Mentally reactivating contextual details from the past often supports episodic memory retrieval. However, these benefits may depend on whether reinstated details align with the actual goal of retrieval, such as "when" an event occurred versus other contextual features. In this eye-tracking study, we tested whether auditory cues during sequence encoding are reflected in gaze behavior, and whether evidence of gaze-related context reinstatement relates to better or worse temporal order memory. Participants viewed sequences of centrally presented objects while listening to tones played in their left or right ear. These lateralized sounds served to group subsets of items into left- or right-sided events, establishing a non-visual spatial structure during encoding. At test, participants were shown pairs of objects from the same auditory event side-by-side and had to choose which object appeared later in the sequence. Three gaze measures were computed: 1) audio-spatial context bias during sequence encoding, indexed by greater dwell bias toward the tone side during pre-item fixation; 2) context reinstatement bias at retrieval, indexed by greater dwell bias toward the item congruent with the original context side; and 3) memory strength, indexed by greater dwell bias toward the correct object choice at retrieval. We found that greater gaze bias toward the context-congruent side predicted poorer temporal order memory. Further, this impairing effect of reinstatement was amplified when audio-spatial context bias was weak and memory signals were stronger. These findings suggest that reactivation of retrieval-irrelevant event details, especially when weakly encoded, creates interference that disrupts episodic memory.
Intrapelvic entrapment of the sciatic and sacral nerve roots can cause chronic pelvic pain, sciatica, and symptoms such as dysmenorrhea, dyspareunia, dyschezia, dysuria, vulvodynia, coccygodynia, and pudendal neuralgia. Conventional spine-focused approaches often overlook this cause. This study assessed whether laparoscopic nerve decompression improves pain and related outcomes. Between November 2022 and April 2024, 25 women (median age: 36 years) with ≥ 2 years of refractory pelvic neuropathic pain underwent laparoscopic decompression of the sciatic and sacral plexus. Diagnosis was confirmed via neuropelveological exam and 3-Tesla MRI. Patient-reported outcomes-Visual Analogue Scale (VAS) for nine pain domains, SF-36, PHQ-9, and OAB-V8-were collected preoperatively and at 1, 6, and 12 months postoperatively. Operative details and complications were recorded. All surgeries were completed laparoscopically with no conversions or motor deficits. Median operative time was 143.5 min. VAS scores decreased by 70-90% at one month (p ≤ 0.001) and remained improved at 6 and 12 months. SF-36 subscales improved significantly by month 1 and peaked at month 6. PHQ-9 dropped from 18.2 to 6.8 at 12 months (p < 0.001). OAB-V8 scores also showed significant improvement (p < 0.05). Laparoscopic decompression of intrapelvic sciatic and sacral nerves appears safe and effective, providing substantial and sustained improvements in pain, quality of life, mood, and bladder symptoms. Further randomized trials are needed to validate these findings.
Malignant hyperthermia (MH) is a pharmacogenetic, hypermetabolic and potentially lethal reaction to potent volatile anaesthetics and the muscle relaxant succinylcholine. To improve the understanding of MH, the aim of this retrospective study was to describe the Swedish cohort with respect to clinical manifestations, demographics and genetic findings. The Swedish MH Registry covers a total of 2852 individuals belonging to 544 different families investigated for MH since 1980. For this study, the index case in each family was included for further description. In total, MH was confirmed in 1555 individuals. Among the 288 index cases with a history of an MH reaction and confirmed MH, 58% were male and 57% were < 18 years of age. MH was confirmed in 41% of index cases where masseter muscle spasm was the only clinical sign of MH. The overall case fatality following an MH reaction in Sweden was 5.2%, but no fatal MH reaction has been reported since 2001. Out of 163 genetically investigated MH families, 61 had a diagnostic variant and 23 had a variant of unknown significance. We found that MH reactions predominantly occur in young individuals and that case fatality has declined over recent decades, with no deaths reported in the past 20 years. Less than 40% of the genetically investigated MH families, corresponding to around 20% of all Swedish MH families, currently have an identified genetic diagnostic variant. This analysis of the national Swedish Malignant Hyperthermia patient registry presents case factors and outcomes from cases among recognised families from the last 45 years. Presenting symptoms and then case confirmation details are presented, along with results from cases and families where genetic variants has been assessed.
