Miracle-dz/UniFAR-FTUs huggingface dataset:
Looking under the lamp-post: quantifying the performance of contact tracing in the United States during the SARS-CoV-2 pandemic

Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens and nascent disease outbreaks. Contact tracing in the United States was conducted during the pre-Omicron phase of the ongoing COVID-19 pandemic. This tracing relied on voluntary reporting and responses, often using rapid antigen tests (with a high false negative rate) due to lack of accessibility to PCR tests. These limitations, combined with SARS-CoV-2s propensity for asymptomatic transmission, raise the question how reliable was contact tracing for COVID-19 in the United States? We answered this question using a Markov model to examine the efficiency with which transmission could be detected based on the design and response rates of contact tracing studies in the United States. Our results suggest that contact tracing protocols in the U.S. are unlikely to have identified more than 1.65% (95% uncertainty interval: 1.62%-1.68%) of transmission events with PCR testing and 0.88% (95% uncertainty interval 0.86%-0.89%) with rapid antigen testing. When considering an optimal scenario, based on compliance rates in East Asia with PCR testing, this increases to 62.7% (95% uncertainty interval: 62.6%-62.8%). These findings highlight the limitations in interpretability for studies of SARS-CoV-2 disease spread based on U.S. contact tracing and underscore the vulnerability of the population to future disease outbreaks, for SARS-CoV-2 and other pathogens.
Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviors, and although strides have been made using genome-wide association studies (GWAS) to identify risk variants, the majority of variants identified have been for nicotine consumption, rather than TUD. We leveraged five biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records, EHR) in 898,680 individuals (739,895 European, 114,420 African American, 44,365 Latin American). We identified 72 independent risk loci; integration with functional genomic tools uncovered 330 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviors in children, and hundreds of medical outcomes, including HIV infection, heart disease, and pain. This work furthers our biological understanding of TUD and establishes EHR as a source of phenotypic information for studying the genetics of TUD.
Maternal Infection with Group B Streptococcus Correlates Inversely with Preeclampsia in Pregnant African American Women

Objective: Preeclampsia is more prevalent in African American women than other races. GBS colonization rate in African American women is the highest among different races. We hypothesized there is an association between GBS colonization and preeclampsia among pregnant African American women. Study Design: We evaluated the relationship between GBS colonization and preeclampsia in 11,766 patients records (93% were African Americans patients) between 2010 and 2017. Results: The preeclampsia rate of GBS colonized patients (2.6%) was 59% less than that of GBS-negative patients (6.3%). This inverse correlation was independently significant after adjusting for other potential risk factors for preeclampsia: chronic hypertension, gestational diabetes mellitus and diabetes mellitus and other covariates. Further analysis among the patients without these risk factors also confirmed that the preeclampsia rate of GBS colonized patients (2.6%) was 55% less than that of GBS negative patients (5.7%). Similarly, patients with HSV+ or HIV+ had lower incidence of preeclampsia than those with HSV- or HIV-. Conclusions: The unexpected finding of an inverse relationship between GBS colonization and preeclampsia suggests that the maternal immune response to GBS infection may be beneficial in reducing preeclampsia among African American patients.
EVALUATION OF A METAGENOMIC NEXT-GENERATION SEQUENCING ASSAY WITH A NOVEL HOST DEPLETION METHOD FOR PATHOGEN IDENTIFICATION IN SEPTIC PATIENTS

Background The traditional diagnosis of sepsis has always been based on microbial blood culture (BC). However, BC suffers from (1) long culture cycle, leading to delay in results, and (2) low diagnostic yields. Metagenomic next-generation sequencing (mNGS) has been proposed as an efficient and agnostic option that potentially overcomes these issues. In this study, a mNGS workflow utilizing a novel filter to specifically capture white blood cells and deplete host DNA background, was evaluated against BC results, as well as mNGS without host depletion, for pathogen identification. Materials and Methods Patients admitted to Taipei Veterans General Hospital (TVGH) with suspected sepsis were recruited to the study approved by the IRB. Blood sample was taken for BC (designated as BC1) before any antibiotic exposure. Upon patient enrolment, blood was taken again and divided in 3 portions with one used for the 2nd BC (BC2). The other two were used for mNGS with one processed with the filter and the other without filtering, to assess the effectiveness of host-depletion by the filter. Results A total of 50 patients were recruited among which 45 had results for all 4 tests. mNGS with filter had the highest positive rate of 74.4%, followed by mNGS without filter and BC1 (51.1% and 50.0% respectively), while the 2nd BC had the lowest positive rate of 22.0%. Further, mNGS was less sensitive to antibiotics exposure as compared to BC. The overall correlation between samples with vs without filtration (R2=0.96) confirmed that filtration does not affect microbial composition in a sample. For the BC positive samples, the effect of host depletion by filtration increased microbial target reads/million QC reads from 46 reads to 243 reads on average. Microbial reads enrichment by the filter appeared to be more effective for the samples with lower microbial concentration, thus increasing the test sensitivity over mNGS without filter. Using the 2nd BC results as reference, mNGS with filter and mNGS without filter exhibited sensitivities of 81.8% and 63.6%. Conclusion The mNGS with filter was able to recover most of the pathogens identified by clinical BC and achieved the highest diagnostic yield. With the clinical implementation to complete the workflow within 24 hours, it has the potential to overcome slow turnaround and low diagnostic yield issues of traditional BC.
Lyapunov-based controller design for bounded dynamic stochastic distribution control

