Miracle-dz/UniFAR-FTUs huggingface dataset:
A heterozygous, intragenic deletion of CNOT2 recapitulates the phenotype of 12q15 deletion syndrome

Only a few individuals with 12q15 deletion have been described, presenting with a disorder characterized by learning disability, developmental delay, nasal speech, and hypothyroidism. The smallest region of overlap for this syndrome was included in a genomic segment spanning CNOT2, KCNMB4, and PTPRB genes. We report on an additional patient harboring a 12q15 microdeletion encompassing only part of CNOT2 gene, presenting with a spectrum of clinical features overlapping the 12q15 deletion syndrome phenotype. We propose CNOT2 as the phenocritical gene for 12q15 deletion syndrome and its haploinsufficiency being associated with an autosomal dominant disorder, presenting with developmental delay, hypotonia, feeding problems, learning difficulties, nasal speech, skeletal anomalies, and facial dysmorphisms.
Association of Step Volume and Intensity With All-Cause Mortality in Older Women.

Importance A goal of 10 000 steps/d is commonly believed by the public to be necessary for health, but this number has limited scientific basis. Additionally, it is unknown whether greater stepping intensity is associated with health benefits, independent of steps taken per day. Objective To examine associations of number of steps per day and stepping intensity with all-cause mortality. Design, Setting, and Participants This prospective cohort study included 18 289 US women from the Women's Health Study who agreed to participate by wearing an accelerometer during waking hours for 7 days between 2011 and 2015. A total of 17 708 women wore and returned their devices; data were downloaded successfully from 17 466 devices. Of these women, 16 741 were compliant wearers (≥10 h/d of wear on ≥4 days) and included in the analyses, which took place between 2018 and 2019. Exposures Steps per day and several measures of stepping intensity (ie, peak 1-minute cadence; peak 30-minute cadence; maximum 5-minute cadence; time spent at a stepping rate of ≥40 steps/min, reflecting purposeful steps). Main Outcomes and Measures All-cause mortality. Results Of the 16 741 women who met inclusion criteria, the mean (SD) age was 72.0 (5.7) years. Mean step count was 5499 per day, with 51.4%, 45.5%, and 3.1% of time spent at 0, 1 to 39 (incidental steps), and 40 steps/min or greater (purposeful steps), respectively. During a mean follow-up of 4.3 years, 504 women died. Median steps per day across low-to-high quartiles of distribution were 2718, 4363, 5905, and 8442, respectively. The corresponding quartile hazard ratios (HRs) associated with mortality and adjusted for potential confounders were 1.00 (reference), 0.59 (95% CI, 0.47-0.75), 0.54 (95% CI, 0.41-0.72), and 0.42 (95% CI, 0.30-0.60), respectively (P < .01). In spline analysis, HRs were observed to decline progressively with higher mean steps per day until approximately 7500 steps/d, after which they leveled. For measures of stepping intensity, higher intensities were associated with significantly lower mortality rates; however, after adjusting for steps per day, all associations were attenuated, and most were no longer significant (highest vs lowest quartile for peak 1-minute cadence, HR = 0.87 [95% CI, 0.68-1.11]; peak 30-minute cadence, HR = 0.86 [95% CI, 0.65-1.13]; maximum 5-minute cadence, HR = 0.80 [95% CI, 0.62-1.05]; and time spent at a stepping rate of ≥40 steps/min, HR = 1.27 [95% CI, 0.96-1.68]; P > .05). Conclusions and Relevance Among older women, as few as approximately 4400 steps/d was significantly related to lower mortality rates compared with approximately 2700 steps/d. With more steps per day, mortality rates progressively decreased before leveling at approximately 7500 steps/d. Stepping intensity was not clearly related to lower mortality rates after accounting for total steps per day.
Genetically predicted levels of DNA methylation biomarkers and breast cancer risk: data from 228,951 women of European descent.

BACKGROUND DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Utilizing a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk. METHODS Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (N=1,595). The prediction models were validated using data from the Women's Health Initiative (N=883). We applied these models to genome-wide association study (GWAS) data of 122,977 breast cancer cases and 105,974 controls to evaluate if the genetically predicted DNA methylation levels at CpGs are associated with breast cancer risk. All statistical tests were two-sided. RESULTS Of the 62,938 CpG sites (CpGs) investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P<7.94 × 10-7, including 45 CpGs residing in 18 genomic regions which have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes. CONCLUSION Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases.
Integrated Protocols to Ensure Security Services in Wireless Sensor Networks

