Miracle-dz/UniFAR-FTUs huggingface dataset:
Anthropometric indices of obesity as predictors of high blood pressure among school children

ABSTRACT Background Hypertension is related to increased body fat, which can be evaluated by anthropometric indicators. The aim of this study was to determine the predictive power of anthropometric indicators and to establish their cutoff points as discriminators of high blood pressure. Methods A cross-sectional study was conducted on 793 schoolchildren aged 10–14 years. Six anthropometric indices were used: body mass index-z-score (BMI-z-score), waist circumference (WC), waist-toheight ratio (WHtR), a body shape index (ABSI), body roundness index (BRI) and conicity index (CI). Elevated blood pressure (EBP) and hypertension (HTN) were characterized by values ≥ 90th and <95th percentile and ≥ 95th percentile for systolic and/or diastolic blood pressure, respectively. The predictive power of anthropometric indices was analyzed by sex using the receiver operating characteristic curve (ROC). Results The prevalence of EBP and HTN was 11.0% and 14.8%, respectively. According to the analyses of the ROC curve, WC provided the largest area under the curve (AUC) value, while CI showed the lowest AUC value in predicting elevated blood pressure in the total sample. The BMI z-score provided the largest area under the curve (AUC) value (0.722), followed by WHtR (0.709) and BRI (0.709), in predicting hypertension in boys. Conclusions BMI z-score and WC may be the best predictors of EBP and BMI z-score for HTN among Jordanian schoolchildren.
scAAVengr, a transcriptome-based pipeline for quantitative ranking of engineered AAVs with single-cell resolution

Background: Adeno-associated virus (AAV)-mediated gene therapies are rapidly advancing to the clinic, and AAV engineering has resulted in vectors with increased ability to deliver therapeutic genes. Although the choice of vector is critical, quantitative comparison of AAVs, especially in large animals, remains challenging. Methods: Here, we developed an efficient single-cell AAV engineering pipeline (scAAVengr) to simultaneously quantify and rank efficiency of competing AAV vectors across all cell types in the same animal. Results: To demonstrate proof-of-concept for the scAAVengr workflow, we quantified – with cell-type resolution – the abilities of naturally occurring and newly engineered AAVs to mediate gene expression in primate retina following intravitreal injection. A top performing variant identified using this pipeline, K912, was used to deliver SaCas9 and edit the rhodopsin gene in macaque retina, resulting in editing efficiency similar to infection rates detected by the scAAVengr workflow. scAAVengr was then used to identify top-performing AAV variants in mouse brain, heart, and liver following systemic injection. Conclusions: These results validate scAAVengr as a powerful method for development of AAV vectors. Funding: This work was supported by funding from the Ford Foundation, NEI/NIH, Research to Prevent Blindness, Foundation Fighting Blindness, UPMC Immune Transplant and Therapy Center, and the Van Sloun fund for canine genetic research.
Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial.

Importance Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures. Objective To determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest. Design, Setting, and Participants Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020. Interventions Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours. Main Outcomes and Measures The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit. Results Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P = .004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively. Conclusions and Relevance In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference. Trial Registration ClinicalTrials.gov Identifier: NCT02011568.
His‐Purkinje conduction system pacing: A systematic review and network meta‐analysis in bradycardia and conduction disorders

His‐Purkinje conduction system pacing (HPCSP) has emerged as an effective alternative to overcome the limitations of right ventricular pacing (RVP) via physiological left ventricular activation, but there remains a paucity of comparative information for His bundle pacing (HBP) and left bundle branch pacing (LBBP).
Dapsone in hidradenitis suppurativa: A case series of 56 patients

Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a challenging treatment. Current guidelines reserve dapsone as a third line agent for patients with mild to moderate HS. To our knowledge, only four small case series have been reported. The objective of this study was to assess the effectiveness and safety of dapsone in our clinical practice. A retrospective observational single‐center study of 56 HS patients who underwent treatment with dapsone from May 1, 2015, to June 1, 2021, was performed. The Hidradenitis Suppurativa Clinical Response (HiSCR) scale was used to evaluate the response to treatment. Fifty‐six patients were included, 66% of which were men, with a median age of 33 years. Most of them had mild or moderate disease and belonged to LC2 follicular phenotype. All patients had been refractory to first‐line treatments. Dapsone was prescribed at doses of 50–150 mg/day. 62.5% of the patients achieved HiSCR after 12 weeks of treatment. No serious adverse reactions were detected. The median duration of treatment was 8 months. After multivariate analysis, an association was found between the presence of fistulous tracts and the risk of non‐response to the drug. In four of the dapsone responders, oral retinoids were added to achieve a sustained response. Limitations include the retrospective and non‐controlled nature of this study. In conclusion, dapsone is an effective and well‐tolerated option for long‐term HS treatment, and in this series, it was mainly chosen for patients with LC2 phenotype. It would be interesting to study combination with retinoids and other management options.
Longitudinal Investigation of Early Motor Development in Neurofibromatosis Type 1.

OBJECTIVE Research indicates that children with neurofibromatosis type 1 (NF1) have weaknesses in fine and gross motor development in early childhood; however, little is known about the stability and developmental trajectory of motor functioning. We investigated (1) whether motor difficulties are evident and stable in the preschool period in children with NF1 and (2) whether there are particular patterns of motor development in this population. METHODS Participants with NF1 and a control group of unaffected siblings were enrolled at ages 3-8 years and were assessed yearly. Motor functioning was assessed longitudinally using the Scales of Independent Behavior-Revised Motor Scale and the Differential Ability Scales-II Copying subtest. Wilcoxon sign tests were used to compare motor functioning at 3 or 4 years to 5 or 6 years old for children with NF1 seen during both time periods (N = 27). Linear mixed model growth curve analyses were used to compare trajectories for both children with NF1 (N = 62) and unaffected siblings (N = 37). RESULTS Children with NF1 made relative gains in raw scores, but not standard scores, across measures. Growth curve analyses revealed a significant effect of NF1 status on gross motor, fine motor, and copying scores, as well as an age by NF1 status effect on fine and gross motor scores. CONCLUSIONS Motor difficulties are evident early in life in children with NF1. Though children with NF1 clearly acquire motor skills over time, they continue to fall behind unaffected siblings, with the gap potentially widening over time. Further implications are discussed.
Revisiting approaches to and considerations for urinalysis and urine culture reflexive testing

Abstract Urinalysis is considered the world’s oldest laboratory test. Today, many laboratories use macroscopic urinalysis as a screening tool to determine when to subject urine samples for a microscopic urinalysis and/or bacterial culture. While reflexive urine microscopy has been practiced for decades, and reflexive urine culture, more recently, evidence-based guidelines regarding optimal reflexive criteria and workflows are lacking. Standard approaches are hindered, in part, by a lack of harmonization of urinalysis and urine culture practices, heterogeneity in patient populations that are studied, and lack of provider adherence to recommended practices. This review summarizes studies that have evaluated the performance of reflexive urine microscopy and reflexive urine culture, particularly in the context of urinary tract infections. It also examines reported clinical outcomes from reflexive urinalysis interventions and their impact on antibiotic stewardship efforts. Finally, it discusses laboratory operational considerations for the implementation of reflexive algorithms.
A specialized spinal circuit for command amplification and directionality during escape behavior

Significance We are constantly faced with a choice moving to the left or right; understanding how the brain solves the selection of action direction is of tremendous interest both from biological and clinical perspectives. In vertebrates, action selection is often considered to be the realm of higher cognitive processing. However, by combining electrophysiology, serial block-face electron microscopy, and behavioral analyses in zebrafish, we have revealed a pivotal role, as well as the full functional connectome of a specialized spinal circuit relying on strong axo-axonic synaptic connections. This includes identifying a class of cholinergic V2a interneurons and establishing that they act as a segmentally repeating hub that receives and amplifies escape commands from the brain to ensure the appropriate escape directionality. In vertebrates, action selection often involves higher cognition entailing an evaluative process. However, urgent tasks, such as defensive escape, require an immediate implementation of the directionality of escape trajectory, necessitating local circuits. Here we reveal a specialized spinal circuit for the execution of escape direction in adult zebrafish. A central component of this circuit is a unique class of segmentally repeating cholinergic V2a interneurons expressing the transcription factor Chx10. These interneurons amplify brainstem-initiated escape commands and rapidly deliver the excitation via a feedforward circuit to all fast motor neurons and commissural interneurons to direct the escape maneuver. The information transfer within this circuit relies on fast and reliable axo-axonic synaptic connections, bypassing soma and dendrites. Unilateral ablation of cholinergic V2a interneurons eliminated escape command propagation. Thus, in vertebrates, local spinal circuits can implement directionality of urgent motor actions vital for survival.
Fatigue in Patients With Multiple System Atrophy