Following developments in the modelling and control of the output probability density function of dynamic stochastic systems, an approach for the controller design is presented using square root approximation, where a set of B-spline functions are used to approximate the square root of the measured output probability density function to guarantee its positiveness. A performance function is defined which measures the tracking error of the output probability density function with respect to a given distribution. Instead of finding an optimal control which minimises this performance function and then analysing the stability of the closed loop system, the new approach directly uses the performance function as a Lyapunov function to design the required controller. As a result, the controller obtained not only guarantees the decreasing of the performance function with respect to time, but also stabilises the closed-loop system, realising an asymptotically tracking performance of the output probability density function with respect to its target distribution. The algorithm described has been tested on a simulated example and desired results have been achieved.
Streptozotocin as a tool for induction of rat models of diabetes: a practical guide

Streptozotocin (STZ) is the most used diabetogenic chemical for creating rat models of type 1 and type 2 diabetes. Despite ~60 years of using STZ in animal diabetes research, some prevailing views about STZ preparation and use are not supported by evidence. Here, we provide practical guides for using STZ to induce diabetes in rats. Susceptibility to the diabetogenic effect of STZ is inversely related to age, and males are more susceptible to STZ than females. Wistar and Sprague-Dawley rats, the most commonly-used rat strains, are sensitive to STZ, but some strains (e.g., Wistar-Kyoto rats) are less sensitive. STZ is mostly injected intravenously or intraperitoneally, but its intravenous injection produces more stable hyperglycemia. Despite the prevailing view, no fasting is necessary before STZ injection, and injection of its anomer-equilibrated solutions (i.e., more than 2 hours of dissolving) is recommended. Mortality following the injection of diabetogenic doses of STZ is due to severe hypoglycemia (during the first 24 h) or severe hyperglycemia (24 h after the injection and onwards). Some measures to prevent hypoglycemia-related mortality in rats include providing access to food soon after the injection, administration of glucose/sucrose solutions during the first 24-48 h after the injection, administration of STZ to fed animals, and using anomer-equilibrated solutions of STZ. Hyperglycemia-related mortality following injection of high doses of STZ can be overcome with insulin administration. In conclusion, STZ is a valuable chemical for inducing diabetes in rats, but some practical guides should be considered to perform well-conducted and ethical studies.
Effects of Linear and Nonlinear Piezoelectricity on the Electronic Properties of InAs/GaAs Quantum Dots

The existence of enormous strain fields in self-assembled quantum dots has led to the expectation of dramatic effects of piezoelectricity. However, only linear piezoelectric tensors were used in all previous calculations. We calculate the piezoelectric properties of self-assembled quantum dots using the linear and quadratic piezoelectric tensors derived from first-principles density functional theory. We find that the previously ignored quadratic term has similar magnitude as the linear term and the two terms tend to cancel each other. We show the effect of piezoelectricity on electron and hole energy levels and wave functions as well as on correlated absorption spectra.
Salvage therapies of autoimmune hepatitis limit proinflammatory immune cells while sparing regulatory T cells

Background: Autoimmune hepatitis (AIH) can be clinically controlled by first-line immunosuppressive therapy in the majority of patients. However, a selective decrease in intrahepatic regulatory T cells (Treg) was observed with immunosuppressive therapy, which was even more pronounced in patients with incomplete responses than in patients who achieved biochemical remission. The effects of salvage therapies on the number of intrahepatic T and B cells, including Treg, are unclear. The hypothesis was that calcineurin inhibitors would further decrease intrahepatic Treg numbers, and the mammalian target of rapamycin inhibitors would increase intrahepatic Treg numbers. Methods: In this retrospective study at 2 centers, CD4+, CD8+ and CD4+FOXP3+ T cells, and CD79a+ B cells were quantified in surveillance biopsies under non–standard-of-care treatment [non-SOC: calcineurin inhibitor (n=10), second-line antimetabolites (n=9), mammalian target of rapamycin inhibitors (n=4)] compared with patients under the standard-of-care treatment (SOC). Results: Intrahepatic T-cell and B-cell counts were not significantly different between patients with biochemical remission under SOC and non-SOC. However, patients with incomplete response under non-SOC had significantly lower liver infiltration with T and B cells, whereas Treg were not reduced compared with SOC. This resulted in an even higher ratio of Treg to T and B cells in non-SOC compared with SOC when biochemical remission was not achieved. The different non-SOC regimens showed no significant difference in liver infiltration with T cells, including Treg and B cells. Conclusions: Non-SOC in AIH partially controls intrahepatic inflammation by limiting the hepatic infiltration of total T and B cells as the main drivers of inflammation without further decreasing intrahepatic Treg. A negative effect of calcineurin inhibitor and a positive effect of mammalian target of rapamycin inhibitors on the number of intrahepatic Treg was not observed.
Safety evaluation of the food enzyme lysozyme from hens' eggs

