Miracle-dz/UniFAR-FTUs huggingface dataset:
Refractory livedoid vasculopathy in a child successfully treated with baricitinib

Dear Editor, Livedoid vasculopathy (LV) is a rare thrombotic condition consisting of reticulated erythematous and purpuric macules, painful ulcers, atrophic porcelain-white scars, and small dilated blood vessels. The most commonly affected sites are the lower extremities, in particular the dorsum of feet and ankles. LV is usually found in female adults. We describe a child with LV who was successfully treated with baricitinib, a Janus kinase (JAK) 1/2 inhibitor as single therapy, which alleviated pain and the ulceration cured in a short time. A 14-year-old girl presented with oedema, ulcers in both feet and ankles with pain for 5 years, the lesions healed and then recurred. Two years ago, ulcers and pain had become more prominent and progressively extended. She accepted oral Chinese medicine decoction consisted with anticoagulants, oral and topical corticosteroids, failed to respond. She and her family members had no deep vein thrombosis or other vascular history. Physical examination revealed multiple irregular necrotic ulcers above the feet and malleolar region with surrounding erythema, swelling, purpura, porcelain-white atrophie
Targeted nanotherapy with everolimus reduces inflammation and fibrosis in scleroderma‐related interstitial lung disease developed by PSGL‐1 deficient mice

Interstitial lung disease (ILD) is the main cause of mortality in systemic sclerosis (SSc), and current therapies available are of low efficacy or high toxicity. Thus, the identification of innovative less toxic and high efficacy therapeutic approaches to ILD treatment is an urgent need. The interaction of P‐selectin glycoprotein ligand‐1 (PSGL‐1) with P‐selectin initiates leukocyte extravasation and deletion of the corresponding gene (Selplg) induces a SSc‐like syndrome with high incidence of ILD in aged mice.
Ecology of Methanonatronarchaeia

Abstract Methanonatronarchaeia represents a deep‐branching phylogenetic lineage of extremely halo(alkali)philic and moderately thermophilic methyl‐reducing methanogens belonging to the phylum Halobacteriota. It includes two genera, the alkaliphilic Methanonatronarchaeum and the neutrophilic Ca. Methanohalarchaeum. The former is represented by multiple closely related pure culture isolates from hypersaline soda lakes, while the knowledge about the latter is limited to a few mixed cultures with anaerobic haloarchaea. To get more insight into the distribution and ecophysiology of this enigmatic group of extremophilic methanogens, potential activity tests and enrichment cultivation with different substrates and at different conditions were performed with anaerobic sediment slurries from various hypersaline lakes in Russia. Methanonatronarchaeum proliferated exclusively in hypersaline soda lake samples mostly at elevated temperature, while at mesophilic conditions it coexisted with the extremely salt‐tolerant methylotroph Methanosalsum natronophilum. Methanonatronarchaeum was also able to serve as a methylotrophic or hydrogenotrophic partner in several thermophilic enrichment cultures with fermentative bacteria. Ca. Methanohalarchaeum did not proliferate at mesophilic conditions and at thermophilic conditions it competed with extremely halophilic and moderately thermophilic methylotroph Methanohalobium, which it outcompeted at a combination of elevated temperature and methyl‐reducing conditions. Overall, the results demonstrated that Methanonatronarchaeia are specialized extremophiles specifically proliferating in conditions of elevated temperature coupled with extreme salinity and simultaneous availability of a wide range of C1‐methylated compounds and H2/formate.
Analyzing the role of resilience and life satisfaction as mediators of the impact of COVID‐19 worries on mental health

Abstract The aim of this study was to test whether resilience and life satisfaction (two traditional protective factors) mediate between COVID‐19 related worries and the development of symptoms of depression, anxiety, and stress in adolescents and young adults. Participants involved 392 adolescents and young adults (70.20% female) aged between 12 and 25 years (M = 17.05 years, SD = 3.08). Participants completed the COVID‐19 related worries scale, the CD‐RISC to analyse resilience, the Satisfaction with Life Scale, and the Depression, Anxiety, and Stress Scales‐21 to study emotional symptoms. Descriptive analyses and Pearson correlations were conducted, together with a structural equation modeling testing a mediational model and multigroup invariance. Results show that resilience and life satisfaction play a mediating role in the relation between the COVID‐19 related worries and emotional symptoms (depression, anxiety, and stress). This study highlights the role of protective factors on adolescents' and young adults' emotional symptoms during the COVID‐19 pandemic.
A mouse model for Li-Fraumeni-Like Syndrome with cardiac angiosarcomas associated to POT1 mutations