Security in current/next generation wireless sensor network (WSN) is challenging, due to its special characteristics and the scarcity of energy, and processing power. Thus, many security methods are trying to solve the problem of security in wireless sensor networks. Many of these methods use symmetric cryptography, and others use asymmetric cryptography. Security in WSN demands authentication, confidentiality, integrity, balancing the energy cost, nonreputation, and scalability services. In this paper, we introduce two protocols to address these main security services. The proposed protocols integrate public key and symmetric key algorithms to ensure optimal usage of sensors’ energy and processing power to provide adequate security in next generation WSN. The proposed protocols utilize Elliptic Curve Cryptography (ECC), Advanced Encryption Standard (AES), Certification Authority (CA), and Registration Authority (RA) to achieve a reasonable tradeoff.
Life course analysis on income and incident AMI: a Danish register-based cohort study

Background Social inequality in ischaemic heart disease has been related to socioeconomic position in childhood, early adulthood and late adulthood. However, the impact of relative level of accumulated income periods across adult life course and the potential gender and age differences have not been investigated. The aim was to investigate the association between relative level of accumulated income across the life course and acute myocardial infarction (AMI) from age 60+ years and to study if the associations differ by gender and in different age groups (30–39 years, 40–49 years and 50–59 years). Methods All Danes born 1935–1954 (N=1 235 139) were followed up in registers for incident AMI (42 669 cases). The accumulated proportional deviation from median equivalised income (APDMEI) for each gender/age/calendar year strata was constructed and divided in quartiles. The associations were analysed by means of Cox’s proportional hazard models. Results Among men, those in the lowest APDMEI quartile had an HR 1.40 (1.35–1.45) of AMI compared with the highest quartile. Those in the second and third highest quartiles had HR of 1.24 (1.20–1.28) and 1.14 (1.10–1.18), respectively. Among women, the lowest quartile had an HR of 1.78 (1.69–1.88), the second 1.45 (1.37–1.53) and the third 1.19 (1.13–1.26). The social gradient was similar across the different age groups. Conclusion The risk of AMI increased with lower levels of relative accumulated income across the life course. While men generally had a higher risk of AMI, the social gradient was steeper in women. There was no indication of a specific sensitive age period for exposure to relative level of accumulated income.
Antioxidant potential of theaflavin ameliorates the activities of key enzymes of glucose metabolism in high fat diet and streptozotocin – induced diabetic rats

ABSTRACT Objectives: The present study was to evaluate the effect of theaflavin on the activities of key enzymes of carbohydrate metabolism in high fat diet and streptozotocin – induced diabetic rats. Methods: Diabetes was induced in male albino Wistar rats by feeding them with high fat diet comprising of standard laboratory rat chow 84.3%, lard 5%, egg yolk powder 10%, cholesterol 0.2% and bile salt 0.5% for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (40 mg/kg b.w). Results: Theaflavin (100 mg/kg b.w /day) was administered orally to diabetic rats for 30 days. At the end of the experimental period, diabetic control rats showed significant increase in plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c) with concomitant decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism, lipid peroxidation markers, antioxidant enzymes, glycogen content and glycogen synthase and glycogen phosphorylase were also altered in diabetic rats. Discussion: Oral administration of theaflavin to diabetic rats significantly ameliorated all the biochemical alterations to near normal levels. The results of the present study suggest that theaflavin exhibits antidiabetic effect through its antioxidant activity.
Toward Automatic Anxiety Detection in Autism: A Real-Time Algorithm for Detecting Physiological Arousal in the Presence of Motion

Objective: Anxiety is a significant clinical concern in autism spectrum disorder (ASD) due to its negative impact on physical and psychological health. Treatment of anxiety in ASD remains a challenge due to difficulties with self-awareness and communication of anxiety symptoms. To reduce these barriers to treatment, physiological markers of autonomic arousal, collected through wearable sensors, have been proposed as real-time, objective, and language-free measures of anxiety. A critical limitation of the existing anxiety detection systems is that physiological arousal is not specific to anxiety and can occur with other user states such as physical activity. This can result in false positives, which can hinder the operation of these systems in real-world situations. The objective of this paper was to address this challenge by proposing an approach for real-time detection and mitigation of physical activity effects. Methods: A novel multiple model Kalman-like filter is proposed to integrate heart rate and accelerometry signals. The filter tracks user heart rate under different motion assumptions and chooses the appropriate model for anxiety detection based on user motion conditions. Results: Evaluation of the algorithm using data from a sample of children with ASD shows a significant reduction in false positives compared to the state-of-the-art, and an overall arousal detection accuracy of 93%. Conclusion: The proposed method is able to reduce false detections due to user motion and effectively detect arousal states during movement periods. Significance: The results add to the growing evidence supporting the feasibility of wearable technologies for anxiety detection and management in naturalistic settings.
Comparative effectiveness of different antihypertensive agents in kidney transplantation: a systematic review and meta-analysis.

