The nature of dark matter, which constitutes 27% of the Universe's matter-energy content, remains one of the most challenging open questions in physics. Over the past two decades, the DAMA/LIBRA experiment has reported an annual modulation in the detection rate of ≈250  kg of NaI(Tl) detectors operated at the Gran Sasso Laboratory, which the collaboration interprets as evidence of the galactic dark matter detection. However, this claim has not been independently confirmed and is refuted under certain dark matter particle and halo model scenarios. Therefore, it is crucial to perform an experiment with the same target material. The ANAIS experiment uses 112.5 kg of NaI(Tl) detectors at the Canfranc underground laboratory and it has been collecting data since August 2017 to model-independently test the DAMA/LIBRA result. This Letter presents the results of the annual modulation analysis corresponding to six years of ANAIS-112 data. Our results, the most sensitive to date with the same target material, NaI(Tl), are incompatible with the DAMA/LIBRA modulation signal at a 4σ confidence level. Such a discrepancy strongly challenges the DAMA/LIBRA dark matter interpretation and highlights the need to address systematic uncertainties affecting the comparison, particularly those related to the response of detectors to nuclear recoils, which may require further characterization of the DAMA crystals.
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The annual modulation signal, claimed to be consistent with dark matter as observed by DAMA/LIBRA in a sodium-iodide based detector, has persisted for over two decades. COSINE-100 and ANAIS-112 were designed to test the claim directly using the same target material. COSINE-100, located at Yangyang Underground Laboratory in South Korea, and ANAIS-112, located at Canfranc Underground Laboratory in Spain, have been taking data since 2016 and 2017, respectively. Each experiment published its respective results independently. In this Letter, we present the results of an annual modulation search as a test of the signal observed by DAMA/LIBRA with the first three respective years of data from COSINE-100 and ANAIS-112. Using a Markov Chain Monte Carlo method, we find best fit values for modulation amplitude of -0.0002±0.0026  cpd/kg/keV in the 1-6 keV and 0.0021±0.0028  cpd/kg/keV in the 2-6 keV energy regions. These results are not compatible with DAMA/LIBRA's assertion for their observation of annual modulation at 3.7σ and 2.6σ, respectively. Performing a simple combination of the newly released 6-year datasets from both experiments finds values consistent with no modulation at 0.0005±0.0019  cpd/kg/keV in the 1-6 keV and 0.0027±0.0021  cpd/kg/keV in the 2-6 keV energy regions with 4.7σ and 3.5σ respective exclusions of the DAMA/LIBRA signal.
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Current global standards for quantification of pathogenic or indicator bacteria in biogas plants primarily rely on culture-based methods using specific media. However, molecular techniques such as quantitative PCR, digital PCR (dPCR), and shotgun metagenomics are increasingly employed in research and may offer more effective pathogen monitoring for industrial applications. This study analyzed samples from five full-scale biogas plants using traditional culture-based methods, dPCR and shotgun metagenomics to monitor indicator bacteria (Escherichia coli, Enterococcus spp. and Clostridium perfringens) and pathogenic species (Salmonella enterica, Listeria monocytogenes, Staphylococcus aureus and Clostridium botulinum). The DNA extraction protocol was optimized to achieve quantification limits of 1.1 copies of gene g-1 wet weight, compatible with regulatory thresholds. Comparing the three methods revealed that shotgun metagenomics detected a greater diversity of pathogenic species in biowaste, including S. aureus and C. botulinum. Acidophilic conditions in hydrolysis tank effectively hygienized the biowaste. In contrast, the four agricultural biogas plants showed limited effect on the three indicator bacteria, as indicated by dPCR. This study demonstrates, for the first time, the added value of combining dPCR and shotgun metagenomics to assess pathogen dynamics in biogas plants. Together, these methods provide a more comprehensive and specific view of microbial contaminants, as illustrated by the detection of Enterococcus cecorum in digestates.
