Small-cell lung cancer (SCLC) is a cancer with poor prognosis. For relapsed extensive-stage (ES) SCLC, second-line treatment options are scarce. Topotecan was the only approved treatment in this setting until 2020. Since topotecan induces significant toxicities, alternative off-label regimens are being used. This study evaluated real-world efficacy and safety of Paclitaxel Gemcitabine chemotherapy in patients with relapsed ES-SCLC. We retrospectively reviewed data from all consecutive patients with relapsed ES-SCLC who received Paclitaxel Gemcitabine chemotherapy from september 2008 to january 2022 in two centers. Patient characteristics (n=188) were: PS≥2: 24.5%; brain metastasis: 42%; platinum-sensitive disease: 41%. Patients received Paclitaxel Gemcitabine as second- (77%) third (18%) or fourth (6%) line of therapy. Median progression-free and overall survival were 2.1 (95CI 1.8–2.4) and 3.8 (95CI 3.3–4.8) months in the overall population, respectively, with 17% response rate (RR) and 28% disease-control rate. PS, history of brain radiation, platinum-sensitive disease, liver, and adrenal gland metastasis were associated with longer survival in univariate analysis. PS was the only prognostic factor in multivariate analysis, with 21% RR and 4.1 months median DOR in PS 0-1 patients. Paclitaxel Gemcitabine chemotherapy may represent a treatment option in PS0-1 relapsed SCLC.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a recognized treatment in Parkinson’s disease (PD), but knowledge is still limited regarding its possible impact on patients with behavioral addiction (BA) who undergo surgery. To assess this effect of STN-DBS, we prospectively studied the follow-up from 3-months pre-surgery to 12-months post-surgery of 12 PD patients with pre-existing BA (9 with pathological gambling disorder, 2 with hypersexual disorder, and 1 with compulsive shopping disorder) in a multicenter study. Patients were assessed for BA, for mental status with anxiety, depression, mania, emotional process and for PD, using the Unified Parkinson’s Disease Rating Scale motor examination (UPDRS3) and cumulative daily L-dopa equivalent daily dose (LEDD). Mean 6 and 12-month post-surgery scores were compared to baseline. After one year of STN-DBS, our results indicated that the treatment remained generally effective and stable. There was no effect on mania state or negative impact on motor signs. A significant improvement of the anxiety score was also observed. The STN is an interesting target for new therapeutic stimulation in BA and works to investigate the precise target in this neurobiological architecture should be performed in the future.

(1) Background: Asthma and Chronic Obstructive Pulmonary Disease (COPD ) are major global health issues, impacting morbidity, mortality, and healthcare costs. Despite the proven benefits of pharmacist involvement in managing these conditions, their potential in hospitals remains underused. This study aimed to identify patients at high risk of rehospitalisation post-exacerbation of asthma or COPD, to target pharmaceutical interventions. (2) Methods: Data from the University Hospital for January-December 2019 on adult admissions for asthma/COPD were analyzed, focusing on demographics, hospitalization, and clinical outcomes. (3) Results: Among the 140 patients enrolled, a significant majority (91%) underwent adjustments in their treatment regimens during their hospital stay, and nearly 59% faced readmission within six months. A survival analysis highlighted a notable disparity in the rates of rehospitalisation-free survival between patients with asthma and those with COPD, identifying COPD patients as having a higher susceptibility to rehospitalisation. (4) Conclusion: The study found COPD pa-tients at greater risk but didn't specify a priority profile, suggesting the necessity for broad, cus-tomized interventions to improve outcomes and reduce healthcare strain.

According to the French Agency for Food, Environmental and Occupational Health & Safety, electromagnetic hypersensitivity affects more than 3 million people in France, and headaches are a very frequent cause of complaint in electrohypersensitive patients, to the point of dominating the clinical picture. These headaches share characteristics with migraine pathology, and clinical improvement with anti-migraine therapy has led us to consider that the headache in the electrohypersensitive patient may be a variant of the migraine disease mediated by the TRPA1 receptor, which if confirmed, would offer effective therapeutic possibilities to relieve the electrohypersensitive patient.

French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there are few data available on the description of parasites circulating in this area, especially on protozoan belonging to the phy-lum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on Oxford Nanopore Technologies sequencing platform using the 18S gene of fourteen Apicomplexa-positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify as Apicom-plexa-positive 10 samples out of 14 and reveal the presence of co-carriages. The same samples were also sequenced with Illumina platform, for validation purposes. On samples identified as Apicomplexa-positive by both platforms, a strong positive correlation at up to genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detec-tion, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.

Engineering properties of bedrock materials at Badlands National Park were used to develop models for Park managers to assess slope erosion and stability for fossil resource protection. Six fully instrumented sites were used to document slope conditions. Bedrock consisted of Oligocene White River Group rocks. Bulk erosion rates correlated to grain size with silty-sandy materials producing higher mass erosion rates as a function of the silt-to-clay ratio and plastic index. Data indicated that as grain size decreased, plastic index increased leading to a decrease in erodibility. These parameters were used to construct a grain-size proxy, ψ, that was substituted for grain size, D, in Bagnold’s entrainment equation and provided significant improvement in calculation of critical entrainment velocities for fine-grained materials. Hydraulic analyses of slope and pediment surface processes indicated surface roughness was a controlling factor and materials washed from rough steep slopes were effectively transported across smooth low-angle pediments with slope-to-pediment angle ratios of nearly 6:1. Slope stability modeling of ten slopes produced high factors of safety for all slopes, even under saturated conditions and was attributable to clay cohesion. All results were used to construct models that predicted years until net slope erosion equaled 2.5 cm (1 inch). Using these results, Park managers were advised to visit erosion-prone sites on a 1 to 6 year schedule, based on site geology and slope aspect, to adequately protect critical fossil resources from destruction.

(1) Background: TNF inhibitors (TNFi) have revolutionized the treatment of rheumatoid arthritis (RA). However, 30-40 % of RA patients do not respond adequately to those biologics. In addition to neutralizing soluble TNF, TNFi have the ability to bind the transmembrane form of TNF, tmTNF. Importantly, tmTNF can act itself as a receptor that induces a “Reverse Signaling” (RS) in cells. We previously showed that certolizumab, a Fab’ TNFi, activates RS in human primary monocytes, at least in part through the transcription factor NRF2 that is known to regulate the expression of genes involved in anti-inflammatory response and oxidative stress. (2) Methods: Here, we have developed an assay for the prediction of clinical response of RA patients to TNF inhibitors. This assay is based on mRNA quantitation of CD36 activation and of 6 genes induced by NRF2 following tmTNF RS in fresh monocytes. (3) Results: We could predict the response to anti-TNF monoclonal antibodies (mAbs) with 93.3 % accuracy. However, our method was not suitable for the prediction of the response to TNF soluble receptor etanercept. (4) Conclusions: We have developed a rather simple, short-term, test that can be standardized. Predicting the response to TNF mAbs will help physicians offer the best available treatment and provide patients with personalized medicine.

Purinergic receptors (P2X) are ATP-gated ion channels with an elusive role in the CNS. While the P2X2 and P2X4 subtypes are widely expressed in most neurons (i.e. at the edge of the postsynaptic densities of excitatory synapses), the direct contribution of P2X to synaptic transmission is uncertain. Several P2X have been shown to participate in receptor cross-talk: an interaction where one receptor (e.g. P2X2) influences the activity of another (e.g. GABA or AMPA receptors.) In this study, we tested for interactions between P2X2 or P2X4 and N-methyl-D-aspartate receptors (NMDARs). Using two-electrode voltage-clamp electrophysiology experiments in X. laevis oocytes, we demonstrate that both P2X2 and P2X4 interact with NMDARs in an inhibitory manner. When investigating the molecular domains responsible for this phenomenon, we found that the P2X2 c-terminus (CT) could interfere with P2X2 and P2X4 interactions with NMDARs. We also report that 11 distal CT residues on the P2X4 facilitate the P2X4-NMDAR interaction, and that a peptide consisting of these P2X4 CT residues (11C) can disrupt the interaction between NMDARs and P2X2 or P2X4. Collectively, these results provide new evidence for the modulatory nature of P2X2 and P2X4, suggesting they might play a more nuanced role in the CNS.

Motor control, movement impairment and postural control recovery targeted in rehabilitation could be affected by pain. The main objective of this comprehensive review is to provide a synthesis of the effect of experimental and chronic pain on postural control throughout the available literature. After presenting the neurophysiological pathways of pain, we demonstrated that pain, preferentially localized at low back or in the leg induced postural control alteration. While proprioceptive and cortical excitability seems modified with pain, spinal modulation assessment might provide new understanding of the pain phenomenon related to postural control. Literature highlight that the motor control of trunk muscles in patient presenting with low back pain could be dichotomized in two populations, where the first one over-activate trunk muscles, the second one under-activate trunk muscles, and both generating increase of tissues loading. Taking account all this findings, will help clinician to provide adapted treatment for managing both pain and postural control.

Background: Gliomas, including the most severe form known as glioblastomas, are primary brain tumors arising from glial cells, with significant impact on adults, particularly men aged 45 to 70. Recent advancements in the WHO classification now correlate genetic markers with glioma phenotypes, enhancing diagnostic precision and therapeutic strategies. Aims and Methods: This scoping review aims to evaluate the current state of deep learning (DL) applications in the genetic characterization of adult gliomas, addressing the potential of these technologies for a reliable virtual biopsy. Results: We reviewed 17 studies, analyzing the evolution of DL algorithms from fully convolutional networks to more advanced architectures (ResNet and DenseNet). The methods involved various validation techniques, including k-fold cross-validation and external dataset validation. Conclusions: Our findings highlight significant variability in reported performance, largely due to small, homogeneous datasets and inconsistent validation methods. Despite promising results, particularly in predicting individual genetic traits, the lack of robust external validation limits the generalizability of these models. Future efforts should focus on developing larger, more diverse datasets and integrating multidisciplinary collaboration to enhance model reliability. This review underscores the potential of DL in advancing glioma characterization, paving the way for more precise, non-invasive diagnostic tools.

(RADA)4 nanoscaffolds are excellent candidates for use as peptide delivery vehicles: they are relatively easy to synthesize with custom bio-functionality, and assemble in situ to allow a focal point of release. This enables (RADA)4 to be utilized in multiple release strategies by embedding a variety of bioactive molecules in an all-in-one ‘construct’. One novel strategy focuses on the local, on-demand release of peptides triggered via proteolysis of tethered peptide sequences. However, the spatial-temporal morphology of self-assembling nanoscaffolds may greatly influence the ability for enzymes to both diffuse into as well as actively cleave substrates. Fine structure and its impact on overall affect on peptide release is poorly understood. In addition, fractal networks observed in nanoscaffolds are linked to the fractal nature of diffusion in these systems. Therefore, matrix morphology and fractal dimension of virgin (RADA)4 and mixtures of (RADA)4 and matrix metalloproteinase 2 (MMP-2) cleavable substrate modified (RADA)4 were characterized over time. Sites of high (GPQG+IASQ, CP1) and low (GPQG+PAGQ, CP2) cleavage activity were chosen. Fine structure was visualized using established according to established methods. After 2 hrs of incubation, nanofiber networks showed an established fractal nature, however nanofibers continued to bundle in all cases as incubation times increased. It was observed that despite extensive nanofiber bundling after 24 hrs of incubation time, the CP1 and CP2 nanoscaffolds were susceptible to MMP-2 cleavage. The properties of these engineered nanoscaffolds characterized herein illustrate that they are an excellent candidate as an enzymatically initiated peptide delivery platform.

Rarely has a chemical elicited as much controversy as has dichloroacetate (DCA). DCA was initially considered a dangerous toxic industrial waste product. Then it was a potential treatment for lactic acidosis. However, the main controversies started in 2008 when DCA was found to have anti-cancer effects in experimental animals. These publications showed contradictory results in vivo and in vitro, so that a thorough consideration of this compound in cancer is merited. Despite 50 years of experimentation, DCA’s future in therapeutics is uncertain. Without adequate clinical trials and lack of health authorities’ approval, DCA has been introduced in off -label cancer treatments in alternative medicine clinics in Canada, Germany, and other European countries. The lack of well-planned clinical trials and its use by people without medical training has discouraged consideration by the scientific community. There are limited thorough clinical studies of DCA, and many publications are individual case reports. Case reports of DCA benefits against cancer have been increasing recently. Furthermore, it has been shown that DCA synergizes with conventional treatments and other repurposable drugs. Beyond the classic DCA target, pyruvate dehydrogenase kinase, new target molecules have also been recently discovered. These findings have renewed interest in DCA. This paper explores whether existing evidence justifies further research on DCA for cancer treatment and it explores the role DCA may play in oncology treatment.

