Canine distemper (CD), caused by Morbilivirus canis of Paramyxoviridae family, is a contagious and potentially fatal viral disease affecting a wide range of domestic and wild canid species. This study aimed to determine the seroprevalence of Canine Distemper Virus (CDV) and associated risk factors among free-roaming dogs in the buffer zone of Bardiya National Park (BNP), Nepal. A total of 91 serum samples were collected from free-roaming dogs and tested for CDV-specific IgG antibodies using an iELISA kit. The apparent seroprevalence was found to be 52.75% (95% CI: 42.5-63.0%), while the Rogan-Gladen adjusted true prevalence was 53.28% (95% CI: 42.92-63.64%). Among seropositive samples, 29.17% had high, 31.25% medium, and 39.58% low antibody titers, indicating mixed stages of exposure. Although older dogs (> 72 months) showed higher seropositivity (80%), no statistically significant association was observed between CDV seropositivity and age, sex, body condition score, and location (p > 0.05). The findings suggest that CDV is enzootic in the free-roaming dog population around BNP, representing a potential reservoir for viral spillover to vulnerable wildlife species such as leopards and tigers.
Early recurrence after curative resection remains common in non-small cell lung cancer (NSCLC). We evaluated whether early postoperative trajectories of the prognostic nutritional index (PNI) improve risk stratification. In a single-center prospective cohort of patients undergoing R0 resection for stage I-III NSCLC (2021-2025), 119 were enrolled; 94 who were alive and recurrence-free at 3 months with complete PNI data formed the landmark cohort. PNI was measured preoperatively and during the first 3 postoperative months and calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3). The primary exposure was 3-month PNI recovery, and the primary endpoint was 2-year recurrence-free survival (RFS) from the 3-month landmark, estimated with Cox models adjusted for stage and adjuvant therapy. Among 94 patients, 51 (54.3%) showed recovered PNI and 43 (45.7%) non-recovered PNI. During follow-up, 27 RFS events occurred, with higher event rates in the non-recovered group (41.9% vs. 17.6%; 2-year RFS 59.2% vs. 82.3%). Non-recovered PNI was independently associated with worse RFS (adjusted hazard ratio 2.3) and improved a clinical model C-index from 0.66 to 0.73. Sensitivity analyses using alternative cutoffs, continuous PNI change, complication adjustment, treatment-timing exclusions, and conservative Cox models were directionally consistent. Failure to recover PNI within 3 months may identify patients at higher risk of recurrence after curative NSCLC resection. Multicenter validation is required before clinical implementation.
We evaluated the effectiveness, adherence, and safety of preservative-free (PF) lubricants in adults with dry eye disease (DED) under real-world clinical conditions. The ENRICHED-PF trial (NCT06162442) was a single-arm, prospective interventional study conducted in Cali, Colombia. A total of 120 adults with mild-to-moderate DED initiated PF propylene glycol 0.3% / polyethylene glycol 0.4% drops for six months. Longitudinal analyses were performed using linear mixed-effects models, with multiple imputation applied under a Missing at Random assumption to handle missing data. At baseline, the median Ocular Surface Disease Index (OSDI) score was 31.2 [19.2-47.4]. Longitudinal model-based estimates showed an OSDI estimated marginal mean (EMM) of 33.9 at baseline, 23.1 at 3 months, and 16.8 at 6 months in the mITT population, corresponding to an estimated change of - 17.1 points at month six (p < 0.001), with 65.4% of the modified intention-to-treat (mITT) population and 58% of the per-protocol (PP) population achieving a clinically meaningful response (≥ 10-point improvement). Tear break-up time increased and corneal staining scores decreased (both p < 0.001), while Schirmer I values remained stable. Additionally, NEI VFQ-25 composite scores improved by 8.9±3.1 points (p<0.001). These findings suggest clinically meaningful improvements in symptoms, tear film stability, and ocular surface integrity over time, which were associated with treatment using PF lubricants. However, given the single-arm design, the absence of a comparator group, and loss to follow-up during the study period, the magnitude of these effects should be interpreted with caution and confirmed in controlled comparative studies.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT06162442.
