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Abstract Background Important differences in excess mortality between European countries during the COVID-19 pandemic have been reported. Understanding the drivers of these differences is essential to pandemic preparedness. Methods We examined patterns in age- and sex-standardized cumulative excess mortality in 13 Western European countries during the first 30 months of the COVID-19 pandemic and the correlation of country-level characteristics of interest with excess mortality. Results In a timeline analysis, we identified notable differences in seeding events, particularly in early 2020 and when the Alpha variant emerged, likely contributing to notable differences in excess mortality between countries (lowest in Denmark during that period). These differences were more limited from July 2021 onwards. Lower excess mortality was associated with implementing stringent non-pharmaceutical interventions (NPIs) when hospital admissions were still low in 2020 (correlation coefficient rho = 0.65, p = 0.03) and rapid rollout of vaccines in the elderly in early 2021 (rho = − 0.76, p = 0.002). Countries which implemented NPIs while hospital admissions were low tended to experience lower gross domestic product (GDP) losses in 2020 (rho = − 0.55, p = 0.08). Structural factors, such as high trust in the national government (rho = − 0.77, p = 0.002) and low ratio of population at risk of poverty (rho = 0.55, p = 0.05), were also associated with lower excess mortality. Conclusions These results suggest the benefit of early implementation of NPIs and swift rollout of vaccines to the most vulnerable. Further analyses are required at a more granular level to better understand how these factors impacted excess mortality and help guide pandemic preparedness plans.

Mpox, caused by monkeypox virus (MPXV), remains a neglected tropical zoonotic disease of forested Central and West Africa (1). Mpox epidemiology is poorly understood, and the MPXV animal reservoir remains [...]

Abstract Purpose The aim of the study was to identify settings associated with SARS-CoV-2 transmission throughout the COVID-19 pandemic in France. Methods Cases with recent SARS-CoV-2 infection were matched with controls (4:1 ratio) on age, sex, region, population size, and calendar week. Odds ratios for SARS-CoV-2 infection were estimated for nine periods in models adjusting for socio-demographic characteristics, health status, COVID-19 vaccine, and past infection. Results Between October 27, 2020 and October 2, 2022, 175,688 cases were matched with 43,922 controls. An increased risk of infection was documented throughout the study for open-space offices compared to offices without open space (OR range across the nine periods: 1.12 to 1.57) and long-distance trains (1.25 to 1.88), and during most of the study for convenience stores (OR range in the periods with increased risk: 1.15 to 1.44), take-away delivery (1.07 to 1.28), car-pooling with relatives (1.09 to 1.68), taxis (1.08 to 1.89), airplanes (1.20 to 1.78), concerts (1.31 to 2.09) and night-clubs (1.45 to 2.95). No increase in transmission was associated with short-distance shared transport, car-pooling booked over platforms, markets, supermarkets and malls, hairdressers, museums, movie theatres, outdoor sports, and swimming pools. The increased risk of infection in bars and restaurants was no longer present in restaurants after reopening in June 2021. It persisted in bars only among those aged under 40 years. Conclusion Closed settings in which people are less likely to wear masks were most affected by SARS-CoV-2 transmission and should be the focus of air quality improvement. ClinicalTrials.gov (03/09/2022) NCT04607941.

In this multicenter study conducted in France, we challenged the hypothesis of the transmission of pathogens other than Borrelia spp. in 22 patients developing erythema migrans following a tick bite. Using a combination of high-throughput microfluidic PCRs and agnostic metagenomics on skin biopsies and blood samples, no microorganisms other than Borrelia spp. was found.