The shelterin protein POT1 has been found mutated in many different familial and sporadic cancers, however, no mouse models to understand the pathobiology of these mutations have been developed so far. To address the molecular mechanisms underlying the tumorigenic effects of POT1 mutant proteins in humans, we have generated a mouse model for the human POT1R117C mutation found in Li-Fraumeni-Like families with cases of cardiac angiosarcoma by introducing this mutation in the Pot1a endogenous locus, knock-in for Pot1aR117C. We find here that both mouse embryonic fibroblasts (MEFs) and tissues from Pot1a+/ki mice show longer telomeres than wild-type controls. Longer telomeres in Pot1a+/ki MEFs are dependent on telomerase activity as they are not found in double mutant Pot1a+/ki Tert-/- telomerase-deficient MEFs. By using complementation assays we further show that POT1a pR117C exerts dominant-negative effects at telomeres. As in human Li-Fraumeni patients, heterozygous Pot1a+/ki mice spontaneously develop a high incidence of angiosarcomas, including cardiac angiosarcomas, and this is associated to the presence of abnormally long telomeres in endothelial cells as well as in the tumors. The Pot1a+/R117C mouse model constitutes a useful tool to understand human cancers initiated by POT1 mutations.
Whole-Genome Sequencing of Staphylococcus aureus and Staphylococcus haemolyticus Clinical Isolates from Egypt

Staphylococci are understudied despite their prevalence within the Middle East. Methicillin-resistant Staphylococcus aureus (MRSA) is endemic to hospitals in Egypt, as are other antibiotic-resistant strains of S. aureus and S. haemolyticus. ABSTRACT Infections caused by antibiotic-resistant Staphylococcus are a global concern. This is true in the Middle East, where increasingly resistant Staphylococcus aureus and Staphylococcus haemolyticus strains have been detected. While extensive surveys have revealed the prevalence of infections caused by antibiotic-resistant staphylococci in Europe, Asia, and North America, the population structure of antibiotic-resistant staphylococci recovered from patients and clinical settings in Egypt remains uncharacterized. We performed whole-genome sequencing of 56 S. aureus and 10 S. haemolyticus isolates from Alexandria Main University Hospital; 46 of the S. aureus genomes and all 10 of the S. haemolyticus genomes carry mecA, which confers methicillin resistance. Supplemented with additional publicly available genomes from the other parts of the Middle East (34 S. aureus and 6 S. haemolyticus), we present the largest genomic study to date of staphylococcal isolates from the Middle East. These genomes include 20 S. aureus multilocus sequence types (MLST), including 3 new ones. They also include 9 S. haemolyticus MLSTs, including 1 new one. Phylogenomic analyses of each species’ core genome largely mirrored those of the MLSTs, irrespective of geographical origin. The hospital-acquired spa t037/ST239-SCCmec III/MLST CC8 clone represented the largest clade, comprising 22% of the S. aureus isolates. Like S. aureus genome surveys of other regions, these isolates from the Middle East have an open pangenome, a strong indicator of gene exchange of virulence factors and antibiotic resistance genes with other reservoirs. Our genome analyses will inform antibiotic stewardship and infection control plans in the Middle East. IMPORTANCE Staphylococci are understudied despite their prevalence within the Middle East. Methicillin-resistant Staphylococcus aureus (MRSA) is endemic to hospitals in Egypt, as are other antibiotic-resistant strains of S. aureus and S. haemolyticus. To provide insight into the strains circulating in Egypt, we performed whole-genome sequencing of 56 S. aureus and 10 S. haemolyticus isolates from Alexandria Main University Hospital. Through analysis of these genomes, as well as all available S. aureus and S. haemolyticus genomes from the Middle East (n = 40), we were able to produce a picture of the diversity in this region more complete than those afforded by traditional molecular typing strategies. For example, we identified 4 new MLSTs. Most strains harbored genes associated with multidrug resistance, toxin production, biofilm formation, and immune evasion. These data provide invaluable insight for future antibiotic stewardship and infection control within the Middle East.
Selpercatinib in RET-fusion positive metastatic non-small cell lung cancer: achievements and gray areas