Automation in cardiac magnetic resonance (CMR) scans holds the potential to improve examination efficiency and workflow consistency. Prospective clinical evidence validating automated scan workflows in routine CMR practice remains limited. In this prospective randomized study, consecutive patients referred for non-stress CMR were assigned to either an automated or a manual free-breathing scanning workflow. The fully automated workflow integrated automated plane prescription of multiple steps required for successful image acquisition. The primary endpoint was total examination time; secondary endpoints included plane prescription accuracy, image quality scores, scanner idle time, and technologist workload. Of 255 screened patients, 221 were included (automated, n = 109; manual, n = 112). All examinations were diagnostically adequate. The automated and manual workflows showed a similarly low incidence of plane prescription misalignment, corresponding to 19.3% (21/109) and 17.9% (20/112) misalignment events per examination, respectively, with no significant difference between groups (0.19 vs. 0.18 events per examination, P = 0.780). No significant differences were observed across imaging planes or technologist experience levels, and image quality scores were comparable between workflows (2.74 ± 0.67 vs. 2.69 ± 0.70, P = 0.547). However, the automated scanning workflow significantly reduced total examination time (19.16 ± 2.32 vs. 21.25 ± 2.25min, P < 0.001) and scanner idle time (7.80 ± 1.80 vs. 10.12 ± 2.03min, P < 0.001), with consistent savings across all experience levels. Operator workload was also substantially lower with automated scanning, evidenced by fewer mouse clicks and keystrokes (both P < 0.01). An automated CMR scanning workflow improves examination efficiency and reduces operator workload without compromising image quality or plane prescription accuracy, supporting its integration in routine clinical CMR practice.
Reconstruction of medium-sized palatal defects following maxillectomy represents a major challenge in maxillofacial surgery. The facial artery musculomucosal (FAMM) flap has become a reliable reconstructive option due to its valid vascular supply and mucosal similarity. Numerous technical variants, have expanded its clinical applicability. However, limitations related to flap rotation through dentition or prosthetic structures may compromise outcomes. This note describes a novel surgical technique employing a superiorly based, reverse-flow FAMM flap transposed through a lateral maxillary sinus window. In a patient treated for invasive oral squamous cell carcinoma, the residual class IIa palatal defect, following the Brown classification, was planned to be reconstructed with a superiorly based FAMM flap. A lateral maxillary sinus access was created to allow direct insertion of the flap into the defect, avoiding conventional transoral passage. Donor site closure was achieved using a Bichat fat pad flap. The flap was successfully rotated through a 180° arc and positioned precisely within the defect, achieving tension-free closure and reliable re-establishment of the oro-antral barrier. No complications were observed. The patient was discharged seven days after surgery, with satisfactory primary healing and preservation of dentition and prosthetic structures. Clinical and radiographical follow-ups were performed every 6 months. Trans-sinus application of a reverse-flow FAMM flap represents a novel and versatile approach for medium-sized palatal defect reconstruction, minimizing mechanical trauma, preserving dental and prosthetic integrity, and offering an alternative to free tissue transfer, supporting functional and aesthetic rehabilitation.
The incidence of early onset (age < 50 years at diagnosis) appendiceal adenocarcinoma (EOAA) is rising alarmingly. Reported data on etiology, treatment, and outcomes is scarce. In this study, we report clinical outcomes for patients with EOAA. Patients diagnosed with appendiceal adenocarcinoma between 2013 and 24 were stratified on the basis of age at diagnosis as having either EOAA (< 50 years) or average-age onset appendiceal adenocarcinoma (AOAA; ≥ 50 years). Clinicopathological and genomic data were abstracted from electronic medical records. Baseline clinicopathologic features and survival outcomes were compared between patients with EOAA and AOAA. Of 181 eligible patients, 49 (27.1%) had EOAA. Median age at diagnosis for patients with EOAA was 42.1 years (interquartile range [IQR], 35.7-46). Of the 76 patients (EOAA = 23 [30.3%] + AOAA = 53 (69.7%)] who had locoregional disease at presentation, 44 (57.9%) remained disease-free for at least 2 years. Within these 44 (conditional survival), the EOAA group showed numerically shorter recurrence-free survival (RFS) and higher risk of recurrence (median RFS, EOAA = 49.5 months versus AOAA = 83.3 months; hazard ratio [HR], 4.07; 95% confidence interval [CI], 1.49-11.18; p = 0.06). Long-term recurrences (≥ 5 years) were seen in 9/15 (60%) patients during the 5-year follow-up period. Of 139 evaluable patients (EOAA = 36 [25.9%] + AOAA = 103 [74.1%]) with metastatic/recurrent disease, patients with EOAA received more non-fluorouracil (FU)-based systemic treatments, including experimental agents, in any line of treatment (8/36, 22.2% versus 6/103, 5.8%; p = 0.009). A higher proportion of patients in the EOAA group received bevacizumab in any line of treatment (24/36, 66.7% versus 49/103, 47.6%; p = 0.055) and three or more lines of systemic therapy (10/36, 27.8% versus 14/103, 13.6%; p = 0.07). There was no significant difference in OS between the EOAA and AOAA groups despite more aggressive therapy in EOAA (median OS, EOAA = 35.2 months versus AOAA = 40.6 months; HR, 0.90; 95% CI, 0.57-1.44; p = 0.66). Among patients who remained disease-free after initial surgical resection for locoregional disease for at least 2 years, recurrence was more frequent in patients with EOAA. Aggressive systemic therapy, including trials and non-FU based therapies were more frequent in patients with EOAA but were not associated with improved survival. EOAA may represent a unique entity within this rare disease, which warrants further exploration.
