The aim of our study is to compare the markers and parameters obtained from complete blood count between patients diagnosed with missed abortion in the first trimester and a healthy pregnant control group. This descriptive, retrospective, case-control study included 166 patients diagnosed with missed abortion according to ultrasound criteria, and an equal number of healthy pregnant controls, who visited the Gynecology and Obstetrics Clinic at a Training and Research Hospital from January 1, 2018, to July 1, 2023. Participants, with 5 to 14 weeks of gestation, were selected using simple random sampling. Data on age, gravida, parity, gestational week, and hemogram results were retrieved from medical records and compared. Statistical significance was set at p < 0.05. No significant differences were observed between the case and control groups in terms of gravida, parity, age, or gestational week (p > 0.05). Likewise, comparisons of hemogram parameters and derived values, did not show statistically significant differences (p > 0.05). However, the multivariate logistic regression analysis revealed that each unit increase in lymphocyte count was linked to a 2.075 times higher risk of missed abortion (p = 0.040). Our study found no significant differences in complete blood count parameters between the missed abortion and healthy pregnant groups. Although lymphocyte count was significant in the multivariate model, this association should be interpreted with caution, as complete blood count values were obtained at the time of diagnosis. Therefore, it does not indicate predictive value, and prospective studies are needed to determine whether lymphocyte count may serve as a pre-diagnostic marker.
Elucidating the evolution and epidemiology of Mycobacterium tuberculosis requires comprehensive characterization of its genomic diversity; however, short-read sequencing fails to resolve part of this variation. Here, we assembled 216 complete genomes from clinical isolates in the Valencia Region, Spain, using long-read sequencing. This dataset, mostly encompassing Lineage 4, provides a refined map of M. tuberculosis genetic diversity across evolutionary scales. Complete genomes uncover a median of 312 (-1 to 792) additional SNPs per pairwise comparison, revealing an estimated evolutionary rate 1.44-fold higher than that inferred from short-read mapping. This diversity is concentrated in discrete hotspots, particularly within the pe/ppe gene family, where gene conversion is a major driver of nucleotide diversity. While most PE/PPE epitopes remain highly conserved, suggesting strong purifying selection, some involved in vaccine candidates are affected by gene conversion, with unknown consequences. At the epidemiological scale, additional resolution is gained from SNPs previously masked and newly resolved indels and structural variation, refining genetic transmission networks. Finally, at the within-host level, the use of patient-specific reference genomes allows us to capture genuine diversity during infection, showing that previous approaches led to false positive calls. Together, these findings delineate the landscape of M. tuberculosis genomic diversity and provide a framework for more accurate inference of pathogen evolution, host-pathogen interactions, and transmission dynamics.
Complete arch intraoral scans for implant-supported prostheses may be affected by cumulative stitching distortion because of limited geometric continuity between scan bodies. Various splinting and auxiliary approaches have been proposed to improve scanning accuracy; however, many require resin fixation, implant-specific components, or additional framework fabrication. This article describes a technique for using a universal, non-calibrated auxiliary geometric device (ScanClamp), inspired by a dental dam clamp design, to augment intraoral scan bodies during complete arch scanning for implant-supported prostheses. The device is fabricated from polyetheretherketone (PEEK) and mechanically retained to individual scan bodies through elastic deformation. Adjustable wing extensions may be oriented to establish continuous surface geometry across the arch. The technique is intended to enhance surface continuity within standard intraoral scanning workflows while remaining modular and implant system-independent.