Abstract Previous studies that intercompared global Level‐4 (L4) sea surface temperature (SST) analyses were centered on the assessment of the accuracy and bias of SST by comparing them with independent near‐surface Argo profile temperature data. This type of assessment is centered on the absolute value of SST rather than on SST spatial properties (gradients), which is more relevant to the study of oceanographic features (e.g., fronts, eddies, etc.) and ocean dynamics. Here, we use, for the first time, the spectrum of singularity exponents to assess the structural and dynamical quality of different L4 gap‐filled products based on the multifractal theory of turbulence. Singularity exponents represent the geometrical projection of the turbulence cascade, and its singular spectrum can be related to the probability density function of the singularity exponents normalized by the scale. Our results reveal that the different schemes used to produce the L4 SST products generate different singularity spectra, which are then used to identify a potential loss of dynamical information or structural coherence. This new diagnostic constitutes a valuable tool to assess the structural quality of SST products and can support data satellite SST producers efforts to improve the interpolation schemes used to generate gap‐filled SST products.

Kévin Jean,1– 3 Ahmed Tawheed,4 Liem Binh Luong Nguyen,5 Tarek Heikal,6 Usama Eldaly,6 Neveen Gaber Elhadidy,7 Ahmed Elghaieb,8 Ahmed Aboudonia,8 Laura Tondeur,5 Amélie Dublineau,5 Arnaud Fontanet,2,5 Mohamed El-Kassas4,9 1Laboratoire MESuRS, Conservatoire national des arts et métiers, Paris, France; 2Unité PACRI, Institut Pasteur & Conservatoire national des arts et métiers, Paris, France; 3IBENS, École Normale Supérieure, CNRS, INSERM, Université Paris Science & Lettres, Paris, France; 4Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt; 5Emerging Diseases Epidemiology Unit, Institut Pasteur, Université Paris-Cité, Paris, France; 6Medical Oncology Department, Damietta Oncology Center, Damietta, Egypt; 7Pharmaceutical Services Department, Damietta Oncology Center, Damietta, Egypt; 8Radiology Department, Damietta Oncology Center, Damietta, Egypt; 9Clinical Research Centre, Air Force Specialized Hospital, Cairo, EgyptCorrespondence: Kévin Jean, Laboratoire MESuRS, Conservatoire national des arts et métiers, 292 Rue Saint Martin, Paris, 75003, France, Email kevin.jean@lecnam.netContext: The difference in prognosis between patients diagnosed with viral versus non-viral hepatocellular carcinoma (HCC) in Egypt remains unclear.Methods: We used data from patients diagnosed with HCC between 2007 and 2019 from a large monocentric retrospective cohort at the Damietta Oncology referral center (northern Egypt). Presentation and treatment were compared between viral versus non-viral etiology HCC patients. Survival was compared relying on univariate and multivariate Cox regressions.Results: Data from 4714 HCC patients were analyzed. Among them, 204 (4.3%) presented with a non-viral etiology. Patients with non-viral versus viral etiology had a similar presentation overall, especially regarding the BCLC stage at HCC diagnosis. After controlling for various individual characteristics, patients with non-viral versus viral etiology had poorer survival (adjusted Hazard Ratio: 1.244; 95% Confidence Interval: 1.069– 1.447).Conclusion: Despite similar features, patients with non-viral- related HCC had poorer survival compared to patients with viral-related HCC.Keywords: hepatocellular carcinoma, liver cancer, viral etiology, non-viral etiology, survival, epidemiology

Abstract Background Besides International Prognostic Index (IPI) score, baseline prognostic factors of post-transplant lymphoproliferative disorders (PTLD) are poorly identified due to the rarity of the disease. New indexes derived from healthy organ uptake in baseline 18F-FDG PET/CT have been studied in immunocompetent lymphoma patients. The aim of this study is to evaluate the performances of the cerebellum-to-liver uptake ratio (denoted as CLIP) as a prognostic factor for PFS and OS. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. The previously published threshold of 3.24 was used for CLIP in these analyses. Results A total of 97 patients was included with a majority of monomorphic diffuse large B-cell lymphoma subtype (78.3%). Both IPI score (≥ 3) and CLIP (

Across 133 confirmed mpox zoonotic index cases reported during 1970–2021 in Africa, cases occurred year-round near the equator, where climate is consistent. However, in tropical regions of the northern hemisphere under a dry/wet season cycle, cases occurred seasonally. Our findings further support the seasonality of mpox zoonotic transmission risk.

