Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Age and Disease Duration on Excess Mortality in Patients With Multiple Sclerosis From a French Nationwide Cohort

Objective To determine the effects of current age and disease duration on excess mortality in multiple sclerosis (MS), we describe the dynamics of excess death rates over these 2 time scales and study the effect of age at MS clinical onset on these dynamics, separately in each initial phenotype. Methods We used data from 18 French MS expert centers participating in the Observatoire Français de la Sclérose en Plaques. Patients with MS living in metropolitan France and having a clinical onset between 1960 and 2014 were included. Vital status was updated on January 1, 2016. For each MS phenotype separately (relapsing onset [RMS] or primary progressive [PPMS]), we used an innovative statistical method to model the logarithm of excess death rates by a multidimensional penalized spline of age and disease duration. Results Among 37,524 patients (71% women, mean age at MS onset ± SD 33.0 ± 10.6 years), 2,883 (7.7%) deaths were observed and 7.8% of patients were lost to follow-up. For patients with RMS, there was no excess mortality during the first 10 years after disease onset; afterwards, whatever the age at onset, excess death rates increased with current age. From current age 70, the excess death rate values converged and became identical whatever the age at disease onset, which means that disease duration had no more effect. Excess death rates were higher in men, with an excess hazard ratio of 1.46 (95% confidence interval 1.25–1.70). In contrast, in patients with PPMS, excess death rates rapidly increased from disease onset, and were associated with age at onset, but not with sex. Conclusions In RMS, current age has a stronger effect on MS mortality than disease duration, while their respective effects are not clear in PPMS.
Effect of different administration and dosage of dexmedetomidine in the reduction of emergence agitation in children: a meta-analysis of randomized controlled trials with sequential trial analysis

Background Beneficial effects of dexmedetomidine (DEX) against emergence agitation (EA) in children remain controversial. We performed a more comprehensive meta-analysis to evaluate the protective effect of different administration routes, timing, patterns, and doses of DEX on EA in children. Methods The randomized controlled trials about DEX preventing EA in children were searched in PubMed, Cochrane Library, Embase, and Web of Sciences up to October 7, 2020. The traditional meta-analysis and subgroup analysis were performed to study the influence of DEX on EA in children. The sequential trial analysis (TSA) further analyzed the pooled results to evaluate meta-analyses’ robustness. Grading of recommendation, assessment, development, and evaluation (GRADE) was used to assess evidence quality. Results Sixty-seven studies with 5,688 pediatric patients were included. DEX significantly decreased EA in children compared to placebo [RR 0.29, 95% confidence intervals (CI): 0.25–0.34] and midazolam (RR 0.34, 95% CI: 0.25–0.45), with firm evidence from TSA. Notably, using DEX significantly reduced severe EA incidence (RR 0.23, 95% CI: 0.16–0.32), with firm evidence by TSA and high quality of GRADE. Pre-specified subgroup analyses revealed firm and high-quality evidence for a reduction of EA, only if the perineural route administers DEX (RR 0.24, 95% CI: 0.14–0.41), as premedication (RR 0.27, 95% CI: 0.20–0.36), as continuous dosage (RR 0.25, 95% CI: 0.18–0.33), at high dose (RR 0.24, 95% CI: 0.18–0.31). The pooled results also showed that DEX reduced the incidence of PONV compared to placebo (RR 0.43, 95% CI: 0.33–0.55). Evidence for DEX’s influence on other secondary outcomes (emergence time, time in PACU, rescue analgesia, hypotension, and bradycardia) is insufficient to draw any conclusion. Conclusions Our findings confirm the beneficial effects of DEX on EA, severe EA, and PONV in children. There was firm and high-quality evidence for the efficacy of DEX in preventing EA in children when perineural routes administered DEX, as premedication, as continuous dosage, and at a high dose. The best dose, route, patterns, and timing of DEX and influence on other outcomes call for further studies.
Equal prevalence of severe cervical dysplasia by HPV self-sampling and by midwife-collected samples for primary HPV screening: a randomised controlled trial