In the UK, Sudden Unexpected Death in Infancy (SUDI) clusters among priority families (those experiencing multiple and complex problems) where universal infant sleep safety guidance is least effective and alternative multi-agency approaches are required. This project implemented and evaluated multi-agency Eyes on the Baby SUDI prevention in Northumberland, a large rural English county. A Steering Group comprising diverse organisations oversaw the programme. The multi-agency workforce was grouped by job roles into three training strands based on frequency and type of contact with priority families. Online training was accessed individually or in teams. Normalisation Process Theory (NPT) supported engagement and embedding SUDI prevention into practice. Pre- and post-training surveys assessed staff knowledge and confidence with SUDI prevention. Follow-up surveys captured staff feedback and engagement at 2, 4 and 12 months post-training. Staff in 187 roles across 25 services were recruited; 607 of the 1007 staff registered completed training. SUDI-prevention knowledge and confidence increased across all strands; knowledge remained high 2 and 4 months after completion. Commitment to SUDI prevention was sustained over time. SUDI-prevention champions helped embed learning into everyday practice. At 1 year, 95% of the 73 staff who responded to follow-up remained actively engaged in SUDI prevention. Staff with limited contact with priority families were the least likely to sustain engagement. At the project conclusion, Northumberland County Council adopted the programme for their pan-Northumberland training platform. Eyes on the Baby can train and sustain staff engagement in multi-agency SUDI prevention. Key stakeholders with diverse experiences of SUDI prevention oversaw the programme. A Steering Group-led implementation approach encouraged staff to accept SUDI prevention within their roles and was reinforced by team leaders. Early adopters rapidly identified their contribution and engaged enthusiastically as SUDI-prevention champions. One year after training, staff remained engaged, although some roles required additional support. In the UK, Sudden Unexpected Death in Infancy (known as SUDI) is more likely to happen in families needing extra support. We looked at whether staff from different organisations working in a wide range of jobs across Northumberland would engage with the Eyes on the Baby programme to learn how they could help these families keep their babies safe.Managers from different organisations oversaw the programme and divided workers into three training groups based on how often and in what ways they had contact with families needing support. Staff completed online training alone or in teams. We used a method called Normalisation Process Theory (NPT) to help get everyone involved in making SUDI prevention a routine part of their work. Surveys completed before and after the training checked staff knowledge about preventing SUDI and confidence in talking to families. Surveys at 2, 4 and 12 months after the training gathered staff feedback.Staff in 187 roles from 25 services took part. Of 1,007 staff who signed up, 607 finished the training. Their knowledge and confidence about SUDI improved in all areas, and their knowledge stayed high 2 and 4 months later. Their commitment was strong over time. One year later, 95% of staff responding to a follow-up survey were still actively using their training. However, staff who had less contact with high-risk families were less likely to stay engaged. At the end of the project, Northumberland County Council put the training on their county-wide staff training platform.The Eyes on the Baby programme helps train staff and keep them involved in working together to prevent SUDI. One year after training, staff were still engaged, although some job roles needed extra support to stay involved.
Respiratory illness contributes to substantial global morbidity and mortality. In Madagascar, an island nation off the southeastern coast of the African continent, hospital-based public health surveillance for respiratory pathogens screens for common respiratory viruses. However, many cases remain undiagnosed. We conducted metagenomic Next Generation Sequencing (mNGS) to identify the pathogen profile of 102 undiagnosed febrile patients who presented to public hospitals with respiratory symptoms and screened negative on a 14-virus multiplex RT-qPCR. We analyzed the diversity of the respiratory microbiome of each patient from mNGS data and identified viral infections potentially linked to undiagnosed fever. We assembled whole genome consensus sequences of viruses with sufficient read depth and coverage, characterized each phylogenetically, and identified any discrepancies with the primers used in the multiplex RT-qPCR panel. Finally, we compared all whole genome sequences against publicly available global databases in a phylogenetic analysis. We identified evidence of infection by a wide range of known human viruses in approximately two thirds (64.7%) of study participants from nine different families of viruses and generated 30 complete or nearly complete consensus sequences of known respiratory viruses including orthopneumoviruses, metapneumoviruses, rhinoviruses, coronaviruses, parainfluenza virus, and bocaparvovirus. mNGS-attributed evidence of infection was predominantly due to orthopneumovirus (also called respiratory syncytial virus [RSV]; n = 24; n = 8 previously diagnosed) and rhinovirus (n = 18) detections, despite previous negative RT-qPCR results for the majority of these cases. Finally, phylogenetic analysis identified two distinct phylogenetic clusters of RSV subtype A, suggesting local transmission following distinct international introductions for this virus. mNGS provides a sensitive pan-pathogenic tool for virus detection. We demonstrate the diversity of viruses associated with undiagnosed respiratory fevers in Madagascar, emphasize the importance and relevance of the existing respiratory surveillance in the country, and highlight the interconnectedness of regional respiratory infection dynamics with global networks of respiratory pathogen transmission.