Objectives: To investigate the etiology of amyotrophic lateral sclerosis (ALS) in an adult female patient. Methods: We conducted trio genome sequencing on a 35-year-old woman with progressive weakness in her left upper limb, as well as on her parents. Prior to sequencing, we performed a comprehensive neurological work-up on the patient, including neurological exam, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Results : The propositus experienced weakness and atrophy in her left hand 6 months before the evaluation. This was associated with brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Genome trio sequencing identified a likely pathogenic de novo variant in the propositus’s KIF1A gene (NM_001244008.2): c.574A>G, p.(Ile192Val). Discussion: Pathogenic variants in the KIF1A gene have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). The present report describe a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.

The real long-term influences of in utero drug exposure in pregnant women on childhood development have yet to be fully determined and depend on the duration of in utero drug exposure and maternal drug levels. Therapeutic drug monitoring (TDM) during pregnancy may help limit fetal drug exposure while maintaining therapeutic drug levels in maternal blood. Most antibody therapies used in patients with Inflammatory Bowel Disease (IBD) are IgG molecules which are actively transported across the placenta, especially during the third trimester of the pregnancy. Here we propose an up to date clinical review to summarize the available findings of serum drug levels in maternal blood during pregnancy, in the blood cord, infants at delivery and in breast milk of patients with IBD treated with biologics. Conversely to adalimumab (ADA) levels, which are relatively stable during pregnancy, infliximab (IFX) drug clearance decreased significantly during the second and third trimesters, leading to increasing maternal IFX concentrations. As most guidelines recommend using live vaccines in infants at the age of one or earlier in case of negative serum drug levels in newborns, statistical models could help clinicians in making a decision to adjust the last dose of the biologic during pregnancy and to determine the optimal date to vaccinate. Altogether, data from the literature offers strong reassurance regarding the safety profile of anti-TNFα therapies during pregnancy not only for IBD patients who intend to conceive, but also for pregnant women and for the physicians taking care of these patients. ADA and IFX levels in breast milk are detectable but very low and therefore it is recommended to pursue breast feeding under anti-TNFα therapy. Our knowledge on ustekinumab or vedolizumab levels in pregnant women remains unclear and scarce. It is currently not recommended in patients with IBD in clinical practice. Therefore, TDM and proactive dose adjustment are not necessary during pregnancy since its impact for making a clinical decision have not yet been clearly demonstrated in routine practice. Overall, drug concentrations in the blood cord, the infant at birth and postpartum serum concentrations in infants, due to active placental drug transfer, may have a greater impact than the limited drug transfer in breast milk during lactation on the risk of infection and developmental outcomes. Ustekinumab and vedolizumab exposure during pregnancy and lactation are both considered low risk by the recent ECCO guidelines despite the limited data currently available.

Introduction: Management of hypoxic-ischemic encephalopathy (HIE) has been the subject of international recommendations. However, some aspects remain within the realm of service practices and appear to vary greatly from one center to another. Objectives: To achieve a multidisciplinary consensus in France regarding management of HIE newborns that are not covered by international and national guidelines. Methods: This is a prospective, multicenter study using the Delphi method from April 21, 2021, to July 15, 2021. Perinatal professionals were contacted through professional societies. Participants received a questionnaire in three successive rounds. Each proposal was rated using a Likert scale from 1 (completely disagree) to 8 (completely agree). An item was considered consensual if at least 70% of responses were in agreement or disagreement. Results: 58 french neonatal professionals participated. A consensus was reached in the first round concerning the use of passive hypothermia in maternity ward, with 84% agreement and to define the target temperature between 35.0°C and 35.5°C at the third round. Regarding hypoglycemia in the delivery room, 79.2% agreed in the first round to correct blood glucose levels below a threshold of <2.2 mmol/l. Parenteral route was the preferred correction method for 91.4% of respondents, while enteral route via nasogastric tube did not reach consensus. Conclusion: This study highlights the variability in definitions and practices among professionals in the management of HIE. Consensus was found regarding certain care practices performed without formal guidelines. The work to harmonize definitions and practices for the management of HIE likely needs to continue.

: Background: A wide variety of coils are available for vascular embolization. This study aims to evaluate the safety and efficacy of a new Prestige coil. Method: Retrospective analysis of a multicentre registry data collected between February 2022 and November 2022. The choice of the embolization agent used was left at the investigator’s discretion to treat peripheral vascular anomalies. Patients for whom at least one Prestige coil was used were included in Series 1. All other patients were included in Series 2. Efficacy and safety were evaluated. Patients were followed up for one month. Results: 220 patients were included, 110 in each series. Patients were 149 men (67.7%) and 71 women (32.3%), of median age 62.5 years [IQR: 35.8-73], similar in the two series. The complete occlusion of the targeted vessel was reported in 96.4% (N=106/110) in Series 1 and in 99.7% (N=109/110) in Series 2. 4 patients experienced non-serious adverse events (1.8%, N=4/220): 1 back pain, 1 vomiting in Series 1, 1 off-target embolization and 1 puncture site hematoma in Series 2. 16 patients (7.2%, N=16/220) were lost to follow up. Improvement of the patient’s general state at one month was reported in 79.0% (N=83/105) in Series 1 and in 74.7% (N=74/99) in Series 2. 10 deaths occurred, 5 in Series 1 (4.8 %, N=5/105) and 5 in Series 2 (5.1%, N=5/99). They all concerned critically ill patients embolized for emergent arterial bleeding. Conclusion: the 1-month follow-up showed that the Prestige coils, alone or in combination, are efficient and safe.

This paper presents a concise mathematical framework for investigating both feed-forward and backward process, during the training to learn model weights, of an artificial neural network (ANN). Inspired from the idea of the two-step rule for backpropagation, we define a notion of F_adjoint which is aimed at a better description of the backpropagation algorithm. In particular, by introducing the notions of F-propagation and F-adjoint through a deep neural network architecture, the backpropagation associated to a cost/loss function is proven to be completely characterized by the F-adjoint of the corresponding F-propagation relatively to the partial derivative, with respect to the inputs, of the cost function.

Following the rapid spread of COVID-19 across the globe, the intense response that was demanded of diagnostic centers and research laboratories prompted the use of numerous products and protocols for the management of SARS-CoV-2 specimens. In these settings, proper handling of such infectious specimen is necessary to ensure the safety of personnel and to reduce the risk of active transmission. Our aim was to evaluate the inactivation efficacy of different inactivating methods, notably from commercial lysis buffers available in diagnostic kits. Heat and sodium dodecyl sulfate detergent were also included in our investigations. A cell culture-based assay was used, and supported by molecular qRT-PCR detection, to show in vitro infectivity reduction after inactivation treatment. Overall, all the investigated methods were successful in inactivating SARS-CoV-2. Ten minutes of contact with the commercial buffers completely stopped in vitro SARS-CoV-2 infectivity. Fifteen minutes at 68°C and 30 minutes at 56°C as well as one hour with sodium dodecyl sulfate detergent at 2, 1, 0.5, and 0.1% yielded the same results. These findings demonstrate the reliability of these protocols with regards to biosafety. Inactivation by heat and sodium dodecyl sulfate detergent are rather simple and can be readily available methods for rendering an infectious SARS-CoV-2 specimen inactive, especially in settings where commercial buffers are not available.

Laparoscopic partial nephrectomy (LPN) after hyperselective embolization of tumor vessels (HETV) in a hybrid operating room (HOR) that combines traditional surgical equipment with advanced imaging technology, is a non-clamping surgical approach to treat localized kidney tumors that have shown promising short-term results. The aim of this study was to evaluate the long-term oncological and functional outcomes of this procedure. All consecutive patients treated for a localized kidney tumor by LPN after HETV between May 2015 and October 2022 in a single academic institution were included in the study. Clinical, pathological and biological data were collected prospectively in the uroCCR database. We evaluated perioperative data, postoperative complications, surgical margin and modification of renal function after surgery. We included 245 patients. Median tumor size was 3.2 (2.5-4.4) cm. The R.E.N.A.L. complexity was low, medium and high for 104 (43.5%), 109 (45.6%) and 26 (10.9%) patients, respectively. Median LPN time was 75 (65 -100) min and median blood loss was 100 (50-300) mL. Surgical postoperative complications occurred in 56 (22.9%) patients with 17 (5.7%) major complications. The median preoperative Glomerular Function Rate (GFR) was 90.5 (77-101.8) mL/min and the median GFR variation at 6 months was -7.5 (-15- -2) mL/min. Malignant tumors were present in 211 (86.1%) patients and 12 (4.9%) patients had positive surgical margins. After a median follow-up of 27 (8-49) months, 20 (8.2%) patients had a tumor recurrence and 4 (1.6%) died from cancer. The use of a HOR to perform LPN after HETV is a safe and efficient non-clamping approach to treat localized kidney tumors.

The purposes of this study were to identify clinician’s characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the information sources influencing medical decision-making about treatment of schizophrenia. We surveyed 202 psychiatrists during 6 regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic and information sources about their clinical decisions were collected. Most of psychiatrists used second-generation antipsychotic (SGA), and preferentially an oral formulation, in the treatment of schizophrenia. SGA LAI was prescribed to 30.4% of schizophrenic patients. The duration and the type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with the higher use of LAI antipsychotics and the lower use of oral SGA. Personal experience, government regulatory approval and guidelines for the treatment of schizophrenia were the 3 main contributing factors guiding the clinical decision-making of clinicians about treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotic. The development of specialised programmes with top specialists should lead to better use of LAI in the treatment of schizophrenia.

Objectives. To show the superiority of eccentric versus concentric strengthening in terms of improving quadriceps strength in knee osteoarthritis (OA). A randomized controlled study was conducted to perform 12 sessions of either eccentric or concentric isokinetic muscle strengthening over 6 weeks Methods. We recruited males and females, aged between 40 and 70 years, with predominantly unilateral femorotibial OA. Exclusion criteria were having a prosthesis, inflammatory arthritis or flare-up of OA, symptomatic patellofemoral OA, cardio-vascular or pulmonary disease that could be a contraindication to the study treatment, and any pathology that could cause muscle weakness. The primary endpoint was the between-group difference in change in maximum concentric isokinetic knee extension peak torque (PT) at 60°/s on the OA side at 6 weeks. Secondary endpoints were between-group difference in change in concentric hamstring PT at 60°/s; eccentric quadriceps and hamstring PT at 30°/s; 10 m and 200 m walking speeds; pain and functional status (WOMAC score) at 6 weeks and 6 months. Results. The sample consisted of 11 females and 27 males, with a mean age of 57.7 ±7.52 years and a body mass index (BMI) of 25.95 ±3.93 kg/m². Quadriceps strength increased more at 6 weeks in the concentric than the eccentric group with no statistical difference. There was a rate of 25% major adverse events in the eccentric group. Conclusion. Eccentric training resulted in a smaller improvement in quadriceps strength than concentric training and was associated with a high risk of muscle injury, particularly to the hamstring muscles.

Aerococcus urinae is an aerobic Gram-positive coccus that grows as tiny alpha-hemolytic colonies. Actinotignum schaalii is a slow-growing facultative anaerobic Gram-positive rod. These bacteria are part of the urogenital microbiota of healthy patients, but can also be involved in urinary tract infections (UTIs), particularly in elderly men and young children [1–3]. Because A. urinae and A. schaalii are fastidious and are difficult to identify with phenotypic methods, they are underestimated causes of UTIs. Their growth is slow and requires a blood-enriched medium and an incubation time of 48 hours under anaerobic or 5% CO2 atmosphere. Furthermore, accurate identification is only possible using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or molecular-based methods. In rare cases, these bacteria can be responsible for invasive infections. We describe here the second case of bacteremic UTI caused by both A. schaalii and A. urinae in an 89-year-old woman who presented dyspnea and asymptomatic bacteriuria. This challenging clinical and microbiological diagnosis was made by our laboratory by Gram staining urine with a leucocyte count &gt;50/μL and/or a bacterial count &gt;14/μL, urinary culture on blood agar plate, and direct bacterial identification on positive blood culture bottles (BCBs) by MALDI-TOF MS. After 10 days of antimicrobial treatment consisting of 2g amoxicillin PO t.i.d the patient was discharged with complete clinical and biological recovery. A. schaalii and A. urinae are probably still underestimated causes of UTIs. Microbiologists should assess the presence of these two bacteria in urine using the appropriate culture and identification methods where direct examination is positive for small Gram-positive cocci or rods, and a urinary dipstick is negative for nitrites and associated with leukocyturia.

