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Abstract Prematurity is associated with lower exercise capacity, which relies on the integrity of the cardiovascular, pulmonary, and skeletal muscle systems. Our animal model mimicking prematurity-associated conditions showed altered muscle composition and atrophy in adulthood. This study aimed to compare muscle composition and strength in adults born preterm versus full-term controls. This observational cohort study recruited 55 adults born preterm, ≤ 29 weeks’ of gestation and 53 full-term controls who underwent musculoskeletal ultrasound imaging to assess morphology of the rectus femoris at rest and during a maximal voluntary contraction. Maximal voluntary contraction of the hands and legs were measured by manual dynamometry. In adults born preterm, there was lower muscle strength (handgrip: − 4.8 kg, 95% CI − 9.1, − 0.6; knee extensor: − 44.6 N/m, 95% CI − 63.4, − 25.8) and smaller muscle area (− 130 mm2, 95% CI − 207, − 53), which was more pronounced with a history of bronchopulmonary dysplasia. Muscle stiffness was increased in the preterm versus term group (0.4 m/s, 95% CI 0.04, 0.7). Prematurity is associated with alterations in skeletal muscle composition, area, and function in adulthood. These findings highlight the necessity to implement preventive and/or curative approaches to improve muscle development and function following preterm birth to enhance overall health in this population.

Abstract ABCB4 is located at the canalicular membrane of hepatocytes and is responsible for the secretion of phosphatidylcholine into bile. Genetic variations of this transporter are correlated with rare cholestatic liver diseases, the most severe being progressive familial intrahepatic cholestasis type 3 (PFIC3). PFIC3 patients most often require liver transplantation. In this context of unmet medical need, we developed a high-content screening approach to identify small molecules able to correct ABCB4 molecular defects. Intracellularly-retained variants of ABCB4 were expressed in cell models and their maturation, cellular localization and function were analyzed after treatment with the molecules identified by high-content screening. In total, six hits were identified by high-content screening. Three of them were able to correct the maturation and canalicular localization of two distinct intracellularly-retained ABCB4 variants; one molecule was able to significantly restore the function of two ABCB4 variants. In addition, in silico molecular docking calculations suggest that the identified hits may interact with wild type ABCB4 residues involved in ATP binding/hydrolysis. Our results pave the way for their optimization in order to provide new drug candidates as potential alternative to liver transplantation for patients with severe forms of ABCB4-related diseases, including PFIC3.

Frost weathering is a key mechanism of rock failure in periglacial environments and landscape evolution. In high-alpine rock walls, freezing regimes are a combination of diurnal and sustained seasonal freeze–thaw regimes, and both influence frost cracking processes. Recent studies have tested the effectiveness of freeze–thaw cycles by measuring weathering proxies for frost damage in low-strength and in grain-supported pore space rocks, but detecting frost damage in low-porosity and crack-dominated alpine rocks is challenging due to small changes in these proxies that are close to the detection limit. Consequently, the assessment of frost weathering efficacy in alpine rocks may be flawed. In order to fully determine the effectiveness of both freezing regimes, freeze–thaw cycles and sustained freezing were simulated on low-porosity, high-strength Dachstein limestone with varying saturation. Frost-induced rock damage was uniquely quantified by combining X-ray computed microtomography (µCT), acoustic emission (AE) monitoring, and frost cracking modelling. To differentiate between potential mechanisms of rock damage, thermal- and ice-induced stresses were simulated and compared to AE activity. Our results underscore the significant impact of initial crack density on frost damage, with µCT scans revealing damage primarily through crack expansion. Discrepancies between AE signals and visible damage indicate the complexity of damage mechanisms. The study highlights frost cracking as the main driver of rock damage during freezing periods. Notably, damage is more severe during repeated freeze–thaw cycles compared to extended periods of freezing, a finding that diverges from field studies. This discrepancy could stem from limited water mobility due to low porosity or from the short duration of our experimental setup.

Summary: Antimicrobial resistance remains a persistent and pressing public health concern. Here, we describe the synthesis of original triazole-containing inhibitors targeting the DNA gyrase, a well-validated drug target for developing new antibiotics. Our compounds demonstrate potent antibacterial activity against various pathogenic bacteria, with notable potency against Mycobacterium tuberculosis (Mtb). Moreover, one hit, compound 10a, named BDM71403, was shown to be more potent in Mtb than the NBTI of reference, gepotidacin. Mechanistic enzymology assays reveal a competitive interaction of BDM71403 with fluoroquinolones within the Mtb gyrase cleavage core. High-resolution cryo-electron microscopy structural analysis provides detailed insights into the ternary complex formed by the Mtb gyrase, double-stranded DNA, and either BDM71403 or gepotidacin, providing a rational framework to understand the superior in vitro efficacy on Mtb. This study highlights the potential of triazole-based scaffolds as promising gyrase inhibitors, offering new avenues for drug development in the fight against antimicrobial resistance.

Abstract Structural fetal body MRI provides true 3D information required for volumetry of fetal organs. However, current clinical and research practice primarily relies on manual slice-wise segmentation of raw T2-weighted stacks, which is time consuming, subject to inter- and intra-observer bias and affected by motion-corruption. Furthermore, there are no existing standard guidelines defining a universal approach to parcellation of fetal organs. This work produces the first parcellation protocol of the fetal body organs for motion-corrected 3D fetal body MRI. It includes 10 organ ROIs relevant to fetal quantitative volumetry studies. We also introduce the first population-averaged T2w MRI atlas of the fetal body. The protocol was used as a basis for training of a neural network for automated organ segmentation. It showed robust performance for different gestational ages. This solution minimises the need for manual editing and significantly reduces time. The general feasibility of the proposed pipeline was also assessed by analysis of organ growth charts created from automated parcellations of 91 normal control 3T MRI datasets that showed expected increase in volumetry during 22–38 weeks gestational age range.

Abstract This study explores the potential of 3D Slice-to-Volume Registration (SVR) motion-corrected fetal MRI for craniofacial assessment, traditionally used only for fetal brain analysis. In addition, we present the first description of an automated pipeline based on 3D Attention UNet trained for 3D fetal MRI craniofacial segmentation, followed by surface refinement. Results of 3D printing of selected models are also presented. Qualitative analysis of multiplanar volumes, based on the SVR output and surface segmentations outputs, were assessed with computer and printed models, using standardised protocols that we developed for evaluating image quality and visibility of diagnostic craniofacial features. A test set of 25, postnatally confirmed, Trisomy 21 fetal cases (24–36 weeks gestational age), revealed that 3D reconstructed T2 SVR images provided 66–100% visibility of relevant craniofacial and head structures in the SVR output, and 20–100% and 60–90% anatomical visibility was seen for the baseline and refined 3D computer surface model outputs respectively. Furthermore, 12 of 25 cases, 48%, of refined surface models demonstrated good or excellent overall quality with a further 9 cases, 36%, demonstrating moderate quality to include facial, scalp and external ears. Additional 3D printing of 12 physical real-size models (20–36 weeks gestational age) revealed good/excellent overall quality in all cases and distinguishable features between healthy control cases and cases with confirmed anomalies, with only minor manual adjustments required before 3D printing. Despite varying image quality and data heterogeneity, 3D T2w SVR reconstructions and models provided sufficient resolution for the subjective characterisation of subtle craniofacial features. We also contributed a publicly accessible online 3D T2w MRI atlas of the fetal head, validated for accurate representation of normal fetal anatomy. Future research will focus on quantitative analysis, optimizing the pipeline, and exploring diagnostic, counselling, and educational applications in fetal craniofacial assessment.