Large vessel occlusion (LVO) recanalization before endovascular thrombectomy (EVT) is known as spontaneous recanalization (SR) or early recanalization (ER) after treatment with intravenous thrombolysis. In this study, we aim to investigate predictors for SR/ER and evaluate its association on functional outcomes. Patients with an anterior circulation LVO who received groin puncture for intended EVT between 2014 and 2019 were included from the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. SR/ER was defined as a presence of a LVO CTA but recanalized on first run of digital subtraction angiography. Multivariable logistic regression was used to evaluate the association between predictor variables and SR/ER. Additionally, we evaluated the association of SR/ER with functional outcomes (modified Rankin Scale [mRS] at 90 days, mortality, and National Institutes of Health Stroke Scale [NIHSS] scores at 24 hours), and performed multivariable ordinal, binary, and linear regression, where appropriate. SR/ER occurred in 251/4448 (5.6%) of patients. Multivariable logistic regression identified male sex (aOR 1.41, 95%CI 1.07-1.84), treatment with intravenous thrombolysis (aOR 3.19, 95%CI 2.03-5), and M2 occlusions (aOR 1.96, 95%CI 1.45-2.66), as independent predictors for higher odds of SR/ER. Higher NIHSS (aOR 0.94, 95%CI 0.92-0.96), use of direct oral anticoagulation (aOR 0.12, 95%CI 0.02-0.91), presence of hyperdense artery sign (aOR 0.62, 95%CI 0.47-0.83), and ICA-T occlusion (aOR 0.18, 95%CI 0.08-0.41), were significant independent predictors for a lower odds of SR/ER. SR/ER resulted in a lower NIHSS at 24 hours (aβ -1.95, 95%CI -3.08- -0.83), a shift towards a lower mRS (acOR 0.67, 95%CI 0.53-0.86), and less mortality (aOR 0.53, 95%CI 0.34-0.82). When compared to patients who achieved successful recanalization through EVT these associations lost significance. SR/ER is associated with male sex, treatment with intravenous thrombolysis, baseline NIHSS, direct oral anticoagulation medication use, hyperdense artery sign, and ICA-T and M2 occlusions. Patients with SR/ER achieved significant better functional outcomes compared to all patients achieving successful recanalization through EVT.
Transitional foods are foods that start as one texture and change to another with minimal chewing required. While transitional foods have been promoted for pharyngeal swallowing dysfunction, their effects on swallowing safety and efficiency are not well understood. The aims of this study were to characterize differences in swallowing efficiency and safety between transitional, pureed, and regular food textures. This was a retrospective study of consecutive outpatient adults who underwent flexible endoscopic evaluation of swallowing (FEES) at a multidisciplinary dysphagia clinic. FEES were used to obtain measures of swallowing safety and efficiency and were included if containing at least one trial of transitional, pureed, and regular food textures. FEES were blindly analyzed by pairs of raters. Multilevel statistical models were used to compare differences in outcome measures across textures. A total of 219 swallowing trials were analyzed. A greater number of swallows was required for pureed compared to transitional foods (p = 0.011). There was a greater amount of epiglottic residue (p < 0.05) and oropharyngeal residue (p < 0.0001) for pureed and regular foods compared to transitional foods (p < 0.05). There was also a greater amount of hypopharyngeal residue for pureed compared to transitional foods (p < 0.0001). Differences in swallowing safety could not be determined. Transitional foods were associated with better swallowing efficiency than pureed and regular food textures in this heterogeneous sampling of dysphagic adults. Future research should prospectively assess the effects of transitional foods on swallowing safety and efficiency in specific dysphagic populations.
Advances in breast cancer (BC) therapy are limited by the absence of well-established biomarkers for DNA-damage targeted treatments. We evaluated the predictive and prognostic value of homologous recombination repair (HRR) deficiency (HRD) by RAD51 nuclear foci and stromal tumour-infiltrating lymphocytes (TILs) in early-stage BC patients with suspected germline susceptibility. Among 291 patients, HRD by RAD51 was found in 78.4% of tumours, and 69.8% had low TILs (<30%). In 178 patients treated with neoadjuvant chemotherapy, pathologic complete response (pCR) was higher in those with HRD vs HRR-proficient (HRP) tumours (52.3% vs 36.4%); RAD51 remained independently associated with pCR (p = 0.03). Overall survival (OS) favoured HRD, with 5-year OS of 89.2% vs 82.8% in HRP (p = 0.009), with stronger evidence in triple-negative TILs-low disease (p = 0.005). These findings support RAD51-based HRD assessment as a predictive and prognostic biomarker that may guide treatment decisions in early-stage BC.
