Miracle-dz/UniFAR-FTUs huggingface dataset:
PASI: A novel pathway method to identify delicate group effects

Pathway analysis is a common approach in diverse biomedical studies, yet the currently-available pathway tools do not typically support the increasingly popular personalized analyses. Another weakness of the currently-available pathway methods is their inability to handle challenging data with only modest group-based effects compared to natural individual variation. In an effort to address these issues, this study presents a novel pathway method PASI (Pathway Analysis for Sample-level Information) and demonstrates its performance on complex diseases with different levels of group-based differences in gene expression. PASI is freely available as an R package.
The Impact of School Nurses in Kentucky Public High Schools

The purpose of this study was to examine the relationship between school nurse presence and graduation rates, absenteeism, and American College Test (ACT) scores. A state-wide survey of all public high schools was undertaken (participation rate of 99.1%). Survey data obtained from individual high schools provided information on the employment status of school nurses. In addition to nurse presence determined by the survey, open-access electronic databases were used to determine graduation rates, absenteeism, ACT scores, money spent per pupil, gender, race–ethnicity proportion, and incarceration data. Study findings showed a possible relationship between students attending schools with a full-time nurse and significantly higher graduation rates, lower absenteeism, and higher ACT scores. The study results suggest that school nurses may contribute not just to health outcomes but to improved academic and economic outcomes as well. Of course, future work is needed to confirm these assertions.
“Chocolate” Gold Nanoparticles—One Pot Synthesis and Biocompatibility

The chemical synthesis of nanoparticles can involve and generate toxic materials. Here, we present for the first time, a one pot direct route to synthesize gold nanoparticles (AuNPs) using natural cacao extract as both a reducing and stabilizing agent. The nanoparticles were characterized by UV-visible spectroscopy (UV-VIS), dynamic light scattering (DLS), and transmission electron microscopy (TEM); and have excellent biocompatibility with human primary dermal fibroblasts.
Central nervous system modulates the neuromechanical delay in a broad range for the control of muscle force.

Force is generated by muscle units according to the neural activation sent by motor neurons. The motor unit is therefore the interface between the neural coding of movement and the musculotendinous system. Here we propose a method to accurately measure the latency between an estimate of the neural drive to muscle and force. Furthermore, we systematically investigate this latency, which we refer to as the neuromechanical delay (NMD), as a function of the rate of force generation. In two experimental sessions, eight men performed isometric finger abduction and ankle dorsiflexion sinusoidal contractions at three frequencies and peak-to-peak amplitudes {0.5, 1, and 1.5 Hz; 1, 5, and 10 of maximal force [%maximal voluntary contraction (MVC)]}, with a mean force of 10% MVC. The discharge timings of motor units of the first dorsal interosseous (FDI) and tibialis anterior (TA) muscle were identified by high-density surface EMG decomposition. The neural drive was estimated as the cumulative discharge timings of the identified motor units. The neural drive predicted 80 ± 0.4% of the force fluctuations and consistently anticipated force by 194.6 ± 55 ms (average across conditions and muscles). The NMD decreased nonlinearly with the rate of force generation ( R2 = 0.82 ± 0.07; exponential fitting) with a broad range of values (from 70 to 385 ms) and was 66 ± 0.01 ms shorter for the FDI than TA ( P < 0.001). In conclusion, we provided a method to estimate the delay between the neural control and force generation, and we showed that this delay is muscle-dependent and is modulated within a wide range by the central nervous system. NEW & NOTEWORTHY The motor unit is a neuromechanical interface that converts neural signals into mechanical force with a delay determined by neural and peripheral properties. Classically, this delay has been assessed from the muscle resting level or during electrically elicited contractions. In the present study, we introduce the neuromechanical delay as the latency between the neural drive to muscle and force during variable-force contractions, and we show that it is broadly modulated by the central nervous system.
US budget impact of increased payer adoption of the Flexitouch advanced pneumatic compression device in lymphedema patients with advanced chronic venous insufficiency and multiple infections