Background and Objectives Nonmotor symptoms are common in patients with multiple system atrophy (MSA), but there is limited knowledge regarding fatigue in MSA. This study aimed to investigate the frequency and evolution of fatigue and the factors related to fatigue and its progression in patients with MSA at an early stage. Methods Patients with probable MSA were comprehensively evaluated at both baseline and the 1-year follow-up, including their motor and nonmotor symptoms. Fatigue and anxiety were assessed using the Fatigue Severity Scale (FSS) and Hamilton Anxiety Rating Scale (HARS), respectively. Orthostatic hypotension (OH) was defined as a decrease in the systolic or diastolic blood pressure by at least 30 and 15 mm Hg, respectively. The binary logistic regression model and linear regression model were used to analyze the factors related to fatigue and its progression, respectively. Results This study enrolled 146 patients with MSA. The frequency of fatigue was 60.3%, 55.1%, and 64.9% in MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C), respectively. The frequency of fatigue and the FSS score in patients with MSA increased from baseline to the 1-year follow-up (p < 0.05). Young age (odds ratio [OR] 0.939, 95% confidence interval [CI] 0.894–0.987), OH (OR 2.806, 95% CI 1.253–6.286), and high HARS score (OR 1.014, 95% CI 1.035–1.177) were associated with fatigue in MSA. OH was associated with fatigue in MSA-P (OR 3.391, 95% CI 1.066–10.788), while high HARS score was associated with fatigue in MSA-C (OR 1.159, 95% CI 1.043–1.287). In addition, only low FSS scores at baseline were associated with the annual progression rate of FSS scores in MSA, MSA-P, and MSA-C (p < 0.05). Neurofilament light chain, α-synuclein, glial fibrillary acidic protein, brain-derived neurotrophic factor, and triggering receptor expressed on myeloid cell-2 were not significantly associated with fatigue and its progression in MSA. Discussion Fatigue was prevalent in early-stage MSA, and it increased and remained persistent over time. This study demonstrated that OH and anxiety were associated with fatigue in patients with MSA.
Clinical utility of procalcitonin and its association with pathogenic microorganisms

Abstract In this review, we summarize the relationship of PCT with pathogens, evaluate the clinical utility of PCT in the diagnosis of clinical diseases, condition monitoring and evaluation, and guiding medical decision-making, and explore current knowledge on the mechanisms by which pathogens cause changes in PCT levels. The lipopolysaccharides of the microorganisms stimulate cytokine production in host cells, which in turn stimulates production of serum PCT. Pathogens have different virulence mechanisms that lead to variable host inflammatory responses, and differences in the specific signal transduction pathways result in variable serum PCT concentrations. The mechanisms of signal transduction have not been fully elucidated. Further studies are necessary to ascertain the PCT fluctuation range of each pathogen. PCT levels are helpful in distinguishing between certain pathogens, in deciding if antibiotics are indicated, and in monitoring response to antibiotics.
Developmental emergence of persistent memory for contextual and auditory fear in mice

The ability to generate memories that persist throughout a lifetime (that is, memory persistence) emerges in early development across species. Although it has been shown that persistent fear memories emerge between late infancy and adolescence in mice, it is unclear exactly when this transition takes place, and whether two major fear conditioning tasks, contextual and auditory fear, share the same time line of developmental onset. Here, we compared the ontogeny of remote contextual and auditory fear in C57BL/6J mice across early life. Mice at postnatal day (P)15, 21, 25, 28, and 30 underwent either contextual or auditory fear training and were tested for fear retrieval 1 or 30 d later. We found that mice displayed 30-d memory for context– and tone–fear starting at P25. We did not find sex differences in the ontogeny of either type of fear memory. Furthermore, 30-d contextual fear retrieval led to an increase in the number of c-Fos positive cells in the prelimbic region of the prefrontal cortex only at an age in which the contextual fear memory was successfully retrieved. These data delineate a precise time line for the emergence of persistent contextual and auditory fear memories in mice and suggest that the prelimbic cortex is only recruited for remote memory recall upon the onset of memory persistence.
EngagINg the COmmunity to Reduce Preterm birth via Adherence To an Individualized Prematurity Prevention Plan (INCORPorATe IP3): intervention development and future pilot study design