ABSTRACT Introduction Selpercatinib is a RET selective tyrosine kinase inhibitor with nanomolar potency against diverse RET alterations, including fusions, activating point mutations, and acquired resistance mutations. Rearranged during transfection (RET) gene is a validated target in non-small-cell lung cancer (NSCLC). Selpercatinib is currently approved for adult patients with metastatic RET fusion-positive NSCLC. Areas covered This review summarizes the efficacy and safety data of selpercatinib in the treatment landscape of RET fusion-positive NSCLC. Expert opinion Globally considered, selpercatinib is an optimal treatment choice, in terms of both (systemic and intracranial) efficacy and safety, in patients affected by advanced NSCLC harboring RET fusions as a driver mechanism. Future challenges include the identification of the most appropriate placement for selpercatinib in the treatment algorithm of RET fusion-positive NSCLC (including early stages), the clarification of resistance mechanisms, as well as of its role in EGFR-mutant NSCLC undergoing progression during osimertinib driven by RET alterations.
Metabolic syndrome following a first episode of psychosis: results of a 1-year longitudinal study conducted in metropolitan Lisbon, Portugal

Objective We aimed to assess the prevalence and course of metabolic syndrome (MetS) and the associated metabolic parameters during the year following a first episode pf psychosis (FEP). Methods We performed a 1-year longitudinal observation of 60 patients who experienced FEP. MetS was defined using the modified definition of the National Cholesterol Education Program Adult Treatment Panel III. We assessed the metabolic parameters and socio-demographic and psychopathological data for the participants. Results The mean age of the participants was 27.1 years, and 33.3% of them were women. There was an increase in the prevalence of MetS from 6.7% to 11.7% during the year following the baseline assessment during the year following the baseline assessment (p = 0.250). There were also significant increases in the prevalences of abnormal triglyceride concentration, waist circumference, and high-density lipoprotein (HDL)-cholesterol concentration during this period. In addition, there was a considerable worsening of the metabolic profile of the participants. No baseline parameters were identified to be predictors of MetS over the 1-year follow-up period. Conclusions We can conclude that metabolic abnormalities are common in patients with FEP and that these rapidly worsen during the first year following the diagnosis of FEP. Studies on interventions are needed to reduce metabolic risk to cardiovascular diseases following the FEP.
High pyrethroid-resistance intensity in Culex quinquefasciatus (Say) (Diptera: Culicidae) populations from Jigawa, North-West, Nigeria

This study examined pyrethroid resistance intensity and mechanisms in Culex quinquefasciatus (Say) (Diptera: Culicidae) populations from Jigawa, North-West Nigeria. Resistance statuses to permethrin, lambda-cyhalothrin and alphacypermethrin were determined with both WHO and CDC resistance bioassays. Synergist assay was conducted by pre-exposing the populations to Piperonyl butoxide (PBO) using the WHO method. Resistance intensities to 2x, 5x and 10x of diagnostic concentrations were determined with the CDC bottle method. Species analysis and presence of knockdown mutation (Leu-Phe) were done using Polymerase Chain Reaction (PCR). Results showed that Cx. quinquefasciatus was the only Culex spp. present and “Kdr-west” mutation was not detected in all analyzed samples. Using WHO method, Cx. quinquefasciatus resistance to permethrin was detected in Dutse (12.2%) and Kafin-Hausa (77.78%). Lambda-cyhalothrin resistance was recorded only in Kafin-Hausa (83.95%) with resistance suspected in Ringim (90%). Resistance to alphacypermethrin was recorded in all locations. Pre-exposure to PBO led to 100% mortality to alphacypermethrin and lambda-cyhalothrin in Ringim while mortality to permethrin and alphacypermethrin in Dutse increased from 12.2% to 97.5% and 64.37% to 79.52% respectively. Using CDC bottle bioassay, resistance was also recorded in all populations and the result shows a significant positive correlation (R2 = 0.728, p = 0.026) with the result from the WHO bioassay. Results of resistance intensity revealed a very high level of resistance in Kafin-Hausa with susceptibility to lambda-cyhalothrin and alphacypermethrin not achieved at 10x of diagnostic doses. Resistance intensity was also high in Dutse with susceptibility to all insecticides not achieved at 5x of diagnostic doses. Widespread and high intensity of resistance in Cx. quinquefasciatus from North-West Nigeria is a major threat to the control of diseases transmitted by Culex and other mosquito species. It is a challenge that needs to be adequately addressed so as to prevent the failure of pyrethroid-based vector control tools.
Cognitive tasks elicit mental fatigue and impair subsequent physical task endurance: Effects of task duration and type

