Miracle-dz/UniFAR-FTUs huggingface dataset:
DIAGNOSTICS FOR THE HOMOGENEITY OF INCLUSION PROBABILITIES IN A BERNOULLI CENSUS

SUMMARY. In a Bernoulli census, the inclusion probabilities often vary with individ-uals. The dispersion score test is applied to test homogeneity of inclusion probabilities.Three graphic diagnostics, the log ratio plot, residual plot and gradient plot, are used todetect the existence of heterogeneity. Conﬁdence bands are available for all three plots.Real data examples are studied as illustration. 1. IntroductionConsider a closed population of ﬁnitely many individuals in which onemay be interested in estimation of the population size through Bernoulli cen-sus. This occurs in ﬁelds like health sciences, system reliability and sociolog-ical research (Chao, 2001). The problem also arises from capture-recaptureexperiments if the captured individuals are not removed and time is assumedto have no aﬀect on capture probabilities. Suppose there are N individualsindexed by i =1,2, . N . We focus on a special case in which each indi-vidual is assumed to have the same probability to be included in totally
Genetic Factors in Congenital Diaphragmatic Hernia Overview of Normal and Abnormal Diaphragm Development

Congenital diaphragmatic hernia (CDH) is a relatively common birth defect associated with high mortalityandmorbidity. Although the exact etiology of most cases of CDH remains unknown, there is a growing body of evidence that genetic factors play an important role in the development of CDH. In this review, we examine key ﬁndings that are likely to form the basis for future research in this ﬁeld. Speciﬁc topics include a short overview of normal and abnormaldiaphragm development, a discussion of syndromic forms of CDH, a detailed review of chromosomal regions recurrently altered in CDH, a description of the retinoid hypothesis of CDH, and evidence of the roles of speciﬁc genes in the development of CDH.
Representation of the polar cone of convex functions and applications

Using a result of Y. Brenier [Comm. Pure Appl. Math. 44 (1991) 375--417] we give a representation of the polar cone of monotone gradient fields in terms of measure-preserving maps, or bistochastic measures. Some applications to variational problems subject to a convexity constraint are given
Muscle and Splanchnic Glutamine and Glutamate

arm muscle in man in both prolonged starvation and in the postabsorptive state, show an uptake of glutamate and a relatively greater production of glutamine. Splanchnic arteriovenous differences in the postabsorptive state show a net uptake of glutamine and lesser rate of glutamate production. These data suggest that muscle is a major site of glutamine synthesis in man, and that the splanchnic bed is a site of its removal. The relative roles of liver and other tissues in the splanchnic circuit were not directly assessed, only the net balance. These data in man are in conflict with most previous studies in other species attributing the major proportion of glutamine production to the liver and, pari passu, to the splanchnic bed.
Comparative Effectiveness of CT- vs. Ultrasound-Guided Percutaneous Radiofrequency Ablation among Medicare Patients 65 Years of Age or Older with Hepatocellular Carcinoma

OBJECTIVE: For hepatocellular carcinoma (HCC) patients not eligible for surgical resection, radiofrequency ablation (RFA) is a promising technique that reduces the risk of disease progression. It is important to evaluate whether the trend of image guidance for RFA is moving toward more expensive CT technology, and to determine the clinical benefits of CT guidance over the ultrasound (US) guidance. METHODS: A cohort of 463 patients identified from the SEER Medicare-linked database. The temporal trends in use of image guidance were assessed using Cochrane-Armitage test. The association between modality of image guidance and survival, complications, and costs were assessed using Cox regression model, logistic regression model and generalized linear model respectively. RESULTS: The use of CT-guided RFA increased sharply, from 20.7% in 2002 to 75.9% in 2011. Compared to CT-guided RFA, those who received US-guided RFA had comparable risk of periprocedural and delayed postprocedural complications. Stratified analyses by tumor size also showed no statistically significant difference. In adjusted survival analysis, no statistically significant difference was observed in overall and cancer-specific survival. However, the costs of CT-guided RFA, $2,847, were higher than US-guided RFA, $1,862. CONCLUSIONS: Despite its rapid adoption over time, CT-guided RFA incurred higher procedural costs than the US-guided RFA but did not significantly improve postprocedural complications and survival. Echoing the American Board of Internal Medicine’s Choosing Wisely campaign and American Society of Clinical Oncology’s Value of Cancer Care initiative, findings from our study call for critical evaluation of whether CT-guided RFA provides high-value care for HCC patients.
Is the p3 (A β 17–40, A β 17–42) peptide relevant to the pathology of Alzheimer’s Disease?