Abstract Objective Non-Hispanic Black birthing individuals are at increased risk of preterm birth compared to other racial and ethnic groups. In our clinical setting, we offer a tailored package of recommendations to reduce the risk of preterm birth known as an individualized prematurity prevention plan (IP3). Patient-centered, community engaged interventions that address patient-perceived barriers to preterm birth prevention are urgently needed. Materials and methods We engaged a group of stakeholders to develop a mutli-level (patient-centered and community-involved) intervention that will increase adherence to an individualized prematurity prevention plan (IP3) by addressing barriers identified during our prior qualitative studies. Results The intervention includes trained doulas from a community-led, Black owned doula group. The doulas will moderate group prenatal social support sessions. In between the group sessions, participants will be encouraged to continue interacting with one another and the doulas using a private Facebook™ group page. We will pilot test the intervention in a cohort of pregnant, self-identified non-Hispanic Black patients with a history of prior preterm birth. Conclusion We present a novel, patient-centered, community engaged intervention to reduce preterm birth in high-risk non-Hispanic Black birthing individuals. If the intervention is feasible based on the pilot study findings, we anticipate conducting an appropriately powered study to determine whether the intervention achieves our goal of reducing preterm birth.
Storm Clouds and Silver Linings: Day-to-Day Life in COVID-19 Lockdown and Emotional Health in Adolescent Girls

Abstract Objective We examined risk and protective factors for emotional health problems in adolescent girls during the COVID-19 pandemic. We investigated pre- to early-pandemic changes in symptoms of anxiety and depression, documented daily activities and perceived positive and negative impacts of the pandemic, and linked perceived positive and negative impacts of the pandemic to real-time changes in emotional health. Methods The study was a 10-day daily diary study with 93 U.S. adolescent girls (aged 12–17; 68% White non-Hispanic) at temperamental risk for anxiety and depression, conducted in April/May 2020 when all participants were under state-issued stay-at-home orders. Girls provided daily reports of positive and negative affect, depressive and anxious symptoms, activities, and positive and negative impacts resulting from the pandemic. Results Girls reported engaging in many activities that may contribute to well-being. Mixed effects analyses revealed positive impacts associated with improved same-day emotional health such as more time for family and relaxation and reduced pressure from school/activities. Negative impacts associated with poorer same-day emotional health included problems with online schooling, lack of space/privacy, lack of a regular schedule, and family conflict. Conclusion Findings highlight the importance of providing in-person or quality online schooling, resources and space for learning, promoting daily routines, and spending time with teens while reducing family conflict. The pandemic also appears to have offered many girls a respite from the chronic stress of modern teen life, with time to relax and engage in creative and healthy pursuits showing benefits for daily emotional health, which should be considered following the return to normal life.
The vertical space–time association

The space–time interaction suggests a left-to-right directionality in the mind’s representation of elapsing time. However, studies showing a possible vertical time representation are scarce and contradictory. In Experiment 1, 32 participants had to judge the duration (200, 300, 500, or 600 ms) of the target stimulus that appeared at the top, centre, or bottom of the screen, compared with a reference stimulus (400 ms) that always appeared in the centre of the screen. In Experiment 2, 32 participants were administered the same procedure, but the reference stimulus appeared at the top, centre, or bottom of the screen and the target stimulus was fixed in the centre location. In both experiments, a space–time interaction was found with an association between short durations and bottom response key as well as between long durations and top key. The evidence of a vertical mental timeline was further confirmed by the distance effect with a lower level of performance for durations close to that of the reference stimulus. The results suggest a bottom-to-top mapping of time representation, more in line with the metaphor “more is up. ”