Abstract Although mentally fatiguing cognitive tasks can impair subsequent physical endurance, the importance of cognitive task duration and the role of response inhibition remain unclear. This study compared the effects of a serial incongruent Stroop color‐classification task (i.e., with response inhibition) and N‐back memory updating task (i.e., without response inhibition) on mental fatigue and subsequent rhythmic handgrip exercise. Participants (N = 90) were randomly assigned to one of three cognitive task groups (Stroop, 2‐back, control) and completed four 10‐min blocks of one cognitive task followed by a 5‐min physical endurance task (self‐paced rhythmic handgrip exercise). Heart rate, heart rate variability, electromyographic forearm activity, and force were recorded throughout along with self‐reported measures of fatigue, exertion, and motivation. From the start, the Stroop and 2‐back tasks elicited higher heart rate and lower heart rate variability as well as greater fatigue, effort, and interest/enjoyment than the control task. From the second block onwards, the Stroop and 2‐back groups produced less force than the control group. There were no group differences in forearm muscle activity. In sum, mental fatigue was induced after performing a cognitive task for 10 mins, whereas muscular endurance was impaired after performing a cognitive task for 20 mins. That these effects were observed for both types of cognitive task indicates that response inhibition is not a necessary condition. The cognitive task duration required to induce mental fatigue and impair rhythmic handgrip endurance performance lay between the durations reported previously for isometric (a few minutes) and whole‐body (half an hour) endurance exercise.
MDMA-assisted therapy for posttraumatic stress disorder: A pooled analysis of ethnoracial differences in efficacy and safety from two Phase 2 open-label lead-in trials and a Phase 3 randomized, blinded placebo-controlled trial

Background: Limited ethnoracial diversity in previous ±3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) trials for posttraumatic stress disorder (PTSD) has prompted questions concerning whether Black, Indigenous, and People of Color (BIPOC) also benefit from this treatment. Methods: Secondary analysis was conducted using a modified intent-to-treat sample pooled from two Phase 2 open-label trials and a Phase 3 randomized, blinded placebo-controlled trial to compare efficacy and safety of MDMA-AT for PTSD between BIPOC and non-Hispanic White participants. Four subgroups were of interest: MDMA-AT, BIPOC (n = 20); MDMA-AT, non-Hispanic White (n = 63); Placebo-assisted therapy (Placebo-AT), BIPOC (n = 17); and Placebo-AT, non-Hispanic White (n = 27). Planned comparisons tested subgroup differences in changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores from baseline to primary endpoint, controlling for study type and baseline scores. Adverse events (AEs) on the day of (day 0) to 2 days post-dosing were reported for each subgroup. Results: In the MDMA-AT group, no significant ethnoracial difference in CAPS-5 change scores was observed. In the Placebo-AT group, BIPOC participants trended toward greater reductions in CAPS-5 scores than non-Hispanic Whites. Among non-Hispanic Whites, MDMA-AT was accompanied by significantly greater reductions in CAPS-5 scores than Placebo-AT. No treatment difference emerged among BIPOC participants. AEs were mostly rated as mild or moderate across subgroups. Conclusions: These findings provide preliminary support for the efficacy and safety of MDMA-AT for treating PTSD across ethnoracial groups. There was also a trend toward greater efficacy with Placebo-AT among BIPOC participants. There was an imbalance in subgroups, highlighting the need for culturally responsive recruitment strategies to diversify future studies.
Modeling Pedestrian Crossing Behavior and Safety at Signalized Intersections