Despite the vast heterogeneity of amyloid plaques isolated from the brains of those with Alzheimer’s Disease (AD), the basis of the Amyloid Cascade Hypothesis (ACH) targets a single peptide, the amyloid- β (A β ) peptide. The countless therapeutic efforts targeting the production and aggregation of this specific peptide have been met with disappointment, leaving many to question the role of A β in AD. An alternative cleavage product of the Amyloid- β Precursor Protein (A β PP), called the p3 peptide, which has also been isolated from the brains of AD patients, has been largely absent from most A β -related studies. Typically referred to as non-amyloidogenic and even suggested as neuroprotective, the p3 peptide has garnered little attention aside from some conflicting findings on cytotoxicity and potential self-assembly to form higher order aggregates. Herein, we report an extensive analysis of the findings surrounding p3 and offer some evidence as to why it may not be as innocuous as previously suggested.
Stigmatization, Resilience, and Mental Health among a Diverse Community Sample of Transgender and Gender Nonbinary Individuals in the United States

Transgender and gender nonbinary (TGNB) individuals were recently designated a health disparity population by the U.S. National Institutes of Health. We examined the effect of gender-related discrimination and resilience factors on the mental health of a community sample diverse in gender identity, age, and race/ethnicity. We report on the baseline data of a longitudinal study of transgender identity development across the lifespan with 330 TGNB individuals recruited through venue-based recruitment in three major metropolitan areas in the U.S. Mean age of participants was 34.4 years (SD = 13.7). Structured interviews collected self-report data on sociodemographics, gender-related discrimination, mental health, and resilience. We used hierarchical regression to examine the association between gender-related discrimination and psychological distress (BSI-18) and tested the moderating effect of family support, transgender community connectedness, gender literacy, and transgender activism on this relationship. In adjusted analyses, gender-related discrimination was positively associated with psychological distress. Family support was negatively associated with psychological distress. Contrary to our expectations, gender literacy and transgender activism were positively associated with psychological distress, while no significant relationship was found for transgender community connectedness. Family support, transgender community connectedness, gender literacy, and transgender activism did not moderate the effect of gender-related discrimination on psychological distress. Future mental health interventions should consider leveraging family support among TGNB individuals. Longitudinal studies are needed to better understand the role of gender literacy and activism with respect to mental health and development of identity and resilience among TGNB people.
Contributions of phonetic token variability and word-type frequency to children’s phonological representations

The experiments here build on the widely reported finding that children are most accurate when producing phonotactic sequences with high ambient-language frequency. What remains controversial is a description of the input that children must be tracking for this effect to arise. We present a series of experiments that compare two ambient-language properties, token and type frequency, as they contribute to phonotactic learning. Token frequency is the raw number of exposures children have to a particular pattern; type frequency refers to a count of abstract entities, such as unique words. Our results suggest that children’s production accuracy is most sensitive to a combination of type and token frequency: Children were able to generalize a target phonotactic sequence to a new word when familiarized with multiple word-types across tokens from multiple talkers, but not when presented with either word-types with no talker variability or multiple talker-tokens of a single word.
A Model of Ca 2+ Dynamics in an Accurate Reconstruction of Parotid Acinar Cells

