Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonparametric Estimation of Additive Models with Shape Constraints

approved: Lan Xue Monotone additive models are useful in estimating productivity curves or analyzing disease risk where the predictors are known to have monotonic effects on the response. Existing literature mainly focuses on univariate monotone smoothing. Available methods for the estimation of monotone additive models are either difficult to interpret or have no asymptotic guarantees. In the first part of this dissertation, we propose a onestep backfitted constrained polynomial spline method for the estimation of monotone additive models. In our proposed method, we obtain monotone estimators by imposing a set of linear constraints on the spline coefficients for each additive component. In the second part of the dissertation, we extend the constrained polynomial spline method to estimate the production frontier that is used to quantify the maximum production output in econometrics. The estimation of frontier functions is more challenging since it is the boundary of the support rather than the mean output function to be estimated. Here, we develop a two-step shape constrained polynomial spline method for the frontier estimation. The first step is to capture the shape of frontier while the second step is to estimate the location of frontier. Both proposed methods in this dissertation give smooth estimators with the desired shape constraints (monotonicity or/and concavity). They are easily implementable and computationally efficient by taking advantage of linear programming. Most importantly, our methods are applicable for multi-dimensions where some existing methods fail to work. For the assessment of properties of the proposed estimators, asymptotic theory is also developed. In addition, the simulation studies and application of our methods to analyze Norwegian Farm data in both parts suggest that our proposed methods have better numerical performance than the existing methods, especially when the data has outliers. c ©Copyright by Lu Wang May 24, 2016 All Rights Reserved Nonparametric Estimation of Additive Models with Shape Constraints
Schizosaccharomyces lindneri sp. nov., a fission yeast occurring in honey

Two strains of fission yeast were isolated from honey. They differ from the type strain of Schizosaccharomyces octosporus by three substitutions in the D1/D2 domain of the nuclear 26S large subunit ribosomal RNA (rRNA) gene sequence, resulting in a 99.5% identity. In the internal transcribed spacer (ITS) region (consisting of ITS1, 5.8S rDNA, and ITS2), the strains differ from S. octosporus by 16 gaps and 91 substitutions, which is equivalent to an identity of 88.1%. Genome sequencing on one of the new strains revealed that the average nucleotide identity (ANI) between its genome and the reference genome of S. octosporus is 90.43% and there exist major genome rearrangements between the two genomes. Mating analysis revealed that S. octosporus and one of the new strains are completely reproductively separated. A strong prezygotic barrier exists and the few mating products consist of diploid hybrids that do not form recombinant ascospores. In the new strains, asci are either zygotic, arising from conjugation, or they develop without conjugation from asexual cells (azygotic). Compared to the currently recognized Schizosaccharomyces species, the spectrum of nutrients that are assimilated by the new strains is restricted. Of the 43 carbohydrates that were included in the physiological standard tests, only 7 were assimilated. According to the results of the genome sequence analysis, the mating trials, and the phenotypic characterization, the new species Schizosaccharomyces lindneri is described to accommodate the two strains (holotype: CBS 18203T and ex‐type: MUCL 58363; MycoBank no.: MB 847838).
Bacterial membrane dynamics: Compartmentalization and repair

In every bacterial cell, the plasma membrane plays a key role in viability as it forms a selective barrier between the inside of the cell and its environment. This barrier function depends on the physical state of the lipid bilayer and the proteins embedded or associated with the bilayer. Over the past decade or so, it has become apparent that many membrane‐organizing proteins and principles, which were described in eukaryote systems, are ubiquitous and play important roles in bacterial cells. In this minireview, we focus on the enigmatic roles of bacterial flotillins in membrane compartmentalization and bacterial dynamins and ESCRT‐like systems in membrane repair and remodeling.
The prevalence and anatomy of the pyramidal lobe of the thyroid gland: A meta‐analysis with implications for thyroid surgery

The pyramidal lobe (PL), also known as the third lobe of the thyroid gland or lobe of Lalouette is an embryological remnant of the caudal end of the thyroglossal tract. The following meta‐analysis aims to provide a detailed analysis of the anatomical variations of the PL using the available data in the literature. Major online medical databases such as PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched in order to find all studies considering the prevalence and anatomy of the PL of the thyroid gland. Finally, a total of 24 studies that met the required criteria and contained complete and relevant data were included in the present meta‐analysis. The pooled prevalence of the PL was found to be 42.82% (95% CI: 35.90%–49.89%). An analysis showed that the mean length was 23.09 mm (SE: 0.56). The mean width was found to be 10.59 mm (SE: 0.77). The pooled prevalence of the PL originating from the left lobe (LL) was established at 40.10% (95% CI: 28.83%–51.92%). In conclusion, we believe that this is the most accurate and up‐to‐date study regarding the complete surgical anatomy of the PL. The PL was prevalent in 42.82% of the cases, being slightly more prevalent in males (40.35%) than females (37.43%). The mean length and width of the PL were 23.09 mm and 10.59 mm, respectively. Our results should be taken into consideration when performing procedures on the thyroid gland, such as thyroidectomies. The presence of the PL can affect the completeness of this procedure and lead to postoperative complications.
Big versus small: The impact of aggregate size in disease

