Miracle-dz/UniFAR-FTUs huggingface dataset:
Propensity score stratification methods for continuous treatments

Continuous treatments propensity scoring remains understudied as the majority of methods are focused on the binary treatment setting. Current propensity score methods for continuous treatments typically rely on weighting in order to produce causal estimates. It has been shown that in some continuous treatment settings, weighting methods can result in worse covariate balance than had no adjustments been made to the data. Furthermore, weighting is not always stable, and resultant estimates may be unreliable due to extreme weights. These issues motivate the current development of novel propensity score stratification techniques to be used with continuous treatments. Specifically, the generalized propensity score cumulative distribution function (GPS‐CDF) and the nonparametric GPS‐CDF approaches are introduced. Empirical CDFs are used to stratify subjects based on pretreatment confounders in order to produce causal estimates. A detailed simulation study shows superiority of these new stratification methods based on the empirical CDF, when compared with standard weighting techniques. The proposed methods are applied to the “Mexican‐American Tobacco use in Children” study to determine the causal relationship between continuous exposure to smoking imagery in movies, and smoking behavior among Mexican‐American adolescents. These promising results provide investigators with new options for implementing continuous treatment propensity scoring.
Using Dairy Value Chains to Identify Production Constraints and Biosecurity Risks

Simple Summary The dairy industry plays a key role in the Indian economy. This study was conducted to understand the dairy inputs and outputs and to identify production constraints and biosecurity. Focus group discussions and key informant interviews were conducted in the Punjab state of India with 119 participants, including veterinarians, paraveterinarians, veterinary academics, dairy farmers and key informants. Farm inputs (e.g., feed and animal health services) and outputs (e.g., milk, animal sales, carcass and manure disposal) were mapped. Production constraints and biosecurity practices were identified and included the availability of green and dry fodder, provision of veterinary services by untrained practitioners, improper disposal of carcass/placenta/excreta, absence of health certification during sale or purchase of animals and absence of testing of village bulls. The government was a major provider of health and management services in the state, although a very high proportion of farmers relied on untrained or partially trained service providers for health advice and veterinary procedures. Improvement in biosecurity practices and adequate use of personal protective equipment is recommended to reduce the incidence of infectious diseases and minimize their impact. Abstract The dairy industry plays an important role in the economy and food security of India. A study of the dairy value chains was conducted in Punjab, India, to identify production constraints and biosecurity risks. Focus group discussions and key informant interviews were conducted during 2018–2019 with a total of 119 participants comprising veterinarians (41), paraveterinarians (15), veterinary academics (12), dairy farmers (46) and key informants (5). Input and output value chains were created, and potential risk nodes were identified that could facilitate the transmission of pathogens between animals, farms and villages. The majority of the participants were male (93%), middle-aged (68%) or worked in rural areas (75%). Most of the farmers self-cultivated their green fodder (82%), used the wheat straw from their own fields (60%) but purchased commercial feed (63%). Artificial insemination was used by 85% of farmers for cattle, but only 68% for buffaloes. Most of the farmers (76%) reported getting their animals vaccinated against foot-and-mouth disease and hemorrhagic septicemia. Animals were sold and purchased without any health certification and testing in most cases. Adoption of biosecurity measures by farmers and the use of personal protective equipment by veterinary personnel were very low. We recommend conducting epidemiological studies to further characterize the identified risk nodes, training of veterinary practitioners and farmers to ensure adequate biosecurity practices and the appropriate use of personal protective equipment.
Epigenomic differences in the human and chimpanzee genomes are associated with structural variation