It has been proven that in standard Einstein gravity, exotic matter (i.e. matter violating the point-wise and averaged weak and null energy conditions) is required to stabilize traversable wormholes. Quantum field theory permits these violations due to the quantum coherent effects found in any quantum field . Even reasonable classical scalar fields violate the energy conditions. In the case of the Casimir effect and squeezed vacuum states, these violations have been experimentally proven. It is advantageous to investigate methods of minimizing the use of exotic matter. One such area of interest is extended theories of Einstein gravity. It has been claimed that in some extended theories, stable traversable wormholes solutions can be found without the use of exotic matter. There are many extended theories of gravity and in this review paper we first explore f(R) theories and then explore some wormhole solutions in f(R) theories including Lovelock gravity.

Introduction: Hospitalization in a COVID-19 unit represents a significant source of stress and psychological distress for patients. Our study aims to determine the factors of psychological distress in the therapeutic and psychosocial management of patients hospitalized with a COVID-19 infection. Methods: This cross-sectional study was carried out over 8 months at the COVID-19 zone of the CHU HASSAN II of FES. 99 patients were evaluated within days of diagnosis by psychometric scales of anxiety, depression, and post-traumatic stress. In the course of this follow-up, we found the presence of psychological impacts in these patients, and we tried to find correlating factors between the occurrence of psychiatric disorders and the set of factors related to sociodemographic data, hospitalization course and treatments taken, as well as family support. Results: 35% of patients had scores in favor of post-traumatic stress disorder, 37% of the patients had definite depression and 50% had anxiety. Post-traumatic stress, depression, and anxiety were correlated with sociodemographic factors, hospitalization, treatments received, and length of stay. Conclusion: The prevalence of anxiety-depressive disorders and post-traumatic stress disorder was high in patients with COVID-19, hence the interest in providing psychological and psychosocial care in the emergency department.

There was no significant difference in bacterial adhesion between the 3 bone graft types tested, regardless of the bacterial strain used (p &gt; 0.22). After 72 hours of culture, there was no significant difference between the Fresh and Frozen bone groups, while the number of CFU in the Decellularised group was significantly lower (p &lt; 0.01), averaging -0.72 +/- 0.08 lg, -0.20 +/- 0.01 lg and -0.78 +/- 0.48 lg with S. epidermidis, S. aureus and E. coli respectively. Absolute values differences are low, and considering fresh bone (equivalent to autograft) as the gold standard due to its low infection rates in clinical studies, we can conclude that adhesion and biolfilm development characteristics are similar between Fresh, Frozen and Decellularised bone grafts..

The Lagrangian and Eulerian structure and dynamics of a strong wind event in the Tokar Gap region are described using a WRF model hindcast for 2008. Winds in the Tokar Gap reach 25 m s-1 and remain coherent as a jet far out over the Red Sea, whereas equally strong wind jets occurring in neighboring gaps are attenuated abruptly by a jump-like hydraulic transition that occur just offshore of the Sudan coast. The transition is made possible by the supercritical nature of the jets, which are fed by air that spills down from passes at relatively high elevation. By contrast, the spilling flow in the ravine-like Tokar Gap does not become substantially supercritical and therefore does not undergo a jump, and also carries more total horizontal momentum. The Tokar Wind Jet carries some air parcels across the Red Sea and into Saudi Arabia, whereas air parcel trajectories in the neighboring jets ascend as they cross through the jumps, then veer sharply to the southeast and do not cross the Red Sea. The mountain parameter Nh/U is estimated to lie in the rage 1.0-4.0 for the general region, a result roughly consistent with a primary gap jet having a long extension, and supercritical jets spilling down from higher elevation passes. The strong event is marked by the formation of a cyclonic cell near the upstream entrance to the Tokar Gap, a feature absent from the more moderate events that occur throughout the summer. The cell contains descending air parcels that are fed into the primary and secondary jets. An analysis of the Bernoulli function along air parcel trajectories reveals an approximate balance between the loss of potential energy and gain of internal energy and pressure, with surprisingly little contribution from kinetic energy, along the path of the descending flow. All jets attain the critical wind speed nominally required to loft dust into the atmosphere, though only the Tokar Gap has a broad, delta region with plentiful deposits of silt.

Clopidogrel is one of the most prescribed antiplatelet drugs for cardiovascular diseases prevention. Clopidogrel is a prodrug metabolised by CYP2C19 in active metabolites with anti-aggregant effect. Pharmacogenetic variants such as CYP2C19*2 variant can alter the anti-aggregant effect of clopidogrel leading to a higher risk of cardiovascular disease relapse. The aim of this study was to evaluate the prescription characteristics of CYP2C19 pharmacogenetics in patients on clopidogrel treatment, based on a specific query in a clinical data warehouse. We evaluated the demographics of patients, prescribers, medical indications, CYP2C19 pharmacogenetic tests and therapeutic changes. Neurologists were the main prescribers of CYP2C19 pharmacogenetic tests associated with clopidogrel treatment in a context of suspicion of stroke relapse. Pharmacogenetic tests were mainly prescribed a posteriori to clopidogrel prescription. Clopidogrel pharmacogenetic resistance was associated with the prescription of lysine acetylsalicylate in substitution of clopidogrel. Clear clinical practice guidelines are needed to position CYP2C19 pharmacogenetic testing for patients on clopidogrel treatment.

Over the past decade, studies have demonstrated the importance of bioactive metabolites derived from the microbiota in the regulation of physiological processes essential for homeostasis and the maintenance of human health. Strategies to modulate the production of these metabolites in the gastrointestinal tract hold promise for combating dysbiosis or inflammatory bowel disease. Metabolic engineering of probiotics could be one of these solutions. In this work, we engineered Escherichia coli Nissle 1917 (EcN) to overproduce spermidine, a metabolite known for its anti-immunosenescence and anti-inflammatory properties. Using a rational synthetic biology approach coupled with analysis by high resolution mass spectrometry, we designed in several steps and validated engineered probiotics overproducing and excreting spermidine. Based on our results, we first added the enzyme substrate putrescine and showed the overproduction of spermidine and decided to add a transporter limiting the production of the acetylated form of spermidine. Next, we used untargeted metabolomics to study the impact of engineering on the central metabolism of E. coli Nissle. Untargeted metabolomics appears to be a good strategy to optimize the metabolic engineering of probiotic strains and thus accelerate their development for personalized medicine.

Purpose: To report the progression of patients diagnosed with birdshot chorioretinopathy (BSCR) initially treated with corticosteroids. Methods: We included 39 BSCR patients followed for ≥1 year. Patients were classified into 2 groups according to their initial treatment: methylprednisolone followed by prednisone (n=28) and prednisone alone (n=11). We analyzed the progression under treatment after 1, 3, 6 months, 1 year, and at the end of follow-up. Results: At the end of follow-up, 31/39 (79.5%) patients had reached inflammation control. Thirteen out of 28 (46.4%) and 6/11 (54.5%) patients were treated exclusively with corticosteroids, and 18/19 (94.7%) of them had reached inflammation control at the end of follow-up; their mean (range) corticosteroid dose was 3.5 (0-10) mg/day. Conclusion: We found that the prolonged corticosteroid therapy treatment strategy resulted in inflammation control in half of BSCR patients. This control was maintained with low doses of cortisone, usually <5 mg/day.

In a context of exponential demographic growth, the imbalance between human resources and public health problems is impelling us to envision other solutions to the difficulties faced in the diagnosis, prevention and large-scale management of the most common diseases. Cardiovascular diseases represent the leading cause of morbidity and mortality worldwide. A large-scale screening program would make it possible to promptly identify patients with high cardiovascular risk in order to manage them adequately. Optical coherence tomography-angiography (OCT-A), as a window into the state of the cardiovascular system, is a rapid, reliable, and reproducible imaging examination that enables prompt identification of at-risk patients through the use of automated classification models. One challenge that limits the development of computer-aided diagnostic programs is the small number of open-source OCT-A acquisitions available. To facilitate the development of such models, we have assembled a set of images of the retinal microvascular system from 499 patients. It consists of 814 angiocubes as well as 2005 en face images. Angiocubes were captured with a swept-source OCT-A device of patients with varying overall cardiovascular risk. To the best of our knowledge, our dataset, RASTA, is the only publicly available dataset comprising such a variety of images from healthy and at-risk patients. This dataset will enable the development of generalizable models for screening of cardiovascular diseases from OCT-A retinal images.

Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). The co-occurrence of ARMs and CSS in an individual is unexpected since both diseases are very rare. A review of the literature enabled us to identify 12 individuals with both CSS and ARMs. Among these 12 individuals, 9 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are likely a rare consequence of CSS, especially for ARID1A-related CSS.

(1) Background: Bronchial artery embolization has been shown to be effective in the management of neoplastic hemoptysis. However, knowledge of pulmonary artery embolization is lacking. To evaluate safety and efficacy of pulmonary artery embolization in patients presenting with hemoptysis related to lung tumors. (2) Methods: This retrospective study reviewed all consecutive patients with cancer and at least one episode of hemoptysis that required pulmonary artery embolization from December 2008 to December 2020. The endpoints of the study were technical success, clinical success, recurrence of hemoptysis and complications. (3) Results: A total of 92 patients were treated with pulmonary artery embolization (63.1 years ± 9.9; 70 men). Most patients had stage III or IV advanced disease. Pulmonary artery embolization was technically successful in 82 (89%) patients and clinically successful in 77 (84%) patients. Recurrence occurred in 49% of patients. Infectious complications occurred in 15 patients (16%). The 30-days mortality rate was 31%. At 3 years, survival rate was 3.6%. Tumor size, tumor cavitation and necrosis and pulmonary artery pseudo-aneurysm were significantly associated with recurrence and higher mortality. (4) Conclusions: Pulmonary artery embolization is an effective treatment to initially control hemoptysis in patient with lung carcinoma but recurrence rate remains high and overall survival remains poor.

Hamstring muscle (HM) flexibility is frequently compromised in people with chronic low back pain (CLBP), contributing to disability and leading to a less favorable recovery. In a previous article, we presented the results of a study on the immediate effect of passive HM stretching on flexibility in 90 people with CLBP. There was considerable variability in the changes after stretching. The objective of this supplementary analysis was to compare the clinical characteristics of individuals who experienced a significant improvement in flexibility with those who did not. We fixed a threshold of 7° to indicate an improvement in passive Straight Leg Raise (SLR) angle and differentiate between 'Responders' and 'Non-responders' to passive HM stretching. Only Body Mass Index differed between groups; it was significantly smaller in Responders (p=0.007). The majority of Non-responders experienced workplace accidents, but this was of marginal difference compared to Responders (p=0.056). Further studies should consider a broader clinical analysis with a larger sample size to understand which factors influence the HM stretching response in CLBP patients.

(1) Background: LUS has emerged as a simple, rapid and non-invasive method for the dynamic assessment of pulmonary congestion, a major prognostic factor and a therapeutic target in AHF. (2) Methods: In the single-center prospective observational study, 42 patients hospitalized for AHF in the post-emergency polyvalent medicine department of CHU Grenoble were successively included between May 2021 and July 2022. Clinical examination, LUS and electrolyte panel results were collected daily. Vital status was assessed 30 days after the last LUS. The primary endpoint was the evolution of the number of B-lines according to the dose of diuretic administered ; (3) Results: We performed 188 LUS. Our patients were elderly (85.8 [SD 8.1]) and comorbid. The median number of B-lines decreased from 17 at admission to 7 in the middle of the hospital stay, then stagnated until discharge. Simultaneously, the median dose of diuretics, initially stable at a maximum of 40 mg/d IV, decreased to 20mg/d IV by the end of hospital stay. Patients with CKD had a higher mean number of B-lines at entry (24.2 [SD 11.6]) compared to those without CKD (8.2 [SD 8.8]). However, the evolution of B-lines number was independent of creatinine levels. 30-day all-causes mortality was significantly related to the number of B-lines at discharge (15.2 [SD 10.1] in deceased patients versus 3.9 [SD 5.4] in living patients, p

Aim To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV melanoma. Materials and methods We conducted a retrospective monocentric observational study over a 3 years period in patients referred for 18F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint or tyrosine kinase inhibitors (ICIs or TKIs) as of January-2017. Imaging reports were analysed by two physicians in consensus. Anatomical site responsible for discordances, as well as induced changes in treatment were noted. Results Eighty patients were included and 195 couples of scans analysed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient’s management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients’ management in 2/13 cases (15%). The more frequent anatomical site involved was subcutaneous for 18F-FDG PET/CT findings and lung or liver for ceCT. Conclusions Treatment monitoring with 18F-FDG

Aim To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV melanoma. Materials and methods We conducted a retrospective monocentric observational study over a 3 years period in patients referred for 18F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint or tyrosine kinase inhibitors (ICIs or TKIs) as of January-2017. Imaging reports were analysed by two physicians in consensus. Anatomical site responsible for discordances, as well as induced changes in treatment were noted. Results Eighty patients were included and 195 couples of scans analysed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient’s management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients’ management in 2/13 cases (15%). The more frequent anatomical site involved was subcutaneous for 18F-FDG PET/CT findings and lung or liver for ceCT. Conclusions Treatment monitoring with 18F-FDG

Area covered: These drugs, particularly calcineurin inhibitors, have very narrow therapeutic windows, i.e., they have numerous drug-related side effects. Herein, we focus on the most frequent immunosuppressive drug-related side effects that we encounter in kidney-transplant recipients: namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). However, other therapies that are used after kidney transplantation, e.g., valcancyclovir, may also contribute to adverse events such as leukopenia. For each side-effect, we suggest how it can be prevented and how to treat it when present.