Abstract The food enzyme lysozyme (peptidoglycan N‐acetylmuramoylhydrolase; EC 3.2.1.17) is produced with hens' eggs and submitted by DSM Food Specialties BV. It is intended to be used in brewing processes, milk processing for cheese production as well as wine and vinegar production. The dietary exposure to the food enzyme–total organic solids (TOS) was estimated to be up to 4.9 mg TOS/kg body weight per day. This exposure is lower than the intake of the corresponding fraction from eggs, for all population groups. Egg lysozyme is a known food allergen. The Panel considered that, under the intended conditions of use, the residual amounts of lysozyme in treated beers, cheese and cheese products as well as wine and wine vinegar may trigger adverse allergenic reactions in susceptible individuals. Based on the data provided, the origin of the food enzyme and an exposure to the food enzyme comparable to the intake from eggs, the Panel concluded that the food enzyme lysozyme does not give rise to safety concerns under the intended conditions of use, except for the known adverse allergic reactions that occur in susceptible individuals.
Hierarchical Linear Models for Multivariate Outcomes

In this article, we develop a class of two-stage models to accommodate three common characteristics of behavioral data. First, behavior is invariably multivariate in its conceptualization and communication. Separate univariate analyses of related outcome variables are fraught with potential interpretive blind spots for the researcher. This practice also suffers, from an inferential standpoint, because it fails to take advantage of any redundant information in the outcomes. Second, studies of behavior, especially in experimental research, employ smaller samples. This situation raises issues of robustness of inference with respect to outlying individuals. Third, the outcome variable may have observations missing because of accidents or by design. The model permits the estimation of the full spectrum of plausible measurement error structures while using all the available information. Maximum likelihood estimates are obtained for various members of a multivariate hierarchical linear model (MHLM), and, in the context of several illustrative examples, these estimates match closely the results from a Bayesian approach to the normal-normal MHLM and to the normal-t MHLM.
Knowledge, beliefs, and practices related to coronavirus disease 2019 (COVID-19) infection and vaccination in healthcare personnel working at nonacute care facilities

Abstract Objective: To characterize experiences, beliefs, and perceptions of risk related to coronavirus disease 2019 (COVID-19), infection prevention practices, and COVID-19 vaccination among healthcare personnel (HCP) at nonacute care facilities. Design: Anonymous survey. Setting: Three non–acute-care facilities in St. Louis, Missouri. Participants: In total, 156 HCP responded to the survey, for a 25.6% participation rate). Among them, 32% had direct patient-care roles. Methods: Anonymous surveys were distributed between April-May 2021. Data were collected on demographics, work experience, COVID-19 exposure, knowledge, and beliefs about infection prevention, personal protective equipment (PPE) use, COVID-19 vaccination, and the impact of COVID-19. Results: Nearly all respondents reported adequate knowledge of how to protect oneself from COVID-19 at work (97%) and had access to adequate PPE supplies (95%). Many HCP reported that wearing a mask or face shield made communication difficult (59%), that they had taken on additional responsibilities due to staff shortages (56%), and that their job became more stressful because of COVID-19 (53%). Moreover, 28% had considered quitting their job. Most respondents (78%) had received at least 1 dose of COVID-19 vaccine. Common reasons for vaccination were a desire to protect family and friends (84%) and a desire to stop the spread of COVID-19 (82%). Potential side effects and/or inadequate vaccine testing were cited as the most common concerns by unvaccinated HCP. Conclusions: A significant proportion of HCP reported increased stress and responsibilities at work due to COVID-19. The majority were vaccinated. Improving workplace policies related to mental health resources and sick leave, maintaining access to PPE, and ensuring clear communication of PPE requirements may improve workplace stress and burnout.
Neuronal accumulation of hyperphosphorylated tau protein predicts stable memory impairment in people living with HIV