In this work, in situ measurements of the radio frequency electromagnetic field exposure have been conducted for an indoor massive MIMO 5G base station operating at 26–28 GHz. Measurements were performed at six different positions (at distances between 9.94 and 14.32 m from the base station), of which four were in line-of-sight and two were in non-line-of-sight. A comparison was performed between the measurements conducted with an omnidirectional probe and with a horn antenna, for scenarios with and without a user equipment used to actively create an antenna traffic beam from the base station towards the measurement location. A maximum exposure of 171.9 mW/m2 was measured at a distance of 9.94 m from the base station. This is below 2% of the ICNIRP reference level. Moreover, the feasibility to measure the power per resource element of the Synchronization Signal Block - which can be used to extrapolate the maximum exposure level - with a conventional spectrum analyzer was shown by comparison with a network decoder.

Integrated STEM education is increasingly present in classrooms and in educational research, as it is proposed as a possible strategy to improve the problems of students’ lack of interest in scientific–technological disciplines. However, this increased interest in STEM education has been paralleled by a loss of cohesion in the interpretations of its theoretical basis and by an ongoing discussion on integrated STEM education’s foundations, making its understanding, translation into real projects, and evaluation difficult to undertake. Published articles defining a STEM theoretical framework have different descriptions, so the aim of this systematic literature review is to analyse these explanations and compare them with each other. Following the PRISMA 2020 guidelines, 27 articles of interest about STEM and STEAM education were obtained and analysed with a focus on the principles and characteristics described in the texts. After organising the information and analysing the similarities and differences in the principles and characteristics, we concluded that there is great consensus on the principles of “integration”, “real-world problems”, “inquiry”, “design”, and “teamwork”. Nonetheless, this review identifies areas of discussion regarding both the principles and their characteristics that invite further analysis to refine our understanding of what integrated STEM education should entail.

Background/Objectives: Janus kinase inhibitors (JAKis) belong to a new class of targeted oral drugs that have been added to the therapeutic arsenal for rheumatoid arthritis (RA). The aim of this study was to evaluate the efficacy and safety profiles of these four available molecules (tofacitinib, baricitinib, filgotinib, and upadacitinib) in real life. Methods: A retrospective, single-center observational study including all patients treated with JAKis for RA from 1 October 2017 to 1 December 2023. We assessed the maintenance rate at 24 months, which is an indirect reflection of the clinical and biological safety and efficacy profiles. Results: The 76 patients in our study were thus treated for the first time with anti-JAK, including 55 patients with baricitinib (BAR), 9 patients with tofacitinib (TOF), 4 patients with upadacitinib (UPA), and 8 patients with filgotinib (FIL). The majority of our patients had BAR introduced as the first intention. The therapeutic maintenance at 2 years for all our patients was 50%. The average maintenance duration was 8.6 months and was similar in all the groups. Of the 76 patients included in this study treated with Baricitinib (72.3%), 38 (50%) discontinued their treatment after two years of follow-up. Conclusions: Although this retrospective study is subject to various biases, it shows that the persistence rates of the four JAKi molecules in daily practice did not differ significantly, thus confirming the long-term efficacy of these drugs.

Acetate-producing Saccharomyces cerevisiae var. boulardii strains could exert improved effects on ulcerative colitis, which here, was preclinically evaluated in an acute dextran sodium sulphate induced model of colitis. Nine-week-old female mice were divided into 12 groups, receiving either drinking water or 2.75% dextran sodium sulphate for 7 days, combined with a daily gavage of various treatments with different levels of acetate accumulation: sham control (phosphate buffered saline, no acetate), non-probiotic control (Baker’s yeast, no acetate), probiotic control (Enterol®, transient acetate), and additionally several Saccharomyces cerevisiae var. boulardii strains with respectively no, high, and extra-high acetate accumulation. Disease activity was monitored daily, and feces samples were collected at different timepoints. On day 14, the mice were sacrificed, upon which blood and colonic tissue were collected for analysis. Disease activity in inflamed mice was lower when treated with the high-acetate-producing strain compared to sham and non-probiotic controls. The non-acetate-producing strain showed higher disease activity compared to the acetate-producing strains. Accordingly, higher histologic inflammation was observed in non- or transient-acetate-producing strains compared to the sham control, whereas this increase was not observed for high- and extra-high-acetate-producing strains upon induction of inflammation. These anti-inflammatory findings were confirmed by transcriptomic analysis of differentially expressed genes. Moreover, only the strain with the highest acetate production was superior in maintaining a stable gut microbial alpha-diversity upon inflammation. These findings support new possibilities for acetate-mediated management of inflammation in inflammatory bowel disease by administrating high-acetate-producing Saccharomyces cerevisae var. boulardii strains.

A low-cost, tri-axial 50 Hz magnetic field monitoring sensor was designed, calibrated and verified. The sensor was designed using off-the-shelf components and commercially available coils. It can measure 50 Hz magnetic fields originating from high-voltage power lines from 0.08 µT to 364 µT, divided into two measurement ranges. The sensor was calibrated both on-board and in-lab. The on-board calibration takes the circuit attenuation, noise and parasitic components into account. In the in-lab calibration, the output of the developed sensor is compared to the benchmark, a narrowband EHP-50. The sensor was then verified in situ under high-voltage power lines at two independent measurement locations. The measured field values during this validation were between 0.10 µT and 13.43 µT, which is in agreement with other reported measurement values under high-voltage power lines in literature. The results were compared to the benchmark, for which average deviations of 6.2% and 1.4% were found, at the two independent measurement locations. Furthermore, fields up to 113.3 µT were measured in a power distribution sub-station to ensure that both measurement ranges were verified. Our network, four active sensors in the field, had high uptimes of 96%, 82%, 81% and, 95% during a minimum 3-month interval. In total, over 6 million samples were gathered with field values that ranged from 0.08 µT to 45.48 µT. This suggests that the proposed solution can be used for this monitoring, although more extensive long-term testing with more sensors is required to confirm the uptime under multiple circumstances.