BACKGROUND We conducted a systematic review and meta-analysis to compare benefits and harms of different antihypertensive drug classes in kidney transplant recipients, as post-transplant hypertension (HTN) associates with increased cardiovascular (CV) morbidity and mortality. METHODS The Ovid-MEDLINE, PubMed and CENTRAL databases were searched for randomized controlled trials (RCTs) comparing all main antihypertensive agents versus placebo/no treatment, routine treatment. RESULTS The search identified 71 RCTs. Calcium channel blockers (CCBs) (26 trials) reduced the risk for graft loss {risk ratio [RR] 0.58 [95% confidence interval (CI) 0.38-0.89]}, increased glomerular filtration rate (GFR) [mean difference (MD) 3.08 mL/min (95% CI 0.38-5.78)] and reduced blood pressure (BP). Angiotensin-converting enzyme inhibitors (ACEIs) (13 trials) reduced the risk for graft loss [RR 0.62 (95% CI 0.40-0.96)] but decreased renal function and increased the risk for hyperkalaemia. Angiotensin receptor blockers (ARBs) (10 trials) did not modify the risk of death, graft loss and non-fatal CV events and increased the risk for hyperkalaemia. When pooling ACEI and ARB data, the risk for graft failure was lower in renin-angiotensin system (RAS) blockade as compared with control treatments. In direct comparison with ACEIs or ARBs (11 trials), CCBs increased GFR [MD 11.07 mL/min (95% CI 6.04-16.09)] and reduced potassium levels but were not more effective in reducing BP. There are few available data on mortality, graft loss and rejection. Very few studies performed comparisons with other active drugs. CONCLUSIONS CCBs could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss. No definite patient or graft survival benefits were associated with RAS inhibitor use over conventional treatment.
Action Observation of Own Hand Movement Enhances Event-Related Desynchronization

A stroke occurs when blood flow to the brain is critically reduced or blocked, potentially resulting in motor paralysis. One of the most promising and effective neurorehabilitation methods for strokes is a closed-loop brain–computer interface (BCI) based on the motor imagery (MI). For the design of MI-based BCI, action observation (AO) during MI facilitates the detection of a user’s motor intention. In this paper, we investigated whether or not the AO’s targeted objects (the hand of a participant or another person) affects brain activity during MI. To investigate the differences in brain activity induced by the targeted objection, we recorded electroencephalography (EEG) data of 15 healthy right-handed males during three different conditions: 1) MI and AO of a participant’s hand (MI + ownAO); 2) MI and AO of a non-participant’s hand (MI + otherAO); and 3) MI only. The results showed that the event-related desynchronization (ERD) responses in the alpha frequency band (8–13 Hz) during MI + ownAO over the sensorimotor area (at the C3 and C4 channel locations) were stronger than those during the other two conditions. The results also showed that the difference between the participants’ and non-participants’ hands affected ERD responses during MI + ownAO and MI + otherAO.
An update in facial gender confirming surgery.

PURPOSE OF REVIEW To summarize current surgical and nonsurgical approaches to facial gender confirming surgery (FGCS) and highlight standards of care and areas of future research. RECENT FINDINGS Gender nonconforming individuals may encounter considerable internal coping and external social stressors that may contribute to gender-associated dysphoria. FGCS provides patients the ability to align facial appearance with gender identity, using recently described advances in surgical and nonsurgical techniques. The majority of FGCS is performed on transwomen (individuals identifying as female), yielding the more common term of facial feminization surgery (FFS). Although no set protocols or standards are in place, certain procedures are commonly performed to alter sex-determining characteristics of the face, and further research may help define guidelines. As many training programs have minimal exposure to FGCS, promotion of transgender health awareness is paramount for diverse and inclusive surgical training. SUMMARY Although demand for FGCS is increasing, there remains a need for improving surgical approaches, developing evidence-based care guidelines, and implementing education and awareness in training programs.
Exopolysaccharides of the phytopathogen Pseudomonas syringae pv. glycinea

Exopolysaccharides (EPS) of the soybean pathogen Pseudomonas syringae pv. glycinea were isolated from culture filtrates and infected soybean leaves. Levan (a polyfructan with a C-2----C-6 backbone and C-2----C-1 branching) or acetylated alginate (a linear polyuronide of C-1----C-4-linked mannuronic and guluronic acids) was isolated from culture filtrates when bacterial strains were grown in a semisynthetic medium containing sucrose or glucose, respectively, as the primary carbon source. Acetylated alginate was the only EPS isolated from soybean [Glycine max (L.) Merr. ] leaves inoculated with compatible (disease-inducing) strains of P. syringae pv. glycinea. The acetyl content of the P. syringae pv. glycinea alginates varied from 3 to 14%, and the amount of guluronic acid varied from less than 1 to 20%. The P. syringae pv. glycinea alginates from in vitro batch cultures were of lower molecular weight and polydispersity than those from in planta cultures, and both were of lower molecular weights than alginates produced by Pseudomonas aeruginosa.
Effect of Ballistic Potentiation Protocols on Elite Sprint Swimming: Optimizing Performance