Objectives: As lifespans increase in people with HIV (PWH), there is concern that age-related neurodegenerative disorders may contribute to cognitive decline. We asked whether brain accumulation of Alzheimer's disease (AD)-associated proteins amyloid-beta (Aβ) and hyperphosphorylated tau (p-tau) predicted cognitive performance in middle-aged PWH. Methods: In a prospectively followed, cognitively-characterized autopsy sample of 135 PWH, we used immunohistochemistry to assess Aβ plaques and neuronal p-tau in medial temporal and lateral frontal lobes. These pathologies were tested for associations with cognitive performance in seven domains: motor, speed of information processing, working memory, memory encoding, memory retrieval, verbal fluency, and abstraction/executive function. Univariate and multivariate analyses accounting for HIV-associated variables, reading level, and comorbidities were conducted. Longitudinal trajectories of memory functions were evaluated in 60 individuals with a median follow-up of 6.0 years. Results: In this population with mean age 51.4 ± 0.9 years, 58% displayed neuronal p-tau and 29% Aβ plaques. Neuronal p-tau, but not Aβ, predicted worse memory encoding and retrieval, but not other cognitive functions. With an ordinal hierarchy of neuronal p-tau locations (entorhinal, hippocampal, neocortical), decreased memory performance correlated with neocortical distribution. Memory function trajectories could not be distinguished between individuals with and without neuronal p-tau, and over 80% of the sample showed no change over time. Conclusion: In this middle-aged sample, neuronal p-tau accumulation contributes to memory deficits, but is not associated with accelerated decline in function over time. In the absence of AD-like deterioration, other etiologies for neuronal p-tau in cognitively impaired PWH must be considered.
Remodeling of E-cadherin subcellular localization during cell dissemination

Given the role of E-cadherin (E-cad) in holding epithelial cells together, an inverse relationship between E-cad levels and cell invasion during the epithelial-mesenchymal transition and cancer metastasis has been well recognized. Here we report that E-cad is necessary for the invasiveness of RasV12-transformed intestinal epithelial cells in Drosophila. E-cad/β-catenin disassembles at adherens junctions and assembles at invasive protrusions–-the actin- and cortactin-rich invadopodium-like protrusions associated with the breach of the extracellular matrix (ECM)–-during dissemination of RasV12-transformed intestinal epithelial cells. Loss of E-cad impairs the elongation of invasive protrusions and attenuates the ability of RasV12-transformed cells to compromise the ECM. Notably, E-cad and cortactin affect each other’s localization to invasive protrusions. Given the essential roles of cortactin in cell invasion, our observations indicate that E-cad plays a role in the invasiveness of RasV12-transformed intestinal epithelial cells by controlling cortactin localization to invasive protrusions. Thus our study demonstrates that E-cad is a component of invasive protrusions and provides molecular insights into the unconventional role of E-cad in cell dissemination in vivo.
Pole assignment problem: a structural investigation

Based on the structure of a closed-loop system under a specified feedback pattern, a qualitative analysis of the problem of pole assignability is considered. The problem is first formulated algebraically, in terms of the relation p = g(f) between the vector p of the closed-loop characteristic polynomial coefficients and the vector f of the non-zero elements of the feedback matrix. Then, translation to the structural framework is achieved by means of two theorems which give graph-theoretical sufficient conditions for solvability. These structural conditions also guarantee genericity of pole assignability.
Definitions, perspectives, and reasons for conscientious objection among healthcare workers, facility managers, and staff in South Africa: a qualitative study

Abstract Conscientious objection (CO) on the part of healthcare providers is a growing threat to safe abortion access. In South Africa, evidence suggests that this legal clause may be manipulated as a justification for public-sector healthcare providers to exempt themselves from their duties to provide essential reproductive health services as required by national laws and protocols. This qualitative study improves our understanding of the definitions, perspectives, and use of CO among providers, staff, and facility managers in South Africa, and CO’s effect on public-sector abortion availability. Using 18 focus group discussions and 23 in-depth interviews, we examined CO attitudes and behaviours of staff from health facilities that provide abortion care in Gauteng, Limpopo, KwaZulu-Natal, and Eastern Cape Provinces. We find that CO is invoked for a variety of reasons, some unrelated to the legal basis for objection. There have been progressive shifts in attitudes towards abortion over time, but stigma against women and girls who seek abortion remains substantial among staff at facilities providing abortion. Providers who offer abortion services also report high levels of discrimination and isolation from colleagues. Such factors, combined with operational barriers to offering quality abortion care (such as lack of training support or financial incentives) and lack of clarity on CO definitions and procedures, may incentivise some providers to invoke CO inappropriately. Dissemination of national guidelines on CO should be prioritised to reduce ambiguity, and interventions addressing abortion stigma should be considered for all facility staff to safeguard abortion availability in South Africa.