Abstract Background Chronic hepatitis C virus (HCV) infection negatively impacts health-related quality of life (HRQL). We aimed to assess patient-reported outcomes (PROs) to evaluate the impact of treating chronic HCV with directly acting antivirals (DAAs) on HRQL. Methods PROs were assessed prospectively using the PROQOL-HCV questionnaire before (week 0), at the end (week 12), and after DAA treatment at week 24. HRQL was measured in six different dimensions: physical health, emotional health, future uncertainty, intimate relationships, social health, and cognitive functions. Results A total of 500 HCV patients receiving DAAs were enrolled; of them, 399 were included in the analysis (median age 57 years, 59% females). HRQL increased significantly between baseline, end of treatment, and week 24 for all dimensions (P

Abstract Text messaging can promote healthy behaviors, like adherence to medication, yet its effectiveness remains modest, in part because message content is rarely personalized. Reinforcement learning has been used in consumer technology to personalize content but with limited application in healthcare. We tested a reinforcement learning program that identifies individual responsiveness (“adherence”) to text message content and personalizes messaging accordingly. We randomized 60 individuals with diabetes and glycated hemoglobin A1c [HbA1c] ≥ 7.5% to reinforcement learning intervention or control (no messages). Both arms received electronic pill bottles to measure adherence. The intervention improved absolute adjusted adherence by 13.6% (95%CI: 1.7%–27.1%) versus control and was more effective in patients with HbA1c 7.5-

Abstract Background French Polynesia (FP) comprises 75 inhabited islands scattered across five archipelagos. Between July and October 2021, the SARS-CoV-2 Delta variant triggered a much stronger second epidemic wave in FP than the original Wuhan strain, which was dominant from August 2020 to March 2021. Although previous seroprevalence surveys made it possible to determine the proportion of the population infected by SARS-CoV-2 on the two most populated islands (Tahiti and Moorea) after the first (20.6% in Tahiti and 9.4% in Moorea) and second (57.7% in Tahiti) epidemic waves, no data are available for more remote islands. We used blood samples and personal data collected before, during, and after the second wave from inhabitants of several islands within the five archipelagos to assess the prevalence of SARS-CoV-2 infections and identify associated factors. Methods Blood samples and personal data were collected between April and December 2021 as part of the MATAEA study, a cross-sectional survey conducted on a random sample of the adult population representative of the five FP archipelagos and stratified by age and gender. IgG antibodies targeting the SARS-CoV-2 nucleocapsid (N) protein were detected using a recombinant antigen-based microsphere immunoassay. Factors associated with anti-SARS-CoV-2-N seropositivity were identified using logistic regression models. Results Of 1,120 participants, 503 (44.9%) tested positive for anti-SARS-CoV-2-N antibodies, corresponding to a weighted prevalence of 56.8% for the FP population aged 18–69 years. The seroprevalence increased from 21.9% to 62.1% before and during/after the Delta wave. Of these infections, only 28.4% had been diagnosed by health professionals. The odds of being seropositive were lower in males, participants recruited before the Delta wave, those who had never been married, those with a diagnosed respiratory allergy, smokers, and those vaccinated against COVID-19. Conclusions Our results confirm the high impact of the Delta wave in FP. By the end of 2021, 56.8% of the FP population aged 18–69 years had been infected by SARS-CoV-2; the majority of these infections went undetected. Individuals with respiratory allergies were found to be less susceptible to SARS-CoV-2 infection.