Structural variation (SV), including insertions and deletions (indels), is a primary mechanism of genome evolution. However, the mechanism by which SV contributes to epigenome evolution is poorly understood. In this study, we characterized the association between lineage-specific indels and epigenome differences between human and chimpanzee to investigate how SVs might have shaped the epigenetic landscape. By intersecting medium-to-large human–chimpanzee indels (20 bp–50 kb) with putative promoters and enhancers in cranial neural crest cells (CNCCs) and repressed regions in induced pluripotent cells (iPSCs), we found that 12% of indels overlap putative regulatory and repressed regions (RRRs), and 15% of these indels are associated with lineage-biased RRRs. Indel-associated putative enhancer and repressive regions are approximately 1.3 times and approximately three times as likely to be lineage-biased, respectively, as those not associated with indels. We found a twofold enrichment of medium-sized indels (20–50 bp) in CpG island (CGI)–containing promoters than expected by chance. Lastly, from human-specific transposable element insertions, we identified putative regulatory elements, including NR2F1-bound putative CNCC enhancers derived from SVAs and putative iPSC promoters derived from LTR5s. Our results show that different types of indels are associated with specific epigenomic diversity between human and chimpanzee.
Vitamin C attenuates vancomycin induced nephrotoxicity through the reduction of oxidative stress and inflammation in HK-2 cells.

BACKGROUND Oxidative stress is one of the possible mechanisms in vancomycin (VCM) induced nephrotoxicity. Some studies suggested that high dose Vitamin C (VC) has protective effect against the nephrotoxicity in mice, but the underlying molecular mechanism is not mentioned. We investigated the potential targets of high dose VC against oxidative stress and inflammation induced by VCM in renal tubular epithelial cells. METHODS We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2). RESULTS VCM added to HK-2 cells caused an increase of cell death, oxidative stress and expression of inflammatory cytokines. Co-treatment with 0.5 and 1 mM VC attenuated 4-8 mM VCM induced cell death and increased the cell viability to 58-90%. VC significantly decreased lipid peroxidation and increased superoxide dismutase activity. The upregulations of NF-κB, TNF-α and IL-6 in HK-2 cells under 4 mM VCM were also reversed by 0.5 mM VC through the inhibition of oxidative stress. CONCLUSIONS This study showed for the first time that VC can attenuate the VCM induced nephrotoxicity by decreasing lipid peroxidation and expression of inflammatory cytokines, and increasing superoxide dismutase 2 (SOD2) activity, this effect may relate to the regulation of ROS/NF-κB pathway.
Impressing for popularity and influence among peers: The connection between employees’ upward impression management and peer-rated organizational influence

ABSTRACT To investigate how employees’ impression management behavior, targeted upward at organizational leaders, relates to their peer-rated organizational influence, this study considers both a mediating role of peer-rated workplace popularity and a moderating role of self-rated social dominance orientation. Multisource, three-wave data from employees and their peers in the power-distant, collectivistic country of Pakistan reveal that upward impression management behavior, despite raising some potential organizational concerns, is associated with peer-rated workplace popularity for employees, who in turn can wield greater influence over colleagues. The mediating role of peer-rated workplace popularity also is more prominent to the extent that employees accept social hierarchies, because this orientation makes their use of upward impression management tactics to advance their own and their peers’ personal interests more purposeful.
Assisted dying and palliative care in three jurisdictions: Flanders, Oregon, and Quebec.

BACKGROUND An increasing number of jurisdictions around the world are legalizing assisted dying. This creates a particular challenge for the field of palliative care, which often precludes producing premature death by the injection or self-administration of lethal medications upon a patient's voluntary request. A 2019 systematic scoping review of the literature about the relationship between palliative care and assisted dying in contexts where assisted dying is lawful, found just 16 relevant studies that included varied and combined stances ranging from complete opposition, to collaboration and integration. Building on that review, the present study was conducted in Quebec (Canada), Flanders (Belgium), and Oregon (USA), with the objective of exploring the relationship between palliative care and assisted dying in these settings, from the perspective of clinicians and other professionals involved in the practice. METHODS Semi-structured in-depth qualitative interviews were conducted with 29 professionals from Oregon [10], Quebec [9] and Flanders [10]. Participants were involved in the development of policy, management, or delivery of end of life care services in each of the jurisdictions. Data was analyzed thematically and followed a procedure of data immersion, and the construction of a thematic and interpretive account. RESULTS Three themes were identified from each of the locations. Flanders: the integrated approach; discontents in palliative care; concerns about liberalization of assisted dying laws. Oregon: the role of hospice; non-standardized protocols and policies; concerns about access to medications and care. Quebec: a contested relationship; the special situation of independent hospice; lack of knowledge about and access to palliative care. CONCLUSIONS No clear and uniform relationship between palliative care and assisted dying can be identified in any of the three locations. The context and practicalities of how assisted dying is being implemented alongside access to palliative care need to be considered to inform future laws. We seek a better understanding of whether and in what ways assisted dying presents a threat to palliative care.
Chronic Pulmonary Aspergillosis Following Nontuberculous Mycobacterial Infections: An Emerging Disease