We have constructed a spatio-temporal model of Ca 2+ dynamics in parotid acinar cells, based on new data about the distribution of inositol trisphophate receptors (IPR). The model is solved numerically on a mesh reconstructed from images of a cluster of parotid acinar cells. In contrast to our earlier model (Sneyd et al., 2017b) , which cannot generate realistic Ca 2+ oscillations with the new data on IPR distribution, our new model reproduces the Ca 2+ dynamics observed in parotid acinar cells. This model is then coupled with a fluid secretion model described in detail in a companion paper: A Mathematical Model of Fluid Transport in an Accurate Reconstruction of a Parotid Acinar Cell, Vera-Sigenza E, Pages N, Rugis J, Yule DI, Sneyd J. 2018. Based on the new measurements of IPR distribution, we show that Class I models (where Ca 2+ oscillations can occur at constant [IP 3 ]) can produce Ca 2+ oscillations in parotid acinar cells, whereas Class II models (where [IP 3 ] needs to oscillate in order to produce Ca 2+ oscillations) are unlikely to do so. In addition, we demonstrate that coupling fluid flow secretion with the Ca 2+ signalling model changes the dynamics of the Ca 2+ oscillations significantly, which indicates that Ca 2+ dynamics and fluid flow cannot be accurately modelled independently. Further, we determine that an active propagation mechanism based on Calcium Induced Calcium Release (CICR) channels is needed to propagate the Ca 2+ wave from the apical region to the basal region of the acinar cell.
Evaluation of venous stenosis angioplasty in a murine AVF model

Purpose: To develop a clinically relevant model of percutaneous transluminal angioplasty (PTA) of venous stenosis in mice with arteriovenous fistula (AVF) and test the hypothesis, that there is increased wall shear stress (WSS) after PTA and histologically characterize the vessels. Methods: Twenty C57BL/6J male mice, 6–8 weeks old underwent partial nephrectomy to create CKD. Twenty-eight days later, an AVF was created from the right external jugular vein to the left carotid artery. Fourteen days later, an angioplasty or sham procedure was performed and the mice were sacrificed 14 days later for histologic evaluation to identify the cells contributing to the vascular remodeling ( α -SMA, FSP-1, CD31, CD68), proliferation (Ki-67), cell death (TUNEL), and hypoxia staining (HIF-1 α ). Histomorphometric analysis was performed to assess lumen area, neointima area and cellular density. Ultrasound was performed weekly after creation of the AVF. Results: Venous stenosis occurs 14 days after creation of AVF. PTA treated vessels have significantly higher WSS, average peak systolic velocity, with increased lumen Conclusion: A clinically relevant model of PTA of venous stenosis in mice was created. PTA treated vessels have increased lumen vessel area and wall shear stress. The alterations in tissue markers of vascular remodeling, tissue hypoxia, proliferation, and cell death may be implications for future design of drug and device development.
Association of Reduced Social Network Drinking with Improved Response Inhibition in Women During Early Recovery from Alcohol Use Disorders: A Pilot Study

BACKGROUND AND AIMS: Social support for recovery from alcohol use disorders (AUDs) is associated with better drinking outcomes and with improvements in self-reported impulsive behavior in individuals treated for AUDs. We build on these findings by using a behavioral task-based measure of response inhibition, a well-defined component of impulsivity, to examine the association of disinhibition with alcohol-specific social network characteristics during early recovery. METHODS: Women (n=28) were recruited from treatment for AUD within 3–4 weeks of their last drink and were assessed at baseline and again 3 months later. Outcome measures were level of disinhibition at baseline and change in disinhibition from baseline to follow-up, measured using a computer-based continuous performance test. The primary independent variables were level of drinking in the social network at baseline, and change in network drinking from baseline to follow-up. Control variables included participants’ recent alcohol consumption, IQ, and self-reported negative urgency. RESULTS: The sample (50% black, age M(SD)=42.3 (9.5)) reported high rates of physical and sexual abuse before age 13 (43%), psychiatric disorder (60%), and previous treatment (71%); these variables were not associated with disinhibition. More drinking in participants’ social networks was associated with greater disinhibition at baseline ( β = 11.8, 95% CI= 6.0, 17.6). A reduction in network drinking from baseline to follow-up was associated with reduced disinhibition (interaction of network drinking x time on disinhibition: β = −5.4, 95% CI=−10.1, −. 59), adjusted for control variables. This study extends previous findings of an association between social networks and self-reported impulsivity to a neurobehavioral phenotype, response inhibition. Replication of these findings would support the potential role of social network drinking in cognitive change during early recovery from AUDs. tolerate discomforts and behavioral In the we build on previous findings that social networks are associated with AUD recovery and, more specifically, with decreases in impulsivity. We examine the association of alcohol-specific network characteristics with respondent’s level of disinhibition during early recovery using a task-based measure of response inhibition. Our broad hypothesis is that social networks can act as an external source of executive control during early recovery from AUD. This is an observational study focused on the social context of recovery and not on specific treatment protocols. Thus, an underlying assumption is that type of treatment is not as important as the context in which
The role of cutaneous type I interferons in autoimmune and autoinflammatory diseases