Abstract Aims: To assess the budget impact to a US commercial health plan of providing access to the Flexitouch (FLX) advanced pneumatic compression device (Tactile Medical) to lymphedema (LE) patients with either comorbid chronic venous insufficiency (CVI) or frequent infections. Methods: Budget impact was calculated over 2 years for a hypothetical US payer with 10-million commercial members. Model inputs were derived from published sources and from a case-matched analysis of Blue Health Intelligence (BHI) claims data for the years 2012–2016. To calculate the budget impact, the Status Quo budget (i.e. total cost for LE and sequelae-related medical treatment) was compared to the budget under each of three Alternate Payer Policy scenarios which assumed that a sub-set of patients was redistributed from their initial treatment groups to a group that received FLX. Model outputs included cumulative payer costs, net budget impact, and breakeven point. Sensitivity analyses were performed to assess the impact of model inputs on results. Results: Increasing access to FLX yielded a favorable budget impact in every scenario. For LE patients with comorbid CVI, the three alternate scenarios resulted in cumulative 2-year budget impacts of –$52,841, –$173,317, and –$375,601, respectively. For LE patients with comorbid frequent infections, the three alternate scenarios resulted in cumulative 2-year budget impacts of –$192,729, –$259,339, and –$613,179, respectively. Limitations: Use of claims data assumes accurate coding and does not allow one to control for disease severity or treatment adherence. Also, the distribution of patients between treatment arms was determined using claims data from a specific payer organization, and could differ for health plans with different coverage policies. Conclusions: While previous studies have illustrated cost savings with adoption of FLX, US commercial health plans may also achieve tangible cost savings by expanding access to FLX for LE patients with comorbid CVI and multiple infections.
Corticosteroids in Sepsis: An Updated Systematic Review and Meta-Analysis

Objective: This systematic review and meta-analysis addresses the efficacy and safety of corticosteroids in critically ill patients with sepsis. Data Sources: We updated a comprehensive search of MEDLINE, EMBASE, CENTRAL, and LILACS, and unpublished sources for randomized controlled trials that compared any corticosteroid to placebo or no corticosteroid in critically ill children and adults with sepsis. Study Selection: Reviewers conducted duplicate screening of citations, data abstraction, and, using a modified Cochrane risk of bias tool, individual study risk of bias assessment. Data Extraction: A parallel guideline committee provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. We assessed overall certainty in evidence using Grading of Recommendations Assessment, Development and Evaluation methodology and performed all analyses using random-effect models. For subgroup analyses, we performed metaregression and considered p value less than 0.05 as significant. Data Synthesis: Forty-two randomized controlled trials including 10,194 patients proved eligible. Based on low certainty, corticosteroids may achieve a small reduction or no reduction in the relative risk of dying in the short-term (28–31 d) (relative risk, 0.93; 95% CI, 0.84–1.03; 1.8% absolute risk reduction; 95% CI, 4.1% reduction to 0.8% increase), and possibly achieve a small effect on long-term mortality (60 d to 1 yr) based on moderate certainty (relative risk, 0.94; 95% CI, 0.89–1.00; 2.2% absolute risk reduction; 95% CI, 4.1% reduction to no effect). Corticosteroids probably result in small reductions in length of stay in ICU (mean difference, –0.73 d; 95% CI, –1.78 to 0.31) and hospital (mean difference, –0.73 d; 95% CI, –2.06 to 0.60) (moderate certainty). Corticosteroids result in higher rates of shock reversal at day 7 (relative risk, 1.26; 95% CI, 1.12–1.42) and lower Sequential Organ Failure Assessment scores at day 7 (mean difference, –1.39; 95% CI, –1.88 to –0.89) (high certainty). Corticosteroids likely increase the risk of hypernatremia (relative risk, 1.64; 95% CI, 1.32–2.03) and hyperglycemia (relative risk, 1.16; 95% CI, 1.08–1.24) (moderate certainty), may increase the risk of neuromuscular weakness (relative risk, 1.21; 95% CI, 1.01–1.52) (low certainty), and appear to have no other adverse effects (low or very low certainty). Subgroup analysis did not demonstrate a credible subgroup effect on any of the outcomes of interest (p > 0.05 for all). Conclusions: In critically ill patients with sepsis, corticosteroids possibly result in a small reduction in mortality while also possibly increasing the risk of neuromuscular weakness.
Displacement of occluder as a rare complication of transcatheter closure of ventricular septal defect