Ambulatory blood pressure monitoring (ABPM) is considered a reference standard for diagnosing hypertension and is recommended for out-of-office blood pressure assessment, yet internal medicine residents receive limited training in its interpretation. We conducted a needs assessment to identify gaps in hypertension and ABPM education and developed an asynchronous e-learning module to address these deficiencies. We then evaluated its impact on residents' self-reported confidence and preparedness in outpatient hypertension management. We conducted a single-center quality improvement study among internal medicine residents (PGY1-4) at the University of Toronto between July 2024 and January 2026. A baseline needs assessment evaluated prior exposure to ABPM, confidence in interpretation, and preparedness to diagnose hypertension. An e-learning module was developed, consisting of a structured "Five Steps of ABPM Interpretation" framework and case-based learning. A post-intervention survey assessed self-reported confidence, preparedness, and educational value. Descriptive statistics were used to summarize outcomes. Between-group comparisons of categorical outcomes were performed using chi-square tests. Sixty-two residents completed the baseline survey, and 26 completed the module and post-intervention survey [1]. At baseline, 56.5% (35/62) reported no prior exposure to ABPM interpretation. Only 22.6% (14/62) felt comfortable interpreting ABPM reports, and 32.3% (20/62) felt prepared to diagnose outpatient hypertension. Following the intervention, 84.6% (22/26) of residents reported feeling comfortable or very comfortable interpreting ABPM, and 92.3% (24/26) reported feeling prepared or very prepared to diagnose hypertension. Learner satisfaction was high, with over 90% of participants reporting that the module was educationally valuable, easy to use, and effective. An asynchronous, case-based e-learning module was feasible, well-received, and associated with higher self-reported confidence and preparedness in ABPM interpretation among internal medicine residents. The observational nature and potential for both response and selection bias limits generalizability of the study.
Pain may be linked to neuropsychiatric symptoms in dementia but the nature of these associations is unclear. The aims of this study were to examine the concurrent validity of pain scales and to investigate the relationship between pain and neuropsychiatric symptoms in community-dwelling people with dementia. This study recruited dyads of people with dementia and their caregivers. Questionnaires measuring pain (Numeric Rating Scale, Brief Pain Inventory Short Form, EQ5D3L) and cognition (Mini- Addenbrookes Cognition Examination) were completed by people with dementia. Dyad partners completed the Neuropsychiatric Inventory Questionnaire (NPI-Q). We examined the degree of agreement between different measures of pain and compared the NPI-Q score and items between people with dementia with and without troublesome pain (NRS ≥ 4, NRS < 4), and between those with single and multisite pain. The study recruited 35 individuals with dementia (49% female, mean age 80 with a range of 65-91 years, mean Mini-ACE 13.6/30) and 35 dyad partners. 66% of people with dementia had troublesome pain and compared to those without troublesome pain they were not significantly different in terms of age, sex, frailty, or other demographic variables, but were more likely to take regular paracetamol. Agreement between the NRS and EQ5D3L pain score was good (Cohen's kappa 0.70, p<0.001), as was agreement between the NRS and BPI-SF with a close to 0 mean difference between the scores on a Bland-Altman plot. The total NPI-Q score was not significantly associated with the presence of troublesome pain. Of all NPI-Q symptoms, only disinhibition showed associations with both painseverity and multisite pain (44% vs 0% and 38% vs 0% respectively, both p<0.05). Community-dwelling people living with dementia can self-report pain using a range of pain scales. Certain neuropsychiatric symptoms may be more common in the presence of pain but requires further study with larger cohorts.