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Military personnel are frequently exposed to traumatic situations that can lead to chronic post-traumatic stress disorder (PTSD). PTSD complicates their reintegration due to the high risk of retraumatization. To support the reintegration of injured servicemen and women, the army has developed the Omega program which includes courses at the Centre des Blessés de l'Armée de Terre (CReBAT). These courses combine physical activity and reintegration workshops to which mindfulness meditation exercises have been integrated, notably through diving. The voluntary involvement of participants in this program relies on good adherence to the various workshops for post-course follow-up, which implies attachment abilities. The aim of this study was to compare the effects of mindfulness diving (MD) with those of a multisport program (MS), mainly carried out in groups, on the clinical improvement of PTSD symptoms in military personnel with PTSD. The primary objective was to measure the impact of these two physical activities on specific PTSD symptoms. The secondary objective was to explore the role of attachment style on clinical impact and professional reintegration at one year after the course. A controlled clinical trial was conducted with 60 military personnel suffering from PTSD, divided into two groups: CReBAT-MD and CReBAT-MS. Participants were included as they enrolled in the Omega program. Symptom severity (PCL5) was assessed at the beginning, at the end and at one to two months after the courses. Reintegration at one year was examined. Attachment style was also assessed at the start of the course to characterize all participants in two categories according to their Internal Operating Model (IOM): positive self-IOM or negative self-IOM. The results showed a slight improvement in PTSD symptoms in both groups (CReBAT-MD and CReBAT-MS) with no significant difference between them. Regarding reintegration at one year, no significant differences were found between the groups. However, positive effects were observed at one-two months after the course for the MS group, notably a reduction in intrusions (P<0.05) and avoidance symptoms (P<0.05). No difference was observed between subjects with positive and negative self-IOM in terms of overall clinical course, except for a trend towards improvement in negative cognitions and effects (P=0.08) for the negative self-IOM group. Nor was there any difference in terms of reintegration. The lack of marked clinical improvement may be explained by the chronic nature of PTSD in military personnel and certain methodological limitations of the study. However, in addition to physical activity, social support and group interactions could play a role in the improvement process. Individuals with a negative IOM of self appeared to benefit more from MS internships, suggesting that group physical activity could enhance self-image and social skills. Further research is needed to better understand the role of physical activity in the management of PTSD, particularly regarding its impact on social cognition and long-term reintegration.
Following a decline during the COVID-19 pandemic, Mycoplasma pneumoniae infections resurged in several countries. We aimed to characterise the clinical presentation of paediatric patients admitted to hospital for M pneumoniae during 2023 and 2024 in France. We conducted a nationwide, multicentre, retrospective, and prospective observational study across 37 French paediatric hospitals (September, 2023-September, 2024). Children younger than 18 years who were hospitalised with laboratory-confirmed M pneumoniae infection (PCR or serology) were included. Demographics (excluding race), clinical features, laboratory and radiological findings, management, and outcomes data were described and analysed. Logistic regression was used to identify factors associated with paediatric intensive care unit (PICU) admission. The trial was registered at ClinicalTrials.gov (NCT06260371) and is complete. We included 969 children and adolescents with M pneumoniae infection (7·3 years [SD 4·5], 426 [44%] of 966 patients were female and 540 [56%] of 966 were male). 936 (97%) of all patients were positive by PCR for M pneumoniae. Pneumonia was diagnosed in 628 (87%) of the 726 patients with respiratory involvement, and cutaneous manifestations were reported in 132 (14%) of 969 patients, including 56 (42%) of 132 who had erythema multiforme. Macrolides were prescribed in 884 (95%) of the 931 patients who were prescribed antibiotics, primarily azithromycin (563 [64%] of 884). Macrolide resistance was detected in one (5%) of the 21 tested samples. In total, 57 (6%) of 969 patients required PICU admission and four (<1%) died. Factors significantly associated with PICU admission included being older than 11 years (adjusted odds ratio 2·0 [95% CI 1·1-3·6]; p=0·023), asthma (2·2 [1·2-4·0]; p=0·0072), other underlying conditions (2·1 [1·2-3·7]; p=0·013), and erythema multiforme (3·7 [1·6-8·8]; 0·0025). The 2023-2024 M pneumoniae epidemic in France resulted in a substantial paediatric hospitalisation burden. Although severe cases were uncommon, children older than 11 years, those with asthma, other comorbidities, and erythema multiforme were at increased risk of PICU admission. Ongoing surveillance and targeted management strategies are warranted for future epidemics. Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV).