Background: Several retreatment strategies exist for rituximab in rheumatoid arthritis (RA). In some countries, reimbursement criteria require a loss of disease control for rituximab retreatment. Understanding the patients’ and rheumatologists’ perceptions regarding this retreatment strategy would be informative in identifying the optimal treatment administration schedule. Objectives: This study aimed to uncover patients’ and rheumatologists’ perceptions regarding retreatment strategies of rituximab. Design: Qualitative study – semi-structured interviews Methods: Patients with RA, treated with rituximab, and rheumatologists were invited to participate in a qualitative study consisting of individual, in-depth, semi-structured interviews. Interviews were analysed according to the Qualitative Analysis Guide of Leuven. Results: A total of 16 patients and 13 rheumatologists were interviewed. Benefits (e.g. decreased risk of overtreatment, cost savings and long-lasting effectiveness of rituximab) and barriers (e.g. fluctuating disease activity, slow mode of action and increased glucocorticoid use) of on-flare retreatment were identified. To effectively treat on-flare, flares must first be identified timely. Both stakeholder groups acknowledged that patients are capable of recognizing flares. However, the patient’s ability to discriminate between inflammatory and other types of pain was perceived as difficult. Furthermore, patients and rheumatologists stressed that patients must timely seek professional help in case of a flare, followed by a swift response from the rheumatologists. Remarkably, retreatment was approached in various ways among rheumatologists, and not always adhering strictly to the on-flare reimbursement criteria. Conclusion: This study revealed that both stakeholder groups perceived the heterogeneity in recognition of and reaction to a flare as important in influencing the effectiveness of the on-flare retreatment strategy. Moreover, this study identified the benefits and barriers of treating on-flare, which could be informative for daily practice decisions.

Summary: Background: Provision of feeds containing hydrolysed, peptide-based proteins and medium-chain triglycerides (MCT), can help mitigate gastrointestinal (GI) intolerance in adults with impaired GI function, maldigestion and/or malabsorption. Aim: This study evaluated a high-protein, peptide-based, MCT-containing oral nutritional supplement (PEHP; 1.5 kcal/mL and 7.5 g protein/100 mL). Methods: Adults with impaired GI function were recruited by their managing dietitian and took PEHP orally for 28-days, with GI tolerance, compliance, weight, energy and protein intake assessed via non-validated questionnaires and a 24-hour dietary recall at baseline and at intervention end. Results: Fifteen, adults (56 years (16), 67 kg (26.0), 24 kg/m2 (7.6)) took part in this study. Intensity of nausea (Z= -2.070, p=0.038, n=15) and abdominal pain (Z= -2.236, p=0.025, n=15) improved significantly compared to baseline. Reductions in the intensity of diarrhoea, constipation, vomiting, flatulence, and burping were observed but were not statistically significant (p>0.05 for all). Compliance was higher with PEHP (81% (24)) than baseline feeds (63% (42)) but not significantly. Weight remained stable between baseline (67 kg (26)) and at intervention end (67 kg (27), p=0.414, n=15). Compared to baseline, total energy intake increased with PEHP albeit not significantly (1661 kcal/day (572) vs 1981 kcal/day (592), p=0.137, n=15). Increases in total protein intake were also observed, this time significantly (61 g/day (23) vs 78 g/day (29), p=0.042, n=15). Conclusions: This study in adults with impaired GI function found that PEHP improved GI tolerance and protein intake compared to feeds taken at baseline (including both polymeric and peptide-based feeds).

Abstract Muscle stem cells, the engine of muscle repair, are affected in myotonic dystrophy type 1 (DM1); however, the underlying molecular mechanism and the impact on the disease severity are still elusive. Here, we show using patients’ samples that muscle stem cells/myoblasts exhibit signs of cellular senescence in vitro and in situ. Single cell RNAseq uncovers a subset of senescent myoblasts expressing high levels of genes related to the senescence-associated secretory phenotype (SASP). We show that the levels of interleukin-6, a prominent SASP cytokine, in the serum of DM1 patients correlate with muscle weakness and functional capacity limitations. Drug screening revealed that the senolytic BCL-XL inhibitor (A1155463) can specifically remove senescent DM1 myoblasts by inducing their apoptosis. Clearance of senescent cells reduced the expression of SASP, which rescued the proliferation and differentiation capacity of DM1 myoblasts in vitro and enhanced their engraftment following transplantation in vivo. Altogether, this study identifies the pathogenic mechanism associated with muscle stem cell defects in DM1 and opens a therapeutic avenue that targets these defective cells to restore myogenesis.

Conclusion: In cases of severe mediastinal adenopathy in a young patient, bacterial lymphadenitis should be considered in the differential diagnosis with lymphoma, germ cell tumor, granulomatosis with polyangiitis, sarcoidosis, histoplasmosis, and inflammatory myofibroblastic tumor.

IntroductionUltra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system.MethodsImages were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM).ResultsThere was no significant difference between temperature before and after scanning (p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy.DiscussionWe demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life.

Activity induced transcription factor ΔFosB plays a key role in different CNS disorders including epilepsy, Alzheimer’s disease, and addiction. Recent findings suggest that ΔFosB drives cognitive deficits in epilepsy and together with the emergence of small molecule inhibitors of ΔFosB activity makes it an interesting therapeutic target. However, whether ΔFosB contributes to pathophysiology or provides protection in drug-resistant epilepsy is still unclear. In this study, ΔFosB was specifically downregulated by delivering AAV-shRNA into the hippocampus of chronically epileptic mice using the drug-resistant pilocarpine model of mesial temporal epilepsy (mTLE). Immunohistochemistry analyses showed that prolonged downregulation of ΔFosB led to exacerbation of neuroinflammatory markers of astrogliosis and microgliosis, loss of mossy fibers, and hippocampal granule cell dispersion. Furthermore, prolonged inhibition of ΔFosB using a ΔJunD construct to block ΔFosB signaling in a mouse model of Alzheimer’s disease, that exhibits spontaneous recurrent seizures, led to similar findings, with increased neuroinflammation and decreased NPY expression in mossy fibers. Together, these data suggest that seizure-induced ΔFosB, regardless of seizure-etiology, is part of a homeostatic mechanism that protects the epileptic brain from further deterioration.

Background: Previous case studies have provided evidence for chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective research is lacking. Hence, we investigated leukoencephalopathy before and after chemotherapy and its association with a serum neuroaxonal damage marker. Methods: This prospective cohort study included 40 patients receiving chemotherapy for breast cancer, and two age- and education-matched control groups, recruited between 2018 and 2021 (31–64 years of age). The latter control groups consisted of 39 chemotherapy-naïve patients and 40 healthy women. Fluid-attenuated inversion-recovery magnetic resonance imaging was used for lesion volumetry (total, juxtacortical, periventricular, infratentorial, and deep white matter) and blood serum to measure neurofilament light chain (NfL) levels. Acquisition took place pre-chemotherapy and three months and one-year post-chemotherapy, or at corresponding intervals. Within/between group differences were compared using robust mixed-effects modeling, and associations between total lesion volume and serum-NfL with linear regression. Results: Stronger increases in deep white matter lesion volumes were observed shortly post-chemotherapy, compared with healthy women (ßstandardized=0.09, pFDR0.70, p

Abstract Increasing lines of evidence suggest deviations from the normal early developmental trajectory could give rise to the onset of schizophrenia during adolescence and young adulthood, but few studies have investigated brain imaging changes associated with schizophrenia common variants in neonates. This study compared the brain volumes of both grey and white matter regions with schizophrenia polygenic risk scores (PRS) for 207 healthy term-born infants of European ancestry. Linear regression was used to estimate the relationship between PRS and brain volumes, with gestational age at birth, postmenstrual age at scan, ancestral principal components, sex and intracranial volumes as covariates. The schizophrenia PRS were negatively associated with the grey (β = −0.08, p = 4.2 × 10−3) and white (β = −0.13, p = 9.4 × 10−3) matter superior temporal gyrus volumes, white frontal lobe volume (β = −0.09, p = 1.5 × 10−3) and the total white matter volume (β = −0.062, p = 1.66 × 10−2). This result also remained robust when incorporating individuals of Asian ancestry. Explorative functional analysis of the schizophrenia risk variants associated with the right frontal lobe white matter volume found enrichment in neurodevelopmental pathways. This preliminary result suggests possible involvement of schizophrenia risk genes in early brain growth, and potential early life structural alterations long before the average age of onset of the disease.

