a training set (n = 884) and testing set (n = 379). A least absolute shrinkage and selection operator (LASSO) regression was used for variable selection and model fitting. Model discrimination was evaluated using area under the receiver operating characteristic (AUROC). Algorithm performance was validated using a combined sample of the testing set and a 2024 birth cohort (n = 622) overall and by gestational age (GA) using sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). Results Among 1,263 preterm infants who received surfactant, 462 (36.6%) received surfactant via LISA and 801 (63.4%) received surfactant via invasive modalities (ETT or INSURE). The LASSO-based model selected 21 variables predictive of LISA methods based on the training set. The model demonstrated strong discrimination (AUROC = 0.87). Using the maximum specificity cut-point (predicted probability ≥0.79), the model achieved Sn = 43.9%, Sp = 96.8%, PPV = 90.0% and NPV = 72.5%, with an overall agreement of 75.9% when evaluated in the combined testing set and 2024 birth cohort. Sn and Sp were consistent across GA subgroups. Conclusions We used a machine-learning approach to develop an algorithm that performed well in identifying surfactant administered via LISA among preterm infants using administrative data. The algorithm demonstrated strong performance and can support future research to evaluate the utilization and outcomes of LISA using RWD.

Supramolecular engineering of amyloid-inspired tripeptide assemblies enabling tunable piezoelectricity

Nutritional prehabilitation in head and neck cancer patients (PreHead) – A randomized controlled trial study protocol

Rationale Up to 60% of patients with head and neck cancer are malnourished upon first presentation. Malnutrition has been associated with a higher risk of adverse events and decreased quality of life and survival. Patients with a high risk of malnutrition often receive pretreatment dietary treatment before surgery or (chemo)radiotherapy, i.e., nutritional prehabilitation. However, previous research suggests that patients with a low or medium risk of malnutrition may also benefit from nutritional prehabilitation. Objective To investigate the effect of nutritional prehabilitation on adverse events, nutritional status, patient-reported quality of life, tumor recurrence, and (disease-specific and overall) survival. To evaluate the cost-effectiveness of nutritional prehabilitation compared with standard care. Study design A single-center, non-blinded, randomized controlled trial. Study population Patients with locoregionally advanced stage (III or IV) primary mucosal squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx treated with curative intent and with a low or medium risk of malnutrition according to the Malnutrition Universal Screening tool. Sample size Based on a power analysis, a total of 128 patients will be included. Intervention The intervention arm will receive nutritional prehabilitation and the control arm will receive standard care (no nutritional prehabilitation). Main study parameters/endpoints Adverse events (i.e., surgical complications and (chemo)radiotherapy toxicity). Complications will be measured within 30 days after surgery using the Clavien-Dindo classification. Toxicity will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), 6 and 12 weeks after the start of (chemo)radiotherapy. Significance It is hypothesized that nutritional prehabilitation, compared with no nutritional prehabilitation, will result in fewer (severe) adverse events, improvement of nutritional status, higher quality of life, equal risk of recurrence and better survival. It is hypothesized that the intervention will be cost-effective. Trial registration The trial is registered in the Dutch Trial Register under registration number NL87676.042.24.

Author Correction: Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution

The impact of grandparent-grandchild interactions on the imagination of aging among Chinese youth groups: The chain mediating role of intergenerational relations and filial piety concept

Centered on respecting elders and intergenerational responsibility, Confucian filial piety culture serves as a core cultural norm in Chinese society. This study integrates this cultural framework with the context of China’s rapid population aging to explore how grandparent-grandchild interactions within Chinese families shape young adults’ aging imagination. Based on a survey of 778 Chinese youth aged 18–35, the findings show that both daily and ritualistic interactions positively predict young adults’ aging imagination, and daily interactions have a stronger predictive effect. Intergenerational relations and filial piety not only serve as independent mediators but also constitute a chain mediating pathway, indicating that emotional bonds and cultural values synergistically foster young people’s positive aging imagination. This study suggests that efforts to strengthen intergenerational interactions and integrate culturally rooted aging education are critical for promoting positive aging attitudes among youth.

Hierarchical Oil–Water–Oil Pickering Double Emulsions Stabilized by Tubular Nanoparticles

Temporal-Spatial Fusion Vision Hardware Enables Streamlined In-Sensor Computing for Dynamic Scenes

Postnatal cytomegalovirus infection and bronchopulmonary dysplasia in very low birth weight infants: Influence of diagnostic criteria and viral load in a propensity score–matched cohort study