Randomized trials evaluating multiarterial grafting (MAG) vs single arterial grafting (SAG) during coronary artery bypass grafting (CABG) have not demonstrated a long-term survival benefit, whereas conventional retrospective studies have consistently reported improved survival with MAG. Whether this discordance reflects true treatment effect heterogeneity or bias from unmeasured confounding in observational analysis remains unclear. Our objective was to evaluate whether the apparent survival advantage associated with MAG in conventional observational analyses persists after accounting for unmeasured confounding using a quasi-experimental instrumental variable (IV) approach and to assess the implications of these findings for long-term survival in an older Medicare population. We retrospectively analyzed Medicare beneficiaries who underwent CABG from 2001 to 2019. Surgeon MAG rate during the 12 months preceding each operation was leveraged as an IV. Flexible parametric survival models with time-dependent effects were developed with MAG vs SAG as the exposure variable. The non-IV model adjusted for patient demographics, pre-existing comorbidities, hospital and surgeon characteristics, and procedural details. The IV model incorporated these same covariates plus the IV (surgeon MAG rate) using a 2-stage residual inclusion approach. Regression standardization was used to derive standardized survival probabilities and their differences. Among 1,291,314 beneficiaries, 1,145,760 (88.7%) underwent SAG and 145,554 (12.3%) underwent MAG. In the non-IV model, MAG recipients had improved risk-adjusted median survival as compared with SAG recipients: 10.74 years (95% CI: 10.70-10.79 years) vs 10.33 years (95% CI: 10.31-10.35 years), a difference of 0.41 years. Across 4,164 surgeons, the MAG rate during the 12 months preceding the index CABG was 7.7% ± 9.5% in SAG recipients and 32.9% ± 25.8% in MAG recipients. In the IV model, MAG recipients had similar risk-adjusted median survival compared with SAG recipients: 10.38 years (95% CI: 10.29-10.48 years) vs 10.38 years (95% CI: 10.35-10.40 years), a difference of 0.01 years. MAG was associated with a modest improvement in long-term survival in a conventional risk-adjusted analysis. However, this association was not robust to a quasi-experimental analysis in which surgeon MAG rate was incorporated as an IV to address unmeasured confounding. The contrast between these models suggests that traditional observational studies may overestimate the survival benefit of MAG because of unmeasured or difficult-to-measure patient characteristics that influence a surgeon's decision to offer MAG.
Robot-assisted surgery has rapidly expanded worldwide. The hinotori™ Surgical System (hinotori), the first domestically developed robotic platform in Japan, has recently been introduced in colorectal surgery. This study aimed to evaluate the clinical outcomes of colorectal procedures performed using the hinotori. A single-center retrospective observational study was conducted on consecutive patients who underwent robot-assisted colorectal surgery with the hinotori at Kyoto University Hospital between August 2023 and November 2025. Patient demographics, operative details, and short-term outcomes were analyzed separately for colon and rectal cancer. A total of 94 patients were included: 53 with colon cancer and 41 with rectal cancer. In the colon cancer group, the median operative time was 255 minutes, and one patient (1.9%) developed a Clavien-Dindo grade II complication; no grade ≥III events occurred. In the rectal cancer group, the median operative time was 327 minutes, and one patient (2.4%) experienced a grade II complication; no grade ≥III complications occurred. No conversions to open surgery and no reoperations within 30 days were observed. The median postoperative hospital stay was 10 days for colon cancer and 12 days for rectal cancer. Robot-assisted colorectal surgery using the hinotori was safe and feasible. This largest case series to date provides data supporting its feasibility and safety.