Resumen Introducción La literatura mundial sugiere que existe una creciente crisis de recursos humanos en el área de rehabilitación. Esta Revisión Sistemática Exploratoria se centra en el desarrollo de capacidades en el área de rehabilitación en países de ingresos bajos y medianos (PIBM). El desarrollo de capacidades es el proceso mediante el cual las personas y las organizaciones obtienen, mejoran y retienen las habilidades, el conocimiento, las herramientas, el equipo y otros recursos necesarios para realizar su trabajo de manera competente. Objetivos Determinar cómo se ha definido, implementado y evaluado el desarrollo de capacidades en rehabilitación en los PIBM; y proporcionar una síntesis sobre la eficacia de las iniciativas de desarrollo de capacidades en rehabilitación en los PIBM. Métodos En la primera de siete etapas, refinaremos las preguntas de la investigación. Luego, identificaremos estudios relevantes mediante la búsqueda de cinco bases de datos y tres bases de datos de literatura gris. Dos revisores en forma independiente seleccionarán los estudios utilizando criterios definidos a priori. Excluiremos registros (artículos y otra literatura) incompletos, publicados antes de 2000 para bases de datos y 2010 para literatura gris, y escritos en idiomas que no sean inglés o español. También excluiremos registros que sobre programas de ingreso a la práctica profesional (académicos). Para el Objetivo 1, extraeremos y analizaremos el texto que define las estrategias/iniciativas de desarrollo de capacidades en rehabilitación utilizando un software de análisis cualitativo. Para el Objetivo 2, un revisor extraerá datos que describen la efectividad de las intervenciones y un segundo revisor verificará la precisión de los datos utilizando una plataforma electrónica. Los desacuerdos entre revisores se resolverán por consenso. Los resultados se presentarán usando tablas y gráficos. Consultaremos con colegas de PIBM sobre la aplicabilidad de los hallazgos. Para la diseminación de resultados, usaremos presentaciones y publicaciones en inglés y español. Discusión Hasta donde sabemos, esta será la primera revisión exploratoria para identificar el desarrollo de capacidades en rehabilitación en los PIBM. Se prevé que los resultados de esta revisión guiarán los esfuerzos futuros de desarrollo de capacidades en la rehabilitación de los PIBM.

Commercial, high-tech upper limb prostheses offer a lot of functionality and are equipped with high-grade control mechanisms. However, they are relatively expensive and are not accessible to the majority of amputees. Therefore, more affordable, accessible, open-source, and 3D-printable alternatives are being developed. A commonly proposed approach to control these prostheses is to use bio-potentials generated by skeletal muscles, which can be measured using surface electromyography (sEMG). However, this control mechanism either lacks accuracy when a single sEMG sensor is used or involves the use of wires to connect to an array of multiple nodes, which hinders patients’ movements. In order to mitigate these issues, we have developed a circular, wireless s-EMG array that is able to collect sEMG potentials on an array of electrodes that can be spread (not) uniformly around the circumference of a patient’s arm. The modular sEMG system is combined with a Bluetooth Low Energy System on Chip, motion sensors, and a battery. We have benchmarked this system with a commercial, wired, state-of-the-art alternative and found an r = 0.98 (p < 0.01) Spearman correlation between the root-mean-squared (RMS) amplitude of sEMG measurements measured by both devices for the same set of 20 reference gestures, demonstrating that the system is accurate in measuring sEMG. Additionally, we have demonstrated that the RMS amplitudes of sEMG measurements between the different nodes within the array are uncorrelated, indicating that they contain independent information that can be used for higher accuracy in gesture recognition. We show this by training a random forest classifier that can distinguish between 6 gestures with an accuracy of 97%. This work is important for a large and growing group of amputees whose quality of life could be improved using this technology.

Background: Combined endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided tissue acquisition (EUS-TA) are accurate procedures for the diagnosis and staging of mediastinal lymph nodes (MLNs) in lung cancer. However, the respective contribution of separate and combined procedures in diagnosis and staging has not been fully studied. The aim of this study was to assess their respective performances. Methods: Patients with suspected malignant MLNs in lung cancer or recurrence identified by PET-CT who underwent combined EBUS-TBNA and EUS-TA were retrospectively reviewed. Results: A total of 141 patients underwent both procedures. Correct diagnosis was obtained in 82% with EBUS-TBNA, 91% with EUS-TA, and 94% with the combined procedure. The overall sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of EBUS-TBNA, EUS-TA, and the combined procedure for diagnosing malignancy were [75%, 100%, 100%, 58%], [87%, 100%, 100%, 75%], and [93%, 100%, 100%, 80%], respectively, with a significantly better sensitivity of the combined procedure (p < 0.0001). Staging (82/141 patients) was correctly assessed in 74% with EBUS-TBNA, 68% with EUS-TA, and 85% with the combined procedure. The overall sensitivity, specificity, PPV, and NPV of EBUS-TBNA, EUS-TA, and the combined procedure for lung cancer staging were [62%, 100%, 100%, 55%], [54%, 100%, 100%, 50%], and [79%, 100%, 100%, 68%], respectively, significantly better in terms of sensitivity for the combined procedure (p < 0.001). Conclusion: The combined EBUS-EUS approach in lung cancer patients showed better accuracy and sensitivity in diagnosis and staging when compared with EBUS-TBNA and EUS-TA alone.

Purinergic receptors and NOD-like receptor protein 3 (NLRP3) inflammasome regulate inflammation and viral infection, but their effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain poorly understood. Here, we report that the purinergic receptor P2X7 and NLRP3 inflammasome are cellular host factors required for SARS-CoV-2 infection. Lung autopsies from patients with severe coronavirus disease 2019 (COVID-19) reveal that NLRP3 expression is increased in host cellular targets of SARS-CoV-2 including alveolar macrophages, type II pneumocytes and syncytia arising from the fusion of infected macrophages, thus suggesting a potential role of NLRP3 and associated signaling pathways to both inflammation and viral replication. In vitro studies demonstrate that NLRP3-dependent inflammasome activation is detected upon macrophage abortive infection. More importantly, a weak activation of NLRP3 inflammasome is also detected during the early steps of SARS-CoV-2 infection of epithelial cells and promotes the viral replication in these cells. Interestingly, the purinergic receptor P2X7, which is known to control NLRP3 inflammasome activation, also favors the replication of D614G and alpha SARS-CoV-2 variants. Altogether, our results reveal an unexpected relationship between the purinergic receptor P2X7, the NLRP3 inflammasome and the permissiveness to SARS-CoV-2 infection that offers novel opportunities for COVID-19 treatment.