Sexual dysfunction associated with psychological reasons is one of the factors impacting unfulfilled marriages. There are limited data on treatment outcomes in this context. The aim of this study was determining the treatment of unconsummated marriage in psychogenic erectile dysfunction in Iranian Couples. A total of 66 cases were selected from individuals referred to the Family Health Clinic (from 2006 to 2019), who had unconsummated marriages and experienced psychogenic erectile dysfunction, meeting the inclusion criteria for the study. Research tools included couples' demographic information, face-to-face interviews, and the International Index of Erectile Function (IIEF). The treatment was based on couple's therapy. In the initial session, a comprehensive assessment of the couples' condition was conducted, and research instruments were completed. Additionally, during this session, the formation of psychogenic erectile dysfunction and the lack of successful foreplay were discussed. In subsequent sessions, desensitization, instruction on foreplay, and intercourse were addressed. Treatment success was defined as the ability to achieve complete vaginal penetration. Data was analyzed using SPSS 16 software. All 66 couples continued the treatment until they achieved successful vaginal penetration. All International Index of Erectile Function (IIEF) domains improved significantly after couple-based behavioral therapy in men with psychogenic erectile dysfunction in unconsummated marriages (all p < .001; large effect sizes for most domains). No significant associations were found between educational level, place of residence, engagement duration, or marriage duration and post-treatment scores (all p > 0.05). Male age correlated negatively with overall ED (r = -.314, P = .001), erectile function (r = -.361, P = .003), intercourse satisfaction (r = -.365, P = .003), and overall satisfaction (r = -.266, P = .031). Similar negative associations were observed for female age with overall ED (r = -.371, P = .002), erectile function (r = -.354, P = .004), intercourse satisfaction (r = -.344, P = .005), and overall satisfaction (r = -.246, P = .047). Psychogenic erectile dysfunction in unconsummated marriage can be addressed through couple-based therapy.
Intra-hospital transfers (IHT) of hospitalized children are unavoidable practices often performed with emergency patients and postoperative patients. Standardizing IHT processes to minimize adverse events might improve children's outcomes. We developed an evidence-based clinical practice IHT guideline for hospitalized children. The aim of this study was to evaluate the implementation process and the effectiveness of the implementation of this guideline on patient outcomes, healthcare professionals' knowledge and behavior, and hospital organizational context. A type III hybrid effectiveness-implementation design was adopted, using a pre-post intervention trial (January-December 2024). Data of patient demographics, transport-related outcomes, and healthcare providers' knowledge and compliance were collected. We used the RE-AIM framework to assess effectiveness across four dimensions: Reach, Effectiveness, Adoption, and Implementation. Totally, 110 healthcare professionals conducted 213 IHTs of eligible children (109 children in the pre-intervention group and 104 in post-intervention group). The Reach outcomes demonstrated that participation among hospitalized children (n = 312) was suboptimal at 33% (104/312). No differences were observed between the pre- and post-intervention group regarding gender, disease distribution, or pediatric early warning scores. The implementation showed favorable outcomes in the dimensions Effectiveness, Adoption, and Implementation. Healthcare professionals engagement was 95%, with 86% (19/22) of the implementation strategies successfully completed. Healthcare professionals' knowledge in the pre-intervention group (n = 109) improved from median 40 (IQR 28;52) to median 76 (IQR 64;84) in the post-intervention group (n = 104; p < 0.001). Clinically, the new guideline reduced adverse events (12 vs 4; p = 0.047), reduced the median minutes of bedside handover time from 5 (IQR 3;7) to 4 (IQR 3;5; p < 0.001), and improved handover information completeness from median score of 5 (IQR 4;6) to 20 (IQR 12;23, p < 0.001). The total transport time increased from 14 to 19 minutes in the post-intervention group (p < 0.05), while no significant changes were observed in handover interruptions or post-transfer vital sign stability (p > 0.05). The RE-AIM-based evaluation confirmed that the implementation strategies effectively enhanced healthcare professionals' knowledge and compliance while reducing adverse events and optimizing handover efficiency. However, the limited patient participation rate and increased transport duration highlight areas requiring further refinement to maximize the guideline's impact. ClinicalTrials.gov, NCT06512805. Registered 27 June 2024.