Protein aggregation results in an array of different size soluble oligomers and larger insoluble fibrils. Insoluble fibrils were originally thought to cause neuronal cell deaths in neurodegenerative diseases due to their prevalence in tissue samples and disease models. Despite recent studies demonstrating the toxicity associated with soluble oligomers, many therapeutic strategies still focus on fibrils or consider all types of aggregates as one group. Oligomers and fibrils require different modeling and therapeutic strategies, targeting the toxic species is crucial for successful study and therapeutic development. Here, we review the role of different‐size aggregates in disease, and how factors contributing to aggregation (mutations, metals, post‐translational modifications, and lipid interactions) may promote oligomers opposed to fibrils. We review two different computational modeling strategies (molecular dynamics and kinetic modeling) and how they are used to model both oligomers and fibrils. Finally, we outline the current therapeutic strategies targeting aggregating proteins and their strengths and weaknesses for targeting oligomers versus fibrils. Altogether, we aim to highlight the importance of distinguishing the difference between oligomers and fibrils and determining which species is toxic when modeling and creating therapeutics for protein aggregation in disease.
Influence of reaction parameters on synthesis of high-quality single-layer graphene on Cu using chemical vapor deposition

Large-area monolayer graphene samples grown on polycrystalline copper foil by thermal chemical vapor deposition with differing CH4 flux and growth time are investigated by Raman spectra, scanning electron microscopy, atomic force microscopy, and scanning tunneling microscopy. The defects, number of layers, and quality of graphene are shown to be controllable through tuning the reaction conditions: ideally to 2–3 sccm CH4 for 30 minutes.
Efficacy and safety of vigabatrin in patients with tuberous sclerosis complex and infantile epileptic spasm syndrome: a systematic review

ABSTRACT Introduction Tuberous sclerosis complex (TSC) is a common genetic cause of epilepsy. Infantile epileptic spasm syndrome (IESS) is often the presenting neurologic feature, progressively evolving into refractory epilepsy. Vigabatrin (VGB) is often used in clinical practice as a first-line therapy in TSC with IESS. This systematic review aims to collect and analyze the efficacy data about VGB in TSC cases with IESS, in order to evaluate the strength of evidence in the literature. Methods A systematic search of trials, observational studies, and case series involving patients with TSC and IESS treated with VGB was performed using MEDLINE, CENTRAL, and the US NIH Clinical Trials Registry. Single case studies, animal and non-English language studies were excluded. Seventeen studies were selected, of which 3 were RCTs and 14 were observational studies. Results An overall response rate of 67% (231/343 responders) resulted from the analysis, with a spasm-free rate restricted to RCTs of 88% (29/33 subjects). Conclusions Although all the studies analyzed reported beneficial effects of VGB in TSC patients with IESS, with higher response rates in comparison to non-TSC subjects with IESS, a low level of evidence and high heterogeneity do not guarantee sufficient strength for therapeutic recommendations.
Unsteady Aerodynamic Characteristics of Cambered Four-digit NACA Airfoils at Low Reynolds Number

Aerodynamics of cambered airfoils are investigated numerically, using NACA four-digit series at low Reynolds number Re = 10, 000, and moderate Mach number M = 0.2, by focusing on the relation of aeroacoustic effects and hydrodynamic flow unsteadiness. In addition, wind-tunnel experiments are conducted in a regular laboratory environment at very low Mach number for flow a visualization purpose. Two-dimensional numerical simulations show that the onset of an acoustic feedback loop (AFL) leads to an abrupt increase of lift force, shifting a separation bubble toward the leading edge. However, this is not reproduced in a wind-tunnel result with a negligible aeroacoustic effect. Providing 6% thickness, a two-dimensional parametric study on airfoil camber shows that the aft camber location is more favorable to increase attainable lift with less drag. The aft camber also exhibits a better performance in three-dimensional calculations, developing longitudinal eddies on the suction side, which prevents bulk separation. Although the boundary layer shows three-dimensional complexity, still the formation of an AFL is strongly suggested, via the comparison of spanwise correlations.
Factors associated with failure to operate and its impact on survival in early‐stage pancreatic cancer

Curative intent for localized pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) requires surgery, but despite improved perioperative outcomes, surgery remains underutilized. This study analyzed the Texas Cancer Registry (TCR) to identify resectable PDAC patients who underwent curative‐intent surgery in Texas between 2004 and 2018. We then evaluated demographic and clinical factors associated with failure to operate and survival (OS).
Cycling matters: Sex hormone regulation of vascular potassium channels