Nuclear spin comagnetometers offer exceptional precision in measurements of spin energy levels and exhibit long-term stability, making them powerful tools for probing spin-dependent physics beyond the standard model as well as for inertial rotation sensing. We describe a new ^{3}He-^{21}Ne Ramsey comagnetometer operating with an in situ ^{87}Rb magnetometer for initialization and sensing of nuclear spins. During free precession of nuclear spins we turn off all lasers and introduce a microwave field to suppress back action from Rb atoms. We demonstrate that scalar and dipolar interactions between nuclear spins can be eliminated via control of the polarized sample geometry. These improvements result in a bias-free measurement with a frequency sensitivity of 0.6 nHz after six hours of integration.
Privacy regulations and limited expert-validation constrain the deployment of large language models (LLMs) for electronic health record structuring. We evaluated locally deployed LLMs to extract 30 prognostic variables from 1,360 head and neck cancer reports (882 patients) using zero-shot prompting. A stratified 50-case subset was reviewed by three radiation oncologists (50 cases, 30 fields, 3 reviewers; 4,500 decisions) to form a majority-vote reference for Llama3.3-70B, which achieved 98.6% F1 with high clinician agreement and processed reports in 53 s/report. Among seven additional models (2.6B-70B) benchmarked against this reference, GPT-OSS-20.9B (F1 89.4%) and MedGemma-27B (F1 88.5%) performed best. Integrating LLM-extracted HPV status, smoking history, and Charlson Comorbidity Score into a multivariate Cox Proportional Hazards model (age, sex, T/N stage) improved disease-free survival (likelihood ratio test p = 0.014; ΔC-index + 0.071) and locoregional failure-free survival (p = 0.026; ΔC-index + 0.108) with 1,000-bootstrap internal validation. This clinician-AI collaborative evaluation shows that on-premises LLMs enable privacy-preserving and efficient tumour board support, longitudinal data curation, and outcome prediction.
Previous epidemiological studies have established associations between fine particulate matter (PM2.5) exposure and maternal thyroid hormone suppression. However, as PM2.5 is a complex chemical mixture, the specific contribution of metallic constituents to PM2.5-induced thyroid disruption remains poorly characterized. This study aimed to evaluate the relationship between maternal thyroid function and exposure to metallic and metalloid components of PM2.5 during pregnancy. In a longitudinal study of 847 pregnant women recruited from three maternal and child healthcare hospitals, we collected fasting blood samples at 10, 17, and 32 weeks of gestation for thyroid hormone assessment. Concurrently, ambient PM2.5 monitoring stations near participating hospitals quantified 11 metallic/metalloid elements. Linear mixed-effects regression models assessed individual element associations with thyroid parameters, while weighted quantile sum (WQS) regression evaluated combined effects of metal mixtures. Significant inverse associations were observed between lead (Pb) exposure and serum thyroid stimulating hormone (TSH) levels. Multiple elements - including aluminum (Al), arsenic (As), cadmium (Cd), lead (Pb), antimony (Sb), selenium (Se) and thallium (Tl) - demonstrated negative correlations with free thyroxine (FT4) and free triiodothyronine (FT3) concentrations. WQS analysis revealed that each inter-decile rise in mixed metal exposure was associated with a 0.52% decrease in TSH (95% CI: -3.84%, 2.91%), a 1.52% reduction in FT₄ (95% CI: -1.95%, -1.09%), and a 1.18% decline in FT₃ (95% CI: -1.60%, -0.77%). Tl, Al, and As emerged as primary contributors to these effects, collectively accounting for 86%- 97% of the weighted mixture impact. These findings demonstrate that metallic components of PM2.5, particularly Tl, Al and As are significantly associated with suppressed maternal thyroid function during pregnancy. This highlights the importance of metal-specific toxicity in PM2.5-related endocrine disruption.