Objective To determine the association between postnatal cytomegalovirus (pCMV) infection and bronchopulmonary dysplasia (BPD) under three different criteria as well as the impact of viral load on clinical outcomes in very low birth weight (VLBW) infants. Methods In this retrospective cohort study, the data for VLBW infants with pCMV infection were collected from de-identified medical records and matched 1:1 with non-infected controls using propensity score matching between January 1, 2014, and December 31, 2024, in a tertiary neonatal intensive care unit in China. The primary outcome was the association between pCMV and BPD according to the 2001 National Institute of Child Health and Human Development (NICHD), 2018 NICHD, and 2019 Neonatal Research Network (NRN) criteria. The secondary outcome was healthcare resource utilization stratified by viral load. Results Seventy-four infants with pCMV infection were matched to 74 infants without pCMV infection. After the adjustment for confounders, pCMV infection was not significantly associated with BPD defined by the 2001 NICHD criteria (adjusted odds ratio [aOR], 8.26; 95% confidence interval [CI], 2.14–31.85; p < 0.01). However, it was associated with BPD under both the 2018 NICHD and 2019 NRN criteria (aOR 11.05, 95% CI, 4.00–30.52; p < 0.001 for both). Moreover, pCMV was significantly associated with higher severity grades (moderate to severe 2001 NICHD: aOR, 10.32; Grade II–III per the 2018 NICHD: aOR, 11.47; Grades 2–3 per the 2019 NRN: aOR, 12.81; all p < 0.001). Infants with high viral loads (≥1.34 × 10 5 copies/mL) require significantly more healthcare resources than infants with low viral loads (all p = 0.001). Conclusions The association between pCMV infection and BPD was influenced by the diagnostic criteria. A higher cytomegalovirus load in VLBW infants was associated with more severe respiratory morbidity and greater healthcare utilization.

Spin magnetic proximity effect in graphene superlattices

Retraction: The impact of agricultural water salvation investment on economics development: Evidence from Eastern China

Structural basis for protein-free catalysis by ribonuclease P ribozyme

Abstract Ribonuclease P (RNase P) is an essential metallonuclease found in all three domains of life. However, the structural basis for the ancient RNase P RNA component acting alone as a ribozyme and catalytic metal-ion chemistry remains unknown. We report a series of cryo-EM structures, at resolutions of 2.8–3.5 Å, of the Geobacillus stearothermophilus RNase P aporibozyme (apoE) in various states of the catalytic cycle. The formation of both the tetraloop/tetraloop-receptor interaction and the interdigitated double T-loop motif in the substrate-specificity domain facilitates substrate binding. The apoE uses two metal ions for catalysis, suggesting a catalytic mechanism and evolutionary importance of the RNase P ribozyme to function without its protein component. Together, our data portray the regulatory RNA-RNA interfaces, dynamic structures, and cation traffic that confer function to a trans-acting ribozyme.

Higher order synthetic lethals are keys to minimize cancer treatment effects on non-tumor cells

Metabolic rewiring in cancer cells facilitates the supply of essential precursors for uncontrolled tumor growth. Exploring these cancer-specific metabolic alterations offers potential selective therapeutic strategies. However, targeting a single essential gene in cancer treatment often faces challenges, including resistance, lack of targetable oncogenes, and potential harm to non-tumor cells. Targeting multiple genes has been proposed as a solution to overcome these issues, e.g., a synthetic lethal (SL) set, defined as a minimal combination of non-lethal genetic perturbations that lead to cell death. This study theoretically examined the potential of SL sets to identify selective drug targets across 13 cancer types and the corresponding non-tumor tissues, utilizing context-specific genome-scale metabolic models. To ensure the minimization of therapeutic side effects, this work introduced the concept of strictly-selective drug targets (SSDTs) and the lack of harmful effects of the identified targets in all 13 different non-tumor tissues was meticulously verified. Accordingly, for 13 types of cancers, over 500 SSDTs were identified, predominantly including higher-order SL sets with more than two targets in each set. Interestingly, for specific cancers where single essential or SL genes could not provide viable therapeutic solutions, SSDTs were provided by higher-order SL sets. Thus, for the first time, this study demonstrates that leveraging higher-order SL sets may offer promising strictly selective therapeutic solutions. Furthermore, nine quadruple SSDTs were identified, which commonly target five different cancers without harming any of the 13 non-tumor tissues. Further experimental validation of these findings is essential to identify the most promising treatment candidates for future clinical studies/applications.

Wireless electrostimulation implants enable sphincter neuromuscular improvement toward mixed urinary incontinence

Abstract Mixed urinary incontinence, involving concurrent or diagnostically unclear components of urge- and stress-related dysfunction, remains poorly addressed by current therapeutic strategies. State-of-the-art electrostimulation relies primarily on sacral neuromodulation for urge-predominant symptoms, requiring bulky (~3 cm³) and costly (>$10,000) implants, while stress incontinence is largely managed by mechanical or surgical interventions that do not restore sphincter neuromuscular function. Here, we propose wireless-powered implanted programmable electrostimulation of sphincters (WIPES) that bypasses long nerve loops and provides on-site stimulation at the urethral sphincter. The adhesive-patch-like soft implant integrates wireless power receiving and tunable pulse generation, enabling long-term controlled stimulation with reduced size (<0.3 cm³) and weight (<0.9 g). In rats with experimentally induced urge or stress incontinence (in separate rat models of urge and stress incontinence established under the same experimental conditions), WIPES delivered free-moving stimulation and achieved average alleviation rates of 90.62% (UUI) and 97.92% (SUI) in voiding frequency and volume. WIPES was associated with peri-urethral neuromuscular remodeling and improved bladder–urethral functional outcomes, supporting its potential role in coordinated continence control.