Phthalate acid esters (PAE) are used as additives in the formulation of plastics, to increase their flexibility and transparency. They can migrate from plastic packaging to food, then cause endocrine disruption in consumers. This migration depends on the conditions of use defined for each plastic. Non-food plastics are likely to release more PAE than food-grade plastics. In Cameroon, non-food grade plastics such as old paint buckets are used by people to preserve liquid food. The present work aimed at studying the conditions and mechanism of migration of total PAE from paint buckets to pap. For this purpose, the effects of seven factors were determined through Plackett-Burman experimental design. The interactions of the most influential factors were determined through a full factorial design. The conditions of the migration of total PAE were obtained via face-centered composite design. Then experimental results of migration kinetics were modelled according to equations of pseudo-first order, pseudo-second order and intra-particle diffusion. The results revealed that the most influential factors were pH, temperature and contact time. The effects of these factors are non-linear, and their interactions have to be considered. When pap is preserved in paint buckets according to the conditions: temperature of pap >70 °C, pH of pap ≤4 or ≥10 and contact time > 2 h, as is the case in donut shops in Cameroon, the amount of total PAE released is greater than 50 μg/L. Migration of total PAE from paint buckets to pap is best described by the pseudo-second order model.

Abstract Background Image-domain motion correction of black-blood contrast T2-weighted fetal cardiovascular magnetic resonance imaging (CMR) using slice-to-volume registration (SVR) provides high-resolution three-dimensional (3D) images of the fetal heart providing excellent 3D visualisation of vascular anomalies [1]. However, 3D segmentation of these datasets, important for both clinical reporting and the application of advanced analysis techniques is currently a time-consuming process requiring manual input with potential for inter-user variability. Methods In this work, we present novel 3D fetal CMR population-averaged atlases of normal and abnormal fetal cardiovascular anatomy. The atlases are created using motion-corrected 3D reconstructed volumes of 86 third trimester fetuses (gestational age range 29-34 weeks) including: 28 healthy controls, 20 cases with postnatally confirmed neonatal coarctation of the aorta (CoA) and 38 vascular rings (21 right aortic arch (RAA), 17 double aortic arch (DAA)). We used only high image quality datasets with isolated anomalies and without any other deviations in the cardiovascular anatomy.In addition, we implemented and evaluated atlas-guided registration and deep learning (UNETR) methods for automated 3D multi-label segmentation of fetal cardiac vessels. We used images from CoA, RAA and DAA cohorts including: 42 cases for training (14 from each cohort), 3 for validation and 6 for testing. In addition, the potential limitations of the network were investigated on unseen datasets including 3 early gestational age (22 weeks) and 3 low SNR cases. Results We created four atlases representing the average anatomy of the normal fetal heart, postnatally confirmed neonatal CoA, RAA and DAA. Visual inspection was undertaken to verify expected anatomy per subgroup. The results of the multi-label cardiac vessel UNETR segmentation showed 100 $$\%$$ % per-vessel detection rate for both normal and abnormal aortic arch anatomy. Conclusions This work introduces the first set of 3D black-blood T2-weighted CMR atlases of normal and abnormal fetal cardiovascular anatomy including detailed segmentation of the major cardiovascular structures. Additionally, we demonstrated the general feasibility of using deep learning for multi-label vessel segmentation of 3D fetal CMR images.

Introduction Incontinence-associated dermatitis (IAD) is irritant contact dermatitis and skin damage associated with prolonged skin contact with urine and/or faeces. Identifying prognostic factors for the development of IAD may improve management, facilitate prevention and inform future research.Methods and analysis This protocol follows the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Prospective and retrospective observational studies or clinical trials in which prognostic factors associated with the development of IAD are described are eligible. There are no restrictions on study setting, time, language, participant characteristics or geographical regions. Reviews, editorials, commentaries, methodological articles, letters to the editor, cross-sectional and case–control studies, and case reports are excluded. MEDLINE, CINAHL, EMBASE and The Cochrane Library will be searched from inception until May 2023. Two independent reviewers will independently evaluate studies. The Quality in Prognostic Studies tool will be used to assess the risk of bias, and the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies-Prognostic Factors checklist will be used for data extraction of the included studies. Separate analyses will be conducted for each identified prognostic factor, with adjusted and unadjusted estimated measures analysed separately. Evidence will be summarised with a meta-analysis when possible, and narratively otherwise. The Q and I2 statistics will be calculated in order to quantify heterogeneity. The quality of the evidence obtained will be evaluated according to the Grades of Recommendation Assessment, Development and Evaluation guidance.Ethics and dissemination No ethical approval is needed since all data is already publicly accessible. The results of this work will be published in a peer-reviewed scientific journal.

Abstract Individuals born preterm are at higher risk of cardiovascular and metabolic diseases in adulthood, through mechanisms not completely understood. White adipose tissue in humans and rodents is a dynamic endocrine organ and a critical player in the regulation of metabolic homeostasis. However, the impact of preterm birth on white adipose tissue remains unknown. Using a well‐established rodent model of preterm birth‐related conditions in which newborn rats are exposed during postnatal days 3–10 to 80% of oxygen, we evaluated the impact of transient neonatal hyperoxia on adult perirenal white adipose tissue (pWAT) and liver. We further assessed the effect of a second hit with a high‐fat high‐fructose hypercaloric diet (HFFD). We evaluated 4‐month‐old adult male rats after 2 months of HFFD. Neonatal hyperoxia led to pWAT fibrosis and macrophage infiltration without modification in body weight, pWAT weight, or adipocyte size. In animals exposed to neonatal hyperoxia vs. room air control, HFFD resulted in adipocyte hypertrophy, lipid accumulation in the liver, and increased circulating triglycerides. Overall, preterm birth‐related conditions had long‐lasting effects on the composition and morphology of pWAT, along with a higher susceptibility to the deleterious impact of a hypercaloric diet. These changes suggest a developmental pathway to long‐term metabolic risk factors observed clinically in adults born preterm through programming of white adipose tissue.