Though there has been a decline in the number of new cases of viral hepatitis-induced acute liver failure in Europe and the United States of America, viral hepatitis still remains the leading cause of acute liver failure in Asia-Pacific and South America. However, the epidemiology of viral-hepatitis-induced acute liver failure in sub-Saharan Africa-the world epicenter of viral hepatitis-is unclear. The aim of this review was to collate data on the incidence, prevalence, specific etiologic agents, features/diagnosis, treatment and prognosis of viral-induced acute liver failure in sub-Saharan Africa. One hundred and forty-seven cases of viral-induced acute liver failure were recorded in 11 studies conducted in six countries between 1981-2020. Etiological agents were: Hepatitis viruses A, B, C, and E, as well as Adenovirus, Enterovirus, Parvovirus, Herpes Simplex Virus (HSV) and EBV. HAV was the most frequent in paediatric subjects: (11/16) 69% and (19/30) 63%. HBV was the only etiological agent in the study that only included adults. HEV (genotype 2 in one study) contracted amidst hepatitis E outbreaks was the most commonly reported cause of ALF in pregnant women. Treatment was mainly supportive, and liver transplantation reported only in South Africa. Where reported, case fatality rates were high. In conclusion, viral-hepatitis induced acute liver failure is largely understudied in sub-Saharan Africa. The few available data are consistent with literature from the other parts of the world regarding aetiologic agents. Liver transplantation is not available in most sub-Saharan African countries, and short-term case fatality rates of individuals with acute liver failure could outstrip current rates from the other world regions.

A lack of data reproducibility (“reproducibility crisis”) is debated across many scientific and medical disciplines. A systematic analysis of the available evidence on the reliability of scientific data revealed that, although the existence of a reproducibility crisis is widely perceived, conclusive data on the scale of the problem are lacking. Most importantly we found that, although the debate is largely focused on methodological issues, researcher conduct defines research standards and in turn data reliability. The availability of reliable methods itself does not guarantee good practice. Moreover, research is typically characterised by a lack of established methods due to its immanent novelty. Despite the crucial importance of researcher conduct, research and conclusive data on the determinants of researcher behaviour are missing. In conclusion, meta-research is urgently needed that establishes an understanding of the factors that determine researcher behaviour. This knowledge can then be used to implement and iteratively improve measures, which incentivise researchers to apply the highest standards resulting in high quality data.

Low 25 OH vitamin D (25(OH)D) in preterm infants is a risk factor of bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and lung histological alterations evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120nmol/L is also a risk factor for BPD or death. This retrospective single-center cohort study included all infants born <31 weeks gestational age without major malformation with at least a determination of 25(OH)D <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120nmol/L (50.5% vs 43.9%, p=0.53). The logistic regression identified weight (OR 0.997, 95%CI [0.995-0.998]) and term (OR 0.737, 95%CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95%CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

The pre-pregnancy BMI and the gestational weight gain are two important determinants of pregnancy outcomes. The aim of this study was to determine obstetric outcomes associated with insufficient gestational weight gain in women with a pre-pregnancy BMI &lt; 18.5 kg/m2. This study was based on observational routinely-collected data from a University Hospital Maternity. The participants were allocated to the group sufficient or insufficient gestational weight gain: ≥ 12.5 kg and &lt; 12.5 kg respectively. Primary outcomes were the adjusted birth weight in percentiles (%) and the proportion of SGA newborns. Secondary outcomes were obstetric and perinatal outcomes. A total of 135 participants with a median age of 28±8 years were included. The adjusted birth weight in percentiles was significantly lower in the insufficient gestational weight gain group (27.2±45.4 vs 42.6±48.8 %; P&lt;0.001). Moreover, the insufficient gestational weight gain is associated with a higher risk of SGA (28.1% vs 11.3%; P=0.017). Our study also showed increased risks of premature rupture of membranes, anaemia and intrauterine growth restriction in women with an insufficient weight gain. Future studies should explore the risk factors associated with insufficient weight gain, in order to develop specific care for underweight pregnant women.

Objectives: To develop a multivariate model for risk factors specific to early onset preeclampsia (EOP) and late onset preeclampsia (LOP) in our entire population (singleton and twin pregnancies). Material and methods: 20 year-observational population-based historical cohort study (2001-2020). All consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion’s maternity. A standardized validated epidemiological perinatal data base. Results: During the 20-year period, there were 81,834 pregnancies and 83,555 infants born, 1232 dichorionic and 350 monochorionic twin pregnancies. There were 2120 cases of preeclampsia, of which 2001preeclamptic singleton pregnancies and 119 twin pregnancies (incidence 7.5% in twin pregnancies vs 2.5% singletons, OR 3.0, p<0.001). Independent risk factors for EOP and LOP in a multivariate model (controlling for the two major confounders: namely maternal ages -both risks for EOP and LOP- and maternal pre-pregnancy BMI – specific risk factor for LOP) were: history of preeclampsia (aOR 11.7 for EOP, 7.8 for LOP, p < 0.0001), chronic hypertension (aOR 7.3 for EOP, 3.9 for LOP, p < 0.0001), history of perinatal death (aOR 2.2 for EOP, p < 0.0001 and 1.48 for LOP, p= 0.007), primipaternity (aOR 3.0 for EOP and 3.6 for LOP, p = 0.001), dizygotic twin pregnancies (aOR 3.7 for EOP, p < 0.0001 and 2.1 for LOP, p = 0.003), monozygotic twin pregnancies (aOR 3.98 for EOP, p = 0.003 and NS for LOP), ovulation induction (aOR 5.6 for EOP, p = 0.004 and NS for LOP), and in vitro fertilization (aOR 2.8 for EOP, p = 0.05 and NS for LOP). Specific to LOP and NS for EOP: renal diseases (aOR for LOP 2.9, p= 0.007) and gestational diabetes mellitus (aOR 1.2, p= 0.04). Conclusions: Maternal ages over 35 years, chronic hypertension , history of preeclampsia, ovulation induction, in vitro fertilizations, history of perinatal deaths and twin pregnancy (in our experience, especially mono zygotic twin pregnancies) are significant risk factors for EOP. New paternity is an independent factor for both EOP and LOP.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with 1-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n=136) and by pain perception for second class patients (n=62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

Background: Myocarditis is commonly diagnosed in the intensive care cardiology unit (ICCU). No current recommendation nor guideline aids aetiological assessment. Methods: From September 2021 to October 2023, 84 patients with acute myocarditis underwent thorough and systematic serum and blood cell panel evaluations to determine the most common causes of the myocarditis. Results: Of the 84 patients (median age 34 years, range 22–41 years, 79% male), 16 presented with complicated myocarditis. The systematic aetiological assessment revealed that 36% of patients were positive for lupus anticoagulant, 12% for antinuclear antibodies, 8% for anti-heart antibodies, and 12% for anti-striated muscle antibodies. Viral serology did not yield any significant results. After the aetiological assessment, one patient was diagnosed with an autoimmune inflammatory disorder (Still’s disease). T-cell subset analyses indicated that myocarditis severity tended to increase with the T-cell lymphopenia status. Conclusions: A comprehensive, systematic aetiological assessment was of limited value in terms of predicting the clinical or therapeutic outcomes in myocarditis patients presenting to the ICCU.

The science around the use of masks by the general public to impede COVID-19 transmission is advancing rapidly. Policymakers need guidance on how masks should be used by the general population to combat the COVID-19 pandemic. In this narrative review, we develop an analytical framework to examine mask usage, considering and synthesizing the relevant literature to inform multiple areas: population impact; transmission characteristics; source control; PPE; sociological considerations; and implementation considerations. A primary route of transmission of COVID-19 is via respiratory droplets, and is known to be transmissible from presymptomatic and asymptomatic individuals. Reducing disease spread requires two things: first, limit contacts of infected individuals via physical distancing and other measures, and second, reduce the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces the transmissibility per contact by reducing transmission of infected droplets in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. The decreased transmissibility could substantially reduce the death toll and economic impact while the cost of the intervention is low. Given the current shortages of medical masks we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory droplets become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask-wearing by infectious people ("source control") with benefits at the population-level, rather than mask-wearing by susceptible people, such as health-care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

Spinal Cord Stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that Awake Anesthesia (AA), consisting in Target Controlled Intra-Veinous Anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with Minimal Invasive Surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or General Anesthesia (MISGA group), or by Laminectomy under General Anesthesia (LGA group). All in all, MISAA appears to show significantly better performance in terms of patient pain coverage, as well as improved secondary outcomes. One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.

In medico-administrative database, certain prognostic factors cannot be taken into account. The main objective was to estimate the performance of two models based on two databases: Epi-thor clinical and medico-administrative databases. For each of the two databases, we randomly sampled a development dataset with 70% of the data and a validation dataset with 30%. Performance of models was assessed by Brier score, the area under the receiver operating characteristic (AUC ROC) curve and the calibration of the model. For Epithor and medico-administrative databases, the development dataset included 10,516 patients (with resp. 227 (2.16%) and 283(2.7%) deaths) and the validation dataset included 4,507 patients (with resp. 93 (2%) and 119 (2.64%) deaths). 15 predictors were selected in the models (including FEV, Body Mass Index, ASA score and TNM stage for Epithor). The Brier score values were similar in the models of the two databases. For validation data, the AUC ROC curve was 0.73 [0.68-0.78] for Epithor and 0.8 [0.76-0.84] for medico-administrative databases. The slope of the calibration plot was less than 1 for the two databases. This work shows the good performances of a model developed from a medico-administrative database, despite the absence of clinical variables used in practice by surgeons, such as FEV1, ASA score or TNM stage.

While Spinal Cord Stimulation (SCS) provides satisfaction to almost 2/3 of Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients implanted for refractory chronic back and/or leg pain when not adequately addressed the back pain component, leaves patients in a therapeutic cul-de-sac. Peripheral Nerve field Stimulation (PNfS) has shown interesting results addressing back pain in the same population. Far from placing these two techniques in opposition, we suggest that these approaches could be combined to better treat PSPS-T2 patients. We designed a RCT (CUMPNS), with a 12-month follow-up, to assess the potential added value of PNfS, as a salvage therapy, in PSPS-T2 patients experiencing a “Failed SCS Syndrome” in the back pain component. Fourteen patients were included in this study and randomized into 2 groups (“SCS + PNfS” group/n=6 vs “SCS only” group/n=8). The primary objective of the study was to compare the percentage of back pain surface decrease after 3 months, using a computerized interface to obtain quantitative pain mappings, combined with multi-dimensional SCS outcomes. Back pain surface decreased significantly greater for the ”SCS+PNfS” group (80.2% ± 21.3%) compared to the “SCS only” group (13.2% ± 94.8%) (p=0.012), highlighting the clinical interest of SCS+PNfS, in cases where SCS fails to address back pain.

The multidimensionality of chronic pain forces us to look beyond isolated pain assessment such as pain intensity, which does not consider multiple key parameters, particularly in patients suffering from post-operative Persistent Spinal Pain Syndrome (PSPS-T2). Our ambition was to provide a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and objective quantitative pain mapping assessments, the objective being to capture patient condition instantaneously, using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in a real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined using exploratory factor analyses to create an optimally accurate MCRI; as a single composite index, using pairwise correlations between measurements, it appeared to better represent all pain dimensions than any other classical score. It appeared to be the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by changing the physician’s perception of patient condition on the basis of objective and holistic metrics, and by providing new insights to therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.

Transarterial embolization (TAE) for high-flow pancreaticoduodenal artery (PDA) aneurysms in patients with celiac-trunk stenosis by the median arcuate ligament (MAL) has been found effective both after rupturing and to prevent rupture. The objective was to describe the TAE techniques used and their effectiveness in excluding PDA aneurysms due to MAL syndrome. This single-center retrospective study done at the Dijon-Bourgogne University Hospital included all patients treated by TAE in 2010–2022 for ruptured or unruptured high-flow PDA aneurysms caused by MAL syndrome. We identified 14 patients (7 women and 7 men; mean age, 64 years). Packing and trapping techniques were used alone or together. Occlusion was with microcoils, co-polymer, or cyanoacrylate glue, used separately or combined. Technical success was achieved in 13 (93%) patients. Clinical success was achieved in 12 (86%) patients. One major and two minor complications were recorded within the first 30 days. No complications occurred after 30 days. Follow-up ranged from 1 to 84 months. No cases of aneurysm recanalization were recorded to date. TAE had high technical and clinical success rates in our patients with unruptured or ruptured PDA aneurysms due to MAL syndrome.