Pedestrian noncompliance behavior is one of the most critical causes of pedestrian involved traffic crashes at intersections in India. Thus, the objectives of this study are to examine how various factors affect pedestrian crossing behavior and to propose models for pedestrian crossing behavior and level of safety at signalized intersections which will be useful to regulate pedestrian flow. The data were collected with video and a user perceptions survey at six selected signalized intersections in Mumbai, India. The differences between pedestrian crossing behavior with respect to personal characteristics, socioeconomic attributes, and existing crossing facilities were identified using Pearson correlation and odd ratio tests. Furthermore, the major reasons for noncompliance behavior were obtained by analysis of field data to prevent noncompliance behavior and enhance pedestrian safety. The results showed that a significant number of the pedestrians violated the traffic signal to save time and for convenience (46%). A binary logit model was developed to evaluate the impacts of contributing factors on pedestrian crossing behavior. Further, an ordered probability model was established to evaluate and estimate the pedestrian level of safety at signalized intersections. Two models were validated, and their statistical results show that the models predict the pedestrian crossing behavior and safety level more precisely. Developed models and study outcomes can help transport planners and designers understand pedestrian crossing behavior on crosswalks at signalized intersections and thus create a safer crossing environment for all pedestrians.
Differences in prevalence and risk factors of non-communicable diseases between young people living with HIV (YLWH) and young general population in Cambodia

Understanding non-communicable diseases (NCDs) among young people living with HIV (YLWH) is critical given the potential for aging-associated comorbidities resulting from HIV, especially in Cambodia where such data are limited. Therefore, we examined the prevalence and correlates of NCDs in YLWH and compared it to a nationally representative sample of young people not otherwise infected. We collected data from a sample of 370 YLWH aged 18–29 years attending three HIV clinics in Cambodia between 2019 and 2020. Our comparison group were 486 young people who participated in the Ministry of Health/WHO 2016 Noncommunicable Disease Risk Factor Surveillance (STEP survey). Both surveys used a standardized questionnaire to collect information on lifestyle factors and World Health Organization protocols for physical and biochemical measurements. We compared the prevalence of diabetes, hypertension, and high cholesterolemia between the two groups and examined the relationship between these conditions and HIV. We found 16 (4%), 22 (6%), and 72 (20%) had diabetes, hypertension, and high cholesterolemia, respectively, among YLWH, compared to 4 (1%), 22 (4%), and 49 (11%) among the general population. In logistic regression, YLWH were at higher odds of diabetes/prediabetes and high cholesterolemia compared with the young general population, aOR = 6.64 (95% CI 3.62–12.19) and aOR = 7.95 (95% CI 3.98–15.87), respectively. Our findings demonstrate that YLWH in Cambodia face multiple metabolic disorders and NCDs despite their young age and that accessible screening measures and treatment for these conditions are needed in order to combat NCDs in the future.
The embodiment of childhood abuse and anorexia nervosa: A body mapping study

Abstract Childhood trauma has long been implicated in the development of anorexia nervosa and is known to impact more women than men. Still, less is known about the meaning women attribute to food and bodily practices and how they contribute to feminine subjectivity. In this article, we examine the subjective experiences of women with histories of childhood abuse and anorexia and women who did not develop an eating disorder. Through a visual narrative analysis of eight body maps and narratives, we identified five themes: “time and the body have a way of showing what matters,” “femininity and family,” “sexual subjectivities and food meanings,” “voices, dissociation, and sexual subjectivities,” and “religion and healthism. ” In women with anorexia, specific eating and bodily practices reconstructed the traumatic events to align with the available cultural discourses related to health, religion, and family and had implications for their feminine and sexual subjectivities and self-worth. This research showcased how arts-based methodologies add value and advance knowledge about the role of culturally available representations in the development of anorexia and has implications for therapy and prevention of anorexia.