Interferons (IFNs) are well known as mediators of the antimicrobial response but also serve as important immunomodulatory cytokines in autoimmune and autoinflammatory diseases. An increasingly critical role for IFNs in evolution of skin inflammation in these patients has been recognized. IFNs are produced not only by infiltrating immune but also resident skin cells, with increased baseline IFN production priming for inflammatory cell activation, immune response amplification and development of skin lesions. The IFN response differs by cell type and host factors and may be modified by other inflammatory pathway activation specific to individual diseases, leading to differing clinical phenotypes. Understanding the contribution of IFNs to skin and systemic disease pathogenesis is key to development of new therapeutics and improved patient outcomes. In this review, we summarize the immunomodulatory role of IFNs in skin, with a focus on type I, and provide insight into IFN dysregulation in autoimmune and autoinflammatory diseases.
Identiﬁcation of Thioredoxin-2 as a Regulator of the Mitochondrial Permeability Transition

Thioredoxin-2 (Trx2) is a multifunctional, mitochondria-speciﬁc protein, which inhibits cell death. The mitochondrial permeability transition (MPT) is a distinct mechanism for cell death activated by oxidants and linked to both necrotic and apoptotic morphologies. We studied mitochondria from Trx2 transgenic mice to determine whether Trx2 protects against oxidant-induced MPT. All experiments were performed in isolated mitochondria. Results showed that Trx2 protected against MPT induced by exogenously added peroxide. Unexpectedly, Trx2 also protected against the MPT induced by Ca 2 1 in the absence of added peroxide. The results indicate that in addition to protecting against oxidative stress, Trx2 is an endogenous regulator of the MPT.
18 F Sodium Fluoride PET/CT in Patients with Prostate Cancer: Quantification of Normal Tissues, Benign Degenerative Lesions, and Malignant Lesions

Understanding the range and variability of normal, benign degenerative, and malignant 18 F sodium fluoride ( 18 F NaF) positron emission tomography/computed tomography (PET/CT) uptake is important in influencing clinical interpretation. Further, it is essential for the development of realistic semiautomated quantification techniques and simulation models. The purpose of this study is to determine the range of these values in a clinically relevant patient population with prostate cancer. 18 F NaF PET/CT scans were analyzed in patients with prostate cancer ( n = 47) referred for evaluation of bone metastases. Mean and maximum standardized uptake values [SUVs (SUV mean and SUV max )] were made in normal background regions ( n = 470) including soft tissues (liver, aorta, bladder, adipose, brain, and paraspinal muscle) and osseous structures (T12 vertebral body, femoral diaphyseal cortex, femoral head medullary space, and ribs). Degenerative joint disease (DJD; n = 281) and bone metastases ( n = 159) were identified and quantified by an experienced reader using all scan information including coregistered CT. For normal bone regions, the highest 18 F NaF PET SUV mean occurred in T12 (6.8 ± 1.4) and it also showed the lowest coefficient of variation (cv = 21%). For normal soft tissues, paraspinal muscles showed very low SUV mean (0.70 ± 0.11) and also showed the lowest variability (cv = 16%). Average SUV mean in metastatic lesions is higher than uptake in benign degenerative lesions but values showed a wide variance and overlapping values (16.3 ± 13 vs 11.1 ± 3.8; P < 0.00001). The normal 18 F NaF PET uptake values for prostate cancer patients in normal background, benign degenerative disease, and osseous metastases are comparable to those reported for a general population with a wide variety of diagnoses. These normal ranges, specifically for prostate cancer patients, will aid in clinical interpretation and also help to establish the basis of normal limits in a semiautomated data analysis algorithm.
Deletion of All Cysteines in Tachyplesin I Abolishes Hemolytic Activity and Retains Antimicrobial Activity and LPS Selective Binding