Chronic pulmonary aspergillosis (CPA) following nontuberculous mycobacterial (NTM) lung disease is being increasingly recognized, especially in countries where tuberculosis is not endemic, with an incidence rate of 3.9–16.7%. NTM lung disease has been identified as a predictor of mortality in CPA patients. The major risk factors for NTM-associated CPA include fibrocavitary NTM lung disease, the presence of pulmonary emphysema, and high-dose corticosteroid use. The onset of CPA is 1.5–7 years following the diagnosis of NTM lung disease. The diagnosis can be made using standard criteria; however, serological diagnosis using Aspergillus precipitin has demonstrated a higher sensitivity and specificity when compared with fungal culture from respiratory specimens. Treatment is challenging since rifampicin and oral triazoles should not be used concomitantly. The prognosis is poor, and the factors associated with worse prognosis are corticosteroid use and high C-reactive protein level.
26—THE GEOMETRY AND DIMENSIONAL PROPERTIES OF PLAIN-KNIT FABRICS

The difficulties encountered in attempting to obtain relationships between the dimensions of knitted fabrics, the properties of the constituent yarns and the variable factors in knitting are discussed. It is suggested that the natural shape of the knitted loop is determined by minimum energy conditions, that the loop tends to this state on relaxation and that this shape is independent of the properties of the yarn or length of stitch. It is shown that, with these assumptions, the dimensional and weight properties of the knitted fabric in a relaxed state are determined uniquely by the length of yarn in the stitch. The relationships derived geometrically are confirmed experimentally by measurements after dry and wet relaxation on wool and cotton fabrics.
Validation of the Attitudes Related to Trauma-Informed Care Scale (ARTIC).

OBJECTIVE The purpose of the current study is to validate the Attitudes Related to Trauma-Informed Care Scale (ARTIC; Baker et al., 2016), a measure of trauma-informed care (TIC) attitudes for human service/health providers and educators. METHOD The current study with 1,395 human services/health providers and educators from 17 settings examined the factor structure, reliability, and construct validity of the ARTIC. RESULTS The 7-factor structure of the ARTIC-45 and the 5-factor structure of the ARTIC-35 were replicated with regard to the absolute fit indices though they failed to meet the cutoff for the incremental fit indices, likely due to the complexity of the measure. Internal consistencies ranged from acceptable to excellent across the instrument's forms, subscales, and versions. Providing support for construct validity, ARTIC scores were predictably related to familiarity with and knowledge about TIC, compassion satisfaction, burnout, and secondary traumatic stress, with effect sizes typically in the medium range. However, predicted relationships between ARTIC scores and training in TIC and trauma-sensitive school elements were not evident. CONCLUSIONS The ARTIC is a direct, efficient, and cost-effective measure of attitudes related to TIC. This study further demonstrates the reliability of the ARTIC and provides some support for its validity. Evaluating the favorability of staff attitudes about TIC plays a key role in ensuring readiness for, effectiveness of, and sustainability of TIC in systems. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Truncating VPS16 Mutations Are Rare in Early Onset Dystonia