ABSTRACT Sex hormones and the reproductive cycle (estrus in rodents and menstrual in humans) have a known impact on arterial function. In spite of this, sex hormones and the estrus/menstrual cycle are often neglected experimental factors in vascular basic preclinical scientific research. Recent research by our own laboratory indicates that cyclical changes in serum concentrations of sex -hormones across the rat estrus cycle, primarily estradiol, have significant consequences for the subcellular trafficking and function of KV7. Vascular potassium channels, including KV7, are essential components of vascular reactivity. Our study represents a small part of a growing field of literature aimed at determining the role of sex hormones in regulating arterial ion channel function. This review covers key findings describing the current understanding of sex hormone regulation of vascular potassium channels, with a focus on KV7 channels. Further, we highlight areas of research where the estrus cycle should be considered in future studies to determine the consequences of physiological oscillations in concentrations of sex hormones on vascular potassium channel function.
Efficacy and safety of endoscopic drainage versus percutaneous drainage for pancreatic fluid collection; a systematic review and meta-analysis

Abstract Background/Aims Pancreatic fluid collections (PFC) are debris or fluid of the pancreas that needs to be drained out. This may result from surgery or necrotizing pancreatitis. This meta-analysis compared the outcomes of PFC through endoscopic and percutaneous interventions. Methods A medical database was searched up to June 2022, comparing the outcomes of endoscopic drainage (ED) and percutaneous drainage (PD) for the PFC. Eligible studies reporting clinical and technical success and adverse events were selected. Results Seventeen studies with 1170 patients were included for meta-analysis, of which 543 patients underwent ED and 627 underwent PD. The odd ratio (OR) of technical success was 0.81 (95% confidence interval (CI) 0.31, 2.1) and clinical success was in the favor of the ED group at OR 2.23 (95% CI 1.45, 3.41). Adverse events OR 0.62 (95% CI 0.27, 1.39) and stent migration OR 0.61 (95% CI 0.10, 3.88) were the same in both groups, but hospital stay pooled mean difference of 15.02 days (95% CI 9.86, 20.18), mortality OR 0.24 (95% CI 0.09, 0.67), and re-interventions OR 0.25 (95% CI 0.16, 0.40) favored ED. Conclusions ED is safe and efficient for PFC with higher clinical success, lower mortality rate, hospital stay, and re-interventions compared with PD.
Covid 19 corruption in the public health sector - Emerging evidence from Bangladesh.

This paper explores the Covid-19-related corruption in Bangladesh. Specifically, we analyse the issue of Covid-19-related corruption in the health sector of Bangladesh. We also explore how denial strategies adapted by government officials have worsened the problem. Using Cohen's (2001) notion of denial strategies, we analyse media reports during the pandemic that highlighted Covid-19-related corruption occurring in the Bangladeshi health sector. Our analyses reveal that the Covid-19 pandemic has given rise to a new wave of corruption, particularly in the procurement of testing kits and personal protective equipment (PPE), as well as the issuance of false COVID-19 certificates. We call for an in-depth investigation of Covid-19-related corruption in Bangladesh and other developing countries that follows similar social, contextual and cultural values via interviews with policymakers and health professionals. Our paper extends the ongoing debate on Covid-19-related corruption and its impacts on the public health sectors.
Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

Population level variation and molecular mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized despite ramifications for personalized nutrition.We now define prototypical insulin secretion dynamics in response to the three macronutrients in islets from 140 cadaveric donors, including those diagnosed with type 2 diabetes. We leverage the insulin response heterogeneity and use transcriptomics and proteomics to identify molecular pathways of specific nutrient responsiveness. Surprisingly, we find robust insulin secretion to fatty acid stimulus in ~8% of donors, challenging the idea that fat has negligible effects on insulin release. By comparing human islets to human embryonic stem cell-derived islet clusters, we show that, unlike glucose-responsiveness, fat hyper-responsiveness is equivalent and may be a hallmark of functionally immature cells. Our study represents the first comparison of dynamic responses to nutrients and multi-omics analysis in human insulin secreting cells. Responses of different people's islets to carbohydrate, protein, and fat lay the groundwork for personalized nutrition.
Comparative analysis of symptom profile and risk of death associated with infection by SARS-CoV-2 and its variants in Hong Kong