Objectives HPV self-sampling is an option for cervical screening. The aim of this randomised study was to investigate the compliance, prevalence of HPV, and prevalence of severe dysplasia in a vaginal self-sampling group in comparison to cervical samples collected by midwives (control arm). The hypothesis was that there would be no difference between vaginal self-sampling and cervical sampling to find high-grade cervical dysplasia or cancer. Methods Vaginal HPV self-sampling kits were sent by regular mail to 14 765 randomly selected women aged 30–64 years old in the screening programme. HPV-positive women were invited for a follow-up examination by their midwife in which they provided a cervical sample for cytological and HPV co-testing. The control arm consisted of 14 839 women who met the same inclusion criteria and were invited to have cervical sampling by midwives for primary HPV screening. All HPV samples were analysed by the Aptima HPV assay (Hologic Inc.). Main results The participation rate was 33.5% in the self-sampling arm and 47.5% in the cervical sampling arm, (P < 0.0001). HPV was detected in 17.1% (95% confidence interval (CI), 16.1–18.23%) in the self-sampling arm and 4.5% (95% CI, 4.0–5.0%) in the cervical sampling arm. Histological, severe dysplasia was observed among 0.48% (95% CI, 0.3–0.72%) and 0.47% (95% CI, 0.3–0.66%) of the self-sampling and the cervical sampling groups, respectively. Conclusion The self-sampling approach detects a similar proportion of severe dysplasia as regular screening. Thus, our study indicates that self-sampling could replace primary HPV screening of cervical samples.
Sex differences in sexual attraction for aesthetics, resources and personality across age

Because sexual attraction is a key driver of human mate choice and reproduction, we descriptively assess relative sex differences in the level of attraction individuals expect in the aesthetic, resource, and personality characteristics of potential mates. As a novelty we explore how male and female sexual attractiveness preference changes across age, using a dataset comprising online survey data for over 7,000 respondents across a broad age distribution of individuals between 18 and 65 years. In general, we find that both males and females show similar distribution patterns in their preference responses, with statistically significant sex differences within most of the traits. On average, females rate age, education, intelligence, income, trust, and emotional connection around 9 to 14 points higher than males on our 0–100 scale range. Our relative importance analysis shows greater male priority for attractiveness and physical build, compared to females, relative to all other traits. Using multiple regression analysis, we find a consistent statistical sex difference (males relative to females) that decreases linearly with age for aesthetics, while the opposite is true for resources and personality, with females exhibiting a stronger relative preference, particularly in the younger aged cohort. Exploring non-linearity in sex difference with contour plots for intelligence and attractiveness across age (mediated by age) indicates that sex differences in attractiveness preferences are driven by the male cohort (particularly age 30 to 40) for those who care about the importance of age, while intelligence is driven by females caring relatively more about intelligence for those who see age as very important (age cohort 40 to 55). Overall, many of our results indicate distinct variations within sex at key life stages, which is consistent with theories of selection pressure. Moreover, results also align with theories of parental investment, the gender similarities hypothesis, and mutual mate choice–which speaks to the fact that the broader discipline of evolutionary mate choice research in humans still contains considerable scope for further inquiry towards a unified theory, particularly when exploring sex-difference across age.
Avoidable Adverse Events Related to Ignoring the Do-Not-Do Recommendations: A Retrospective Cohort Study Conducted in the Spanish Primary Care Setting