Africa has a uniquely rich cattle diversity of ~150 breeds comprising the Bos taurus indicus sub-species, Bos taurus taurus, and their crosses. These represent ~23% of the global cattle population. However, high quality, representative assemblies are limited for African cattle and especially for indicine breeds. Here we built high quality de novo assemblies for five important African indigenous cattle breeds using PacBio HiFi sequencing: Lagune (Bos taurus taurus), Gudali, Iringa Red and Singida White (Bos taurus indicus), and Mpwapwa (Bos taurus taurus x Bos taurus indicus). These new assemblies are the most contiguous and complete African cattle assemblies produced so far, with genome sizes of 3.25-3.36 Gb, contiguity N50s ranging from 83.59 Mb to 97.87 Mb and scaffold N50s from 100.30 Mb to 113.37 Mb. BUSCO genome completeness scores were also higher than 99.68%, indicative of highly contiguous assemblies. These improved and highly contiguous genome assemblies are consequently a valuable resource for future African and global livestock genomic studies.
Perspective-taking refers to one's ability to infer one's own and others' mental states. The existing perspective-taking tasks mainly focus on healthy individuals and overlook the potential confounding effect of prompt type. The current study developed a perspective-taking task for social anxiety research by including both ambiguous and unambiguous prompts and a social context. Analysing two community samples with either ambiguous (N = 69) or unambiguous (N = 89) prompts found that both prompts cued self-perspective-taking and other perspective-taking as required. However, while unambiguous prompts cue perspective switching, the ambiguous prompts failed to do so. Thirty-two participants of the two samples completed the tasks with both prompt types and showed no differences in perspective-taking. Findings suggest that the newly developed task measures self-perspective-taking and other perspective-taking as prompted, regardless of prompt type. Furthermore, the unambiguous prompts may be more sensitive and appropriate for measuring perspective switching and offer greater applicability in neural research.
The prevalence of diabetes in Belgium has steadily increased since 2001, reaching 6.9% in 2024, with type 2 diabetes (T2D) accounting for approximately 90% of cases. Diabetes-related healthcare expenditures were estimated at €2 billion in 2022. The European Care4Diabetes Joint Action aimed to transfer and adapt the evidence-based Dutch lifestyle program Reverse Diabetes2 Now to 12 European countries. This study evaluated the transferability and potential effectiveness of the Care4Diabetes lifestyle intervention on metabolic, behavioral, and subjective health outcomes among Belgian adults with T2D in primary care. This quasi-experimental implementation study was conducted in two primary care centers in Wallonia. Forty-three participants initiated the program and 37 completed the 12-month follow-up. The intervention included a 6-month intensive phase with five thematic group sessions and one individual check-up, followed by an additional check-up and a refresher session at Month 12. Primary outcomes were changes in HbA1c and T2D medication use. Secondary outcomes included anthropometric measures, lipid profile, behavioral outcomes, and subjective health indicators. Linear mixed models were used to assess changes over time, accounting for repeated measures. At Month 12, 46% of participants had no change in T2D medication, 43% underwent medication de-intensification, and 11% required intensification. After adjustment for T2D medication changes, HbA1c decreased significantly from baseline to Month 6 by 5.4 mmol/mol (0.49%; p = 0.002), but the reduction was attenuated at Month 12 to 2.8 mmol/mol (0.26%; p = 0.06). Sensitivity analyses restricted to participants without T2D medication changes showed significant decreases in HbA1c at Month 6 and Month 12. Body weight decreased significantly (- 3.6 kg at Month 12, p < 0.001). Improvements were also observed in dietary behaviors and perceived general health, and satisfaction among participants and healthcare providers was high. The Care4Diabetes program demonstrated good transferability and promising effectiveness in primary care in Wallonia. Larger studies across Belgium are needed to further assess clinical effectiveness and potential economic benefits.