Poly(ADP-ribose) polymerase (PARP) inhibition has emerged as a prominent approach in cancer treatment, leading to the development of several poly(ADP-ribose) polymerase inhibitors (PARPi), which have demonstrated substantial progress in clinical trials and efficacy in the management of ovarian cancer (OC), breast cancer (BC), and solid tumors (STs). These PARPi are approved for several cancers, including BC and OC. Among PARPi, Talazoparib (Talzenna®) is a potent therapy for patients with locally advanced or metastatic BC (mBC) with germline BRCA mutations (gBRCAm) and HER2-negative status, demonstrating the highest potency (IC50 = 0.57 nM), which is 4-10 times lower than that of other PARP inhibitors; olaparib (2.0 nM), rucaparib (1.9 nM), and veliparib (4.7 nM), indicating superior efficacy. This review describes the role of BRCA1/2 in BC and OC, highlighting key discovery milestones and providing an overview of available PARP inhibitors (PARPi) at various stages of development. Additionally, it details the discovery and development of talazoparib, one of the key PARPis, its current clinical status, and therapeutic implications. The latest advancements in talazoparib research, including all related clinical trials (Phase 1-3) for the treatment of BC, OC, and other solid tumors (STs), are also summarized. A comprehensive analysis of all clinical trials involving talazoparib, whether as monotherapy or in combination with other drugs, elucidates its potential to improve clinical outcomes, address drug resistance, and explore synergistic combinations with other PARPi or novel agents, thereby providing insights into the clinical utility of talazoparib.
Here, we present a protocol for the functional rescue of small ubiquitin-like modifier (SUMO)ylation-defective proteins using a SUMO fusion-based gain-of-function approach. Using Panx involved in the Piwi-piRNA-mediated genome defense in Drosophila, we describe the restoration of transcriptional silencing by stable fusion of a non-cleavable SUMO variant. We then detail procedures for the quantitative evaluation of transcriptional repression. This approach enables causal analysis of SUMO-dependent protein function beyond conventional loss-of-function strategies. For complete details of this protocol, please refer to Wu et al.1.
Population aging is causing the rise in physical and mental illnesses, leading to the higher disability among the elderly. Despite advancements in healthcare, neglect of mental healthcare negatively impacts quality of life. Changes in the mental health status of the elderly people over time remains unexplored. To assess changes in the mental health status of elderly individuals in rural Puducherry, India, focusing on depressive symptoms, cognitive impairment, and factors associated with poor mental health. Conducted in Thondamanatham, Puducherry, India, from March 2023 to March 2024, this panel study included individuals aged 60 and above. Elderly participants from a previous survey on mental health status in 2013 in the same village were traced and followed-up. Three hundred twenty participants (72 from 2013 survey) were interviewed by using a Semi-structured questionnaire including the scales Geriatric depression scale-short form (GDS-15), Hindi Mini-Mental Status Examination (HMSE), Instrumental Activities of Daily Living (IADL), and the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) in addition to the socio-demographic and self-reported morbidity details. Descriptive statistics and logistic regression were employed to analyses associations between mental health indicators and demographic variables. Participants' average age was 69.8 years, with a majority falling within the 60-69 age group. Common health issues included vision impairment (53.1%), hypertension (41.9%), and diabetes mellitus (35.9%). The prevalence of cognitive impairment (54.4%) was notably higher than that of depressive symptoms (25.3%) and showed significant associations with employment status and hearing impairment. Depressive symptoms declined by 6.9%, while CI increased by 8.3% among 2013 participants. The study revealed decreasing depressive symptoms and increasing cognitive impairment among the elderly, along with positive behavioral changes regarding substance use.