Supplemental digital content is available in the text. Objective This study aimed to measure the frequency and severity of avoidable adverse events (AAEs) related to ignoring do-not-do recommendations (DNDs) in primary care. Methods A retrospective cohort study analyzing the frequency and severity of AAEs related to ignoring DNDs (7 from family medicine and 3 from pediatrics) was conducted in Spain. Data were randomly extracted from computerized electronic medical records by a total of 20 general practitioners and 5 pediatricians acting as reviewers; data between February 2018 and September 2019 were analyzed. Results A total of 2557 records of adult and pediatric patients were reviewed. There were 1859 (72.7%) of 2557 (95% confidence interval [CI], 71.0%–74.4%) DNDs actions in 1307 patients (1507 were performed by general practitioners and 352 by pediatricians). Do-not-do recommendations were ignored more often in female patients (P < 0.0001). Sixty-nine AAEs were linked to ignoring DNDs (69/1307 [5.3%]; 95% CI, 4.1%–6.5%). Of those, 54 (5.1%) of 1062 were in adult patients (95% CI, 3.8%–6.4%) and 15 (6.1%) of 245 in pediatric patients (95% CI, 3.1%–9.1%). In adult patients, the majority of AAEs (51/901 [5.7%]; 95% CI, 4.2%–7.2%) occurred in patients 65 years or older. Most AAEs were characterized by temporary minor harm both in adult patients (28/54 [51.9%]; 95% CI, 38.5%–65.2%) and pediatric patients (15/15 [100%]). Conclusions These findings provide a new perspective about the consequences of low-value practices for the patients and the health care systems. Ignoring DNDs could place patients at risk, and their safety might be unnecessarily compromised. Trial Registration Number NCT03482232.
The effect of ketogenic diet escalation in adolescents and adults with drug-resistant epilepsy: a prospective study

ABSTRACT Background Ketogenic diet (KD) is an accepted and effective treatment modality in patients with drug-resistant epilepsy (DRE). Different versions of ketogenic diets have been studied, however, the effect of ratio escalation in adolescence and adults has not been previously investigated. Methods The current open-labeled interventional study was conducted on 80 patients with drug-resistant epilepsy DRE, 40 patients (intervention group) were exposed to dietary intervention besides their regular antiseizure medication (ASM) and compared to 40 control patients. The intervention group received Ketogenic diet in 2:1 ratio for 1 month then were divided into 2 subgroups, group A1 continued the 2:1 ratio for another 2 months while group A2 escalated to 3:1 dietary regimen. Socio-demographic, anthropometric measurements, epilepsy clinical parameters, and laboratory tests were recorded in addition to safety and tolerability documentation. The response rate was recorded after 1month and 3month. Results Significant decrease in seizure frequency and severity were detected in Group A1 and A2 patients compared to controls after the 3 month period of intervention with significant improvement of quality of life scores in both subgroups. Both subgroups also showed comparable results regarding their response rate to KD. Better acceptance of diet taste were reported by subgroup A1 with a significantly higher lipid profile detected in subgroup A2. Conclusion KD has a beneficial effect as adjunctive treatment in adolescents and adults with DRE. Escalation from 2:1 to 3:1 ratio is associated with less compliance rather than better response in patients with DRE.
Order among chaos: Cross-linguistic differences and developmental trajectories in pseudoword reading aloud using pronunciation Entropy

In this work we propose the use of Entropy to measure variability in pronunciations in pseudowords reading aloud: pseudowords where participants give many different pronunciations receive higher Entropy values. Monolingual adults, monolingual children, and bilingual children proficient in different European languages varying in orthographic depth were tested. We predicted that Entropy values will increase with increasing orthographic depth. Moreover, higher Entropy was expected for younger than older children, as reading experience improves the knowledge of grapheme-phoneme correspondences (GPCs). We also tested if interference from a second language would lead to higher Entropy. Results show that orthographic depth affects Entropy, but only when the items are not strictly matched across languages. We also found that Entropy decreases across age, suggesting that GPC knowledge becomes refined throughout grades 2-4. We found no differences between bilingual and monolingual children. Our results indicate that item characteristics play a fundamental role in pseudoword pronunciation variability, that reading experience is associated with reduced variability in responses, and that in bilinguals’ knowledge of a second orthography does not seem to interfere with pseudoword reading aloud.
Trends in Viral Respiratory Infections During COVID-19 Pandemic, South Korea

We compared weekly positivity rates of 8 respiratory viruses in South Korea during 2010–2019 and 2020. The overall mean positivity rate for these viruses decreased from 54.7% in 2010–2019 to 39.1% in 2020. Pandemic control measures might have reduced the incidence of many, but not all, viral respiratory infections.
Comprehensive analysis of clinical spectrum and genotype associations in Chinese and literature reported KBG syndrome