We have read with great interest the study by Steel et al linking heterozygous, loss-of-function mutations in the VPS16 (vacuolar protein sorting 16 homolog) gene to early onset dystonia (EOD). In the initial screening phase, the authors detected 5 carriers of truncating variants and an additional carrier of a microdeletion including the whole VPS16 gene among 138 mostly white European EOD patients, suggesting a prevalence of VPS16 mutations of 4%. We follow a similarly sized population of EOD patients who are also predominantly of white European origin and wanted to see how frequently we would discover truncating VPS16 mutations in our population. After exclusion of mutations in TOR1A and THAP1, we screened the coding region of VPS16 by Sanger sequencing in 114 EOD patients (age at onset [AAO] ≤ 20 years) from Germany. Written informed consent and approval by the local ethics committee were obtained. Patients had a mean age of 38.6 ± 16.7 years and mean AAO of 7.1 ± 5.4 years, and 46% were male. Most patients had generalized (73%) or segmental/multifocal dystonia (25%). Dystonia was reported to be complex (co-occurring with a neurodevelopmental disorder) in 16%; family history for dystonia was reportedly positive in 26% of patients. We identified only one truncating VPS16 mutation in a single individual (0.9%; Fig). The novel frameshift mutation (c.244_259delinsGAGAGC, p.K82Efs*124; see Fig) in this 42year-old patient with generalized dystonia is considered pathogenic. He had developed right-sided writer’s cramp unresponsive to dopaminergic treatment at age 16 years that spread stepwise to involve the tongue and pharynx, neck, and trunk accompanied by myoclonic jerks (Supplementary Video S1). He responded well to deep brain stimulation (DBS). The legs were not affected. There was no cognitive or major psychiatric involvement, no tremor, and no parkinsonian features. Family history was negative. Genetic testing for HTT mutations and gene panel analysis of 29 previously known dystonia genes were negative. Wilson disease has also been excluded. A brain magnetic resonance imaging was unremarkable except for discrete nonspecific gliosis. The phenotype in our patient closely resembles the description by Steel and colleauges, including the good response to DBS. Although our observations confirm a role of heterozygous, truncating VPS16 mutations in EOD, in our population this mechanism was responsible for less than 1% of cases. There is phenotypic overlap with DYT-THAP1, but mutation frequency in VPS16-linked dystonia may be lower than that reported by Steel et al or compared to THAP1. Further studies in populations of different origin would be of interest.
The Impact of African Ancestry on Prostate Cancer Disparities in the Era of Precision Medicine

Prostate cancer disproportionately affects men of African ancestry at nearly twice the rate of men of European ancestry despite the advancement of treatment strategies and prevention. In this review, we discuss the underlying causes of these disparities including genetics, environmental/behavioral, and social determinants of health while highlighting the implications and challenges that contribute to the stark underrepresentation of men of African ancestry in clinical trials and genetic research studies. Reducing prostate cancer disparities through the development of personalized medicine approaches based on genetics will require a holistic understanding of the complex interplay of non-genetic factors that disproportionately exacerbate the observed disparity between men of African and European ancestries.
Can the detection dog alert on COVID-19 positive persons by sniffing axillary sweat samples? A proof-of-concept study

The aim of this proof-of-concept study was to evaluate if trained dogs could discriminate between sweat samples from symptomatic COVID-19 positive individuals (SARS-CoV-2 PCR positive) and those from asymptomatic COVID-19 negative individuals. The study was conducted at 2 sites (Paris, France, and Beirut, Lebanon), followed the same training and testing protocols, and involved six detection dogs (three explosive detection dogs, one search and rescue dog, and two colon cancer detection dogs). A total of 177 individuals were recruited for the study (95 symptomatic COVID-19 positive and 82 asymptomatic COVID-19 negative individuals) from five hospitals, and one underarm sweat sample per individual was collected. The dog training sessions lasted between one and three weeks. Once trained, the dog had to mark the COVID-19 positive sample randomly placed behind one of three or four olfactory cones (the other cones contained at least one COVID-19 negative sample and between zero and two mocks). During the testing session, a COVID-19 positive sample could be used up to a maximum of three times for one dog. The dog and its handler were both blinded to the COVID-positive sample location. The success rate per dog (i.e., the number of correct indications divided by the number of trials) ranged from 76% to 100%. The lower bound of the 95% confidence interval of the estimated success rate was most of the time higher than the success rate obtained by chance after removing the number of mocks from calculations. These results provide some evidence that detection dogs may be able to discriminate between sweat samples from symptomatic COVID-19 individuals and those from asymptomatic COVID-19 negative individuals. However, due to the limitations of this proof-of-concept study (including using some COVID-19 samples more than once and potential confounding biases), these results must be confirmed in validation studies.
Gamma irradiation of coumarin in aqueous solution