To develop an accurate optic disc (OD) and optic cup (OC) segmentation model for early glaucoma detection and differentiation from high myopia through precise cup-to-disc ratio (CDR) calculation. Timely intervention and differential diagnosis between high myopia and glaucoma are crucial for disease progression and treatment effectiveness. Retrospective cross-sectional study of 3 independent ophthalmic data sets. 2814 fundus images from 3 public data sets:ORIGA (650 images); REFUGE (1200 images); G1020 (964 images). Proposed Multiscale Attention Unet (MAUnet) integrates: (1) Incorporating multiscale convolutional (3 × 3 and 5 × 5 kernels) for hierarchical feature extraction. (2) Efficient Channel Attention modules integrate the Efficient Channel Attention Network into the Unet architecture to enhance region-of-interest localization. (3) Hybrid loss function combining Dice loss (macro-structures) and cross-entropy loss (microdetails, λ = 0.5) to solve class imbalance and boundary ambiguity. Dice Similarity Coefficient (DSC) for OD/OC; Intersection over Union; Absolute CDR error; Boundary F1-score. Multiscale Attention Unet demonstrated superior segmentation performance across all benchmark data sets. On the ORIGA data set, it achieved DSCs of 0.958 for OD and 0.912 for OC, with an absolute CDR error of 0.038. For the REFUGE data set, the model attained DSC values of 0.972 (OD) and 0.931 (OC), alongside a CDR error of 0.026. Evaluation on the G1020 data set yielded DSCs of 0.963 (OD) and 0.906 (OC), with a CDR error of 0.041. Crucially, MAUnet significantly outperformed comparator models in OC segmentation, evidenced by a mean Boundary F1-score of 0.887 versus the comparator range of 0.812 to 0.852 (P < 0.001), highlighting its exceptional precision for detection and further diagnosis. The proposed MAUnet model shows superior performance in OD and OC segmentation, proving to be a clinically reliable tool for early glaucoma detection and monitoring. Its multiscale attention mechanism and balanced loss function enable accurate segmentation, particularly for challenging edge and detail detection, improving glaucoma screening and early diagnosis across diverse populations. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
In the computer vision community, the preference for pre-training visual models has largely shifted toward sRGB images due to their ease of acquisition and compact storage. However, camera RAW images preserve abundant physical details across diverse real-world scenarios. Despite this, most existing visual perception methods that utilize RAW data directly integrate image signal processing (ISP) stages with subsequent network modules, often overlooking potential synergies at the model level. Building on recent advances in adapter-based methodologies in both NLP and computer vision, we propose RAW-Adapter, a novel framework that incorporates learnable ISP modules as input-level adapters to adjust RAW inputs. At the same time, it employs model-level adapters to seamlessly bridge ISP processing with high-level downstream architectures. Moreover, RAW-Adapter serves as a general framework applicable to various computer vision frameworks. Furthermore, we introduce RAW-Bench, which incorporates 17 types of RAW-based common corruptions, including lightness degradations, weather effects, blurriness, camera imaging degradations, and variations in camera color response. Using this benchmark, we systematically compare the performance of RAW-Adapter with state-of-the-art (SOTA) ISP methods and other RAW-based high-level vision algorithms. Additionally, we propose a RAW-based data augmentation strategy to further enhance RAW-Adapter's performance and improve its out-of-domain (OOD) generalization ability. Extensive experiments substantiate the effectiveness and efficiency of RAW-Adapter, highlighting its robust performance across diverse scenarios.
Antigen escape and PD-L1/PD-1 axis-mediated immunosuppression in the tumor microenvironment (TME) are the predominant drivers of treatment failure in adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). CD19-targeted CAR-T monotherapy has limited ability to overcome these two core resistance mechanisms, and achieving long-term durable remission remains a critical unmet clinical need in adults with high-risk, chemorefractory B-ALL. This is a single-center, retrospective case report of an adult patient with early-relapsed, chemorefractory B-ALL. Two independent CAR-T products were manufactured from the patient's autologous peripheral blood mononuclear cells (PBMCs): (1) CD19 CAR-T cells containing an anti-CD19 single-chain variable fragment (scFv), a CD28 transmembrane domain, a 4-1BB co-stimulatory domain, and a CD3ζ signaling domain; (2) PD-L1-armored CD22 CAR-T cells containing an anti-CD22 scFv, a CD8 transmembrane domain, a 4-1BB co-stimulatory domain, a CD3ζ signaling domain, and a membrane-tethered anti-PD-L1 scFv for spatially restricted immune checkpoint modulation. The two CAR-T products were co-infused at doses of 5.0×105 cells/kg (CD19 CAR-T) and 3.1×105 cells/kg (PD-L1-armored CD22 CAR-T), respectively. We evaluated the feasibility, anti-leukemic efficacy, and long-term