Rationale: Ventricular septal defects are the most common congenital heart defect in children. As this method avoids sternotomy, the post-procedural morbidity is lower. However, transcatheter closure of perimembranous ventricular septal defects are still associated with complications such as arrhythmia (particularly, Atrioventricular Block), device embolization, atrioventricularvalve and/or aortic valves regurgitation, residual shunts. Some complications can be life threatening and require urgent surgical intervention. Patient concerns: An 32-months-old boy was admitted for a significant precordial systolic murmur. The patient underwent transcatheter perimembranous ventricular septal defects closure. 12 months later, Transthoracic echocardiography revealed the device displaced, 4 mm shunt acrocss the ventricular septum and moderate tricuspid regurgitation detected. Diagnosis: According to the echocardiography result, the patient was diagnosed with displacement of the ventricular septal defect occluder and tricuspid regurgitation. Interventions: After the diagnosis, the patient underwent removal of the ventricular septal defect occluder and closure of the perimembranous ventricular septal defect. Outcomes: The post-operative recovery was uneventful. One year post-procedural follow-up transthoracic echocardiography showed there was no residual shunt and no tricuspid regurgitation. Lessons: Transcatheter closure of Ventricular septal defects is an attractive alternative to surgery in simple perimembranous ventricular septal defects. Proper follow-up should be emphasized to the patient.
Balance- and Strength-Training Protocols to Improve Chronic Ankle Instability Deficits, Part I: Assessing Clinical Outcome Measures.

CONTEXT Functional rehabilitation may improve the deficits associated with chronic ankle instability (CAI). OBJECTIVE To determine if balance- and strength-training protocols improve the balance, strength, and functional performance deficits associated with CAI. DESIGN Randomized controlled clinical trial. SETTING Athletic training research laboratory. PATIENTS OR OTHER PARTICIPANTS Participants were 39 volunteers with CAI, which was determined using the Identification of Functional Ankle Instability Questionnaire. They were randomly assigned to 1 of 3 groups: balance-training protocol (7 males, 6 females; age = 23.5 ± 6.5 years, height = 175.0 ± 8.5 cm, mass = 72.8 ± 10.9 kg), strength-training protocol (8 males, 5 females; age = 24.6 ± 7.7 years, height = 173.2 ± 9.0 cm, mass = 76.0 ± 16.2 kg), or control (6 males, 7 females; age = 24.8 ± 9.0 years, height = 175.5 ± 8.4 cm, mass = 79.1 ± 16.8 kg). INTERVENTION(S) Each group participated in a 20-minute session, 3 times per week, for 6 weeks. The control group completed a mild to moderately strenuous bicycle workout. MAIN OUTCOME MEASURE(S) Participants completed baseline testing of eccentric and concentric isokinetic strength in each ankle direction (inversion, eversion, plantar flexion, and dorsiflexion) and the Balance Error Scoring System (BESS), Star Excursion Balance Test (SEBT), and side-hop functional performance test. The same variables were tested again at 6 weeks after the intervention. Two multivariate repeated-measures analyses of variance with follow-up univariate analyses were conducted. The α level was set a priori at . 05. RESULTS We observed time-by-group interactions in concentric ( P = .02) and eccentric ( P = .01) inversion, eccentric eversion ( P = .01), concentric ( P = .001) and eccentric ( P = .03) plantar flexion, BESS ( P = .01), SEBT ( P = .02), and side hop ( P = .004). With pairwise comparisons, we found improvements in the balance- and strength-training protocol groups in concentric and eccentric inversion and concentric and eccentric plantar flexion and the BESS, SEBT, and side hop (all P values = .001). Only the strength-training protocol group improved in eccentric eversion. The control group did not improve in any dependent variable. CONCLUSIONS Both training protocols improved strength, balance, and functional performance. More clinicians should incorporate hop-to-stabilization exercises into their rehabilitation protocols to improve the deficits associated with CAI.
Alveolar echinococcosis in a dog; analysis of clinical and histological findings and molecular identification of Echinococcus multilocularis