Tachyplesin-I is a cyclic β -sheet antimicrobial peptide isolated from the hemocytes of Tachypleus tridentatus . The four cysteine residues in Tachyplesin I play a structural role in imparting amphipathicity to the peptide which has been shown to be essential for its activity. We investigated the role of amphipathicity using an analog of tachyplesin I (TP-I), CDT (KWFRVYRGIYRRR-NH2), in which all four cysteines were deleted. Like TP-I, CDT shows antimicrobial activity and disrupts E. coli outer membrane and model membranes mimicking bacterial inner membranes at micromolar concentrations. The CDT peptide does not cause hemolysis up to 200 μ g/mL while TP-I showed about 10% hemolysis at 100 μ g/mL and about 25% hemolysis at 150 μ g/mL. Peptide-into-lipid titrations under isothermal conditions reveal that the interaction of CDT with lipid membranes is an enthalpy driven process. Binding assays performed using fluorimetry demonstrate that the peptide CDT binds and inserts into only negatively charged membranes. The peptide-induced thermotropic phase transition of MLVs formed of DMPC and DMPC/DMPG (7:3) mixture suggest specific lipid-peptide interactions. The circular dichroism study shows that the peptide exists as an unordered structure in an aqueous buffer and adopts a more ordered β -structure upon binding to negatively charged membrane. The NMR data suggest that CDT-binding to negatively charged bilayers induces a change in the lipid head group conformation with the lipid head group moving out of the bilayer surface towards the water phase and therefore a barrel stave mechanism of membrane-disruption is unlikely as the peptide is located near the head group region of lipids. The lamellar phase 31 P chemical shift spectra observed at various concentrations of the peptide in bilayers suggest that the peptide may neither function via fragmentation of bilayers nor by promoting non-lamellar structures. NMR and fluorescence data suggest that the presence of cholesterol inhibits the peptide binding to the bilayers. These properties help to explain that cysteine residues may not contribute to antimicrobial activity, and that the loss of hemolytic activity is due to lack of hydrophobicity and amphipathicity. are used to understand the role of anionic lipids and cholesterol, two key components by which the bacterial and mammalian cell membrane compositions differ, in the antimicrobial activity and selectivity of CDT.
Effects of ACL Reconstruction on In-Vivo, Dynamic Knee Function

Synopsis The purposes of this article are to discuss key factors for assessing joint function, to present some recent findings and to address the future directions for evaluating the function of the ACL-injured/ reconstructed knees. Well-designed studies, using state-of-the art tools to assess knee kinematics under in vivo, dynamic, high-loading conditions, are necessary to evaluate the relative performance of different procedures for restoring normal joint motion.
3D extrusion bioprinting of single- and double-network hydrogels containing dynamic covalent crosslinks

, Abstract The fabrication of three-dimensional (3D) scaffolds is indispensable to tissue engineering and 3D printing is emerging as an important approach towards this. Hydrogels are often used as inks in extrusion-based 3D printing, including with encapsulated cells; however, numerous challenging requirements exist, including appropriate viscosity, the ability to stabilize after extrusion, and cytocompatibility. Here, we present a shear-thinning and self-healing hydrogel crosslinked through dynamic covalent chemistry for 3D bioprinting. Specifically, hyaluronic acid was modified with either hydrazide or aldehyde groups and mixed to form hydrogels containing a dynamic hydrazone bond. Due to their shear-thinning and self-healing properties, the hydrogels could be extruded for 3D printing of structures with high shape fidelity, stability to relaxation, and cytocompatibility with encapsulated fibroblasts (>80% viability). Forces for extrusion and filament sizes were dependent on parameters such as material concentration and needle gauge. To increase scaffold functionality, a second photocrosslinkable interpenetrating network was included that was used for orthogonal photostiffening and photopatterning through a thiol-ene reaction. Photostiffening increased the scaffold’s modulus (~300%) while significantly decreasing erosion (~70%), whereas photopatterning allowed for spatial modification of scaffolds with dyes. Overall, this work introduces a simple approach to both fabricate and modify 3D printed scaffolds.