Endovenous thermal methods are superseding surgical stripping for treating chronic superficial venous disease but require tumescent anesthesia and can cause heat-related nerve injuries. Endovenous cyanoacrylate ablation is a more recent technique that does not share these drawbacks. Retrospective observational study of consecutive adults managed with endovenous cyanoacrylate in 2018–2021 at a single university center. Follow-up was 18 months. We identified factors associated with target vein closure at 18 months and measured changes in quality of life using the generic 36-item Short-Form tool (SF-36) and the venous disease-specific VEINES-QOL/Sym questionnaire. Adverse events were collected. In the 55 study patients with 67 treated veins, the closure rate at 18 months was 94% (95%CI, 85%–98%). Target vein diameter ≥9.5 mm had 81% sensitivity and 75% specificity for predicting recanalization. Both quality-of-life scores improved significantly (P&lt;0.001 for both). The only adverse event was a type IV allergic reaction to cyanoacrylate that resolved with corticosteroid and histamine-antagonist therapy. Endovenous cyanoacrylate ablation was highly effective and safe in experienced hands. Studies are warranted to determine whether changes in the protocol increase the closure rate in patients with target veins ≥9.5 mm in diameter.

Abstract The aim of this research is to conduct a systematic review analysing the role of the physiotherapy interventions in palliative care. PRISMA as a critical appraisal tool was utilised for the selection of the research articles. The inclusion criteria were based on the year of publication, ease of availability, language, geographical location, and study type. To ensure the credibility, databases such as Elsevier, Proquest, and EBSCO Host were used to filter the grey content. Data published in the past ten years (2009-onwards) was only included to ensure the selection of the most recent interventions used by the physiotherapists. A total of 11 articles were selected which determined that physiotherapy interventions involving breathing exercises, aerobic exercises, manual therapies, and educational awareness were critical to promoting the functional capability and empower the patients.

While paresthesia-based spinal cord stimulation (SCS) has been proven effective to treat chronic neuropathic pain, initial benefits may lead to the development of “Failed SCS Syndrome’ (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neu-rostimulation adapters, in patients already implanted with SCS and experienced LoE. We retro-spectively analyzed a cohort of patients who were offered new SCS programs/waveforms through an implanted adapter between 2018 and 2021. Patients were evaluated before, and at 1, 3, 6 and 12-month follow-up. Outcomes included pain intensity rating with Visual Analog Scale (VAS), pain/coverage mappings and stimulation preferences. Last follow-up evaluations (N=27) showed significant improvement in VAS (p = 0.0001), ODI (p = 0.021) and Quality of Life (p=0.023). In the 11/27 patients with LoC, SCS efficacy on pain intensity (36.89%) was accompa-nied by paresthesia coverage recovery (55.57%) and pain surface decrease (47.01%). At 12-month follow-up, 81.3% preferred to keep tonic stimulation in their waveform portfolio. SCS conver-sion using adapters appears promising as a salvage solution, with an emphasis on paresthesia recapturing enabled by spatial retargeting. In light of these results, adapters could be integrated to SCS rescue algorithms or should be considered in SCS rescue.

Purpose: Prostate cancer is the most common male prevalent malignancy in Europe. Biological recurrence occurs in 20-40% of patients within 10 years following treatment. [18F]F-Choline PET/CT is the most used technique for detecting recurrent disease but is rarely positive for low PSA levels. [18F]PSMA-1007 PET/CT allows early detection of recurrence sites. Methods: We conducted a prospective multicenter study. Each patient had access to a [18F]F-Choline and [18F]PSMA PET/CT. The primary endpoint was to determine the therapeutic impact of the [18F]PSMA comparative to [18F]F-Choline PET/CT. Secondary endpoints were the diagnostic performance and the correlation between PET/CT parameters and prognostic factors of prostate disease. Results: 47 patients were included. A therapeutic modification was observed in 36% of them between what the clinicians expected after the [18F]F-Choline PET/CT and what they finally decided after the [18F]PSMA PET/CT. Diagnostic performance of [18F]F-Choline was 28% versus 70% for [18F]PSMA with a significant difference. With [18F]PSMA PET/CT, there was a significative correlation between PSA level of biological recurrence and SUVmax but not between ISUP score and SUVmax of the selected lesion. Conclusion: This study found a modification in therapeutic management following [18F]PSMA PET/CT in one third of patients. This change could result in earlier and better management with detection of lesions at a lower PSA level than is possible with [18F]F-Choline.

About half of the transcatheter aortic valve replacement (TAVR) recipients exhibit some degree of coronary artery disease (CAD), and controversial results have been reported regarding the impact of the presence and severity of CAD on clinical outcomes post-TAVR. In addition to coronary angiography, promising data has been recently reported on the use of both cardiac computed tomography angiography and the functional invasive assessment of coronary lesions whether by FFR or iFR in the work-up pre-TAVR. Despite mitigated available data, percutaneous revascularization of significant coronary lesions has been the routine strategy in TAVR candidates with CAD. Also, scarce data exists on the incidence, characteristics and management of coronary events post-TAVR, and increasing interest exist on potential coronary access challenges in patients requiring coronary angiography/intervention post-TAVR. This review provides an updated overview of the knowledge of CAD in TAVR recipients, focusing on its prevalence, clinical impact, pre- and post-procedural evaluation and management.

Background and Objectives: Botulinum toxin injections are commonly used for the treatment of spasticity. However, injection procedures are associated with pain and procedural anxiety. While pharmacological approaches are commonly used to reduce these, inno-vative technology might be considered as a potential non-pharmacological alternative. Given this context, immersive virtual reality (VR) has shown effectiveness in the man-agement of procedural pain[1]. Our retrospective pilot study aimed to assess the potential added value of virtual reality in the management of pain and anxiety during intra-muscular injections of botulinum toxin. Materials and Methods: Twenty-one adult patients receiving botulinum toxin injections were included. A numerical rating scale was used to assess pain and anxiety during the injection procedure. The patient reported the pain experienced during previous injections without VR before injection and the pain expe-rienced in the current procedure with VR after the end of the procedure. Level of satis-faction of VR experience, if they agreed to reuse VR for the subsequent toxin botulinum injection, and if they would recommend VR to other patients were assessed. Results: The use of virtual reality showed a decrease of 1.8 pain-related points compared to without technology. No significant improvement in the level of anxiety was reported. Patients were very satisfied by their VR experience (7.9 out of 10) and would agree to reuse VR in their next injection procedure (88%) and to recommend the use of VR in other patients (100%). Conclusion: VR was useful for managing procedural pain related to botulinum toxin injection in adults, with a high level of satisfaction reported by the patient. VR should be considered as a valuable alternative to pharmacological approach to manage procedural pain during Botulinum toxin injection in adults.

The objective of this work is to analyze the improvement of heat transfer in trapezoidal fin heat exchangers using numerical simulation. Heat exchangers are essential components frequently used in contemporary electronic gadgets to effectively disperse heat produced by high-power components. Nevertheless, as electronic devices continue to advance and become more powerful, the heat transfer capacity of heat exchangers is facing more requirements, therefore requiring enhanced heat dissipation efficiency. Afterwards, various fin angles were adjusted, and the heat transmission efficiency was compared. Modifying the angles can significantly improve the effi-ciency of convective heat dissipation. Moreover, it has been found that employing an optimized trapezoidal fin structure can further enhance the efficiency of heat transfer. The results indicate that trapezoidal fin heat exchangers provide superior heat dissipation efficiency compared to conventional heat exchangers. This is important for enhancing the thermal dissipation capabili-ties of electrical gadgets, hence guaranteeing steady functionality and extending their longevity. Subsequent study might explore supplementary methods to boost heat transmission in different heat exchanger configurations in order to meet the growing requirements for heat dissipation.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

Recently a measure termed F* was described, as an interpretable transformation of the F measure, also known as the Dice coefficient. Using elementary mathematical methods, it is shown that F* is in fact identical to a previously described measure, monotonically related to the F measure, and variously termed in previous publications, dating from the late 19^th to the late 20^th century, as the ratio of verification, the Jaccard similarity measure or index, the threat score, the Tanimoto index, and the critical success index. The origins of these different terms in different disciplines (weather forecasting, ecology, machine learning) may explain the repeated independent redescription of this measure.

The objective of this study was to compare the mental well-being of French women who were and were not pregnant during the first COVID-19 pandemic lockdown. We performed a nationwide online quantitative survey including all women between 18 and 45 years of age during the second and third weeks of global lockdown (March 25–April 07, 2020). The main outcome measures was the mental well-being measured by the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). This study analysed 275 responses from pregnant women and compared them with those from a propensity score–matched sample of 825 non-pregnant women. The median WEMWBS score was 49.0 and did not differ by pregnancy status. Women living in urban areas reported better well-being, while those with sleep disorders or who spent more than an hour a day watching the news reported poorer well-being. During the first lockdown in France, women had relatively low mental well-being scores, with no significant difference between pregnant and non-pregnant women. More than ever, health-care workers need to find a way to maintain their support for women’s well-being. Minor daily annoyances of pregnancy, such as insomnia, should not be trivialised because they are a potential sign of poor well-being.

Cochlear implantation (CI) allows rehabilitation for patients with severe to profound hearing impairment. Although the use of a robotic assistant provides technical assistance to the surgeon, the assessment of the impact of its use on auditory outcomes remains uncertain. We aim to com-pare the hearing results of patients who underwent bilateral cochlear implantation, one side was performed with manual insertion and the other side with robot-assisted insertion. The electrode array intrascalar positioning and the surgery duration were also studied. This retrospective intra-individual study involved 10 patients who underwent bilateral cochlear implantation. The study included 2 infants and 8 adults. The unique composition of this cohort enabled us to utilize each patient as their own control. Regarding speech disyllabic recognition, pure tone average, ECAP, ratio of array translocation, basilar membrane rupture, percentage of translocated electrodes there was no difference between manual and robot-assisted CI groups. This study is the first to compare intra-individual hearing performance after cochlear implantation either manually or robot-assisted. The number of patients and the time delay between manual and robotic implantation may have led to a lack of power, but there was no apparent difference in hearing performance between manual and robotic implantation.

Purpose: Melanoma’s incidence is increasing, and elderly people could be significantly impacted since the majority occurs in people over 65 years of age. Combined targeted therapies (TT) are current standard regimen for BRAF mutated metastatic melanoma (MM). Except for subgroups of pivotal trials, little data are available for TT in this population. Materials and Methods: Outcomes were explored in real life patients from MelBase, a French multicentric biobank dedicated to the prospective follow-up of unresectable stage III or IV melanoma. Patients treated by BRAF TT and/or MEK TT combined or not, were included from 2013 to 2017 in 2 groups: group 1 <65-year-old (yo), group 2 >65 yo, analyzed for tolerance and efficacy. Results: 353 patients were included: 231 in group 1, 122 in group 2. Median follow-up was 12 months (M). Median time of treatment was 6.9 M. A total of 80% had at least one Adverse Effect (AE). Most frequent AE (all grades) were mainly skin and subcutaneous, general, and gastrointestinal disorders. A total of 31% of AE were grade 3–4: 28% in group 1 and 39% in group 2 (p = 0.05). No differences were observed in all AE grades proportion, dose modifications, interruptions, and discontinuations. For each group, median overall survival was 20.3 M (CI 95%: 15.5–27.9) and 16.3 M (CI: 14.5–26.9), respectively (p = 0.8). Median progression free survival was 7.8 M (6.4–9.9) and 7.7 M (CI: 5.8–11.3) (p = 0.4). Objective response rate was 59% and 50% (p = 0.6). Conclusion: This study on a large multicentric cohort is the first to assess that TT is well tolerated in elderly BRAF-mutated patients such as in patients younger than 65. Efficacy was similar between groups with outcomes reaching those from pivotal studies. There is thus no argument against using TT in elderly people, although an onco-geriatric opinion is welcome for the most vulnerable.

