Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating coverage bias in next-generation sequencing of Escherichia coli

Whole-genome sequencing is essential to many facets of infectious disease research. However, technical limitations such as bias in coverage and tagmentation, and difficulties characterising genomic regions with extreme GC content have created significant obstacles in its use. Illumina has claimed that the recently released DNA Prep library preparation kit, formerly known as Nextera Flex, overcomes some of these limitations. This study aimed to assess bias in coverage, tagmentation, GC content, average fragment size distribution, and de novo assembly quality using both the Nextera XT and DNA Prep kits from Illumina. When performing whole-genome sequencing on Escherichia coli and where coverage bias is the main concern, the DNA Prep kit may provide higher quality results; though de novo assembly quality, tagmentation bias and GC content related bias are unlikely to improve. Based on these results, laboratories with existing workflows based on Nextera XT would see minor benefits in transitioning to the DNA Prep kit if they were primarily studying organisms with neutral GC content.
Optimal use of radiotherapy in the definitive treatment of non-bulky IB–IIA cervical cancer: A population-based long-term survival analysis

Purpose Although current clinical guidelines recommend surgery or radiotherapy for non-bulky IB-IIA cervical cancer, clinical data supporting the curative role of radiotherapy in the early-stage disease are insufficient. We evaluated the prognostic implications of definitive radiotherapy and determined its optimal use in clinical practice. Methods Patients with non-bulky (<4 cm) IB-IIA cervical cancer who underwent hysterectomy or primary radiotherapy between 1988 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Based on the use of brachytherapy and/or chemotherapy, the primary radiotherapy group was classified into three cohorts: hysterectomy vs. radiotherapy overall, with/without brachytherapy and/or chemotherapy (cohort A); radiotherapy and brachytherapy with/without chemotherapy (patients with external beam radiation alone were excluded, cohort B); radiotherapy with brachytherapy and chemotherapy (patients who did not receive chemotherapy were additionally excluded, cohort C). Disease-specific survival (DSS) after hysterectomy was compared to that after primary radiotherapy in each cohort. Results Among the 9,391 initially identified patients, 1,762, 1,244, and 750 patients were classified into cohorts A, B, and C, respectively, after propensity score matching. In cohort A, DSS after primary radiotherapy was inferior to that after hysterectomy (P = 0.001). In cohort B, a trend toward differential survival in favor of hysterectomy was observed with marginal significance (P = 0.061). However, in cohort C, DSS after primary radiotherapy was not significantly different to that after hysterectomy (P = 0.127). According to hazard rate function plots, patients receiving external beam radiation alone had an increased short-term risk of disease-specific mortality, whereas patients without evidence of chemotherapy had a distinct late risk surge at approximately 15 years of follow-up. Conclusion Optimizing radiotherapy methods with brachytherapy and the use of chemotherapy should be considered for the long-term curative efficacy of primary radiotherapy for non-bulky IB-IIA cervical cancer. Further studies are warranted to corroborate our results.
A Volumetric Metric for Monitoring Intracranial Aneurysms: Repeatability and Growth Criteria in a Longitudinal MR Imaging Study

BACKGROUND AND PURPOSE: The reliability of contrast-enhanced MRA in monitoring serial volumetric changes of unruptured intracranial aneurysms has not been established. We aimed to determine the coefficient of variance of contrast-enhanced MRA in measuring aneurysm volumes, thus establishing criteria for aneurysm growth and permitting identification of variables predictive of growth. MATERIALS AND METHODS: Aneurysm volumes were measured from serial contrast-enhanced MRA studies of patients with untreated intracranial aneurysms who underwent >2 sequential MR imaging evaluations. After coregistering all sequential studies in 3D space for each aneurysm and signal intensity normalization, aneurysm volume was determined across all time points. A linear mixed effects model was built to estimate the coefficient of variance of the measurement as well as to determine predictive variables. Growth was defined as relative growth exceeding 2 times the measurement coefficient of variance (sudden growth, as 4 times the coefficient of variance). RESULTS: A total of 95 patients with 112 aneurysms were included (5.9 scans during 4.0 years on average, 616 scan measurements in total). The coefficient of variance was 5.5% of the aneurysm volume, and the relative growth rate was dependent on the location: anterior cerebral artery, 4.52% per year; vertebral artery, 2.46% per year; middle cerebral artery, 2.74% per year; basilar artery, 2.36% per year; internal carotid artery, 1.14% per year. Thirty-six of 112 (32%) aneurysms were characterized as growing, and 11/36 of them had an episode of sudden growth. CONCLUSIONS: Volume measurement of unruptured intracranial aneurysms by contrast-enhanced MRA seems a reliable metric for tracking the growth trajectory of aneurysms. Furthermore, the aneurysm growth rate differs among different locations.
The risk of intrapartum cesarean delivery in advanced maternal age