Scoring functions are ubiquitous in structure-based drug design as an aid to predicting binding modes and estimating binding affinities. Ideally, a scoring function should be broadly applicable, obviating the need to recalibrate and refit its parameters for every new target and class of ligands. Traditionally, drugs have been small molecules, but in recent years biologics, particularly antibodies, have become an increasingly important if not dominant class of therapeutics. This makes the goal of having a transferable scoring function, i.e., one that spans the range of small-molecule to protein ligands, even more challenging. One such broadly applicable scoring function is the Solvated Interaction Energy (SIE), which has been developed and applied in our lab for the last 15 years, leading to several important applications. This physics-based method arose from efforts to understand the physics governing binding events, with particular care given to the role played by solvation. SIE has been used by us and many independent labs worldwide for virtual screening and discovery of novel small-molecule binders or optimization of known drugs. Moreover, without any retraining, it is found to be transferrable to predictions of antibody-antigen relative binding affinities and as accurate as functions trained on protein-protein binding affinities. SIE has been incorporated in conjunction with other scoring functions into ADAPT (Assisted Design of Antibody and Protein Therapeutics), our platform for affinity modulation of antibodies. Application of ADAPT resulted in the optimization of several antibodies with 10-to-100-fold improvements in binding affinity. Further applications included broadening the specificity of a single-domain antibody to be cross-reactive with virus variants of both SARS-CoV-1 and SARS-CoV-2, and the design of safer antibodies by engineering of a pH switch to make them more selective towards acidic tumors while sparing normal tissues at physiological pH.

Introduction Currently, the healthcare sector is under tremendous financial pressure, and many acknowledge that a dramatic shift is required as the current system is not sustainable. Furthermore, the quality of care that is delivered varies strongly. Several solutions have been proposed of which the conceptual framework known as value-based healthcare (VBHC) is further explored in this study for psoriasis. Psoriasis is a chronic inflammatory skin disease, which is associated with a high disease burden and high treatment costs. The objective of this study is to investigate the feasibility of using the VBHC framework for the management of psoriasis.Methods and analysis This is a prospective clinical study in which new patients attending the psoriasis clinic (PsoPlus) of the Ghent University Hospital will be followed up during a period of 1 year. The main outcome is to determine the value created for psoriasis patients. The created value will be considered as a reflection of the evolution of the value score (ie, the weighted outputs (outcomes) divided by weighted inputs (costs)) obtained using data envelopment analysis. Secondary outcomes are related to comorbidity control, outcome evolution and treatment costs. In addition, a bundled payment scheme will be determined as well as potential improvements in the treatment process. A total of 350 patients will be included in this trial and the study initiation is foreseen on 1 March 2023.Ethics and dissemination This study has been approved by the Ethics Committee of the Ghent University Hospital. The findings of this study will be disseminated by various means: (1) publication in one or more peer-reviewed dermatology and/or management journals, (2) (inter)national congresses, (3) via the psoriasis patient community and (4) through the research team’s social media channels.Trial registration number NCT05480917.

Abstract We present a patient who developed, after an early‐onset, a stable course of spastic paraplegia and ataxia for 4 decades and eventually succumbed to two episodes of postinfectious lactic acidosis. Diagnostic workup including muscle biopsy and postmortem analysis, oxymetric analysis, spectrophotometric enzyme analysis, and MitoExome sequencing revealed a necrotizing leukoencephalomyelopathy due to the so far unreported biallelic variant of the NDUFV1 gene (p.(Pro122Leu)). This case extends our understanding of NDUFV1 variants with a 14‐fold longer lifetime than so far reported cases, and will foster sensitivity toward respiratory chain disease also in adult patients with sudden deteriorating neurological deficits.

Summary: Metformin (MET) is the most prescribed antidiabetic drug, but its mechanisms of action remain elusive. Recent data point to the gut as MET’s primary target. Here, we explored the effect of MET on the gut glucose transport machinery. Using human enterocytes (Caco-2/TC7 cells) in vitro, we showed that MET transiently reduced the apical density of sodium-glucose transporter 1 (SGLT1) and decreased the absorption of glucose, without changes in the mRNA levels of the transporter. Administered 1 h before a glucose challenge in rats (Wistar, GK), C57BL6 mice and mice pigs, oral MET reduced the post-prandial glucose response (PGR). This effect was abrogated in SGLT1-KO mice. MET also reduced the luminal clearance of 2-(18F)-fluoro-2-deoxy-D-glucose after oral administration in rats. In conclusion, oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of SGLT1 in enterocytes, which may contribute to the clinical effects of the drug.

Bisphenols are known to be endocrine disruptors. They are ubiquitous in the environment and also in plastic materials such as those used in food packaging. They can lead to the contamination of food in contact with environmental products or plastic packaging. In Africa, there a few studies on the assessment of the amount of bisphenols in foods; hence, most African countries do not have policies guiding on their utilization. The present work is aimed at assessing bisphenol levels in sachet water, bagged whisky, crude palm oil and traditional alcoholic beverages of Cameroon, in Central Africa. A sensitive method based on liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the simultaneous determination of bisphenol A, B and F (BPA, BPB and BPF). This method showed that recoveries were from 72 to 120% and the limits of quantification for BPA, BFB and BPF from aqueous samples were 0.09, 0.10, and 0.09 µg L−1 respectively. Estimation of the contribution to dietary exposure of BPA from these matrices were lower than temporary Tolerable Daily Intake (t-TDI) (4 µg/kg of body weight/day) defined by The European food safety authority (EFSA). One brand of sachet water contained BPF at 14.5 ± 1.1 µg L−1.

What is this summary about? This summary presents findings from recent research involving people with psoriasis, based on an article originally published in the Journal of the European Academy of Dermatology and Venereology. Psoriasis is a condition that primarily affects the skin. However, it can also influence people’s mental health, social activities, work, and relationships too. Current assessment tools used by doctors and nurses do not cover the complete experience of people with psoriasis, which often include other medical conditions and can leave these individuals feeling that treatment has not been successful. Researchers conducted a study in which people with psoriasis, doctors, and nurses were asked in virtual meetings and via questionnaires what freedom from disease in psoriasis means to them. What were the results? In addition to skin symptoms, the areas of mental health, well-being, treatment, and relationships with healthcare teams were found to be important aspects to be addressed. What do the results of the study mean? Focusing on all five aspects of freedom from disease will help people with psoriasis manage their psoriasis with confidence.

Yeast cells maintain an intricate network of nutrient signaling pathways enabling them to integrate information on the availability of different nutrients and adjust their metabolism and growth accordingly. Cells that are no longer capable of integrating this information, or that are unable to make the necessary adaptations, will cease growth and eventually die. Here, we studied the molecular basis underlying the synthetic lethality caused by loss of the protein kinase Sch9, a key player in amino acid signaling and proximal effector of the conserved growth-regulatory TORC1 complex, when combined with either loss of the cyclin-dependent kinase (CDK) Pho85 or loss of its inhibitor Pho81, which both have pivotal roles in phosphate sensing and cell cycle regulation. We demonstrate that it is specifically the CDK-cyclin pair Pho85-Pho80 or the partially redundant CDK-cyclin pairs Pho85-Pcl6/Pcl7 that become essential for growth when Sch9 is absent. Interestingly, the respective three CDK-cyclin pairs regulate the activity and distribution of the phosphatidylinositol-3 phosphate 5-kinase Fab1 on endosomes and vacuoles, where it generates phosphatidylinositol-3,5 bisphosphate that serves to recruit both TORC1 and its substrate Sch9. In addition, Pho85-Pho80 directly phosphorylates Sch9 at Ser726, and to a lesser extent at Thr723, thereby priming Sch9 for its subsequent phosphorylation and activation by TORC1. The TORC1-Sch9 signaling branch therefore integrates Pho85-mediated information at different levels. In this context, we also discovered that loss of the transcription factor Pho4 rescued the synthetic lethality caused by loss of Pho85 and Sch9, indicating that both signaling pathways also converge on Pho4, which appears to be wired to a feedback loop involving the high-affinity phosphate transporter Pho84 that fine-tunes Sch9-mediated responses.