Background Patients with KBG Syndrome due to ANKRD11 mutations and 16q24.3 microdeletions including ANKRD11 were identified. Classical and most frequent phenotypes include various degrees of intelligence disability (ID), short stature (SS), delayed bone age, macrodontia, distinctive facial features and skeletal anomalies. The variable expressivity of KBG syndrome makes it challenging to establish genotype-phenotype correlations, which also affects further studies for this novel syndrome. We aim to report three unrelated patients with KBG syndrome caused by ANKRD11 gene pathological variants and to evaluate potential associations among ANKRD11 gene variant types, the 16q24.3 microdeletion, and the clinical spectrum of KBG syndrome. Methods The genetic etiology of three unreported KBG patients was identified by whole exome sequencing and confirmed via Sanger sequencing. Literature review was conducted to summarize the phenotype-genotype relationship based on three unreported Chinese cases and 186 reported cases. Results Two pathological variants (c.7407dupC, p.P2530Rfs*61; c.G3046A, p.D1016N) and one reported variant (c.6792dupC, p. P2271Pfs*8) were detected in our patients. Compared with the 16q24.3 microdeletion, patients harboring ANKRD11 gene mutations showed significantly higher frequency of malformations including macrodontia, long philtrum, abnormal eyebrows, widely spaced eyes, anteverted nares, eyelid ptosis, brachydactyly, brachycephaly (P<0.05), and significantly lower risk of congenital heart diseases and frontal bossing (P<0.05). The intellectual disability (ID) was significantly milder among patients carrying truncating variants located between repression domain 1 (RD1) and activation domain (AD) than those carrying mutations disrupting repression domain 2 (RD2) alone and disrupting all functional domain (RD1, AD or RD2) (P<0.05). Conclusions Novel pathological variants harbored in the ANKRD11 gene contribute to the KBG syndrome variant spectrum. ANKRD11 gene variants disrupting RD1 and RD2 or RD2 alone are more likely to have more severe ID, which warrants different intervention strategies for KBG syndrome.
Intestinal stricture in Crohn's disease: A 2020 update

Crohn's disease (CD) is a chronic and relapsing–remitting inflammatory disorder of the gastrointestinal tract. Approximately 70% of patients inevitably develop fibrosis‐associated intestinal stricture after 10 years of CD diagnosis, which seriously affects their quality of life. Current therapies play limited role in preventing or reversing the process of fibrosis and no specific anti‐fibrotic therapy is yet available. Nearly half of patients thus have no alternative but to receive surgery. The potential mechanisms of intestinal fibrosis remain poorly understood; extracellular matrix remodeling, aberrant immune response, intestinal microbiome imbalance and creeping fat might exert fundamental influences on the multiple physiological and pathophysiological processes. Recently, the emerging new diagnostic techniques have markedly promoted an accurate assessment of intestinal stricture by distinguishing fibrosis from inflammation, which is crucial for guiding treatment and predicting prognosis. In this review, we concisely summarized the key studies published in the year 2020 covering pathogenesis, diagnostic modalities, and therapeutic strategy of intestinal stricture. A comprehensive and timely review of the updated researches in intestinal stricture could provide insight to further elucidate its pathogenesis and identify novel drug targets with anti‐fibrotic potentiality.
Serum electrolytes and renal alterations in HIV-seropositive Mexican subjects