Echinococcus multilocularis is a zoonotic tapeworm of medical and veterinary importance that occasionally infects accidental intermediate hosts causing severe disease or even death. In dogs, alveolar echinococcosis has been reported mainly in central Europe and Canada. The paper presents clinical, biochemical and histological signs of alveolar echinococcosis in a dog from Slovakia and the results of mitochondrial nad1 gene analysis. In 2016, 11-years old Siberian husky female suffering from inappetence was presented to the Veterinary Clinic in Žilina. Biochemical blood examination and blood count showed only minor changes, but abdominal ultrasonography showed the hepatomegaly and the presence of nonhomogeneous hypodense lobulated formation in the left liver lobe. Histological and molecular examinations of excided tissue confirmed the diagnosis of alveolar echinococcosis of the liver. BLAST analysis of E. multilocularis nad1 gene revealed that the nucleotide sequence did not exactly match the previously identified M1 (AJ237639) and/or M2 genotype (AJ237640). In total, two single nucleotide polymorphisms (SNPs) occurred within overlapping region of nad1 gene. In the discussion, clinical and laboratory findings of the infection in other dog patients are compared and the possibilities of diagnosis and therapy of the disease are discussed.
Safety of obinutuzumab alone or combined with chemotherapy for previously untreated or relapsed/refractory chronic lymphocytic leukemia in the phase IIIb GREEN study

The safety of obinutuzumab, alone or with chemotherapy, was studied in a non-randomized, open-label, non-comparative, phase IIIb study (GREEN) in previously untreated or relapsed/refractory chronic lymphocytic leukemia. Patients received obinutuzumab 1000 mg alone or with chemotherapy (investigator’s choice of fludarabine-cyclophosphamide for fit patients, chlorambucil for unfit patients, or bendamustine for any patient) on days 1, 8 and 15 of cycle 1, and day 1 of cycles 2–6 (28-day cycles), with the cycle 1/day 1 dose administered over two days. The primary end point was safety/tolerability. Between October 2013 and March 2016, 972 patients were enrolled and 971 treated (126 with obinutuzumab monotherapy, 193 with obinutuzumab-fludarabine-cyclophosphamide, 114 with obinutuzumab-chlorambucil, and 538 with obinutuzumab-bendamustine). Grade ≥3 adverse events occurred in 80.3% of patients, and included neutropenia (49.9%), thrombocytopenia (16.4%), anemia (9.6%), and pneumonia (9.0%); rates were similar in first-line and relapsed/refractory patients, and in first-line fit and unfit patients. Using expanded definitions, infusion-related reactions were observed in 65.4% of patients (grade ≥3, 19.9%; mainly seen during the first obinutuzumab infusion), tumor lysis syndrome in 6.4% [clinical and laboratory; highest incidence with obinutuzumab-bendamustine (9.3%)], and infections in 53.7% (grade ≥3, 20.1%). Serious and fatal adverse events were seen in 53.1% and 7.3% of patients, respectively. In first-line patients, overall response rates at three months post treatment exceeded 80% for all obinutuzumab-chemotherapy combinations. In the largest trial of obinutuzumab to date, toxicities were generally manageable in this broad patient population. Safety data were consistent with previous reports, and response rates were high. (clinicaltrials.gov identifier: 01905943).
mTOR acts as a pivotal signaling hub for neural crest cells during craniofacial development

mTOR is a highly conserved serine/threonine protein kinase that is critical for diverse cellular processes in both developmental and physiological settings. mTOR interacts with a set of molecules including Raptor and Rictor to form two distinct functional complexes, namely the mTORC1 and mTORC2. Here, we used novel genetic models to investigate functions of the mTOR pathway for cranial neural crest cells (NCCs), which are a temporary type of cells arising from the ectoderm layer and migrate to the pharyngeal arches participating craniofacial development. mTOR deletion elicited a proliferation deficit and excessive apoptosis of post-migratory NCCs, leading to growth arrest of the facial primordia along with midline orofacial clefts. Furthermore, NCC differentiation was impaired. Thus, NCC derivatives, such as skeletons, vasculatures and neural tissues were either rudimentary or malformed. We further demonstrate that disruption of mTOR caused P53 hyperactivity and cell cycle arrest in cranial NCCs, and lowering P53 activity by one copy reduction attenuated the severity of craniofacial phenotype in NCC-mTOR knockout mice. Remarkably, NCC-Rptor disruption caused a spectrum of defects mirroring that of the NCC-mTOR deletion, whereas NCC-Rictor disruption only caused a mild craniofacial phenotype compared to the mTOR and Rptor conditional knockout models. Altogether, our data demonstrate that mTOR functions mediated by mTORC1 are indispensable for multiple processes of NCC development including proliferation, survival, and differentiation during craniofacial morphogenesis and organogenesis, and P53 hyperactivity in part accounts for the defective craniofacial development in NCC-mTOR knockout mice.
Seasonal variation of Pseudomonas aeruginosa in culture positive otitis externa in South East England