Physicians increasingly deliver health information and medical support through online medical teams (OMTs) in telemedicine platforms, where patients interact with multiple physicians within a single consultation episode. Yet limited research has systematically examined how physician collaboration influences team effectiveness in OMTs. This study investigates the impact of physician collaboration on team effectiveness using a panel dataset of 1,181 OMTs from 2017 to 2023 on a leading Chinese telemedicine platform. We employ a difference-in-differences design and large language models to identify the effects of physician collaboration and uncover the underlying mechanisms. Our results show that physician collaboration reduces team effectiveness. To unpack the underlying mechanisms, we further examine two potential effects: the cognitive-load effect and the free-riding effect. The empirical results reveal that the cognitive-load effect significantly decreases team effectiveness, whereas there is no empirical evidence to support the free-riding effect. Additionally, heterogeneity analyses indicate that the negative effect of collaboration is mitigated when more experienced physicians are involved. These results provide theoretical insights into team performance in telemedicine contexts and advance health communication research. The findings also offer practical guidance for platform designers to strengthen communication management in team-based telemedicine platforms.
Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of metabolism caused by a deficiency of branched-chain ketoacid dehydrogenase, the enzyme involved in the second step of branched-chain amino acid catabolism. Of the three branched-chain amino acids (leucine, valine, and isoleucine), accumulation of leucine is the predominant factor causing acute metabolic decompensation in patients with MSUD. In February 2025, eight expert physicians met to discuss the management of acute metabolic decompensation and propose recommendations after literature review (four guidelines and 20 other articles of interest). A practical clinical algorithm was established. Newborn screening was acknowledged to be a successful method of diagnosing MSUD at birth, facilitating early intervention to prospectively manage MSUD and reduce the frequency and severity of acute metabolic decompensation, although it was noted that infants with severe MSUD often present with acute metabolic decompensation before being diagnosed. The experts also identified several barriers to and gaps in the management of acute metabolic decompensation, and MSUD more generally, proposing potential actions to improve clinical outcomes. Acute metabolic decompensation requires prompt, effective treatment by a multidisciplinary team to ensure that circulating plasma leucine levels are rapidly reduced without causing complications (particularly cerebral edema). Where available, intravenous branched chain amino acid-free solutions (e.g., Maapliv, now approved in Europe) may represent an important treatment option. Adequate resources (treatments, laboratory services, dialysis units) are essential for effective management of acute metabolic decompensation. Liver transplantation is an accepted viable option for the long-term prevention of acute metabolic decompensation in eligible patients. Research is ongoing into new treatment options for MSUD, such as gene therapy. Optimal management of acute metabolic decompensation in patients with MSUD requires prompt, effective treatment to reduce leucine levels without causing complications. A ready-to-use branched chain amino acid-free intravenous solution has been recently approved in Europe and research into new treatment options is ongoing.
This study evaluated the prognostic value of the 12th thoracic vertebra skeletal muscle mass index (T12-SMI) before and after neoadjuvant chemoimmunotherapy (NACI) in patients with esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed 211 patients with ESCC who underwent NACI followed by esophagectomy between 2020 and 2022. According to their SMI at T12, the patients were divided into a muscle attenuation group (MAG) and a normal group (NG) before or after NACI. The perioperative outcomes and survival data were compared between the two groups. The pathological complete response (pCR) rates and major pathological response rates were comparable between the MAG and NG before and after NACI (all P > 0.05). The postoperative complication rates and 90-day mortality rates were also comparable (all P > 0.05). However, compared with the NG, the MAG had significantly worse overall survival and disease-free survival, both before and after NACI (all P < 0.05). Multivariate analyses confirmed that muscle attenuation post-NACI was an independent prognostic factor for overall survival (hazard ratio 2.977; 95% confidence interval 1.733-5.113; P < 0.001) and disease-free survival (hazard ratio 2.355; 95% confidence interval 1.339-4.142; P = 0.003). Post-NACI, the MAG had higher overall recurrence rates (41.7% vs. 21.1%, P = 0.009), particularly for distant metastases (22.2% vs. 9.1%, P = 0.024). Sarcopenia at the T12 level after NACI is an independent predictor of poor survival for patients with ESCC and is associated with increased postoperative recurrence risk, especially for distant metastases.