Gallbladder cancer (GBC) is highly fatal and, unlike most cancers, is more common in women than in men. Most GBC cases have gallstones, but most people with gallstones do not develop GBC. Thus, a critical question is what drives the risk of GBC in the presence of gallstones. We designed a case-control study to complement the Chile Biliary Longitudinal Study (Chile BiLS) cohort, enriching the number of GBC cases and enhancing our ability to evaluate risk factors for GBC. Starting in July 2022, we began to recruit non-cohort prevalent (diagnosed between January 1, 2016, and July 18, 2022) and incident (diagnosed on or after July 19, 2022) GBC cases, as well as patients with high-grade dysplasia (HGD), in a high-risk area of Chile. Individuals with GBC or HGD are considered cases (HGD +). We are matching gallstone cholecystectomy patients to cases at an approximate 1:1 ratio. We also include unmatched controls (adjudicated) who were initially suspected of having cancer but had benign findings on gallbladder pathology. If a case or control is deceased, we conduct proxy interviews to maximize the potential for detailed epidemiological data collection. Through August 31, 2025, we recruited 196 prevalent and 117 incident HGD + cases. Of these cases, 189 (96%) prevalent and 108 (92%) incident cases were diagnosed with GBC. All prevalent and 98.3% of incident cases have matched controls. Participation rates are 70.8% for HGD + cases and 67.8% for matched controls. The Chile BiLS case-control study is conducted in an area with high risk of GBC and a high proportion of people with Mapuche Amerindian ancestry. This study will provide important insights into the factors associated with GBC among people with gallstones. Here, we provide a thorough description of the design of the study, field procedures, and biological resources, as well as research opportunities, which will enable a more complete picture of the etiology of GBC by combining epidemiological, molecular, digital imaging, and clinical data. This study represents a powerful resource for the identification of new targets for cancer prevention and treatment, which are particularly needed in populations at high risk of GBC.
Bell's palsy (idiopathic peripheral facial nerve paralysis) is uncommon in children and is particularly rare in infants younger than one year of age. Its occurrence following viral infections, including coronavirus disease 2019 (COVID-19), is exceedingly rare. We report a case of Bell's palsy in an infant following COVID-19 infection and provide a review of the relevant pediatric literature. We report the case of a 2-month-old female infant who developed left-sided facial weakness shortly after a COVID-19 infection. She had previously been healthy, except for a COVID-19-positive upper respiratory infection at the age of 4 weeks. Three weeks after her infection resolved, her parents noticed the sudden onset of left facial drooping, which progressed over the following three days. A diagnosis of peripheral facial nerve palsy following COVID-19 infection was proposed. Given the absence of clear treatment guidelines for infants, management options were carefully considered. The patient was ultimately started on oral prednisolone in addition to protective eye care. She demonstrated gradual clinical improvement during treatment, and at follow-up several weeks later, complete recovery of normal facial movement was observed. This case highlights that Bell's palsy, although extremely rare in infancy, may occur following a viral infection such as COVID-19. A prompt and thorough evaluation is essential to exclude alternative causes of facial paralysis. Despite no clear guidelines or recommendations favoring corticosteroid treatment vs conservative management in this age category, a decision of pharmacologic treatment was taken. In this case, corticosteroid treatment was well tolerated, and no adverse events were observed. Further studies are needed to evaluate the correlation between COVID-19 infection and facial palsy in infants, and to further assess the efficacy and safety of oral prednisolone in this age group.