First described in 1760 by the anatomist Morgagni, CoA is a congenital heart defect characterized by narrowing the aorta, typically distal to the left subclavian artery. It accounts for approximately 5-8% of all congenital heart diseases, with an incidence estimated at 4 per 10,000 live births. In 1944, the Swedish surgeon Clarence Crafoord achieved the first successful surgical CoA repair by performing an aortic end-to-end anastomosis on two patients aged 12 and 27 years old. Presently, the most prevalent techniques for surgical repair, particularly in infants and neonates with isolated coarctation, involve resection with end-to-end anastomosis (EEA) and the modified Crafoord technique (extended resection with end-to-end anastomosis (EEEA)). Subclavian flap aortoplasty (SCAP) is an alternative surgical option for CoA repair in patients under two years of age. In cases where the stenosis extends beyond resection and end-to-end anastomosis feasibility, patch aortoplasty (PP) employing a prosthetic patch can augment the stenotic region, especially for older patients. Despite advances in pediatric cardiology and cardiac surgery, recoarctation remains a significant concern after surgical or interventional repair. This comprehensive review aims to provide a thorough analysis of coarctation management, covering the pioneering techniques introduced by Crafoord using head-to-tail anastomosis and now extending to the contemporary era marked by percutaneous interventions as well as the recoarctation rate associated with each type.

Poor therapeutic outcomes have been attributed to inter-individual and interethnic variability in cytochrome P450 (CYP450)-dependent metabolism and altered drug retention associated with P-glycoprotein (P-gp). An individualized pharmacotherapeutic approach would benefit the genetically diverse South African population. The study aim was to develop a validated, targeted, analytical method to quantify seven probe drugs and their metabolites in dried blood spots (DBS) using the Mitra™ volumetric absorptive micro-sampling device for blood collection. An Agilent liquid chromatography (LC) system coupled to a Sciex 4000 QTRAP tandem mass spectrometer (MS) was used for method optimization and validation. Targeted LC-MS/MS methods were validated according to ICH guidelines. The validated LC-MS/MS method met the required bioanalytical standards for specificity, sensitivity, linearity, accuracy, precision, carry-over, and stability. This study successfully validated the use of DBS, collected with the Mitra™ microsampling device, to measure expected probe drug and metabolite concentrations using the “Geneva phenotyping cocktail” for the purpose of simultaneous phenotyping of in vivo CYP450 metabolic activity of the CYP1A2, -2B6, -2C9, -2C19, -2D6, and -3A4 enzymes, and P-gp transport activity. However, statistical analysis using Bland-Altman plots showed that not all analytes exhibited linear distribution pharmacokinetics between DBS and plasma, which influenced the predicted vs real plasma concentrations based on measurements in a DBS matrix. These findings were attributed to the blood-to-plasma concentration ratio, the physicochemical properties and stability of the analytes, and the extraction efficiency of the Mitra™ sampler. More research is required before DBS sampling can be substituted for conventional plasma sampling

To compare the quality of low-energy VMIs obtained with three DECT platforms according to phantom diameter. Three sections of the Mercury Phantom 4.0 were scanned on two generations of split-filter CTs (SFCT-1st and SFCT-2nd) and on one Dual-source CT (DSCT). Noise power spectrum (NPS), task-based transfer function (TTF) and detectability index (d’) were assessed on VMIs from 40 to 70keV. Highest noise magnitude values were found with SFCT-1st and noise magnitude was higher with DSCT than with SFCT-2nd for 26-cm (10.2±1.3%) and 31-cm (7.0±2.5%), and the opposite for 36-cm (-4.2±2.5%). The highest average NPS spatial frequencies and TTF values at 50% (f50) values were found with DSCT. For all energy levels, f50 values were higher with SFCT-2nd than SFCT-1st for 26-cm (3.2±0.4%) and the opposite for 31-cm (-6.9±0.5%) and 36-cm (-5.6±0.7%). The lowest d’ values were found with SFCT-1st. For all energy levels, d’ values were lower with SFCT-2nd than with DSCT for 26-cm (-6.2±0.7%), similar for 31-cm (-0.3±1.9%) and higher for 36-cm (5.4±2.7%). In conclusion, compared to SFCT-1st, SFCT-2nd exhibited lower noise magnitude and higher detectability values. Compared with DSCT, SFCT-2nd had lower noise magnitude and higher detectability for the 26-cm but the opposite was true for the 36-cm.

A popular approach to learning about admixture from population genetic data is by computing the allele-sharing summary statistics known as f-statistics. Compared to some methods in population genetics, f-statistics are relatively simple, but interpreting them can still be complicated at times. In addition, f-statistics can be used to build admixture graphs (multi-population trees allowing for admixture events), which provide more explicit and thorough modeling capabilities but are correspondingly more complex to work with. Here, I discuss some of these issues to provide users of these tools with a basic guide for protocols and procedures. My focus is on the kinds of conclusions that can or cannot be drawn from the results of f₄-statistics and admixture graphs, illustrated with real-world examples involving human populations.

Abstract: Characterization the 3-D structure of clouds is needed for a more complete understanding of the Earth's radiative and latent heat fluxes. Here we develop and explore a “ray casting” algorithm applied to the Multi-angle Imaging SpectroRadiometer (MISR) on board the Terra satellite, to reconstruct 3-D cloud volumes for observed clouds. The ray casting algorithm is first applied to geometrically simple synthetic clouds to show that, under the assumption of perfect, clear-conservative cloud masks, the reconstruction method yields overestimation whose magnitude depends on the cloud geometry and the resolution of the reconstruction grid relative to the image pixel resolution. The method is then applied to two select MISR scenes, fully accounting for MISR’s viewing geometry for reconstructions over the Earth’s ellipsoidal surface. The MISR Radiometric Camera-by-camera Cloud Masks at 1.1 km resolution and custom cloud masks at 275 m resolution independently derived from MISR RGB channels are used as input cloud masks. A wind correction method, termed “cloud spreading”, is devised and applied to the cloud masks to offset potential cloud movements over short time intervals (around 7 minutes at maximum) between the cameras. The MISR cloud top height product is used as a constraint to reduce the overestimation at the cloud top. The reconstruction results show that their uncertainty is significant when the wind correction is applied, and that they have more refined structures when the input cloud mask has a higher resolution. Recommendations for improving the presented cloud volume reconstructions as well as for future passive remote sensing satellite missions are discussed.

Background: The two-stage technique combining the Endoscopic Retrograde CholangioPancreatography (ERCP) with common bile duct (CBD) clearance carried out before the laparoscopic cholecystectomy represents the most common approach for CBD stones. Over time, different techniques have been proposed to manage cholecysto- choledocholithiasis (CCL) advantageously in one stage. Among these, the laparoendoscopic rendez-vous (LERV) addresses the CCL issue with a laparoscopic cholecystectomy with insertion of a guide wire performed at initial stage of the procedure, followed by the clearance of the bile duct carried out by the endoscopists. The goal of this study was to evaluate the efficacy and safeness of LERV procedure recording results and complications, also making a comparison between our results and current literature. Methods: We reviewed our experience of all consecutive patients with cholecysto-choledocholithiasis managed with LERV between January 2018 and December 2023. LERV success rate, operative time, length of hospital stay, stone recurrence, incidence of endoscopic and surgical complications were analysed. Results: A total of 120 patients underwent LERV in our facilities. We reported a 97% LERV success rate, 1.6% conversion-to-open rate, a median intraoperative time of 122 (range 95-220) min. The median hospital stay was 4 (range 2-38) days. An overall morbidity of 15% was reported (18/120): 15 Clavien-Dindo type 1/2, 2 type 3a and one type 3b. In two cases a re-operation during the hospital stay was necessary. At a median follow-up of 14 months (3-59) five patients experienced stone recurrence requiring redo-ERCP in two cases. Conclusion: LERV offers the significant advantage of a single stage procedure and hospitalisation along with a lower risk of post-ERCP pancreatitis, failed CBD cannulation and complications. Our experience confirms safety and effectiveness of the technique for CCL management.

Spectacular shifts have been led to by The COVID-19 crisis in consumer behavior. Retailers will have to work hard to meet ever-evolving customer service experience with respect to the ways in which it may be differently affected by offline or online transactions in order to win and stay relevant. We suggest an integrative framework and construct customer service experience hypotheses, based on its antecedents and consequences that will contribute to academic study as well as managerial implications. The hypotheses are tested by a simultaneous equation model employing two data sets of the retail industry's offline and online customers. In this study, 571 samples of these businesses, 319 and 252 respondents from offline and online retail channels, respectively, were collected by means of an online web survey of consumers. The results show that the impact of consequences and antecedents of CSX differs based on the media utilized. The integrative framework of CSX in its online medium is far more effective than its explanatory power offline. The outcomes are reasonably counterintuitive in so far as they demonstrate that while most elements of CSX where a service is selected offline is the same in terms of customer loyalty and value equity, the emotional element related to the service provider is higher when the service is selected offline rather than online. These outcomes indicate that, contrary to popular fears, the online medium enables firms to develop a loyal customer foundation. These findings offer perceptivity into how an online channel could be used to better complement the offline channel, contributing towards new knowledge and understanding on CSX and how it may be utilized for managerial decision-making.

Persistent Pain after Spinal Surgery can be successfully addressed by Spinal Cord Stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outcomes, WITH OR WITHOUT lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that ma-chine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, Regularized Logistic Regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient boosted trees to test this hypothesis and to perform internal and external validations, the objec-tive being to confront model predictions with lead trial results using a 1-year composite out-come from 103 patients. While almost all models have demonstrated superiority on lead trial-ing, the RLR model appears to represent the best compromise between complexity and inter-pretability in prediction of SCS efficacy. These results underscore the need to use AI based-predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.

Litsea martabanica root's antioxidant and AChE activity showed promise as a pesticide detoxification agent in our previous study. In addition to roots, its leaves can help mitigate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in many countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally cut down whole trees to obtain them. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extracts from L. martabanica leaves instead of its roots through in vitro and in vivo investigations. The findings showed that L. martabanica water extracts and fractions demonstrated varied antioxidant activity. The water extract, obtained using traditional extraction methods, was chosen for in vivo experiments. Rats received the extract followed by chlorpyrifos exposure for 16 days. Results indicated reduced acetylcholinesterase activity in chlorpyrifos-exposed rats, while treatment with leaf extract led to increased activity, suggesting its potential as a detoxifying agent. Histopathological examination revealed no liver cell necrosis and showed liver cell regeneration, indicating potential protection against free radical-induced liver damage without affecting rat liver weight or biochemical profiles. Utilizing L. martabanica leaves for healthcare purposes holds promise without negative environmental impact.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015 TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of the production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015, TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The present study aims to measure the technical efficiency and establish core factors effecting rice production in Cambodia. Four-years dataset generated from the central government document “Profile on Economics and Social” of entire 25 provinces between 2012-2015 and the stochastic production frontier model (SFA) was applied. The results indicated that the level of output (quantity) of Cambodian rice production varied according to the different level of capital investment in agricultural machineries, total rice actual harvested area, and technically fertilizers application within provinces. Furthermore, evidence revealed the overall mean efficiency of rice production is 78.4% implies that there is still room to further improve technical efficiency by given the same level of inputs and technology. More importantly, the findings revealed that irrigation, production technique and amount of agricultural supporting staffs are being as the most important influencing factors of rice production’s technical efficiency in Cambodia. In conclusion, present study strongly recommends the development of irrigation systems and good water management practices to be considered and bring into more effective actions by the central government as well as related agencies for improving rice production in Cambodia in addition to capital investment and improving technical skills of supporting staffs and rural farmers.

It is now well accepted that most chronic diseases have a common feature which is “low-grade” inflammation. Whether inflammation is causal or rather consequent to these diseases is still a matter of debate. A key factor of inflammation is considered to be “oxidative stress”, which is the result of an alteration of redox homeostasis which is critical for the regulation of physiological cell and organ metabolism and proliferation. The term “oxidative stress” is how-ever often used in an inappropriate manner as the primary target of the initial oxidative radical, superoxide ion, is nitric oxide which, being in large excess, acts as a “buffer”, yielding reactive nitrogen species. It is only once the superoxide fluxes exceed the nitric oxide fluxes that true “oxidative stress” occurs. Nitro-oxidative stress is a more appropriate term which takes into account the evolving generation of reactive nitrogen and oxygen species and their effects on cell and organ pathophysiology. The molecular bases of redox homeostasis and nitro-oxidative stress will be presented and discussed using obesity-linked inflammation as a path-ophysiological example.