Abstract Waddingham, DP, Millyard, A, Patterson, SD, and Hill, J. Effect of ballistic potentiation protocols on elite sprint swimming: optimizing performance. J Strength Cond Res 35(10): 2833–2838, 2021—Warming-up before an athletic event is important for performance; however, in some competition scenarios, there is a long wait between completing the warm-up and the event. Thus, potentiation protocols are becoming increasingly popular in a competition environment. The aim of the study was to determine the effects of practical potentiation protocols on 15-m start performance in national level swimmers. Eleven national level swimmers participated in the study. Using a randomized cross-over design, subjects completed a 15-m swimming start following 4 different experimental conditions (swim-specific control, resisted band squat, weighted countermovement jumps, and drop jumps from a 45-cm box), each separated by at least 48 hours. A repeated-measures analysis of variance showed a significant difference in 15-m swimming start performance following different warm-up protocols (F(1.646, 14.810) = 6.968, p = 0.01). A post hoc Bonferroni test indicated that 15-m start time was significantly quicker with the band squat protocol compared with the swim-specific protocol (6.65 ± 0.43 vs. 6.78 ± 0.43 seconds, respectively, p = 0.04). The results conclude that practical potentiation protocols are able to enhance 15-m swim start performance when combined with a swim-specific warm-up and supports the use of postactivation potentiation during competitive swimming environments.
An intuitive visualization for rapid data analysis: using the DNA metaphor for eye movement patterns

Eye tracking has become a valuable approach in user-centered studies, because it adds an additional source of information that can be recorded for later analysis, instead of just relying on the task completion and the time to completion. Without proper analysis of eye tracking data, important information can remain untold. In this paper, we present an intuitive visualization for rapid data analysis of eye movement patterns. Compared to heat maps or scan path visualizations, AOI-DNAs are easy to implement and take less effort to detect eye movement patterns. Therefore, they are viable for visual data mining and offer capabilities for user interactions for extended visual analytics. In conclusion, we implemented the first prototype to use AOI-DNAs and the first version of a fuzzy search to highlight eye movement patterns. We applied the proposed visualizations in a preliminary analysis to a well-known dataset to illustrate the practical usefulness as a case study in this paper.
Identification of Plasmodium falciparum and host factors associated with cerebral malaria: description of the protocol for a prospective, case-control study in Benin (NeuroCM)

Introduction In 2016, an estimated 216 million cases and 445 000 deaths of malaria occurred worldwide, in 91 countries. In Benin, malaria causes 26.8% of consultation and hospitalisation motif in the general population and 20.9% in children under 5 years old. The goal of the NeuroCM project is to identify the causative factors of neuroinflammation in the context of cerebral malaria. There are currently very few systematic data from West Africa on the aetiologies and management of non-malarial non-traumatic coma in small children, and NeuroCM will help to fill this gap. We postulate that an accurate understanding of molecular and cellular mechanisms involved in neuroinflammation may help to define efficient strategies to prevent and manage cerebral malaria. Methods and analysis This is a prospective, case-control study comparing cerebral malaria to uncomplicated malaria and non-malarial non-traumatic coma. This study takes place in Benin, precisely in Cotonou for children with coma and in Sô-Ava district for children with uncomplicated malaria. We aim to include 300 children aged between 24 and 71 months and divided in three different clinical groups during 12 months (from December 2017 to November 2018) with a 21 to 28 days follow-up for coma. Study data, including clinical, biological and research results will be collected and managed using CSOnline-Ennov Clinical. Ethics and dissemination Ethics approval for the NeuroCM study has been obtained from Comité National d’Ethique pour la Recherche en santé of Benin (n°67/MS/DC/SGM/DRFMT/CNERS/SA; 10/17/2017). NeuroCM study has also been approved by Comité consultatif de déontologie et d’éthique of Institut de Recherche pour le Développement (IRD; 10/24/2017). The study results will be disseminated through the direct consultations with the WHO’s Multilateral Initiative on Malaria (TDR-MIM) and Roll Back Malaria programme, through scientific meetings and peer-reviewed publications in scientific or medical journals, and through guidelines and booklets.
Nasal Coarticulation and Prosody in Kakataibo

Abstract This paper presents the first phonetic description of the patterns of nasal coarticulation in Kakataibo. While closely related Panoan languages have been described as having anticipatory nasal coarticulation in VN sequences, there are only a few reports of other types of nasal coarticulation. Based on a detailed investigation of the aerodynamic properties of nasality, we account for the full variety of nasal coarticulation patterns in Kakataibo and discuss their interaction with prosody. This paper shows that nasal coarticulation occurs in all contexts in which there is vowel-nasal contiguity, although the amount and patterns of nasal coarticulation are dependent on the directionality of the process, the presence or absence of a syllable boundary and stress.