Leishmaniasis is a neglected tropical disease that urgently requires safer and more effective therapeutic strategies. Rhoifolin (RF), a natural flavonoid with anti-inflammatory and antiparasitic potential, has shown promising biological activities against several infectious diseases. In the present study, the antileishmanial effects of free RF and its niosomal formulation (NRF), alone and in combination with meglumine antimoniate (MA), were investigated against Leishmania major. Niosomes were prepared using Span 40, Tween 40, and cholesterol, resulting in high encapsulation efficiency (90.9%) and a sustained drug-release profile. The antileishmanial activity of RF, NRF, MA, and their combinations against promastigotes was evaluated using both MTT and trypan blue exclusion assays, while anti-amastigote activity was assessed in infected macrophages. NRF exhibited greater efficacy than free RF against both promastigote and amastigote forms of L. major. Combination treatments demonstrated additive interactions (combination index ≈ 1.0) and higher selectivity indices, indicating enhanced efficacy and safety. In addition, treatment with RF, NRF, and their combinations significantly increased LDH release and ROS production in infected macrophages compared with untreated controls. Molecular docking analysis revealed a strong binding affinity of RF toward caspase-3. Furthermore, treatment with RF and NRF significantly modulated apoptosis-related mediators, including increased expression of CASP3, CASP8, and Bax, along with reduced Bcl-2 expression. Immunological analyses also demonstrated macrophage polarization toward the M1 phenotype through upregulation of TNF-α, IFN-γ, IL-12, and iNOS/NO, accompanied by downregulation of IL-10, TGF-β, and ARG1. These immunomodulatory and apoptosis-associated effects were more pronounced in the NRF and NRF + MA groups. Overall, our findings suggest that niosomal RF represents a promising lipid-based delivery system for enhancing the antileishmanial efficacy of RF. The NRF + MA combination may provide a potential therapeutic strategy for improving treatment outcomes and reducing the limitations associated with current therapies for cutaneous leishmaniasis.
B7-H3 targeted therapies are an upcoming promising treatment option for a variety of solid tumors. High levels of B7-H3 expression have only been reported for a few sarcoma subtypes in previous studies, but a systematic analysis in an untreated sarcoma cohort and across many different sarcoma subtypes has not yet been conducted. One hundred thirty-three sarcoma samples of previously untreated patients from different sarcoma entities including soft tissue sarcoma (STS, n = 103) and bone sarcoma (BS, n = 30) were collected from two sarcoma centers in South-West Germany. Samples were centrally immunohistochemically stained and assessed for membranous B7-H3 expression. For further analysis of B7-H3 expression, H-Scores were calculated. Baseline characteristics such as sex, age, histology, grading, staging as well as outcome data like treatments, event-free and overall survival were collected. B7-H3 was found to be broadly expressed (97%) across all tested sarcoma subtypes, with only four samples (3%) without B7-H3 expression. 45% of all samples had low (H-Score 1-100), 33% intermediate (H-Score 101-200) and 19% high (H-Score 201-300) membranous B7-H3 expression. Highest expression was found in pleomorphic liposarcoma (median 202.5), osteosarcoma (median 175) and angiosarcoma (median 167.5), whereas expression was lowest in myxoid and well differentiated liposarcoma (medians 44.5 & 62.5) and chondrosarcoma (median 60). H-Scores were found to significantly correlate positive with histological grading irrespective of histological sarcoma subtype. Pre-treatment B7-H3 H-Scores did predict event-free but not overall survival. B7-H3 is a promising treatment target in sarcomas as it is highly expressed particular in high grade bone and soft tissue sarcomas, such as pleomorphic liposarcomas and osteosarcomas.