Through repeated practice, humans acquire skills and develop a high level of expertise, but this learning process is sometimes long and costly. It may even be impossible to train in situ, although training in virtual environments can offer an alternative. Such supports also have the capacity to automatically collect a large amount of behavioral data, which can be used to personalize training based on learners' requirements. To help identify individual needs, the present study focuses on the three phases characterizing the acquisition of a new skill and distinguishable at behavioral, cognitive, and neuropsychological levels. We present a behavioral approach to phase identification based on the number of times learners consult instructions and the number of incorrect actions they make. Sixty-three participants were asked to repeat an assembly procedure in a virtual environment in two sessions, one week apart. Analyses of activity logs and mental workload (NASA-TLX) throughout the two sessions revealed a progressive acquisition of the procedure, with evidence of retrieval from long-term memory. The identified phases align with the behavioral and cognitive patterns described in the Adaptive Control of Thought-Rational (ACT-R) theory and prior research. Further validation of the proposed phase-identification method could involve physiological measures and a dual-task paradigm to more effectively assess automaticity and phase transitions. Overall, these findings provide a real-time, non-intrusive, and validated method for identifying learning phases, offering prospects for developing adaptive virtual environments tailored to training and rehabilitation.
Objective structured clinical examinations (OSCEs) have recently been integrated as one of the academic assessment tools for French undergraduate medical students. Data are scarce regarding the correlation between OSCE (practical skills) and written examination (pure knowledge) scores, especially in pediatrics. We mainly sought to 1) measure the correlation between pediatric OSCE and written examination scores in undergraduate medical students, and 2) assess student perceptions of the OSCE experience. This was a single-center retrospective analysis of two consecutive classes of fifth-year medical students, university years 2021 (class 1, n=345) and 2022 (class 2, n=492). Both raw and weighted (individual student score/mean class score) formative OSCE and written examination scores were collected, and correlations were tested (Spearman rank tests). Student perceptions regarding OSCE preparation and performance were evaluated through an anonymous online survey (n=289 answers). We evidenced significant but weak correlations between OSCE and written examination scores (weighted scores, Class 1: rho=0.29, p<0.001, Class 2: rho=0.21, p<0.001). Only 45.3% of students who scored above the 66th percentile in written examinations also scored above the 66th percentile in the OSCEs. Students who had prior OSCE exposure during informal training while on placements reported feeling better prepared for this type of assessment. Weak correlation existed between pediatric formative OSCE scores and written examination performance. Exposing students regularly to formative OSCEs made them feel better prepared, with a likely positive impact on anxiety related to this mode of assessment. N/A The online version contains supplementary material available at 10.1186/s12909-026-08999-x.
Despite recent advances, refractory celiac disease (RCD) poses challenging questions. In type 2 RCD (RCD2), the lack of response to the gluten-free diet is attributed to an intestinal intraepithelial lymphoma-carrying driver JAK1 or STAT3 mutations. However, it remains unclear whether these can be safely targeted for therapy. In RCD1, pathogenic insights are still lacking. Duodenal biopsy specimens and peripheral blood mononuclear cells from patients with RCD1, RCD2, active celiac disease (CeD), CeD in remission, and controls were analyzed. Lymphocyte populations were characterized using single-cell transcriptomic, genomic, and TCR repertoire profiling. Functional and exome sequencing analyses were performed on patient-derived RCD2 cell lines exposed to JAK inhibitors. We show that clonal malignant RCD2 lymphocytes exhibit interpatient similarities but substantial intratumoral heterogeneity, and provide in vitro evidence that JAK inhibitors can select drug-resistant tumor cells, arguing against their use as monotherapy. In RCD1, we identified clonal T-cell expansions harboring mutations that enhance the JAK-STAT pathway. The detection of both RCD2 and a CD4+ lymphoproliferation in a patient initially diagnosed with RCD1 further illustrates the diversity of lymphoproliferative outcomes in CeD. These findings suggest that RCD subtypes may share underlying mechanisms driven by clonal evolution and JAK-STAT dysregulation. They also highlight the potential limitations of JAK inhibitor monotherapy and the importance of molecularly informed therapeutic strategies.