Abstract Otitis externa is the inflammation of the external auditory canal. The disease is common and shows a seasonal variation with a greater incidence in warmer months. Pseudomonas aeruginosa is a common pathogen in otitis externa and in this retrospective study, we show a corresponding seasonal variation in the proportional incidence of P. aeruginosa isolates from otitis externa in South East England. In total 7770 patients were diagnosed with otitis externa over a period of 9 years from January 2008 to December 2016. P. aeruginosa was isolated from 2802 patients (proportional incidence of 36%). Incidence was higher in the months of August, September and October and in patients between 5 and 15 years of age. We postulate a combination of increased contact with water during warm weather in the holiday season and increased rainfall in the preceding season as a putative mechanism for the seasonal trends.
Noncontrast Head CT in Children: National Variation in Radiation Dose Indices in the United States

BACKGROUND AND PURPOSE: Radiologists should manage the radiation dose for pediatric patients to maintain reasonable diagnostic confidence. We assessed the variation in estimated radiation dose indices for pediatric noncontrast head CT in the United States. MATERIALS AND METHODS: Radiation dose indices for single-phase noncontrast head CT examinations in patients 18 years of age and younger were retrospectively reviewed between July 2011 and June 2016 using the American College of Radiology CT Dose Index Registry. We used the reported volume CT dose index stratified by patient demographics and imaging facility characteristics. RESULTS: The registry included 295,296 single-phase pediatric noncontrast head CT studies from 1571 facilities (56% in male patients and 53% in children older than 10 years of age). The median volume CT dose index was 33 mGy (interquartile range = 22–47 mGy). The volume CT dose index increased as age increased. The volume CT dose index was lower in children's hospitals (median, 26 mGy) versus academic hospitals (median, 32 mGy) and community hospitals (median, 40 mGy). There was a lower volume CT dose index in level I and II trauma centers (median, 27 and 32 mGy, respectively) versus nontrauma centers (median, 40 mGy) and facilities in metropolitan locations (median, 30 mGy) versus those in suburban and rural locations (median, 41 mGy). CONCLUSIONS: Considerable variation in the radiation dose index for pediatric head CT exists. Median dose indices and practice variations at pediatric facilities were both lower compared with other practice settings. Decreasing dose variability through proper management of CT parameters in pediatric populations using benchmarks generated by data from registries can potentially decrease population exposure to ionizing radiation.
Patterns of management of translocation renal cell carcinoma.

OBJECTIVE Translocation renal cell carcinoma (TRCC) represents 1% to 5% of all cases of renal cell carcinoma (RCC), with the highest frequency among children and young adults. Management of these tumors is ill defined. We sought to characterize clinicopathological features of TRCC and patterns of medical and surgical management in a middle eastern health institute. MATERIAL AND METHODS Clinical and pathological data of 23 patients from a single institution diagnosed with TRCC between January 2005 and July 2017 were retrospectively reviewed. We dichotomized patients based on demographics, methods of surgical approach and pathologic tumor stage. We then evaluated the methods of medical management for metastatic disease and response to treatment based on cancer-specific survival (CSS) and progression-free survival (PFS). RESULTS The median age at diagnosis was 37 years. Fifteen (65%) patients were male. Most of the patients were diagnosed incidentally (65%) during abdominal imaging for other reasons. The mean tumor size was 9 cm, 47% of the patients had pathologic ≥ T3 stage. Eleven patients had lymph node dissection for clinically enlarged lymph nodes, 7 of which (64%) had lymph node metastasis. Partial nephrectomies were performed for three tumors. Eight patients had metastasis (34.7%), and 3 of them had metastasis at the time of diagnosis. Six patients received sunitinib for the treatment of metastatic disease, one patient had complete response, 4 patients had stable disease and one had disease progression. Three patients died during follow-up period because of development of metastasis at postoperative 4 (n=1), and 21 (n=1) months, and cerebral hemorrhage (n=1). The mean follow-up period was 35 months and 3-year disease-free survival was 75%. CONCLUSION TRCC is rarely seen but carries significant risk of disease progression with potential response to targeted therapy.