In recent years, the problem of ecosystem degradation caused by human activities has become increasingly serious. Vegetation restoration is a key means to solve this problem, which has increased. To address the suitability and structural optimization of vegetation restoration in the Loess Plateau, the MaxEnt model was used to quantify the impacts of environmental and human activities on the planting suitability of vegetation restoration species at the raster scale. Three layers of trees, shrubs, and herbs with 12 common vegetation restoration species were selected. The factor index system was constructed by combining climatic, ecological, and socio-economic data, and the MaxEnt model predicted land suitability. It was found that human activities significantly increased the unsuitable planting area. This especially affected Robinia pseudoacacia in the tree layer and Amorpha fruticosa in the shrub layer. Highly suitable and moderately suitable areas were mainly located in sparsely populated areas with close water sources. Through maximum suitability optimization, it was identified that the overall spatial distribution of the three layers in the study area was relatively consistent, and the structural dominance of trees + shrubs + herbs and single herbs in the vertical structure was obvious, which were concentrated in the southwestern and northeastern parts of the study area, respectively. In addition, organic content (OC) and distance from the road to woodland (RW) were the dominant factors affecting land suitability, with a contribution rate of more than 50% and up to 80%. These results provide a scientific basis for optimizing planting structures. They are of significant theoretical and practical significance in guiding vegetation restoration work.

Stratified Taylor Couette Flow (STCF) undergoes transient growth. Recent studies have shown that there exists transient amplification in the linear regime of counter-rotating STCF. It is reported that as Gr increases, the maximum amplification factor ($G_0$) initially decays before it eventually starts growing after reaching a certain critical value Gr$_{c}$. Assuming other parameters of the model are kept constant, the value Gr$_{c}$ changes with respect to different speed ratios of the cylinders. The observed decay/growth pattern of $G_0$ is attributed to the interplay between the induced shear and buoyancy. In this study, the mechanism that triggers this observed pattern is investigated. The kinetic budget of the optimal transient perturbation is analysed numerically to simulate the interaction of the shear production (SP), buoyancy production (BP) and other energy components that contributes to the total optimal transient kinetic energy. These contributions affect the total energy by influencing the perturbation to extract kinetic energy (KE) from the mean flow. The decay of $G_0$ resulted from the positive amplification of both BP and SP, while the growth is attributed to the negative and positive amplification of BP and SP, respectively. The optimal SP is positively amplified, implying that there is the possibility of constant linear growth. These findings agree with the linear growth rate for increasing values of Gr.

The Indian meal moth, Plodia interpunctella, poses a significant threat to global agricultural products. Although pheromone-based technologies show promise for P. interpunctella management, limitations like single-sex targeting necessitate exploring complementary strategies. Vegetable-based oils represent a potential alternative, but their efficacy, sex-specificity, and interaction with sex pheromones remain unclear. To answer these questions, we first examined attraction of P. interpunctella female and male adults to ten different vegetable oils, i.e., camellia, corn, olive, peanut, rapeseed, sesame, soybean, sunflower, walnut, and a blended oil (mixture of sunflower seed, rapeseed, soybean, peanut, and sesame oils), in the semi-field conditions. Sesame, olive, and blended oils demonstrated most attractive, capturing significantly more adults compared to other oils. We then evaluated effectiveness of these three attractive oils and their combinations with P. interpunctella sex pheromone in a grain warehouse. Traps baited with these oils captured significantly more females and males compared to control traps without attractants. However, sex pheromone addition did not improve male capture and significantly reduced female capture, suggesting an inhibitory effect. Our findings highlight the potential of blended, olive, or sesame oil trap alone as alternative monitoring and trapping tools for P. interpunctella, delivering novel insights into the development of efficient integrated pest management strategies for stored products.

In this work, we explore a the different forms of a new type of modified gravity, namely f(φ) gravity. We construct the Big Rip type for the energy density and the curvature of the universe. We show that dark energy is a result of the transformation of the field φ mass (dark matter) to energy. In addition, we provide that Ω_{m}≈0,050, Ω_{DM}≈0,2, Ω_{DE}≈0,746, is in excellent agreement with observation data. We explore a generalized formalism of braneworld modified gravity. We also construct a new field equations, which generalize the Einstein field equations. We provide a relation between the extra dimension in 3-brane with the vacuum energy density. We show that the energy density of matter depends directly on the number of dimensions. We manage to find the value of the Gauss-Bonnet coupling α=1/4 which is a good agreement with the results in the literature, this correspondence creates a passage between f(R) gravity and Gauss-Bonnet gravity, this comparison leads to a number of bulk dimensions equal to D=10¹²¹+4.

In many application problems, F-transform algorithms are very efficient. In F-transform techniques, we replace the original signal or image with a finite number of weighted averages. The use of weighted average can be naturally explained, e.g., by the fact that this is what we get anyway when we measure the signal. However, most successful applications of F-transform have an additional not-so-easy-to-explain feature: the partition requirement, that the sum of all the related weighting functions is a constant. In this paper, we show that this seemingly difficult-to-explain requirement can also be naturally explained in signal-measuring terms: namely, this requirement can be derived from the natural desire to have all the signal values at different moments of time estimated with the same accuracy.

In this paper we have defined the effect of bulk viscosity on Quintessence model and scaler field potential as well as on classical field. We have shown the same effect for modified gravity with f(R,T)= R+f(T). In the derivation we have predicted the possibility of time dependent evolution of gravitational constant G and anisotropy.

The compatibility between the de Sitter Swampland conjecture and Ho\v{r}ava-Lifshitz $F(\bar{R})$ theories with a flat FLRW metric is studied. We first study the standard $f(R)$ theories and show that the only way in which the dS conjecture can be made independent of $R$ is by considering a power law of the form $f(R)\sim R^{\gamma}$. The conjecture and the consistency of the theory puts restrictions on $\gamma$ to be greater but close to $1$. For the $F(\bar{R})$ theories described by its two parameters $\lambda$ and $\mu$ we use the equations of motion to construct the function starting with an ansatz for the scale factor in the Jordan frame of the power law form. By doing a conformal transformation on the three metric to the Einstein frame we can obtain an action of gravity plus a scalar filed by relating the parameters of the theory. The non-projectable and projectable cases are studied and the differences are outlined. The $F(\bar{R})$ function obtained consists of terms of the form $\bar{R}^{\gamma}$ with the possibility of having negative power terms. The dS conjecture leads to inequalities for the $\lambda$ parameter, in both versions it gets restricted to be greater but close to $1/3$. For the general case in which $\mu$ and $\lambda$ are considered as independent, the action contains an extra term but we propose that the conjecture is still applicable. Once again the non-projectable and projectable cases are studied. The $F$ function obtained has the same form as before, the consistency of the theory and the dS conjecture lead to a set of inequalities on both parameters that are studied numerically. In all cases $\lambda$ is restricted by $\mu$ around $1/3$ and we obtain $\lambda\to1/3$ if $\mu\to0$. Finally we consider the $f(R)$ limit $\mu,\lambda\to1$ and we obtain consistent results.

Demand-Side Management (DSM) is an essential tool to ensure power system reliability and stability. In future smart grids, certain portions of a customer’s load usage could be under the automatic control of a cyber-enabled DSM program, which selectively schedules loads as a function of electricity prices to improve power balance and grid stability. In this scenario, the security of DSM cyberinfrastructure will be critical as advanced metering infrastructure and communication systems are susceptible to cyber-attacks. Such attacks, in the form of false data injections, can manipulate customer load profiles and cause metering chaos and energy losses in the grid. The feedback mechanism between load management on the consumer side and dynamic price schemes employed by independent system operators can further exacerbate attacks. To study how this feedback mechanism may worsen attacks in future cyber-enabled DSM programs, we propose a novel mathematical framework for (i) modeling the nonlinear relationship between load management and real-time pricing, (ii) simulating residential load data and prices, (iii) creating cyber-attacks, and (iv) detecting said attacks. In this framework, we first develop time-series forecasts to model load demand and use them as inputs to an elasticity model for the price-demand relationship in the DSM loop. This work then investigates the behavior of such a feedback loop under intentional cyber-attacks. We simulate and examine load-price data under different DSM-participation levels with three types of random additive attacks: ramp, sudden, and point attacks. We conduct two investigations for the detection of DSM attacks. The first studies a supervised learning approach, with various classification models, and the second studies the performance of parametric and nonparametric change point detectors. Results conclude that higher amounts of DSM participation can exacerbate ramp and sudden attacks leading to better detection of such attacks, especially with supervised learning classifiers. We also find that nonparametric detection outperforms parametric for smaller user pools, and random point attacks are the hardest to detect with any method.

Non-normal mode stability analysis has long been employed to study linear transient characteristics of wall bounded shear flows. However, the application of this approach to investigate shear flows with stratified thermal conditions (STCF) has received limited attention. This paper examines thermal effects on Taylor-Couette flow. The results in this study indicate the possibility of a subcritical bifurcation in stratified Taylor-Couette flow.

In kidney transplant recipients, belatacept is usually pursued indefinitely after it has been started. In the setting of the belatacept shortage and after having evaluated the benefit-risk ratio, we established a strategy consisting of time-limited belatacept therapy / transient calcineurin inhibitor withdrawal, whose results are analyzed in that study. We considered all the kidney transplant recipients that had been switched from conventional immunosuppressive therapy to belatacept and then for whom belatacept has been withdrawn intentionally. Furthermore, in the first 8 patients, we assessed changes in peripheral blood mononuclear cells (PBMC) transcriptome using RNAseq before and 3 months after belatacept withdrawal. Over the study period, 28 out of 94 patients had belatacept intentionally withdrawn including 25 (89%) switched to low-dose CNI. One rejection due to poor compliance occurred. The eGFR after 12 months remained stable from 48 ± 19 ml.1.73m^-2 to 46 ±17 ml.1.73m^-2 (p = 0.68). However, patients that resumed belatacept / withdrew CNIs (n=10) had a trend towards a better eGFR comparing with the others (n =15): 54 ± 20 ml.1.73m^-2 vs eGFR 43 ± 16 ml.1.73m^-2 respectively (p = 0.15). The only factor associated with belatacept resumption was when the withdrawal took place during the COVID-19 outbreak. Transcriptome analysis of PBMCs, did not support rebound in alloimmune response. These findings underpin the use of belatacept as part of a time-limited therapy, in selected kidney transplant recipients, possibly as an approach to allow efficient vaccination against SARS-Cov-2.

Background: Understanding SARS-CoV-2 dynamics and transmission is a serious issue. Its propagation needs to be modeled and controlled. The Alsace region in the East of France has been among the first French COVID-19 clusters in 2020. Methods: We confront evidence from three independent and retrospective sources: a population-based survey through internet, an analysis of the medical records from hospital emergency care services, and a review of medical biology laboratory data. We also check the role played in virus propagation by a large religious meeting that gathered over 2,000 participants from all over France mid-February in Mulhouse. Results: Our results suggest that SARS-CoV-2 was circulating several weeks before the first officially recognized case in Alsace on February 26^th 2020 and the sanitary alert on March 3^rd. The religious gathering seems to have played a role for secondary dissemination of the epidemic in France, but not in creating the local outbreak. Conclusions: Our results illustrate how the integration of data coming from multiple sources could help trigger an early alarm in the context of an emerging disease. Good information data systems, able to produce earlier alerts, could have avoided a general lockdown in France.

Ciguatera fish poisoning (CFP) is one of the most common causes worldwide of marine poisoning associated with fish consumption from tropical areas. Its incidence is underreported. CFP cases seem to increase with grouped cases reported during summer. Exposure to ciguatoxin, the toxin responsible for CFP with sodium-channel agonistic, cholinergic, and adrenergic activities, may result in a large spectrum of manifestations. We aimed to describe the clinical characteristics, management, and outcome of CFP in Martinique, French West Indies. We conducted an observational retrospective single-center study for six years (October 2012 to September 2018) including all CFP patients managed by the prehospital medical services, admitted to the university hospital emergency department, or declared to the regional health agency. One hundred and forty-nine CFP patients (81females/63males; median age, 46 years [interquartile range, 34-61]) were included. Acute features consisted of general (91%; mainly, myalgia pruritus, and asthenia), gastrointestinal (90%; mainly diarrhea, abdominal pain, and nausea), neurological (72%; mainly, paresthesia, dysgeusia, and impairment of hot/cold feeling), and cardiovascular manifestations (22%; bradycardia, hypotension, and heart conduction disorders). Management was supportive. No patient died but symptoms persisted in 40% of the 77 patients with follow-up on day 15. CFP was mainly attributed to the ingestion of trevallies (59%), snappers (13%), and king mackerels (8%) with collective contaminations (71%). Unusual fish (tuna, salmon, and spider conchs) were suspected in rare cases. Ingestion of trevallies was associated with significantly higher persistent symptoms (odds ratio, 3.00; 95% confidence interval, [1.20-8.00]; p=0.03). CFP incidence was 0.67 cases per 10,000 patient-years in Martinique over the study period. To conclude, CFP represents an increasing public health issue in Martinique like in other Caribbean islands. Patients present usual but possibly life-threatening features. The outcome is excellent despite frequently prolonged manifestations.