Brain death after hanging-induced cardiac arrest is a fatal complication about which few data are available. We aimed at identifying the early predictors of progression to brain death in patients with hanging-induced cardiac arrest. Retrospective study including adults with return of spontaneous circulation from hanging-induced cardiac arrest admitted to 34 ICUs in France and Belgium between 2000 and 2024. Logistic multivariate regression was performed to identify factors associated with progression to brain death. Of the 554 patients with hanging-induced cardiac arrest, brain imaging was performed on admission in 443 (80.0%) patients. Overall, 169/554 (30.5%) and 142/443 (32.1%) patients progressed to brain death within a median time of 3 days, and up to 12 days, after the hanging-induced cardiac arrest. In 443 patients with brain imaging, five factors were independently associated with a higher risk of progression to brain death: female (OR, 1.76; 95% CI, 1.06-2.90; p = 0.03), asystole as first recorded rhythm (OR, 2.03; 95% CI, 1.27-3.29; p = 0.004), low-flow time > 30 min (OR, 1.84; 95% CI, 1.07-3.17; p = 0.03), total Logistic Organ Dysfunction System Score at day 1 (OR, 1.93/per point; 95% CI, 1.14-3.29; p = 0.02), and cerebral oedema and/or ischemic complication on brain CT scan at ICU admission (OR, 1.62; 95% CI, 1.01-2.61, p = 0.04). Conversely, age > 50 years (OR, 0.59; 95%CI, 0.35-0.98, p = 0.04) and status myoclonus ≤ day 2 (OR, 0.24; 95%CI, 0.09-0.54, p = 0.001) were associated with a lower risk of progression to brain death after hanging-induced cardiac arrest. Our findings emphasise the very high rate of brain death after hanging-induced cardiac arrest. In our population, factors associated with brain death after hanging induced cardiac arrest predominantly reflect initial injury severity.
Female genital mutilation (FGM) refers to socio-cultural practices involving the partial or total removal of a woman's external genitalia for non-medical purposes. These procedures are associated with numerous short- and long-term physical and psychological complications. While such complications are relatively well documented in adults, pediatric cases remain insufficiently reported. Forensic physicians are often the first - and sometimes the only - healthcare providers to detect and document these complications, particularly in asylum contexts. We report the case of an 8½-year-old Guinean girl with a history of type IIb FGM, examined by a forensic physician during an asylum application. The medico-legal examination revealed a 3 cm mobile mass at the clitoral site, causing pelvic pain and urinary dysfunction. Her father had allegedly threatened to perform a second excision. Protective measures were implemented in coordination with child welfare authorities before surgical intervention, which resulted in complete resection of the clitoral mass. Histopathology confirmed the diagnosis of an epidermoid cyst. This case underscores the critical role of forensic physicians in identifying rare pediatric complications of FGM and initiating both protective and therapeutic interventions. By enabling surgical treatment and preventing long-term psychological harm, it highlights the integrative function of forensic medicine at the intersection of health, law, and child protection.
Disorders of consciousness pose major therapeutic challenges owing to the complexity of underlying brain dysfunctions. Current pharmacological interventions explored in disorders of consciousness target distinct molecular systems, including dopaminergic modulators (amantadine, levodopa, apomorphine, bromocriptine, selegiline, methylphenidate, and modafinil), GABAergic agents (zolpidem and baclofen), and other neuromodulatory compounds acting on glutamatergic, opioid, or serotonergic receptors (ketamine, remifentanil, and psilocin). These treatments aim to modulate disrupted neural circuits, including the mesocircuit, a thalamocortical-striatal network critically involved in consciousness and motor control. This review explores the pathophysiological mechanisms underlying disorders of consciousness and the pharmacological profile of these agents. It summarizes reported clinical improvements and discusses determinants of therapeutic response, highlighting the role of biomarkers derived from neurophysiological and neuroimaging assessments. Safety profiles associated with these treatments are also critically evaluated to guide clinical decision making. By integrating current knowledge on pharmacological modulation of key neural systems, including dopaminergic and GABAergic pathways, this article provides a comprehensive framework for understanding treatment strategies in disorders of consciousness.
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Powered two-wheeler (PTW) riders are most frequently injured seriously to the thorax. Some thorax protective devices have been developed in order to reduce thorax injuries. Nevertheless, actual tests and standard lack real-world accident representativeness. The aim of the study was to determine realistic trunk impact conditions for accidents likely to result in thorax injury. The study is divided into two phases: a literature review to classify accident scenarios based on rider kinematics, and numerical simulations to analyze the riders impact conditions. Three accident scenarios have been found through a literature review and their main configurations have been numerically investigated via multi-body modeling. The 912 performed simulations were used to explore body contacts with counterparts over time, relative velocities and relative body orientation at impact. The results have highlighted the necessity of a conservative activation time delay for triggering protective devices. They have also led to propose three realistic impact conditions that can be used in future test protocols.