Abstract Objective We aimed to investigate the association of advanced maternal age with intrapartum cesarean delivery and to assess its risk factors and perinatal outcomes. Study Design A retrospective cohort study of all women with singleton pregnancies who attempted a trial of labor (≥24 + 0 weeks of gestation) in a single center (2011–2017). The study population was stratified by parity (nulliparous or multiparous) and further sub-categorized into three cohorts: (1) women <35 years at birth (reference group), (2) women aged 35–40 years, and (3) women >40 years. Labor and delivery characteristics and neonatal outcomes were compared. Results Overall, 55,089 women were included: 39, 192 (71.1%) were under 35 years old, 15,90712,892 (28.923.4%) were 35-40 y and 3,015 (5.5%) were >40 y. For nulliparas, the rate of intrapartum Cesarean deliveries increased with maternal age and approached 25.3% in those >40 y as compared to 8.9% for those <35 y. The positive association between Cesarean section rates and maternal age extends beyond nulliparas and is also seen in multiparas, although to a smaller degree. After adjusting for confounders, maternal age was significantly and independently associated with intrapartum cesarean delivery in a dose-dependent manner in nulliparous women, [adjusted Odd Ratio (aOR) 1.56 (95% Confidence Interval (CI) 1.39–1.76) and 2.53 (2.07–3.09)] among women aged 35–40 y and >40 y, respectively. Maternal age was not significantly associated with adverse neonatal outcome. Conclusion Advanced maternal age is an independent risk factor for intrapartum Cesarean delivery. Yet, the majority of older gravidae who attempt a trial of labor, even if nulliparous, deliver vaginally without an increase in adverse neonatal outcome.
Quercetin mediated attenuation of cadmium‐induced oxidative toxicity and apoptosis of spermatogenic cells in caprine testes in vitro

Cadmium (Cd), an environmental toxic heavy metal, has been reported to cause testicular toxicity, which contributes to the recent decline in male fertility worldwide. Quercetin (Qcn), a major dietary antioxidant, has been shown to have protective effects under various pathological conditions. However, whether Qcn provides protection against Cd‐stimulated testicular toxicity remains obscured. The present study was therefore aimed at investigating the ameliorative effect of Qcn supplementation on Cd‐induced toxicity in the goat testis in vitro in a dose‐(10, 50, and 100 μM) and time‐dependent (4 and 8 h) manner. Different cytotoxicity, genotoxicity, and biochemical analyses have been carried out using appropriate methods. Cytotoxicity in testicular cells induced by Cd treatment was apparently mitigated by Qcn treatment, evidenced by decreased apoptotic attributes or frequency in Qcn plus Cd‐treated groups compared to the only Cd‐treated groups. Qcn treatment provides substantial protection to the Cd‐triggered aggression in oxidative (increased MDA levels) and total antioxidant capacity (reduced FRAP activity) in testicular tissue, indicating the anti‐oxidative function of Qcn against Cd exposure. Moreover, Cd‐induced decline in antioxidant status (CAT, SOD, and GST activity) was markedly restored by Qcn supplementation in testicular tissue. In conclusion, this study shows that Qcn treatment significantly attenuated the Cd‐evoked testicular damage, suggesting its beneficial potential in preventing or at least in managing the gonadotoxicity in males induced by steadily increasing Cd contamination in the environment.
Prospective Validation of the Preschool Confusion Assessment Method for the ICU to Screen for Delirium in Infants Less Than 6 Months Old