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.
To investigate the use of contrast-enhanced mammography (CEM) for preoperative prediction of lymphovascular invasion (LVI) status in invasive breast cancer. A total of 243 female patients diagnosed with invasive breast cancer (median age: 49 years; range: 27-77 years) who received preoperative CEM examination in our hospital between September 2018 and February 2024 were retrospectively collected and analyzed. The study population were chronologically divided into training and test datasets in an approximate ratio of 7:3. LVI status was determined using postoperative histopathologic examination. CEM features were analyzed on the low energy and the recombined images. To identify independent predictors for LVI status, univariable and multivariable logistic regression analyses were performed on CEM and clinicopathologic features. Logistic regression and six machine learning methods were used to construct prediction models in the training dataset, and their performance were evaluated with ROC curve in the test dataset. In training and test datasets, the rates of LVI-positive were 39% (67 of 172) and 34% (24 of 71), respectively. High Ki67 index, BI-RADS category 5, breast composition category c/d, axillary adenopathy, mild to marked background parenchymal enhancement level, and lesion with complete enhancement or enhancement extending on CEM images were significantly correlated with LVI-positive (all P < 0.05) and were incorporated to construct prediction models. The AUCs of seven prediction models were in the range of 0.713-0.850 in the test datasets, where the logistic regression model yielded an AUC of 0.835 (95%CI: 0.717-0.924), showing similar or higher AUC than the six machine learning models. CEM could be useful for preoperative noninvasive prediction of LVI status in invasive breast cancer. The prediction model integrating contrast-enhanced mammography features and Ki67 index may serve as a complementary tool to assist clinicians in preoperative prediction of lymphovascular invasion status in patients with invasive breast cancer.
Trigeminal neuralgia (TN) is characterized by severe facial pain, transitioning from peripheral vascular compression to central sensitization. However, the core central pathophysiological mechanisms-particularly how the brain structurally and functionally reorganizes to maintain pain or recover after surgical treatment (primarily microvascular decompression or percutaneous interventions)-remain to be fully elucidated. We employed a longitudinal multi-scale design using a graph harmonic model to quantify structure-function (S-F) coupling, a metric reflecting brain network integrity. We analysed multimodal magnetic resonance imaging data from 87 patients with TN and 42 healthy controls (HCs). Post-treatment follow-up data were acquired for 46 patients, of whom 39 had complete longitudinal paired data. We further utilised partial least squares (PLS) regression with rigorous spatial permutation testing (spin-tests) to bridge macroscopic imaging changes with microscopic transcriptomic data from the Allen Human Brain Atlas. Patients exhibited significantly reduced global S-F coupling, particularly in the somatomotor and dorsal attention networks. Notably, this decoupling was negatively correlated with baseline pain severity and disease duration. Following treatment, global S-F coupling returned to levels statistically indistinguishable from healthy baselines ([Formula: see text]). Crucially, the magnitude of postoperative reorganization ([Formula: see text]S-F coupling) significantly correlated with postoperative pain reduction percentages and long-term follow-up NRS scores. This recovery extended beyond focal repair, involving extensive adaptive reorganization in the visual and default mode networks. Molecularly, disease-related decoupling was spatially associated with genes linked to neuronal energy metabolism, cellular ionic homeostasis, and neuroinflammation. Conversely, treatment-induced plasticity strongly correlated with genes modulating chemical synaptic transmission and endogenous opioid signaling. TN pathophysiology is closely linked to ion channel-mediated neuronal metabolism and progressive network decoupling. Effective treatment restores homeostatic brain network coupling primarily by facilitating synaptic plasticity-based adaptive reorganization rather than merely through focal repair. This work offers a new perspective on the neural circuits underlying pain maintenance and provides potential imaging indicators for developing brain network-targeted therapeutic strategies.