Abstract Background We aimed to study the source of infection for recently SARS-CoV-2-infected individuals from October 2020 to August 2022 in France. Methods Participants from the nationwide ComCor case–control study who reported recent SARS-CoV-2 infection were asked to document the source and circumstances of their infection through an online questionnaire. Multivariable logistic regression was used to identify the factors associated with not identifying any source of infection. Results Among 584,846 adults with a recent SARS-CoV-2 infection in France, 46.9% identified the source of infection and an additional 22.6% suspected an event during which they might have become infected. Known and suspected sources of infection were household members (30.8%), extended family (15.6%), work colleagues (15.0%), friends (11.0%), and possibly multiple/other sources (27.6%). When the source of infection was known, was not a household member, and involved a unique contact (n = 69,788), characteristics associated with transmission events were indoors settings (91.6%), prolonged (> 15 min) encounters (50.5%), symptomatic source case (64.9%), and neither the source of infection nor the participant wearing a mask (82.2%). Male gender, older age, lower education, living alone, using public transportation, attending places of public recreation (bars, restaurants, nightclubs), public gatherings, and cultural events, and practicing indoor sports were all independently associated with not knowing the source of infection. Conclusion Two-thirds of infections were attributed to interactions with close relatives, friends, or work colleagues. Extra-household indoor encounters without masks were commonly reported and represented avoidable circumstances of infection. Trial registration ClinicalTrials.gov registration number: NCT04607941.

The nasal mucosa is a crucial filtering organ to prevent attachment and invasion of pathogens. To assess nasal health in relation to lung health, transverse cross sections of the nasal turbinates of 121 pigs suffering from respiratory disease and sent for diagnostic necropsy were scored visually and by an artificial intelligence (AI) medical diagnostic application (AI DIAGNOS), resulting in a high correlation of both scores (p < 0.001). Nasal samples of the diseased pigs were examined only for Bordetella (B.) bronchiseptica (PCR and bacteriological culture) and Pasteurella (P.) multocida (bacteriological culture). All pigs showed various degrees of inflammatory lung tissue alterations, and 35.5% of the pigs had atrophy of the nasal turbinates with no relation to detection rates of B. bronchiseptica (54.5%) and P. multocida (29.0%) in the nose. All P. multocida strains from nose samples were negative for the toxA gene so non-progressive atrophic rhinitis was diagnosed. Pigs positive for B. bronchiseptica in the nose were more often positive for B. bronchiseptica in the lung (p < 0.001) and for other bacterial species in the lower respiratory tract (p = 0.005). The new diagnostic application for scoring cross sections of nasal turbinates is a valuable tool for a fast and reproducible diagnostic.

Context. One of the long-term goals of exoplanet science is the atmospheric characterization of dozens of small exoplanets in order to understand their diversity and search for habitable worlds and potential biosignatures. Achieving this goal requires a space mission of sufficient scale that can spatially separate the signals from exoplanets and their host stars and thus directly scrutinize the exoplanets and their atmospheres.Aims. We seek to quantify the exoplanet detection performance of a space-based mid-infrared (MIR) nulling interferometer that measures the thermal emission of exoplanets. We study the impact of various parameters and compare the performance with that of large single-aperture mission concepts that detect exoplanets in reflected light.Methods. We have developed an instrument simulator that considers all major astrophysical noise sources and coupled it with Monte Carlo simulations of a synthetic exoplanet population around main-sequence stars within 20 pc of the Sun. This allows us to quantify the number (and types) of exoplanets that our mission concept could detect. Considering single visits only, we discuss two different scenarios for distributing 2.5 yr of an initial search phase among the stellar targets. Different apertures sizes and wavelength ranges are investigated.Results. An interferometer consisting of four 2 m apertures working in the 4–18.5 μ.m wavelength range with a total instrument throughput of 5% could detect up to ≈550 exoplanets with radii between 0.5 and 6 R⊕ with an integrated S/N ≥ 7. At least ≈160 of the detected exoplanets have radii ≤1.5 R⊕. Depending on the observing scenario, ≈25–45 rocky exoplanets (objects with radii between 0.5 and 1.5 R⊕) orbiting within the empirical habitable zone (eHZ) of their host stars are among the detections. With four 3.5 m apertures, the total number of detections can increase to up to ≈770, including ≈60–80 rocky eHZ planets. With four times 1 m apertures, the maximum detection yield is ≈315 exoplanets, including ≤20 rocky eHZ planets. The vast majority of small, temperate exoplanets are detected around M dwarfs. The impact of changing the wavelength range to 3–20 μm or 6–17 μm on the detection yield is negligible.Conclusions. A large space-based MIR nulling interferometer will be able to directly detect hundreds of small, nearby exoplanets, tens of which would be habitable world candidates. This shows that such a mission can compete with large single-aperture reflected light missions. Further increasing the number of habitable world candidates, in particular around solar-type stars, appears possible via the implementation of a multi-visit strategy during the search phase. The high median S/N of most of the detected planets will allow for first estimates of their radii and effective temperatures and will help prioritize the targets for a second mission phase to obtain high-S/N thermal emission spectra, leveraging the superior diagnostic power of the MIR regime compared to shorter wavelengths.