(1) Background: The COVID-19 pandemic had a devastating impact on the world, causing widespread illness and death. It is essential to focus on prevention strategies to limit the spread of the disease. Despite the advent of vaccines, maintaining a vigilant approach to prevention remains paramount. While vaccines are essential, they do not guarantee absolute immunity, and their protective effect may diminish over time; (2) Methods: We reviewed effective strategies to prevent COVID-19 transmission. We focused on me-ta-analyses (MA), literature reviews (LR) and the health care context. Various prevention measures and interventions were reviewed. Both es-tablished practices and unresolved issues were considered; (3) Results: Standard precautions (SP) as the cornerstone of infection control, with hand hygiene and mask use as key components. Debate about the relative importance of droplet versus aerosol transmission led to differences in recommendations between agencies at the onset of the pandemic. We have clarified the role of personal protective equipment (PPE), including eye protection. The effectiveness of masks in pre-venting transmission is reviewed. The use of surgical masks is recommended to prevent droplet transmission, while eye protection is recommended in combination with masks. Although data show some risk reduction, the clear superiority of N95/FFP2 over surgical masks remains unproven. In terms of room occupancy, ventilation is critical in reducing the risk of transmission in poorly ventilated environments. The use of negative pressure isolation rooms (NPIRs) is being investigated. The presence of viral RNA on surfaces does not necessarily indicate infectivity, and the risk of transmission by surface contact is low if surfaces are properly maintained and hand hygiene is practised regularly. Testing for SARS-CoV-2 in asymptomatic persons in healthcare settings may help prevent transmission; (4) Conclusions: Prevention of SARS-CoV-2 transmission requires a multifaceted approach, including reducing particle emissions from infected persons by wearing masks, eliminating aerosols by ventilation, ensuring physical separation, and protecting exposed persons with masks and eye protection.

Background: Our objective was to conduct a comprehensive analysis of the reproducibility of foot and ankle anthropometric measurements with a three-dimensional (3D) optical scanner. Methods: We evaluated thirty-nine different anthropometric parameters obtained with 3D Laser UPOD-S Full-Foot Scanner in a healthy population of twenty subjects. We determined the variance of the measurements for each foot/ankle, and the average variance among different subjects. Results: For 40 feet and ankles (15 women and 5 men; mean age 35.62 +/- 9.54 years, range 9-75 years), the average variance was 1.4 ± 2 (range 0,1 to 8). Overall, the mean absolute measurement error was < 1 mm, with a maximum variance percentage of 8.3%. Forefoot and midfoot circumferences had a low variance < 2.5, with variance percentages < 1%. Hindfoot circumferences, malleolar heights, and the length of the first and fifth metatarsal to the ground contact points showed the highest variance (range 1 to 7). Conclusion: This optical scanner achieved a good reproducibility of a large set of foot and ankle anthropometric measurements. It is a valuable tool for clinical and research purposes.

Temperature Cycle Induced Deracemization (TCID) offers a promising approach to obtain enantiopure solids from racemic mixtures. By combining rapid racemization in solution and temperature swings, homochirality is theoretically achieved. Despite theoretical expectations of doubled yields compared to traditional chiral separation methods, such as in Preferential Crystallization, experimental validation remains lacking. We applied TCID to (1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl) pentan-3-one) (Cl-TAK), introducing a post-TCID cooling step to enhance yield and a washing step to augment enantiopurity. This refinement yielded an 89.8% mass yield with 99.1% enantiomeric excess in the crystal phase (c.e.e.) within 24 hours on an 8.75g scale, showcasing improved performance with insignificant process duration extension. Additionally, we explored the stochasticity of deracemization, observing the development from low initial crystal enantiomeric excesses(1-6% c.e.e0) at a 2.5 g scale. Kinetic analysis revealed that a 2% c.e.e0 effectively mitigates chiral flipping risks and induction time in our system. Our study underscores the potential for reduced initial c.e.e. to expedite deracemization and presents a straightforward method to optimize yield and purity, facilitating industrial application.

We investigate alternative candidates to dark energy that can explain the current state of the universe in the framework of the generalized teleparallel theory of gravity f(T ) where T denotes the torsion scalar. To achieve this, we carried out a series of reconstruction taking into account to the ordinary and entropy-corrected versions of the holographic and new agegraphic dark energy models. These models used as alternative to dark energy in the literature in order describe the current state of our universe. It is remarked that the models reconstructed indicates behaviors like phantom or quintessence models. Furthermore, we also generated the EoS parameters associated to entropy-corrected models and we observed a transition phase between quintessence state and phantom state as showed by recent observational data. We also investigated on the stability theses models and we created the {r − s}. The behavior of certains physical parameters as speed of sound and the Statefinder parameters are compatible with current observational data.

The risk of malignant transformation of induced pluripotent stem cells (iPSC)-derived cells in response to DNA damage is a potential concern as the tumor suppressor genes TP53 and CDKN2A are transiently inactivated during reprogramming. Here, we evaluated the integrity of cellular senescence pathways and DNA double-strand break (DSB) repair in iPSC-derived human fibroblasts (i-HF) compared to their parental skin fibroblasts (HF). Using a variety of functional assays, we show that the capacity of i-HF to enter senescence and repair DSB is not compromised after damage induced by ionizing radiation (IR) or overexpression of H-RASV12. Still, i-HF lines are transcriptionally different from their parental lines, showing enhanced metabolic activity and higher expression of p53-related effector genes. As a result, i-HF lines generally exhibit increased sensitivity to various stresses, have an elevated senescence-associated secretory phenotype (SASP) and cannot be immortalized unless p53 expression is knocked down. In conclusion, while our results suggest that i-HF are not at a greater risk of transformation, their overall hyperactivation of senescence pathways may impede their function as a cell therapy product.

In this work we present a novel steganography algorithm, based on Fractal Transform domain, combined with the principles of Cryptography. The proposed method uses a private key, which will indicate which segment of the image will be taken and encoded with the Fractal Transform, to then insert the secret bits in the transformed coefficients, thus generating the stego image.

The objective of this study was to investigate the umami characteristics of soy sauce using electronic tongue evaluation and amino acid composition and Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. The soy sauce peptides were isolated from soy sauce using XAD-16 macroporous resin combined with ethanol solution. Results showed that the soy sauce peptide fraction eluted by 60% ethanol (SS-60%) exhibited a prominent umami taste and the umami scores were highly positively correlated with the amino acid nitrogen contents of soy sauces. The umami scores of SS-60% were significantly positively correlated with the contents of free amino acids. Especially, Phe showed the highest positive correlation with the umami scores. In addition, five characteristic ion peaks with m/z at 499, 561, 643, 649, and 855 were identified in the peptide mass fingerprinting. Therefore, this study provides new insights into the umami characteristics for the flavor evaluation and reality identification of soy sauce.

In South Western Indian ocean (IO), Extended-Spectrum β-Lactamase producing Enterobacteriaceae (ESBL) are a main public health issue. In livestock, ESBL burden was unknown. The aim of this study was estimating the prevalence of ESBL on commercial farms in Reunion, Mayotte and Madagascar and genes involved. Secondly, risk factors of ESBL occurrence in broiler, beef cattle and pig farms were explored. In 2016-2017, commercial farms were sampled using boot swabs and samples stored at 4°C before microbiological analysis for phenotypical ESBL and gene characterization. A semi-directive questionnaire was performed. Prevalences observed in all production types and territories were elevated, except for beef cattle in Reunion which differed significantly. The most common ESBL gene was the CTX-M-1 subtype. Generalized linear models explaining ESBL occurrence varied between livestock production sectors and allowed identifying main protective (e.g., water quality control and detergent use for cleaning) and risk factors (e.g., recent antibiotic use, other farmers visiting the exploitation, pet presence). This study is the first to explore tools for antibiotic resistance management in IO farms. It provides interesting hypothesis to explore about antibiotic use in IO and ESBL transmission between pig, beef cattle and humans in Madagascar.

Purpose: While resultant maximal voluntary contraction (MVC) is commonly used to assess muscular performance, the simultaneous activation of antagonist muscles could dramatically underestimate the strength of the agonist muscles. While quantification of antagonist torque has been performed in plantar- (PF) and dorsi-flexion (DF) joint in isometric conditions, it has yet to be determined in anisometric (concentric and eccentric) conditions. Methods: The experiment was performed in 9 participants through 2 sessions (reliability). The MVCs in DF and PF were measured in isometric, concentric and eccentric conditions (10°.s^-1). Electromyographic (EMG) activities from the soleus, gastrocnemius medialis and lateralis, and tibialis anterior muscles were simultaneously recorded. The EMG biofeedback method was used to quantify antagonist torque, where participants were asked to maintain a level of EMG activity, corresponding to antagonist EMG activity and related to the muscle contraction type, according to a visual EMG bio-feedback displayed on a screen. Results: Resultant torque significantly underestimated agonist torque in DF MVC (30-65%) and to a lesser extent in PF MVC (3%). Triceps surae antagonist torque was significantly modified with muscle contraction type, showing higher antagonist torque in isometric (29 Nm) than eccentric (23 Nm, p < 0.001) and concentric (14 Nm, p < 0.001) conditions and resulting in modification of the DF MVC torque-velocity shape. The difference between DF eccentric and concentric MVC was attenuated when considered agonist torque (12%) rather than resultant torque (45%). Conclusion: Estimation of the antagonist torque in isometric or anisometric condition brings new insights to assessment of muscular performance and could result in costly misinterpretation in strength training and/or rehabilitation programs.

This paper uses panel data to find the determinants of tracking errors in exchange traded funds (ETFs) in the Hong Kong stock market. A comparison of tracking errors between physical and synthetic ETFs also indicates that the synthetic ETFs have higher tracking errors. The magnitude of tracking errors is found to be negatively related to size but positively related to dividend yield, trading volumes of funds, and market risk. However, this study also finds that expense ratio has a negative impact on tracking error, which is not consistent with previous studies, and which this paper addresses.

Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6 weeks to 12 months old infants presenting at emergency department with moderate to severe acute bronchiolitis. Viral testing was performed and we found 98% positive samples including 90% Respiratory Syncytial Virus, 34% Human Rhino Virus, and 55% viral co-detections with predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, Coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in the later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) do exist. Role of virus detection and burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.

This study aimed evaluating 7 years’ outcome in 118 very preterm newborn (VPN, gestational age=26±1.4wks) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS) requiring ventilation for 14±2 days post-natal age (PNA). Repeated instillation of 200mg/kg Poractant alfa (SURF) did not improve early bronchopulmonary dysplasia, but SURF infants needed less re-hospitalization than controls for respiratory problem at 1- and 2-years PNA. There was no growth difference at 7.1±0.3 years for 41 SURF vs. 36 controls (80% eligible children); 7.9% SURF vs. 28.6% controls presented asthma (p=0.021). Children underwent cogni-tive assessment (WISC IV) and pulmonary function testing (PFT) measuring spirometry, lung volumes and airway resistance. Spirometry showed differences (p<0.05) between SURF and con-trols (mean±standard deviation (median z-score)) for FEV1 (L/s) (1.188±0.690(-0.803) vs. 1.080±0.243(-1.446)); FEV1 after betamimetics (1.244±0.183(-0.525) vs. 1.091±0.209(-1.342)); FVC (L) (1.402±0.217 (-0.406) vs. 1.265±0.267(-1.141)), and FVC after betamimetics 1.452±0.237 (-0.241) vs. 1.279±0.264(-1.020)). PFT showed no difference in volumes or airway resistance. Global IQ median [Inter-quartile Range] was 89[82:99] vs. 89[76:98] with 61% children >85 in both groups. Former VPN presenting severe neonatal RDS treated with repeated Surfactant have improved lung function and less asthma at 7 years PNA. There were no differences in neurodevelopmental outcome

Spinal Cord (SC) Anatomy is often assimilated to a morphologically encapsulated neural entity, but its functional anatomy remains only partially understood. We hypothesized that it could be possible to reexplore SC neural networks by performing live electrostimulation mapping, based on “super-selective” Spinal Cord Stimulation (SCS), originally designed as a therapeutical tool to address chronic refractory pain. As a starting point, we initiated a systematic SCS lead programming approach using live electrostimulation mapping on a chronic refractory perineal pain patient, previously implanted with multicolumn SCS at the level of the conus medullaris (T12-L1). It appeared possible to (re)explore the classical anatomy of the conus medullaris using statistical correlations of paresthesia coverage mappings, resulting from 165 different electrical configurations tested. We highlighted that sacral dermatomes were not only located more medially but also deeper than lumbar dermatomes at the level of the conus medullaris, in contrast with classical anatomical descriptions of SC somatotopical organization. As we were finally able to find a morpho-functional description of ‘Philippe-Gombault’s triangle’, in 19th century historical textbooks of neuroanatomy, matching remarkably with these conclusions, the concept of “Neuro-Fiber-Mapping” was introduced.