The AMP-activated protein kinase (AMPK) and the target of rapamycin complex 1 (TORC1) are central kinase modules of two opposing signaling pathways that control eukaryotic cell growth and metabolism in response to the availability of energy and nutrients. Accordingly, energy depletion activates AMPK to inhibit growth, while nutrients and high energy levels activate TORC1 to promote growth. Both in mammals and lower eukaryotes such as yeast, the AMPK and TORC1 pathways are wired to each other at different levels, which ensures homeostatic control of growth and metabolism. In this context, a previous study (Hughes Hallett et al., 2015) reported that AMPK in yeast, that is Snf1, prevents the transient TORC1 reactivation during the early phase following acute glucose starvation, but the underlying mechanism has remained elusive. Using a combination of unbiased mass spectrometry (MS)-based phosphoproteomics, genetic, biochemical, and physiological experiments, we show here that Snf1 temporally maintains TORC1 inactive in glucose-starved cells primarily through the TORC1-regulatory protein Pib2. Our data, therefore, extend the function of Pib2 to a hub that integrates both glucose and, as reported earlier, glutamine signals to control TORC1. We further demonstrate that Snf1 phosphorylates the TORC1 effector kinase Sch9 within its N-terminal region and thereby antagonizes the phosphorylation of a C-terminal TORC1-target residue within Sch9 itself that is critical for its activity. The consequences of Snf1-mediated phosphorylation of Pib2 and Sch9 are physiologically additive and sufficient to explain the role of Snf1 in short-term inhibition of TORC1 in acutely glucose-starved cells.

Background: Although chemotherapy-induced leukoencephalopathy has been described in case and cohort studies, literature remains inconclusive about its prevalence and mechanisms. Therefore, we investigated the presence of leukoencephalopathy after multiagent chemotherapy in women treated for breast cancer and potential underlying neuroinflammatory processes. Methods: In this exploratory study, 15 chemotherapy-treated and 15 age-matched chemotherapy-naïve patients with early-stage breast cancer, as well as 15 healthy controls underwent simultaneous PET-MR neuroimaging, including T1-weighted MPRAGE, T2-weighted FLAIR and dynamic PET with the 18-kDA translocator protein (TSPO) radioligand [18F]DPA-714. Total and regional (juxtacortical, periventricular, deep white matter and infratentorial) lesion burden were compared between the groups with one-way ANOVA. With paired t-tests, [18F]DPA-714 volume of distribution [VT, including partial volume correction (PVC)] in lesioned and normal appearing white matter (NAWM) were compared within subjects, to investigate inflammation. Finally, two general linear models were used to examine the predictive values of neurofilament light-chain (NfL) serum levels on (1) total lesion burden or (2) PVC [18F]DPA-714 VT of lesions showing elevated inflammation. Results: No significant differences were found in total or localized lesion burden. However, significantly higher (20–45%) TSPO uptake was observed in juxtacortical lesions (p ≤ 0.008, t ≥ 3.90) compared to NAWM in both cancer groups, but only persisted for chemotherapy-treated patients after PVC (p = 0.005, t = 4.30). NfL serum levels were not associated with total lesion volume or tracer uptake in juxtacortical lesions. Conclusion: This multimodal neuroimaging study suggests that neuroinflammatory processes could be involved in the development of juxtacortical, but not periventricular or deep white matter, leukoencephalopathy shortly after chemotherapy for early-stage breast cancer.

Abstract Ultrasound-guided injections are an alternative to evaluate in the management of low back pain associated with osteoarthritis of the lumbar facet joints: it eliminates the risk of ionizing radiation for both the patient and the practitioner. This study aims to compare the short-term clinical efficacy of lumbar facet joints injections between ultrasound-guided injections and fluoroscopy-guided injections. Observational, retrospective, single-center study. Patients received one or two lumbar zygapophyseal joints injections under fluoroscopy or ultrasound and a follow-up consultation at one month. Data from 54 patients was collected. The median of the evolution of VAS at one month was − 30 mm [−50.0; −20.0] in the ultrasound group and – 29.5 mm [−47.0; −15.0] (p

Efflux transporters of the RND family confer resistance to multiple antibiotics in Gram-negative bacteria. Here, the authors identify pyridylpiperazine-based compounds that potentiate antibiotic activity in E. coli through allosteric inhibition of its primary RND transporter.

Abstract The design of superior biologic therapeutics, including antibodies and engineered proteins, involves optimizing their specific ability to bind to disease-related molecular targets. Previously, we developed and applied the Assisted Design of Antibody and Protein Therapeutics (ADAPT) platform for virtual affinity maturation of antibodies (Vivcharuk et al. in PLoS One 12(7):e0181490, https://doi.org/10.1371/journal.pone.0181490 , 2017). However, ADAPT is limited to point mutations of hot-spot residues in existing CDR loops. In this study, we explore the possibility of wholesale replacement of the entire H3 loop with no restriction to maintain the parental loop length. This complements other currently published studies that sample replacements for the CDR loops L1, L2, L3, H1 and H2. Given the immense sequence space theoretically available to H3, we focused on the virtual grafting of over 5000 human germline-derived H3 sequences from the IGMT/LIGM database increasing the diversity of the sequence space when compared to using crystalized H3 loop sequences. H3 loop conformations are generated and scored to identify optimized H3 sequences. Experimental testing of high-ranking H3 sequences grafted into the framework of the bH1 antibody against human VEGF-A led to the discovery of multiple hits, some of which had similar or better affinities relative to the parental antibody. In over 75% of the tested designs, the re-designed H3 loop contributed favorably to overall binding affinity. The hits also demonstrated good developability attributes such as high thermal stability and no aggregation. Crystal structures of select re-designed H3 variants were solved and indicated that although some deviations from predicted structures were seen in the more solvent accessible regions of the H3 loop, they did not significantly affect predicted affinity scores.

We present a case of a transient acquired zinc deficiency in a breast-fed, 4-month-old-male prematurely born infant, with acrodermatitis enteropathica-like symptoms such as crusted, eroded, erythemato-squamous eruption in periorificial and acral patterns. The laboratory investigations showed low zinc levels in the infant’s and the mother’s serum and in the mother’s milk; genetic analysis did not show any mutation in the SLC39A4 gene, involved in acrodermatitis enteropathica. Acquired zinc deficiency is often found in premature infants because of their increased requirement, the low serum and milk zinc levels in breastfeeding women being also an important risk factor, as in this case. A prompt zinc supplementation is essential for the good prognosis of the disease.