safety profile of this regimen as a bridging strategy to allogeneic hematopoietic stem cell transplantation (allo-HSCT). This treatment was administered under an institutional compassionate use program approved by the Ethics Committee of the Second Hospital of Hebei Medical University (approval number: 2017-R207), with written informed consent obtained from the patient prior to all treatment procedures. Comprehensive diagnostic workup for B-ALL was performed using 8-color multiparameter flow cytometry (MFC), conventional G-banding cytogenetic analysis, and multiplex leukemia fusion gene screening. Serial lumbar punctures with triple intrathecal chemotherapy (dexamethasone 5 mg + methotrexate 10 mg + cytarabine 30 mg) were performed throughout the treatment course; no abnormalities were detected in cerebrospinal fluid (CSF) routine, biochemistry, or flow cytometry assays, and no evidence of central nervous system (CNS) leukemia involvement was observed at any time point. This study is a retrospective observational analysis of a single clinical case, not a prospective interventional clinical trial, and thus was exempt from clinical trial registration requirements in accordance with institutional and national regulatory guidelines for retrospective observational studies. The patient achieved minimal residual disease (MRD)-negative complete remission (CR) on day 14 post-infusion, as confirmed by 8-color MFC (detection sensitivity: 0.01%) and next-generation sequencing (NGS) of immunoglobulin heavy chain (IGH) gene rearrangements (limit of detection [LOD]: 10-6). Peak in vivo expansion of CAR-T cells was observed on day 10 post-infusion, with CD19 CAR-T cells accounting for 43.25% and CD22 CAR-T cells accounting for 14.58% of circulating CD3+ T lymphocytes. Only grade 1 cytokine release syndrome (CRS), per the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria, occurred and resolved completely with supportive care; no immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. Following consolidative allo-HSCT, rapid hematopoietic reconstitution was achieved, with neutrophil engraftment on day +12 and platelet engraftment on day +14, consistent with the median engraftment timeline for haploidentical HSCT at our institution. Complete donor chimerism (99.86%) was confirmed by short tandem repeat (STR) analysis on day +30 post-transplantation. Notably, the patient maintained MRD-negative sustained remission for 7 consecutive years, with no occurrence of acute or chronic graft-versus-host disease (GVHD) or late treatment-related adverse events. Complete immune reconstitution was achieved by 24 months post-transplantation, with sustained functional immune recovery and a Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) total score of 158/172 at the 7-year follow-up. This case report details the clinical course of an adult patient with early-relapsed, chemorefractory B-ALL who achieved 7-year MRD-negative sustained remission after treatment with PD-L1-armored CD19/CD22 dual-targeted CAR-T cell co-infusion followed by consolidative allo-HSCT. Our preliminary clinical observation demonstrates that this integrated regimen may mitigate antigen escape and immunosuppressive TME-mediated drug resistance, and effectively function as a bridging strategy to allo-HSCT in high-risk patient populations. The 7-year event-free survival (EFS) and sustained disease control observed in this case provide valuable clinical insights for the structural optimization of armored CAR-T constructs and the design of future prospective clinical trials for R/R B-ALL.
Lymphatic filariasis (LF) remains a significant public health challenge in many tropical regions where the disease is endemic. In Malaysia, LF is found in small pockets across the country. Asymptomatic carriers play a critical role in transmission but are often undetected. This report details an investigation of an asymptomatic filariasis reported by local health authorities involving an 83-year-old female patient residing in the Bako area, Sarawak. Despite being immobile due to a stroke, routine screening identified an infection with Brugia malayi through microscopy and a rapid diagnostic test. Interestingly, the patient exhibited no acute or chronic symptoms typically associated with filariasis. Contact tracing among her family members revealed that her son was also infected. Both patients received treatment with diethylcarbamazine (DEC) at a dosage of 6 mg/kg, along with albendazole 400 mg and ivermectin 12 mg. Preventive measures included health education, entomological studies, and the implementation of a 'Test & Treat Filariasis' program in the village. By documenting both the index case and a secondary asymptomatic case within the same household, the study provides a strong example of how routine screening and contact tracing can identify hidden sources of infection. This adds significant value to LF elimination strategies and emphasizes the importance of community-level surveillance programs. Coordinated efforts by health authorities, including contact tracing, environmental assessments, and targeted treatment, are essential for controlling the spread of LF and safeguarding public health.