Pediatric renal stone surgery aims to achieve complete stone clearance with minimal perioperative morbidity. Mini-percutaneous nephrolithotomy (mini-PCNL) is widely used for larger stones, yet factors influencing postoperative residual fragments and bleeding risk in children are not fully clarified. This study evaluated outcomes after pediatric mini-PCNL and identified predictors of residual fragments and bleeding-related morbidity in a large single-center cohort. This single-center retrospective cohort included 371 renal units in children treated with mini-PCNL (2011-2024) using 14-20 French (Fr) access sheaths. Stone-free rate (SFR) was defined as 0-mm residual fragments on 1-month kidney-ureter-bladder (KUB) radiography and ultrasonography (US). Computed tomography (CT) was not routinely performed and was obtained only when clinically indicated, which may have resulted in underestimation of very small residual fragments. Multivariable logistic regression evaluated predictors of 1-month residual fragments and bleeding-related morbidity. One-month SFR was 79.2% (294/371) and increased to 88.4% (328/371) by 3 months after auxiliary procedures. Staghorn morphology was associated with residual fragments (aOR 5.01, 95% CI 1.86-13.51); operative time was also associated (aOR 1.12 per 10-minute increase, 95% CI 1.04-1.20). Complications occurred in 12.9%, mainly low-grade according to the Clavien-Madadi classification, with no grade IV-V events. Transfusion was required in 2.2% (8/371). Bleeding-related morbidity increased with operative time (aOR 1.16 per 10-minute increase, 95% CI 1.07-1.25). Compared with 14 Fr, 20 Fr demonstrated a nonsignificant trend toward higher odds of bleeding-related morbidity (aOR 3.20, 95% CI 0.93-11.05), whereas 16 Fr showed no statistically significant association (aOR 1.75, 95% CI 0.56-5.47). With a stringent 0-mm stone-free definition, mini-PCNL provided high clearance rates and low major morbidity in this large pediatric cohort. Staghorn stones remained the strongest predictor of residual fragments. Prolonged operative time was consistently associated with increased bleeding-related morbidity, while the use of 20 Fr access demonstrated only a modest, nonsignificant elevation in bleeding risk.
Long-term androgen deprivation therapy (LT-ADT) with radiotherapy is standard-of-care for high-risk localized prostate cancer, with abiraterone added for clinically very high-risk disease. Given the toxicity and cost of abiraterone, a predictive biomarker to refine patient selection is needed. We evaluated a digital pathology multimodal artificial intelligence (MMAI) model, previously validated as a prognostic biomarker, for prediction of abiraterone benefit amongst non-metastatic clinically very high-risk prostate cancer. MMAI scores were generated for patients enrolled in two sequential abiraterone trials (no shared controls) in the STAMPEDE platform protocol (NCT00268476) using digital pathology images, prostate specific antigen (PSA), tumor stage, and age. We applied the previously-established 75th percentile threshold to classify patients as MMAI very high-risk or standard high-risk. The primary endpoint was metastasis-free survival (MFS). Treatment effects and risk estimates were obtained using Cox regression and Kaplan-Meier method, respectively. Prediction was assessed using a treatment-by-biomarker interaction Cox model. In total, 1137 patients randomized to LT-ADT (N=583) or LT-ADT with abiraterone (N=554), were included. The MMAI very high-risk group (N=268) demonstrated significant MFS improvement from adding abiraterone (HR 0.47; 95% CI 0.31-0.70), with 5-year MFS increasing from 62% (95% CI 53-70%) in LT-ADT to 81% (95% CI 74-87%) in LT-ADT with abiraterone. Limited abiraterone benefit was observed in the MMAI standard high-risk group (N=869; HR 0.83; 95% CI 0.63-1.09), with a 5-year MFS of 82% (95% CI 78-85%) versus 84% (95% CI 80-87%, interaction p-value=0.02). This differential effect was consistent in local node-negative and node-positive subgroups. In this post-hoc study of randomized clinical trial data, a locked digital pathology MMAI test displayed a strong prognostic association and predicted abiraterone efficacy in very high-risk, non-metastatic prostate cancer. This biomarker could be implemented clinically to maximize benefit from treatment intensification whilst avoiding unnecessary toxicity.