PurposeTo investigate the short-term cerebral metabolic effects of intravenous chemotherapy and their association with long-term fatigue/cognitive complaints.Experimental designUsing [18F]-FDG-PET/CT whole-body scans, we retrospectively quantified relative cerebral glucose metabolism before and after neoadjuvant chemotherapy in a cohort of patients treated for non-metastatic breast cancer (2009-2019). Self-report of cognitive complaints and fatigue were prospectively assessed 7 ± 3 years after therapy. Metabolic changes were estimated with i) robust mixed-effects modelling in regions-of-interest (frontal, parietal, temporal, occipital, and insular cortex) and ii) general-linear modelling of whole-brain voxel-wise outcomes. iii) The association between metabolic changes and self-reported outcomes was evaluated using linear regression-analysis.ResultsOf the 667 screened patients, 263 underwent PET/CT before and after chemotherapy and 183 (48 ± 9 years) met the inclusion criteria. After chemotherapy, decreased frontal and increased parietal and insular metabolism were observed (|ß|>0.273, pFDR0.244, pFDR≤0.048). Voxel-based analysis (pcluster-FWE

Background and study aims Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is an emerging and minimally invasive technique that seems promising for treatment of focal pancreatic and peripancreatic lesions. Our aim was to prospectively evaluate the feasibility, safety, and technical and clinical success of pancreatic and extra-pancreatic EUS-RFA. Patients and methods We prospectively collected clinical and technical data for all patients who underwent EUS-RFA at two Belgian academic centers from June 2018 to February 2022. Feasibility, adverse events (AEs), and follow-up were also assessed. Results Twenty-nine patients were included, accounting for 35 lesions: 10 non-functioning neuroendocrine tumors (29 %), 13 pancreatic insulinomas (37 %), one adenocarcinoma (3 %), and 11 intra-pancreatic and extra-pancreatic metastatic lesions (31 %). Technical success was achieved in 100 % of cases, with a median of three power applications per lesion (interquartile range 2). The majority of patients (59 %) presented no collateral effects, three (10.3 %) developed non-severe acute pancreatitis, and four (14 %) had mild abdominal pain. At 6 months follow-up (n = 25), 36 % of patients showed radiological complete response, 16 % presented a significant partial response and 48 % showed 50 % decrease in diameter. Hypoglycemia related to insulinoma was immediately corrected in all 13 cases, with no recurrence during follow-up. Conclusions EUS-RFA is feasible, safe, and effective for treatment of pancreatic and peripancreatic tumors. Larger and longer multicenter prospective studies are warranted to establish its role in management of focal pancreatic lesions and oligometastatic disease. Symptomatic insulinoma currently represent the best indication.

Teaching Point: Dural sinus stenosis are a rare cause of increased intracranial pressure and can be treated in some cases by stenting.

The development of perinatal brain connectivity underpins motor, cognitive and behavioural abilities in later life. Diffusion MRI allows the characterisation of subtle inter-individual differences in structural brain connectivity, though individual brain connectivity maps (connectomes) are by nature high in dimensionality and complex to interpret. Machine learning methods are a powerful tool to uncover properties of the connectome which are not readily visible and can give us clues as to how and why individual developmental trajectories differ.In this manuscript we used Deep Neural Networks and Random Forests to predict demographic and neurodevelopmental characteristics from neonatal structural connectomes in a large sample of babies (n = 524) from the developing Human Connectome Project. We achieved an accurate prediction of postmenstrual age (PMA) at scan in term-born infants (mean absolute error (MAE) = 0.72 weeks, r = 0.83 and p

Background: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer survivors with CRCI. Methods: Female breast cancer survivors reporting cognitive complaints (n = 117) were randomly assigned to a mindfulness-based intervention (n = 43), physical training (n = 36), or waitlist control condition (n = 38). Region-of-interest (ROI) and graph theory analyses of resting state functional MRI data were performed to study longitudinal group differences in functional connectivity and organization in the default mode, dorsal attention, salience, and frontoparietal network. Additionally, bead-based immunoassays were used to investigate the differences in inflammatory profiles on serum samples. Measures were collected before, immediately after and three months post-intervention. Results: No ROI-to-ROI functional connectivity changes were identified. Compared to no intervention, graph analysis showed a larger decrease in clustering coefficient after mindfulness and physical training. Additionally, a larger increase in global efficiency after physical training was identified. Furthermore, the physical training group showed a larger decrease in an inflammatory profile compared to no intervention (IL-12p70, IFN-γ, IL-1β, and IL-8). Conclusion: Both mindfulness and physical training induced changes in the functional organization of networks related to attention, emotion processing, and executive functioning. While both interventions reduced functional segregation, only physical training increased functional integration of the neural network. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI.

In the original publication [...]

Sudden death, especially at a young age, may be caused by an underlying genetic cause. Hereditary conditions with an increased risk of sudden death at a young age include cardiomyopathies, arrhythmia syndromes, and hereditary thoracic aortic aneurysms and dissections. The identification of a genetic cause allows for genetic testing and cardiological surveillance in at-risk relatives. Three sudden death cases from our hospital illustrate the value of autopsy, genetic, and cardiological screening in relatives following a sudden death. On autopsy, histology consistent with hereditary cardiomyopathy is a reason for the referral of relatives. In addition, in the absence of an identifiable cause of death by autopsy in young sudden death patients, arrhythmia syndrome should be considered as a potential genetic cause.

Background: Baricitinib (BARI) or Tofacitinib (TOFA) were the first Janus Kinase Inhibitors (JAKi) to be marketed in rheumatoid arthritis (RA). Concerns regarding venous thromboembolism (VTE) risk have emerged during the past years. The aim of the study was to compare the baseline characteristics of patients initiating BARI or TOFA in RA before versus after European Medicine Agency (EMA)’s VTE warnings and to compare real-world persistence with these two drugs. Methods: In this multicentric cohort study, RA patients initiating BARI or TOFA were included from October 2017, date of BARI marketing authorization in France, to September 2020. Baseline characteristics regarding VTE risk were compared (before vs. after May 2019) by using pre-specified statistical tests. Comparison of persistence was assessed by using propensity-score methods. Results: 232 patients were included; 155 with BARI and 77 with TOFA. Baseline characteristics of patients regarding VTE risk factors were not statistically different when Janus Kinase inhibitor (JAKi) was initiated before vs. after EMA’s warnings although a trend towards a lower proportion of VTE history was observed. Five VTE events occurred, four with BARI, one with TOFA. Cumulative persistence rate at 2 years was similar between BARI and TOFA: HR 0.96; 95% Cl: 0.52 to 1.74; p = 0.89. Conclusions: Our study did not show a significant change in patients characteristics starting a JAKi after the EMA’s warnings, probably due to a lack of power. Though, the lower proportion of VTE history in patients after May 2019 suggests that rheumatologists have taken into account the potential VTE risk. These results need to be confirmed by further evidence.