Abstract Aqueous solutions of coumarin become fluorescent on gamma irradiation. The main fluorescent product formed, 7-hydroxy coumarin, shows a dependence on oxygen. The yield in the presence of oxygen is three times that in the nitrogen saturated condition. The effect of cysteine, dimethyl sulfoxide, thymine and sodium nitrite on the gamma response of coumarin suggests the involvement of hydroxyl radicals in the formation of the fluorescent product. The hydroxyl rate constant for coumarin was determined using isopropanol as the co-competitor. The G (coumarin) in the aerated and nitrogen saturated conditions was also determined.
Long-term persistence of infectious Zika virus: Inflammation and behavioral sequela in mice

The neurodevelopmental defects associated with ZIKV infections early in pregnancy are well documented, however the potential defects and long-term consequences associated with milder infections in late pregnancy and perinatal period are less well understood. To model these, we challenged 1 day old (P1) immunocompetent C57BL/6 mice with ZIKV. The animals developed a transient neurological syndrome including unsteady gait, kinetic tremors, severe ataxia and seizures 10–15 days post-infection (dpi) but symptoms subsided after a week, and most animals survived. Despite apparent recovery, MRI of convalescent mice show reduced cerebellar volume that correlates with altered coordination and motor function as well as hyperactivity and impulsivity. Persistent mRNA levels of pro-inflammatory genes including Cd80, Il-1α, and Ifn-γ together with Cd3, Cd8 and perforin (PrfA), suggested persistence of low-grade inflammation. Surprisingly, the brain parenchyma of convalescent mice harbor multiple small discrete foci with viral antigen, active apoptotic processes in neurons, and cellular infiltrates, surrounded by activated astrocytes and microglia as late as 1-year post-infection. Detection of negative-sense strand viral RNA and isolation of infectious virus derived from these convalescent mice by blinded passage in Vero cells confirmed long-term persistence of replicating ZIKV in CNS of convalescent mice. Although the infection appears to persist in defined reservoirs within CNS, the resulting inflammation could increase the risk of neurodegenerative disorders. This raises concern regarding possible long-term effects in asymptomatic children exposed to the virus and suggests that long-term neurological and behavioral monitoring as well as anti-viral treatment to clear virus from the CNS may be useful in patients exposed to ZIKV at an early age.
Bone marrow niche ATP levels determine leukemia-initiating cell activity via P2X7 in leukemic models.

How particular bone marrow niche factors contribute to the leukemogenic activities of leukemia-initiating cells (LICs) remain largely unknown. Here, we showed that ATP levels were markedly increased in the bone marrow niches of mice with acute myeloid leukemia (AML), and LICs preferred to localizing to the endosteal niche with relatively high ATP levels, as indicated by a sensitive ATP indicator. ATP could efficiently induce the influx of ions into LICs in an MLL-AF9-induced murine AML model via the ligand-gated ion channel P2X7. P2x7 deletion led to notably impaired homing and self-renewal capacities of LICs and contributed to an ~5-fold decrease in the number of functional LICs but had no effect on normal hematopoiesis. ATP-P2X7 signaling enhanced the calcium flux-mediated phosphorylation of CREB, which further transactivated the Phgdh expression to maintain serine metabolism and LIC fates. P2X7-knockdown resulted in a markedly extended survival of recipients transplanted with either human AML cell lines or primary leukemia cells. Blockade of ATP-P2X7 signaling could efficiently inhibit leukemogenesis. Here, we provide a unique perspective for understanding how ATP-P2X7 signaling sustains the LIC activities, which may benefit the development of specific strategies for targeting LICs or other types of cancer stem cells.