Although blood sampling and medical imaging are well-established techniques in clinical diagnostics, they often require long post-processing procedures. Fast and simple quantification of signaling molecules can enable efficient health monitoring and improve diagnoses. Thyroid hormones (THs) treatment relies on trial-and-error dose adjustments, and requires constant tracking via blood tests. Thus, a fast and reliable method that can constantly track THs levels could substantially improve patient quality of life by reducing their visits to doctors. Synthetic biosensors have shown to be inexpensive and easy tools for sensing molecules, with their use in healthcare increasing over time. This study describes the construction of an engineered THs bacterial biosensor, consisting of a split-intein-based TH receptor ligand binding domain (LBD) biosensor that reconstitutes green fluorescence protein (GFP) after binding to TH. This biosensor could quantitatively measure THs concentrations by evaluating fluorescence intensity. In vitro sensing using Escherichia coli produced GFP over a wide dynamic range. The biosensor was further optimized by adding a double LBD, which enhanced its dynamic range until it reached healthy physiological conditions. Moreover, a mathematical model was developed to assess the dynamic properties of the biosensor and to provide a basis for the characterization of other intein-mediated biosensors. This type of biosensor can be used as the basis for novel treatments of thyroid diseases and can be adapted to measure the concentrations of other hormones, giving rise to a series of mathematically characterized modular biosensors.

BackgroundNKX2-1, a crucial transcription factor in thyroid, lung, and brain development, is associated with rare disorders featuring thyroid dysfunction, neurological abnormalities, and respiratory symptoms. The primary challenge in managing NKX2-1-related disorders (NKX2-1-RD) is early diagnosis of the genetic defect and treating specific endocrine disorders. Levothyroxine (LT4) serves as the standard hypothyroidism treatment, with required dosages influenced by the severity of the individual's disorder, which varies widely among affected individuals.ObjectivesThis systematic review aims to assess the effectiveness of LT4 treatment in NKX2-1-RD and explore optimal dosing strategies. The primary focus is on the challenges associated with the prompt diagnosis of genetic defects, rather than the established treatment protocols for individual endocrine failures.MethodsAdhering to PRISMA guidelines, the review includes 42 studies involving 110 genetically confirmed NKX2-1-RD patients with hypothyroidism. The study investigates congenital hypothyroidism as the most prevalent endocrine alteration, along with gestational and overt hypothyroidism. The administration of LT4 treatment, dosages, and patient responses are analyzed.ResultsAmong the findings, congenital hypothyroidism emerges as the predominant endocrine alteration in 41% of patients. Notably, LT4 treatment is administered in only 10% of cases, with a mean dose of 52 μg/day. The variability in initiation and dosage is likely influenced by the age at diagnosis. Positive responses, characterized by TSH adjustments within normal ranges, are observed in 11 monitored patients.ConclusionsEarly detection of congenital hypothyroidism is emphasized for timely LT4 initiation. Challenges in standardization are highlighted due to the variability in clinical manifestations and diagnostic procedures across NKX2-1-RD cases. While this review provides valuable insights into thyroid and pituitary disease treatment, limited details on LT4 treatment represent a significant study limitation. Key reporting points for future case studies are proposed to enhance the understanding and management of NKX2-1-RD hypothyroidism.