Accurate preoperative grading of pediatric brain tumors is crucial for formulating individualized treatment plans. Traditional methods rely on subjective experience, while existing deep learning models have limitations in capturing long-distance dependencies and local details. This study aims to develop and validate an innovative 3D hybrid deep learning model (3D C-Vit) for pediatric brain tumor grading and analyze its performance and interpretability. This retrospective study included 340 cases of pediatric brain tumors (143 low-grade cases and 197 high-grade cases). Tumor regions were independently annotated by two senior radiologists with consistency achieved. The data were divided into training, validation, and test sets in a ratio of 70:15:15. The model input included five MRI sequences: CE-T1WI, T1WI, T2WI, FLAIR, and ADC. The proposed 3D C-Vit model integrates the Channel Attention-Enhanced Feature Fusion (CAEFF) module, Multi-Scale Feature Extraction (MSFE) module, and Multi-Head Self-Attention (MHSA) mechanism. Model performance was evaluated using AUC, accuracy (ACC), precision, recall, and F1-score. Chi-square test and LASSO regression were used for feature selection and interpretability analysis. The 3D C-Vit model performed optimally on the test set: AUC was 91.36%, ACC was 86.53%, and F1-score was 89.29. Ablation experiments confirmed that CAEFF, MSFE, and MHSA modules increased ACC by 6.92%, 11.67%, and 1.64%, respectively, and AUC by 6.79%, 11.14%, and 1.66%, respectively. Among the radiomics models, LASSO regression screened out 59 key features. The 3D C-Vit model was significantly superior to the clinical model (ACC 69.23%, AUC 79.09%) and the best radiomics models (SVM, ACC 77.55%, AUC 86.14%) in all assessment metrics. The 3D C-Vit model proposed in this study can effectively and automatically grade pediatric brain tumor, and its performance significantly surpasses traditional clinical methods and existing radiomics models. The model combines the local feature extraction capability of CNN with the global modeling advantage of Transformer and effectively improves the grading accuracy through the innovative CAEFF and MSFE modules. Its high accuracy and interpretability provide clinicians with a reliable preoperative tumor grading tool, which is helpful for quickly formulating precise individualized treatment plans.
Ambient artificial intelligence (AI) scribes for chart documentation have seen rapid adoption in clinical practice, but their educational impact on medical students has not been described. The purpose of this study is to determine the impact of an AI scribe on pre-clerkship medical student note writing. In this prospective non-randomized pre/post design study, all first-year medical students (n=104) at a single U.S. medical school submitted "human-only" notes based on a summative observed structured clinical examination (OSCE) station in May 2025. An AI scribe generated independent AI notes post-OSCE from recorded audio. A sub-group of students (n=47) consented to complete a second "hybrid" note by revisiting their human-only note and incorporating AI notes as perceived necessary, followed by a brief survey about the AI notes. Trained, blinded fourth-year medical student raters were randomly assigned to score all notes on 10 elements using QNOTE acceptability criteria (0=Unacceptable, 50=Partially, 100=Fully). A post-hoc, exploratory element-level review was then conducted. Across all elements, median evaluation scores of human-only notes were high (range 81.3 - 100) and were similar between students who participated in "hybrid" notes and those who did not. In paired analyses between "human-only" and "hybrid" notes, the only notable element-level change was a decline in Chief Complaint scores (P=.05). Symptom duration was omitted in the Chief Complaint section in 8 of 47 (17%) AI notes. No score differences were observed in QNOTE elements requiring documentation of pertinent findings and prioritized lists. Participants agreed that the AI note "was more concise than my note" (37/47, 79%) and would be "helpful as a first draft" (31/47, 66%); 26 out of 47 (55%) agreed that the AI note "left out important details", and 10 out of 47 (21%) agreed that the AI note "may reduce my ability to learn how to write a good note." Interaction with AI notes among pre-clerkship medical students had little impact on quality of "hybrid" notes. Chief Complaint scores likely declined due to conciseness in AI notes that often omitted symptom duration. Our findings suggest that among students who predominantly write close to fully acceptable "human-only" notes, there was no detriment to clinical reasoning, and students were discerning in balancing AI's conciseness and its omissions. The lack of impact on note quality may have been due to the workflow employed in this study, in which students were required to generate independent judgments before exposure to AI-generated content. Future work must explore longitudinal use of such tools using standard workflows seen in clinical settings, where AI notes serve as true first drafts. Especially for lower-performing students, AI scribes could enhance students' own note writing, though educational safeguards are necessary given the potential for harm due to overreliance on automated systems. The study was granted approval by the Yale School of Medicine Committee to Review Student Participation in Research on January 14, 2025, and an exemption from full review due to the minimal-risk educational nature of the project by the Yale Human Research Protection Program on January 23, 2025 (IRB Protocol ID 2000039478).
Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium responsible for severe infections such as pneumonia, septicemia, and keratitis. It poses a significant treatment challenge due to its extensive antibiotic resistance and its capacity to form biofilms, which provide bacterial communities with a protective barrier against antibiotics. An increasing number of studies have identified phage therapy as a potential therapeutic solution amidst the current crisis of antibiotic resistance in medicine. Here, we isolated three novel phages in the campus environment and selected one, PW01, for detailed analysis. Host range was determined against clinical isolates, and biological features were evaluated through growth kinetics and biofilm inhibition assays. Whole genome sequencing and annotation were conducted to confirm its lytic nature. In vivo efficacy was assessed using a murine wound infection model. PW01 displayed a relatively broad host spectrum and effectively suppressed bacterial growth in vitro. It disrupted established biofilms and showed genomic features consistent with a strictly lytic lifestyle. In mice, treatment with PW01 combined with antibiotics resulted in greater bacterial reduction compared with either treatment alone. These findings demonstrate that PW01 possesses both in vitro and in vivo activity against P. aeruginosa and support the potential of phage-antibiotic combination therapy as an effective strategy against multidrug-resistant (MDR) infections.
This pilot study evaluated the efficacy of a novel electronic cognitive training program aimed at alleviating anxiety in vocational college students. The intervention uniquely combined bilateral eye movements, drawing on principles of EMDR, with inhibitory control training. Fifty-four vocational college students with high anxiety symptoms were randomly assigned to the experimental group (n = 18) or the waiting control group (n = 33). The experimental group received a 1-month CogniMove program training, while the control group received no intervention for the time being. Results indicated that participants in the experimental group exhibited significantly greater reductions in anxiety compared to controls. Longitudinal analyses further revealed that improvements in self-control partially mediated the intervention's anxiolytic effects, highlighting the role of self-regulatory mechanisms. These findings suggest that combining response inhibition training with bilateral eye movements constitutes a promising and accessible approach for reducing anxiety in educational contexts.
This study documents the first confirmed case of JSRV-associated nasal adenocarcinoma in a goat through a comprehensive analysis combining histopathological, immunohistochemical, and molecular techniques.An autopsy was conducted on a 12-month-old goat exhibiting progressive nasal obstruction. Tissue samples from the nasal mass were examined histologically using H&E staining. Immunohistochemical (IHC) analysis was performed to detect JSRV capsid protein expression and to assess cellular proliferation markers (Ki-67 and PCNA). Molecular screening via PCR was carried out using primers specific for JSRV, ENTV-1, ENTV-2. The JSRV-positive PCR amplicon was sequenced and subjected to phylogenetic analysis.PCR analysis confirmed the presence of JSRV proviral DNA (385 bp) in the tumor tissue, while results for ENTV-1 and ENTV-2 were negative. Histopathological examination identified a mixed glandular adenocarcinoma arising from the surface and glandular epithelium, with evidence of turbinate bone invasion. IHC revealed multifocal positivity for JSRV capsid antigen and indicated a high proliferation index (30-35%). Phylogenetic analysis classified the detected viral strain within the exogenous JSRV group. The infected goat originated from a herd with no documented contact with sheep.This case provides the first conclusive evidence of JSRV-induced nasal adenocarcinoma in a goat, indicating a potential expansion of the virus's host and tissue tropism. These findings highlight the necessity for further investigation into the viral envelope-receptor interactions and promoter elements that govern JSRV tropism.