OBJECTIVES: ICU delirium is a predictor of greater morbidity and higher mortality in the pediatric population. The diagnostic obstacles and validity of delirium monitoring among neonates and young infants have yet to be fully delineated. We sought to validate the Preschool Confusion Assessment Method for the ICU in neonates and young infants and determine delirium prevalence in this young population. DESIGN: Prospective cohort study to validate the Preschool Confusion Assessment Method for the ICU for the assessment of ICU delirium in neonates and young infants compared with the reference standard, Child and Adolescent Psychiatry. SETTING: Tertiary medical center PICU, including medical, surgical, and cardiac patients. PARTICIPANTS: Infants less than 6 months old admitted to the PICU regardless of admission diagnosis. MEASUREMENTS AND MAIN RESULTS: We enrolled 49 patients with a median age of 1.8 months (interquartile range, 0.7–4.1 mo), 82% requiring mechanical ventilation. Enrolled patients were assessed for delirium in blinded-fashion by the research team using the Preschool Confusion Assessment Method for the ICU and independently assessed by the psychiatry reference rater using Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A total of 189 paired assessments were completed, and the Preschool Confusion Assessment Method for the ICU performed with a sensitivity of 95% (95% CI, 89–100%), specificity of 81% (68–90%), “negative and positive predictive values” of 97% (94–100%) and 69% (55–79%), respectively, compared with the reference rater. Delirium prevalence was 47%, with higher rates of 61% observed among neonates (< 1 mo old) and 39% among infants 1–6 months old. CONCLUSIONS: The Preschool Confusion Assessment Method for the ICU is a valid screening tool for delirium monitoring in infants less than 6 months old. Delirium screening was feasible in this population despite evolving neurocognition and arousal architecture. ICU delirium was prevalent among infants. The consequence of acute brain dysfunction during crucial neurocognitive development remains unclear. Future studies are necessary to determine the long-term impact of ICU delirium and strategies to reduce associated harm in critically ill infants.
Microfluidic-based imaging of complete Caenorhabditis elegans larval development

ABSTRACT Several microfluidic-based methods for Caenorhabditis elegans imaging have recently been introduced. Existing methods either permit imaging across multiple larval stages without maintaining a stable worm orientation, or allow for very good immobilization but are only suitable for shorter experiments. Here, we present a novel microfluidic imaging method that allows parallel live-imaging across multiple larval stages, while maintaining worm orientation and identity over time. This is achieved through an array of microfluidic trap channels carefully tuned to maintain worms in a stable orientation, while allowing growth and molting to occur. Immobilization is supported by an active hydraulic valve, which presses worms onto the cover glass during image acquisition only. In this way, excellent quality images can be acquired with minimal impact on worm viability or developmental timing. The capabilities of the devices are demonstrated by observing the hypodermal seam and P-cell divisions and, for the first time, the entire process of vulval development from induction to the end of morphogenesis. Moreover, we demonstrate feasibility of on-chip RNAi by perturbing basement membrane breaching during anchor cell invasion.
Decision-Feedback Stages Revealed by Hidden Markov Modeling of EEG

Decision response and feedback in gambling are interrelated. Different decisions lead to different ranges of feedback, which in turn influences subsequent decisions. However, the mechanism underlying the continuous decision-feedback process is still left unveiled. To fulfill this gap, we applied the hidden Markov model (HMM) to the gambling electroencephalogram (EEG) data to characterize the dynamics of this process. Furthermore, we explored the differences between distinct decision responses (i.e. choose large or small bets) or distinct feedback (i.e. win or loss outcomes) in corresponding phases. We demonstrated that the processing stages in decision-feedback process including strategy adjustment and visual information processing can be characterized by distinct brain networks. Moreover, time-varying networks showed, after decision response, large bet recruited more resources from right frontal and right center cortices while small bet was more related to the activation of the left frontal lobe. Concerning feedback, networks of win feedback showed a strong right frontal and right center pattern, while an information flow originating from the left frontal lobe to the middle frontal lobe was observed in loss feedback. Taken together, these findings shed light on general principles of natural decision-feedback and may contribute to the design of biologically inspired, participant-independent decision-feedback systems.
Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene

The enlarged vestibular aqueduct (EVA) is the commonest malformation of inner ear accompanied by sensorineural hearing loss in children. Three genes SLC26A4, FOXI1, and KCNJ10 have been associated with EVA, among them SLC26A4 being the most common. Yet, hotspot mutation screening can only diagnose a small number of patients.
Effects of Foods Fortified with Zinc, Alone or Cofortified with Multiple Micronutrients, on Health and Functional Outcomes: A Systematic Review and Meta-Analysis