This study examined whether habitual exercise timing and sex are associated with lower-limb injury prevalence and frequency in physically active young adults. A total of 454 recreationally active university students (48% males; age = 22.1 ± 2.4 years) completed a validated survey assessing training exposure, experience, and injury history. Habitual physical activity timing was classified into three defined categories: morning (08:00-11:00), midday/afternoon (11:00-17:00), and evening/night (17:00-24:00). Group differences were examined using chi-square and log-linear analyses. Zero-inflated Poisson (ZIP) and multivariable logistic regression models were used to identify factors associated with injury counts and occurrence, adjusting for age, fat mass index (FMI), training load, and experience. Injury prevalence was higher in males than females (p = 0.048). Injury frequency differed across time-of-day categories (p = 0.004), with the highest burden among participants exercising evening/night. In ZIP models, males, exercising evening/night, and higher FMI were associated with higher injury counts, whereas older age was associated with fewer injuries. Logistic regression showed similar associations for injury occurrence (AUC = 0.74, 95% CI: 0.69-0.79). Lower-limb injury risk in young, physically active adults is consistently associated with habitual exercise timing, sex, and adiposity. These findings highlight the importance of considering exercise scheduling patterns and FMI in injury-prevention strategies.
The large 2025 Mpox clade IIb outbreak in Sierra Leone underscores the urgent need for portable, low-cost diagnostics in decentralized settings. While CRISPR-based assays offer high sensitivity and flexibility, their deployment during active outbreaks remains limited. Here we show the rapid development and field evaluation of Mpox SHINE, a CRISPR-Cas13 assay that integrates lyophilized reagents, ambient-temperature lysis, and automated fluorescence detection on the portable DxHub device. The assay achieves analytical sensitivity down to 10 copies/µL. Clinical validation in Sierra Leone, using 56 clinical specimens, confirms complete concordance with qPCR, demonstrating 100% sensitivity and 100% specificity. Crucially, Mpox SHINE also detects the virus directly from unextracted lesion swabs while maintaining 100% sensitivity and specificity. The mean time-to-result is fast, averaging 11.4 minutes for extracted samples and 27.9 minutes for unextracted samples. These findings demonstrate that CRISPR-based diagnostics translate quickly from genomic sequence to clinically validated, deployable tools within a single outbreak window.
Oxidative stress represents a fundamental pathological driver of the secondary injury cascade following traumatic spinal cord injury (SCI). Although the pan-histone deacetylase inhibitor Trichostatin A (TSA) exhibits neuroprotective properties in various contexts, its capacity to modulate the endogenous NRF2/HO-1 antioxidant defense system within the human spinal cord microenvironment remains to be elucidated. In this study, we utilized human induced pluripotent stem cell-derived spinal cord organoids (hSCOs) as a sophisticated, human-relevant platform to investigate these mechanisms. In vitro analyses revealed that TSA preconditioning significantly bolsters the resilience of hSCOs against oxidative damage, manifesting as enhanced cellular viability, diminished accumulation of reactive oxygen species and malondialdehyde, and elevated superoxide dismutase activity. Mechanistic evaluations suggested that this protection is mediated by NRF2 nuclear translocation and subsequent HO-1 upregulation, an effect completely reversed following the pharmacological inhibition of NRF2. Furthermore, the transplantation of TSA-preconditioned hSCOs, encapsulated within a GelMA hydrogel, into a rat contusion model led to marked structural and functional restoration. Compared to untreated organoid grafts, the TSA-primed hSCOs significantly promoted motor function recovery, diminished lesion cavitation, and enhanced neuronal survival, while simultaneously attenuating glial scarring, neuroinflammation, and axonal degeneration. These findings indicate that pharmacological priming with TSA optimizes the therapeutic efficacy of organoid transplantation in a manner involving NRF2/HO-1 activation, establishing a highly promising combinatorial strategy for clinical neural regeneration.