Abstract To examine potential risk factors associated with biochemical alterations in renal function in a population diagnosed with HIV/AIDS undergoing antiretroviral treatment. This is an observational, transversal, and relational design study that included 179 HIV-seropositive subjects. Glucose serum, cholesterol, triglycerides, total proteins, albumin, creatine, urea, blood urea nitrogen (BUN), and electrolytes levels were determined for each individual. Renal function was evaluated through the glomerular filtration rate (GFR), using the CKD-EPI equation. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2. Univariate model significant variables, with a 95% confidence interval (CI), were included in a multivariate logistic regression analysis. CKD prevalence in patients was 7.3%, with comorbidities of 7.8% for type 2 diabetes mellitus, 7.3% for arterial hypertension, and 35.2% for dyslipidemia. Additionally, both hypernatremia and hypophosphatemia were detected in 57% (n = 102) of the patients. Multivariate logistic regression suggested that CD4+ T cell count < 200 (P = .02; OR 0.2; CI 95% 0.08–0.8) was associated to hyponatremia; similarly, detectable viral load was associated to hypokalemia (P = .02; OR 5.1; CI 95% 1.2–21.3), hypocalcemia (P = .01; OR 4.1; CI 95% 1.3–12.3), and hypermagnesemia (OR 3.9; CI 95% 1.1–13.6). Patient age was associated to both hypophosphatemia (P = .01; OR 2.4; CI 95% 1.1–5.0) and hypermagnesemia (P = .01; OR 2.8; IC 95% 1.1–7.0), and high creatinine levels were associated to nucleoside reverse transcriptase inhibitor treatment (P = .001; OR 42.5; CI 95% 2.2–806.9). Lastly, high BUN levels were associated to age (P = .03; OR 3.8; CI 95% 1.0–14.4), while GFR 60 to 89 mL/min/1.73 m2 was associated to dyslipidemia (P = .02; OR 2.2; CI 95% 1.1–4.5). CD4+ T cell and viral load were the main factors associated with renal biochemical alterations.
Association of managerial position with cardiovascular risk factors: A fixed-effects analysis for Japanese employees

Objectives: Although higher occupational classes have been reported to be associated with better health, researchers do not fully understand whether such associations derive from the position or individual characteristics of the person in that position. We examined the association between being a manager and cardiovascular disease (CVD) risk factors using unique panel data in Japan that annually observed employees’ occupational class and health conditions. Methods: We analyzed data for 45 888 observations from a Japanese company from 2013 through 2017. The association between being a manager and CVD risk factors (metabolic risks and health-related behaviors) were evaluated using simple pooled cross-sectional analyses with adjustment for age, sex, marital status, and overtime-working hours. We further incorporated employee-level fixed-effects into the models to examine whether the associations were subject to individual time-invariant factors. Results: The pooled cross-sectional analyses showed that, compared to non-managers, managers had 2.0 mg/dl lower low density lipoprotein cholesterol (LDL-C) level, 1.4 mmHg-lower systolic blood pressure, and 0.2 kg/m2 lower body mass index (BMI). After adjusting for employee-level fixed-effects, being a manager was associated with a significantly 2.2 mg/dl higher LDL-C level. However, the associations between an individual’s management status and blood pressure or BMI were not significant. Furthermore, managers were 5.5% less likely to exercise regularly and 6.1% less likely to report sufficient sleep in the fixed-effects models, although the pooled cross-sectional analyses did not demonstrate these significant associations. Conclusions: Our findings suggest the necessity of considering these unfavorable health risks associated with being promoted to a manager.
Injuries Suggestive of Physical Abuse in Young Children With Subconjunctival Hemorrhages

Objective The aim of this study was to compare the demographic characteristics, clinical presentations, medical evaluation, and injuries identified in a cohort of children with and without subconjunctival hemorrhage who were evaluated by a child abuse specialist. Methods This was a case-control study that used data from the ExSTRA (Examining Siblings to Recognize Abuse) research network. Subjects with a subconjunctival hemorrhage(s) were designated as cases. Four controls matched for age and participating center were included for each case. Descriptive statistics were used to compare cases and controls. Results Fifty of the 2890 subjects in the parent study had a subconjunctival hemorrhage(s) and were designated as cases. The cases had a median (interquartile range) age of 5.0 months (2.0–23.6 months). Two hundred controls were matched to the cases. There was no difference in the demographics, clinical characteristics, medical evaluation, or rate of occult injuries identified in cases and controls. Almost one-quarter of children with subconjunctival hemorrhages had no other external sign of trauma but had the same rate of occult injuries as children with bruises. Conclusions These data suggest that subconjunctival hemorrhages are relatively rare among children undergoing evaluation by a child abuse specialist, but that they are often an indicator of occult injury. Even in the absence of other external signs of trauma, the presence of subconjunctival hemorrhages should prompt an age-appropriate evaluation for physical abuse.