Abstract Seventeen per cent of the world's population is estimated to be at risk of inadequate zinc intake, which could in part be addressed by zinc fortification of widely consumed foods. We conducted a review of efficacy and effectiveness studies to ascertain the effect of zinc fortification [postharvest fortification of an industrially produced food or beverage; alone or with multiple micronutrients (MMN)] on a range of health outcomes. Previous reviews have required that the effect of zinc be isolated; because zinc is always cofortified with MMN in existing fortification programs, we did not impose this condition. Outcomes assessed were zinc-related biomarkers (plasma or serum, hair or urine zinc concentrations, comet assay, plasma fatty acid concentrations, and the proportion of and total zinc absorbed in the intestine from the diet), child anthropometry, morbidity, mortality, cognition, plasma or serum iron and copper concentrations, and for observational studies, a change in consumption of the food vehicle. Fifty-nine studies were included in the review; 54 in meta-analyses, totaling 73 comparisons. Zinc fortification with and without MMN increased plasma zinc concentrations (efficacy, n = 27: 4.68 μg/dL; 95% CI: 2.62–6.75; effectiveness, n = 13: 6.28 μg/dL; 95% CI: 5.03–7.77 μg/dL) and reduced the prevalence of zinc deficiency (efficacy, n = 11: OR: 0.76, 95% CI: 0.60–0.96; effectiveness, n = 10: OR: 0.45, 95% CI: 0.31–0.64). There were statistically significant increases in child weight (efficacy, n = 11: 0.43 kg, 95% CI: 0.11–0.75 kg), improvements in short-term auditory memory (efficacy, n = 3: 0.32 point, 95% CI: 0.13–0.50 point), and decreased incidence of diarrhea (efficacy, n = 3: RR: 0.79, 95% CI: 0.68–0.92) and fever (efficacy, n = 2: RR: 0.85, 95% CI: 0.74–0.97). However, these effects cannot be solely attributed to zinc. Our review found that zinc fortification with or without MMN reduced the prevalence of zinc deficiency and may provide health and functional benefits, including a reduced incidence of diarrhea.
Deep learning-based automated left ventricular ejection fraction assessment using 2D echocardiography.

BACKGROUND Deep-learning (DL) has been applied for automatic left ventricle (LV) ejection fraction (EF) measurement, but the diagnostic performance was rarely evaluated for various phenotypes of heart disease. This study aims to evaluate a new DL algorithm for automated LVEF measurement using two-dimensional echocardiography (2DE) images collected from 3 centers. The impact of 3 ultrasound machines and 3 phenotypes of heart diseases on the automatic LVEF measurement was evaluated. METHODS AND RESULTS Using 36890 frames of 2DE from 340 patients, we developed a DL algorithm based on U-Net (DPS-Net) and the biplane Simpson's method was applied for LVEF calculation. Results showed a high performance in LV segmentation and LVEF measurement across phenotypes and echo systems by using DPS-Net. Good performance was obtained for LV segmentation when DPS-Net was tested on the CAMUS dataset (Dice coefficient of 0.932 and 0.928 for ED and ES). Better performance of LV segmentation in study-wise evaluation was observed by comparing the DPS-Net v2 to the EchoNet-dynamic algorithm (p = 0.008). DPS-Net was associated with high correlations and good agreements for the LVEF measurement. High diagnostic performance was obtained that the area under receiver operator characteristic curve was 0.974, 0.948, 0.968 and 0.972 for normal hearts and disease phenotypes including atrial fibrillation, hypertrophic cardiomyopathy, dilated cardiomyopathy, respectively. CONCLUSION High performance was obtained by using DPS-Net in LV detection and LVEF measurement for heart failure with several phenotypes. High performance was observed in a large-scale dataset, suggesting that the DPS-Net was highly adaptive across different echocardiographic systems.
Sleep microstructure in attention deficit hyperactivity disorder according to the underlying sleep phenotypes