Introduction: The recurrent multi-wave nature of COVID-19 necessitates updating its symptomatology. Before the omicron era, Hong Kong was relatively unscathed and had a low vaccine uptake rate among the old-old, giving us an opportunity to study the intrinsic severity of SARS-CoV-2 variants. A comparison of symptom patterns across variants and vaccination status in Hong Kong has yet to be undertaken. The intrinsic severity of variants and symptoms predictive of severe outcomes are also understudied as COVID-19 evolves. We therefore aim to characterize the effect of variants on symptom presentation, identify the symptoms predictive and protective of death, and quantify the effect of vaccination on symptom development. Methods: With the COVID-19 case series in Hong Kong from inception to 25 August 2022, an iterative multi-tier text-matching algorithm was developed to identify symptoms from free text. Cases were fully vaccinated if they completed two doses. Multivariate regression was used to measure associations between variants, symptom development, death and vaccination status. A least absolute shrinkage and selection operator technique was used to identify a parsimonious set of symptoms jointly associated with death. Results: Overall, 70.9% (54450/76762) of cases were symptomatic. We identified a wide spectrum of symptoms (n=102), with cough, fever, runny nose and sore throat being the most common (8.16-47.0%). Intrinsically, the wild-type and delta variant caused similar symptoms, with runny nose, sore throat, itchy throat and headache more frequent in the delta cohort; whereas symptoms were heterogeneous between the wild-type and omicron variant, with seven symptoms (fatigue, fever, chest pain, runny nose, sputum production, nausea/vomiting and sore throat) more frequent in the omicron cohort. With full vaccination, omicron was still more likely than delta to cause fever. Fever, blocked nose and shortness of breath were robustly jointly predictive of death as the virus evolved. Number of vaccine doses required for reduction in occurrence varied by symptoms. Discussion: This is the first large-scale study to evaluate the changing symptomatology by COVID-19 variants and vaccination status using free-text reporting by patients. We substantiate existing findings that omicron has a different clinical presentation compared to previous variants. Syndromic surveillance can be bettered with reduced reliance on symptom-based case identification, increased weighing on symptoms robustly predictive of mortality in outcome prediction, strengthened infection control in care homes through universal individual-based risk assessment to enable early risk stratification, adjusting the stockpile of medicine to tally with the changing symptom profiles across vaccine doses, and incorporating free-text symptom reporting by patients.
Penalised neural network with weight correlation descent for predicting polygenic risk score

Polygenic risk scores (PRS) have demonstrated substantial potential in predicting complex human traits and diseases. Nevertheless, conventional PRS methods, which primarily encapsulate linear genetic effects, frequently encounter issues with overestimation. In this study, we introduce an innovative PRS model that employs a deep neural network (DNN) integrated with weight correlation descent (WCD). This method, diverging from traditional PRS strategies, leverages the DNN to capture a broad spectrum of genetic interactions and utilizes WCD to mitigate the overfitting issues inherent in DNNs. Utilizing real-world data from the UK Biobank, our method displayed enhanced predictive performance for breast and prostate cancer compared to established methodologies such as P+T, PRSice, PRS-CS, and DNN without WCD. By improving prediction accuracy, this novel approach holds potential to significantly contribute to personalized healthcare, enhancing risk assessment and preventive strategies for complex diseases.
Effects of visual arts on persistent pain: A systematic review

Background: Persistent pain impacts 30% of people worldwide. Evidence on the effectiveness of visual arts in treating persistent pain seems to be emerging. Thus, the aim of this systematic review was to investigate the impact of visual arts on patients with persistent pain. Methods: Studies were identified by searching seven databases from perception until Jan-2019, then screened by two independent reviewers. Studies were included if they were published controlled trials investigating the impact of visual arts on participants with persistent pain. Studies were excluded if they were abstracts, sampled participants who could not express pain, did not report relevant outcome measures, or did not have a comparator group. The study qualities were assessed by the PEDro scale. Results: After removing duplicates, 2,732 titles and abstracts were screened. Of 125 full-texts, four satisfied the eligibility criteria; all published within the last decade. Three of four controlled studies were randomised-controlled trials. Studies were conducted in inpatient settings (n=2) and outpatient clinics (n=2). Three studies included elderly participants (>60y/o), while one included patients with HIV (>18y/o). Visual arts interventions included painting, drawing, crafting, and others. Two studies utilised visual arts as the sole treatment, while two studies used visual arts as part of a multimodal treatment. Comparators received usual care in two studies, a music intervention in one, and an art-therapy video in another. The common outcome measure in all studies was pain level (0-to-10 scale). All studies also included psychosocial outcome measures. Quality of studies ranged from grade four to eight on PEDro scale; two had high quality, and two had fair quality. All studies reported statistically significant improvements in pain within intervention groups. Conclusions: Visual arts seem to benefit patients with persistent pain. Further investigation on the clinical significance of these positive findings on pain and other biopsychosocial factors are required.
A simple check for VAR representations of DSGE models

The present paper shows that there is a simple way to check whether a DSGE model can be represented by a finite order VAR. This consists in verifying that the eigenvalues of a certain matrix defined in Fernandez-Villaverde et al. (2007) are all equal to zero. Further we show that this condition is equivalent to the one in Ravenna (2007), which is, however, not easily applicable.