A full set of ICRP mesh-type reference computational phantoms (MRCPs), including adult, paediatric, and pregnant-female phantoms, is under development to produce dose coefficients for the next General Recommendations. The MRCPs are high-fidelity human models for radiation protection dosimetry, including all the source and target regions for effective dose calculations. The phantoms include micron-thick stem cell layers in the respiratory and alimentary tract organs, urinary bladder, and skin. The phantoms also include very detailed eye models and skeletal models. The MRCPs are developed in the fourth-generation phantom geometry, i.e. tetrahedron mesh geometry. This geometry, classified as an unstructured volume mesh, provides several key advantages. Firstly, it allows the phantoms to be directly incorporated into various Monte Carlo codes, such as Geant4, MCNP6, PHITS, and EGSnrc, without the need for voxelisation. This preserves the original high fidelity of the mesh phantoms during dose calculations, ensuring the most accurate results. The tetrahedron mesh geometry is volume representation, not surface or boundary representation, and provides the capability of suborgan/structure density variation modelling using the tetrahedra. A notable aspect of the mesh technology is its flexibility, allowing the phantoms to be easily adjusted for different body shapes and postures as required. In this article, the deformability of the MRCPs will be highlighted by reporting that the MRCPs were deformed into a library of 212 phantoms for adults and 637 phantoms for adolescents and children to represent different body sizes and shapes. It will also be reported that the phantoms were deformed into several different postures.
One of the most common malignancies occurring in women worldwide is breast cancer, which highlights the high necessity of new and more efficient therapeutic interventions. Over the last several years, benzimidazole-based compounds have received much scientific attention because of their wide range of biological activities. The current study offers a detailed discussion of the more recent developments in benzimidazole derivatives for the management of breast cancer with a particular focus on their structure-activity relationships (SAR), molecular pathobiology, and therapeutic consequences. Recent studies between 2019 and 2025 have shown that benzimidazole derivatives are able to effectively react with a number of key molecular targets, including peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1), epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (Bcl-2), vascular endothelial growth factor receptor (VEGFR-2), topoisomerases, tubulin, and histone deacetylases. In such interactions, the compounds trigger apoptosis, cell-cycle arrest, autophagy, and the generation of oxidative stress in malignant cells-and usually exhibit minimal toxicity to normal tissues. The present work summarizes recent information about benzimidazole pharmacophores -, including their pharmacological targets, SAR, and mechanisms of action, and defines future directions for the development of selective, potent, and clinically viable benzimidazole-based compounds for the treatment of breast cancer.
The spread of aquatic invasive species and pathogens over the last few decades has disrupted sportfishing, imposed economic costs on local industries, and threatened freshwater ecosystems. A significant but unquantified pathway for the spread of aquatic invasive species and pathogens in the United States is the long-distance transport of live baitfish. Despite the large scale of American baitfish production, policymakers lack high-quality, quantitative data on the movement of these fish across state lines, hindering rigorous risk assessment and regulatory efforts. This study addresses this knowledge gap by systematically collecting and synthesizing data on the interstate trade of live freshwater baitfish, obtained using freedom-of-information requests lodged with state governments across the United States. Our dataset captured the cross-border transport of 39.3 million live baitfish between 2022-24 in addition to 746 transport events where fish quantity was not recorded. Using this data, we detail trade flows disaggregated by species and explore the importance of key source states like Arkansas, South Dakota, and Minnesota. We highlight the variability in state government record-keeping, with data gaps existing in some states. By identifying high-traffic trade routes and quantifying species data, this study provides actionable insights for state agencies to strengthen biosecurity and environmental policy.