BackgroundNKX2-1-related disorders (NKX2-1-RD) are rare conditions affecting lung, thyroid, and brain development, primarily caused by pathogenic variants or deletions in the NKX2-1 gene. Congenital hypothyroidism (CH) is a common endocrine manifestation, leading to irreversible intellectual disability if left untreated.ObjectivesThe aim was to evaluate the current evidence for the use of screening and diagnostic techniques for endocrine alterations in patients with NKX2-1-RD.MethodsThis systematic review was reported following the PRISMA guidelines. Two separate research questions in PICO format were addressed to cover initial screening and diagnosis procedures for endocrine diseases in patients with NKX2-1-RD. Eligibility criteria focused on patients with genetic confirmation of the disease and hypothyroidism. Various databases were searched, and data were extracted and assessed independently by two reviewers.ResultsOut of 1012 potentially relevant studies, 46 were included, for a total of 113 patients. CH was the most frequent endocrine alteration (45% of patients). Neonatal screening was reported in only 21% of patients based on blood TSH measurements. TSH thresholds varied widely across studies, making hypothyroidism detection ranges difficult to establish. Diagnostic tests using serum TSH were used to diagnose hypothyroidism or confirm its presence. 35% of patients were diagnosed at neonatal age, and 42% at adult age. Other hormonal dysfunctions identified due to clinical signs, such as anterior pituitary deficiencies, were detected later in life. Thyroid scintigraphy and ultrasonography allowed for the description of the thyroid gland in 30% of cases of hypothyroidism. Phenotypic variability was observed in individuals with the same variants, making genotype-phenotype correlations challenging.ConclusionThis review highlights the need for standardized protocols in endocrine screening for NKX2-1-RD, emphasizing the importance of consistent methodology and hormone threshold levels. Variability in NKX2-1 gene variants further complicates diagnostic efforts. Future research should concentrate on optimizing early screening protocols and diagnostic strategies.

Resumen: El objetivo principal del tratamiento para los trastornos de ansiedad es aliviar síntomas, prevenir recaídas y evitar secuelas. Se debe plantear un enfoque terapéutico integral (psicosocial, biológico y farmacológico).Los antidepresivos y los ansiolíticos son los pilares del tratamiento farmacológico.En la prescripción los pacientes deben ser informados de los objetivos terapéuticos, la duración y los posibles efectos secundarios. Hay que considerar la edad, tratamiento previo, tolerancia, embarazo y efectos secundarios.En España existe un aumento incesante en la prescripción y consumo de antidepresivos y ansiolíticos: los datos de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) confirman que el consumo de antidepresivos en España ha pasado de 26,5 DHD (dosis diaria definida por 1.000 habitantes/día) en el año 2000 a 79,5 DHD en el año 2013, representando un incremento de 200%. Y respecto a los ansiolíticos, la DHD se ha incrementado de 50,88 en 2012, a 58,09 en 2022. Abstract: The main objective of the treatment for anxiety disorders is to relieve symptoms, prevent relapse and avoid sequels. An integral therapeutic approach most be considered (psychosocial, biologic and pharmacologic). The antidepressants and anxiolytics are the mainstay pharmacological treatment. When the prescription is made, the patient must be informed of therapeutic objectives, duration and possible side effects. Age, previous treatment, tolerance, pregnancy and side effects most be considered. In Spain there is a high rate of prescription and consume of antidepressants and anxiolytics: the data of “Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)” support that the consume of antidepressants in Spain has passed from 26.5 DHD (Daily doses per 1000 habitants/Dose per day per 1000 habitants) in the year 2000 to 79.5 DHD in the year 2013; translating and increment of 200%. Regarding the anxiolytics the DHD has increased from 50.88 in 2012 to 58.09 in 2022.