The analysis of sleep microstructure in attention deficit hyperactivity disorder (ADHD) revealed an under‐representation of the EEG slow component during NREM sleep. Previous studies either excluded or did not characterize objectively sleep disorders, which notoriously affect sleep architecture. The present study aimed to investigate the cyclic alternating pattern in a real clinical sample of children with ADHD, in whom sleep disorders could be considered. Twenty‐seven consecutively enrolled drug‐naïve children (mean age, 10.53 years; nine females) and 23 controls (mean age, 10.22 years; 11 females) underwent a full sleep investigation, including attended video‐polysomnography. Visual cyclic alternating pattern analysis was performed in a blinded way. Children with ADHD had one or more sleep disorders (a narcolepsy‐like phenotype was found in two cases, sleep onset insomnia in three cases, arousal disorder in one case, movement disorder phenotype in six cases and obstructive sleep apnea in 11 cases, and six children had sleep‐related epileptiform discharges). Children with ADHD and normal controls showed a similar microstructure with a cyclic alternating pattern rate of about 50%. Children with obstructive sleep apnea had a significantly higher cyclic alternating pattern rate during stage N3. Despite not reaching statistical differences, a lower cyclic alternating pattern rate and A1 index were found in children without epileptic abnormalities/obstructive sleep apnea. Our analysis might allow differentiation of the “primary form” of ADHD associated with a decrease of NREM instability from those forms associated with sleep apnea and epileptic activity.
Formulation and In Vitro Characterization of PLGA/PLGA-PEG Nanoparticles Loaded with Murine Granulocyte-Macrophage Colony-Stimulating Factor

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has demonstrated notable clinical activity in cancer immunotherapy, but it is limited by systemic toxicities, poor bioavailability, rapid clearance, and instability in vivo. Nanoparticles (NPs) may overcome these limitations and provide a mechanism for passive targeting of tumors. This study aimed to develop GM-CSF-loaded PLGA/PLGA-PEG NPs and evaluate them in vitro as a potential candidate for in vivo administration. NPs were created by a phase-separation technique that did not require toxic/protein-denaturing solvents or harsh agitation techniques and encapsulated GM-CSF in a more stable precipitated form. NP sizes were within 200 nm for enhanced permeability and retention (EPR) effect with negative zeta potentials, spherical morphology, and high entrapment efficiencies. The optimal formulation was identified by sustained release of approximately 70% of loaded GM-CSF over 24 h, alongside an average size of 143 ± 35 nm and entrapment efficiency of 84 ± 5%. These NPs were successfully freeze-dried in 5% (w/v) hydroxypropyl-β-cyclodextrin for long-term storage and further characterized. Bioactivity of released GM-CSF was determined by observing GM-CSF receptor activation on murine monocytes and remained fully intact. NPs were not cytotoxic to murine bone marrow-derived macrophages (BMDMs) at concentrations up to 1 mg/mL as determined by MTT and trypan blue exclusion assays. Lastly, NP components generated no significant transcription of inflammation-regulating genes from BMDMs compared to IFNγ+LPS “M1” controls. This report lays the preliminary groundwork to validate in vivo studies with GM-CSF-loaded PLGA/PEG-PLGA NPs for tumor immunomodulation. Overall, these data suggest that in vivo delivery will be well tolerated.
Serine hydroxymethyltransferase 2 expression promotes tumorigenesis in rhabdomyosarcoma with 12q13-14 amplification.

The 12q13-q14 chromosomal region is recurrently amplified in 25% of fusion-positive (FP) rhabdomyosarcoma (RMS) cases and is associated with a poor prognosis. To identify amplified oncogenes in FP RMS, we compared the size, gene composition and expression of 12q13-q14 amplicons in FP RMS with other cancer categories (glioblastoma multiforme, lung adenocarcinoma and liposarcoma) in which 12q13-q14 amplification frequently occurs. We uncovered a 0.2 Mb region that is commonly amplified across these cancers and includes CDK4 and six other genes that are overexpressed in amplicon-positive samples. Additionally, we identified a 0.5 Mb segment that is only recurrently amplified in FP RMS and includes four genes that are overexpressed in amplicon-positive RMS. Among these genes, only SHMT2 was overexpressed at the protein level in an amplicon-positive RMS cell line. SHMT2 knockdown in amplicon- positive RMS cells suppressed growth, transformation and tumorigenesis, whereas overexpression in amplicon-negative RMS cells promoted these phenotypes. High SHMT2 expression reduced sensitivity of FP RMS cells to SHIN1, a direct SHMT2 inhibitor, but sensitized cells to pemetrexed, an inhibitor of the folate cycle. In conclusion, our study demonstrated that SHMT2 contributes to tumorigenesis in FP RMS and that SHMT2 amplification predicts differential response to drugs targeting this metabolic pathway.