The newly discovered family of nonmagnetic kagome metals AV_{3}Sb_{5} (A=K, Rb, or Cs) provides a unique platform for exploring the interplay between charge-density wave (CDW) order, superconductivity, nontrivial topology, and spontaneous time-reversal symmetry breaking. Although characterizing the CDW phase is essential for understanding and modeling these exotic phenomena, its nature remains unresolved. In this Letter, we employ first-principles free-energy calculations, accounting for both ionic kinetic energy and anharmonic effects, to resolve the atomistic phase diagram of CsV_{3}Sb_{5} and its charge ordering structure. Our results uncover that the CDW ground state is formed by reconstructed vanadium kagome layers in a triangular-hexagonal pattern, featuring energetically degenerate different stacking orders. This accounts for the various out-of-plane modulations observed experimentally and supports the coexistence of multiple domains. The discovered symmetry-broken ground state is consistent with the absence of any electronic anisotropy in transport experiments. By combining anharmonic phonons with the calculation of electron-phonon matrix elements, we predict a superconducting critical temperature for the CDW phase in agreement with experiments showing that superconductivity is phonon mediated. These findings not only resolve a long-standing structural puzzle, but also clarify the impact of the CDW in superconductivity, highlighting its fundamental importance in shaping the low-temperature quantum phase diagram of kagome metals.
Although icodextrin was initially developed for rapid transporters (type 1 UFF), emerging evidence suggests its effects might be independent of peritoneal membrane transport characteristics. This study aimed to evaluate the suitability of 7.5% icodextrin for all PD patients with UFF. We enrolled 19 patients with UFF and 24 non-UFF PD controls. All participants underwent standard, modified, Mini-, and Double-Mini peritoneal equilibrium tests (PET). Key parameters assessed included sodium sieving (∆DNa60, ∆D/PNa60), osmotic conductance to glucose, small-pore ultrafiltration (UFSP), free water transport (FWT), and net ultrafiltration. Correlation analyses were conducted between icodextrin-induced UF and these metrics. Descriptive analysis revealed variations in icodextrin UF, ∆D/PNa60, and FWT were identified across the four UFF types. Numerically, icodextrin UF was highest in type 1 and type 2 UFF, while FWT appeared lower in type 2. Net icodextrin UF correlated positively with ∆D/PNa60, ∆DNa60, and UFSP. Our findings indicate that 7.5% icodextrin may be suitable for PD patients with type 1 and 2 UFF, but appears perhaps less effective in those with type 3 and 4 UFF.Moreover, icodextrin ultrafiltration may be predictable through UFSP measurement, offering a potential clinical tool for patient management.
Linguistic and psychometric validation of the French version of the COSI questionnaire (Client-Oriented Scale of Improvement) assessing perceived improvement with hearing aids. A single-center prospective study was conducted in 100 patients with hearing aids (NCT06108609). They filled out the COSI and IOI-HA questionnaires (International Outcome Inventory for Hearing Aids). COSI is a free-choice questionnaire in which the respondent chooses 5 out of 16 items corresponding to the main auditory problems. Psychometric analysis followed the COSMIN guidelines. Test-retest reliability was assessed on intra-class correlation coefficient (ICC) in 36 patients. Correlations between COSI subscores and between COSI and global IOI-HA score were assessed. Median COSI subscores were 3.8 [IQR: 3.2-4.2] for "degree of change" and 3.6 [IQR: 3.0-4.2] for "final ability". Internal consistency was good, with Cronbach alpha 0.76 and 0.79 respectively. ICC was 0.68 (95% CI: 0.45-0.82) for "degree of change" and 0.81 (95% CI: 0.66-0.90) for "final ability". There was a strong correlation between the 2 subscores: r=0.73 (95% CI: 0.62-0.81); P<0.001 There were moderate positive correlations between COSI and IOI-HA scores: r=0.59 and r=0.63; P<0.001. The French version of the COSI questionnaire showed satisfactory psychometric properties. Its reliability, internal consistency and clinical relevance are sufficient for inclusion in everyday practice for personalized evaluation of hearing aids.
In this study, raw finger millet (FM) and solid-state fermented finger millet (FFM) were incorporated into composite noodles (FMN and FFMN respectively) by replacing wheat flour at 0%, 5%, 10%, and 15% substitution levels. The cooking quality, textural properties, tensile properties, sensory attributes and in vitro digestibility of noodles were evaluated. Results indicated that FM and FFM addition shortened the optimal cooking time of noodles, significantly enhanced free phenolic content (from 15.70 mg/g to 23.04 mg/g for FMN, and to 24.83 mg/g for FFMN), and reduced the extent of starch digestion (the estimated maximum starch hydrolysis extent decreased from 86.60% to 73.15% for FMN and 68.52% for FFMN). However, the hardness of FMN increased while that of FFMN decreased. Noticeably, FFMN exhibited superior performance to those with FMN, and FFMN with 10% substitution exhibited best sensory characteristics. This study offered a new strategy for the application of FFM in noodles.