Integrated malaria service delivery and its determinants among pregnant women in Ethiopia: Multi level analysis of 2021/22 National Service Provision Assessment Survey

Background Malaria in pregnancy poses significant health risks to mothers and their, fetuses, and newborns children in Tropical and subtropical countries including Ethiopia. The delivery of integrating essential malaria services into routine antenatal care is crucial for effective prevention and control. However, evidence on the extent and determinants of this integration in Ethiopia remains limited. Objective This study aimed to assess the delivery of integrated malaria services during ANC visit and its determinants among pregnant women in Ethiopia. Methods We conducted a secondary analysis of the Ethiopia Service Provision Assessment Survey 2021/22, a nationally representative cross‑sectional study. The final sample included 4273 pregnant women nested across 662 health facilities. Factors were identified based on the WHO Malaria in Pregnancy framework. Multilevel logistic regression models were applied to identify significant factors influencing integrated service uptake. Result Only 7.9% of pregnant women attended ANC visits where all components of integrated malaria services were delivered concurrently, with substantial regional disparities. At the client level, women with two previous pregnancies (AOR = 1.67, 95% CI: 1.06–2.62), attending three or more ANC visits (AOR = 1.58, 95% CI: 1.04–2.40) and client who received an Insecticide-Treated Net during ANC (AOR = 2.81, 95% CI: 1.29–6.12) were more likely to attend ANC visits in which integrated malaria services were delivered. Furthermore, clients attending facilities with malaria-trained providers were more likely to receive integrated malaria services during ANC than those attending facilities without such training (AOR = 4.24, 95% CI: 1.80–10.00). Rural facility attendance was also positively associated with integrated malaria service delivery compared with urban facility attendance (AOR = 2.73, 95% CI: 1.04–7.19). Conclusion Integrated malaria service delivery during ANC remains unacceptably low in Ethiopia, constrained by regional disparities and multilevel factors. Strengthen continuity of ANC follow up, updating policy on ITN distribution, strengthening providers’ capacity, and addressing geographic disparities to accelerate progress toward WHO maternal health targets.

SLC1A5 prevents aortic aneurysm and dissection by glutaminolytic-epigenetic orchestration of vascular smooth muscle cell homeostasis

Perspectives of women, healthcare providers and health managers on Group Antenatal Care implementation in Geita, Tanzania: A qualitative study

Background Among the root causes of high maternal and neonatal mortality is low utilization of antenatal care (ANC) services and sub-optimal quality of care during pregnancy. Group Antenatal Care (G-ANC) is an innovative model of care where pregnant women with similar gestational age (GA) meet for their antenatal care visits as a group, rather than individually. This approach promotes peer support, shared learning, and a sense of community among pregnant women, and enhance the quality of care. This study aimed to assess the perspectives of healthcare providers (HCPs), women and health managers to determine the experience and acceptability of G-ANC in low resource settings. Methods The project was implemented from February 2023 to June 2024. However, participant recruitment for the qualitative component commenced in June to September 2024. Data was collected through six Focus Group Discussions (FGDs) with pregnant women and postnatal women who had recently attended G-ANC sessions. Key Informant Interviews (KIIs) were conducted with HCPs, facility leaders (in-charge) and district / regional health managers. Respondents were selected through purposive sampling, and discussions were conducted using semi-structured interview guides. Audio recorded interviews were transcribed, and thematic analysis was conducted using NVIVO software. Results Findings revealed positive experience, satisfaction and acceptability of G-among women and HCPs. Women reported increased knowledge on maternal health, emotional support, and enhanced communication with HCPs. Healthcare providers highlighted improved efficiency, better patient engagement, and peer support among clients. Health managers demonstrated contribution of G-ANC in promoting increased ANC attendance and more interactive care. However, challenges such as limited space, need for facilitator training, and resource constraints were identified. Conclusion Group Antenatal Care demonstrated significant benefits for maternal health education, peer support, and healthcare delivery efficiency. These findings add evidence to other existing literature supporting the adoption of this intervention in low resource settings. However, successful implementation requires investments in infrastructure (space for G-ANC meetings), adequate and trained HCPs, service integration and male engagement. Institutionalizing G-ANC as a standard antenatal care could be the best option to address the low coverage of ANC visits, suboptimal quality care, and promotion of institutional deliveries in low resource settings.

Mesoscopic Hydrophobic Microenvironment Engineering on a Single-Atom Catalyst for Steering CO ₂ Photoreduction to CH ₄