Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of hepatic macrophages and evaluation of inflammatory response in heme oxygenase-1 deficient mice exposed to scAAV9 vectors

Adeno-associated viral (AAV) vectors are characterised by low immunogenicity, although humoral and cellular responses may be triggered upon infection. Following systemic administration high levels of vector particles accumulate within the liver. Kupffer cells (KCs) are liver resident macrophages and an important part of the liver innate immune system. Decreased functional activity of KCs can contribute to exaggerated inflammatory response upon antigen exposure. Heme oxygenase-1 (HO-1) deficiency is associated with considerably reduced numbers of KCs. In this study we aimed to investigate the inflammatory responses in liver and to characterise two populations of hepatic macrophages in adult wild type (WT) and HO-1 knockout (KO) mice following systemic administration of one or two doses (separated by 3 months) of self-complementary (sc)AAV9 vectors. At steady state, the livers of HO-1 KO mice contained significantly higher numbers of monocyte-derived macrophages (MDMs), but significantly less KCs than their WT littermates. Three days after re-administration of scAAV9 we observed increased mRNA level of monocyte chemoattractant protein-1 (Mcp-1) in the livers of both WT and HO-1 KO mice, but the protein level and the macrophage infiltration were not affected. Three days after the 1st and 3 days after the 2nd vector dose the numbers of AAV genomes in the liver were comparable between both genotypes indicating similar transduction efficiency, but the percentage of transgene-expressing MDMs and KCs was higher in WT than in HO-1 KO mice. In the primary culture, KCs were able to internalize AAV9 particles without induction of TLR9-mediated immune responses, but no transgene expression was observed. In conclusion, in vivo and in vitro cultured KCs have different susceptibility to scAAV9 vectors. Regardless of the presence or absence of HO-1 and initial numbers of KCs in the liver, scAAV9 exhibits a low potential to stimulate inflammatory response at the analysed time points.
Breast cancer incidence in the regions of Belarus and Ukraine most contaminated by the Chernobyl accident: 1978 to 2016

Even 30 years after the accident, an association between breast cancer incidence and ionizing radiation exposure from Chernobyl fallout remains uncertain. We studied breast cancer incidence in the most contaminated regions of Belarus (Gomel and Mogilev) and Ukraine (Kyiv, Zhytomyr and Chernihiv) before (1978‐1986) and after (1987‐2016) the accident. Breast cancer cases and female population size data were received from the national cancer registries and the state departments of statistics. The study included 85 132 breast cancers with 150 million person‐years at risk. We estimated annual rayon (district)‐average absorbed doses to the breast from external and internal irradiation of the adult female population over the period of 1986‐2016. We studied an association between rayon‐average cumulative absorbed breast dose with 5‐year lag, that is, excluding the exposure in 5 years prior to breast cancer diagnosis, and breast cancer incidence using negative binomial regression models. Mean (median) cumulative breast dose in 2016 was 12.3 (5.0) milligray (mGy) in Belarus and 5.7 (2.3) mGy in Ukraine, with the maximum dose of 55 mGy and 54 mGy, respectively. Breast cancer incidence rates statistically significantly increased with calendar year and attained age, and were higher in urban than in rural residents. Adjusting for time, age and urbanicity effects, we found no evidence of increasing incidence with rayon‐average 5‐year lagged cumulative breast dose. Owing to ecological study design limitations, a case‐control study covering this area with individually reconstructed absorbed breast doses is needed testing for association between low‐dose protracted radiation exposure and breast cancer risk after Chernobyl.
The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis

ABSTRACT In sexually reproducing metazoans, spermatogenesis is the process by which uncommitted germ cells give rise to haploid sperm. Work in model systems has revealed mechanisms controlling commitment to the sperm fate, but how this fate is subsequently executed remains less clear. While studying the well-established role of the conserved nuclear hormone receptor transcription factor, NHR-23/NR1F1, in regulating C. elegans molting, we discovered that NHR-23/NR1F1 is also constitutively expressed in developing primary spermatocytes and is a critical regulator of spermatogenesis. In this novel role, NHR-23/NR1F1 functions downstream of the canonical sex-determination pathway. Degron-mediated depletion of NHR-23/NR1F1 within hermaphrodite or male germlines causes sterility due to an absence of functional sperm, as depleted animals produce arrested primary spermatocytes rather than haploid sperm. These spermatocytes arrest in prometaphase I and fail to either progress to anaphase or attempt spermatid-residual body partitioning. They make sperm-specific membranous organelles but fail to assemble their major sperm protein into fibrous bodies. NHR-23/NR1F1 appears to function independently of the known SPE-44 gene regulatory network, revealing the existence of an NHR-23/NR1F1-mediated module that regulates the spermatogenesis program. Summary: NHR-23, a well-characterized regulator of C. elegans molting, is identified as a critical regulator of spermatogenesis in both hermaphrodite and male animals.
Mitochondrial divergence between three cytotypes of the Anatolian Mole Rat, Nannospalax xanthodon (Nordmann, 1840)

Abstract The Blind Mole Rats of Anatolia (Nannospalax xanthodon (Nordmann, 1840)) are characterised by prolific chromosomal diversification. While the geographic distribution of various cytotypes is well documented, opinions on their taxonomic ranking varies amongst authorities. A partial sequence (630 bp) of mitochondrial cytochrome b gene in 13 Blind Mole Rats from the Konya basin, central Anatolia, which represented three distinct cytotypes (2n=40, 58, and 60) yielded nine cyt b haplotypes. Phylogenetic reconstructions recognized three well supported lineages which matched diploid number counts. Genetic divergences between cytotypes were high (K2P between 8.16% ± 1.19 and 11.33% ± 1.42) and application of the 2% divergence rate to the net divergence estimates suggests their divergence about 3.84 and 5.43 Mya (95% confidence interval=1.53–8.19 Mya). If one would rely on genetic operational criteria in species delimitation, there would be little doubt that the three Nannospalax cytotypes analysed in this study belong to distinct allopatric species. Before translating the results into formal taxonomy, more genetic information should be acquired on different Nannospalax cytotypes occupying the eastern Mediterranean.
Genes regulating membrane-associated E-cadherin and proliferation in adenomatous polyposis coli mutant colon cancer cells: High content siRNA screen

Truncating mutations in the tumour suppressor gene APC occur frequently in colorectal cancers and result in the deregulation of Wnt signalling as well as changes in cell-cell adhesion. Using quantitative imaging based on the detection of membrane-associated E-cadherin, we undertook a protein coding genome-wide siRNA screen to identify genes that regulate cell surface E-cadherin in the APC-defective colorectal cancer cell line SW480. We identified a diverse set of regulators of E-cadherin that offer new insights into the regulation of cell-cell adhesion, junction formation and genes that regulate proliferation or survival of SW480 cells. Among the genes whose depletion promotes membrane-associated E-cadherin, we identified ZEB1, the microRNA200 family, and proteins such as a ubiquitin ligase UBE2E3, CDK8, sorting nexin 27 (SNX27) and the matrix metalloproteinases, MMP14 and MMP19. The screen also identified 167 proteins required for maintaining E-cadherin at cell-cell adherens junctions, including known junctional proteins, CTNND1 and CTNNA1, as well as signalling enzymes, DUSP4 and MARK2, and transcription factors, TEAD3, RUNX2 and TRAM2. A better understanding of the post-translational regulation of E-cadherin provides new opportunities for restoring cell-cell adhesion in APC-defective cells.
Vaccine attitudes among young adults in Asia: a systematic review

ABSTRACT Introduction: Young adults may be facing growing threats from vaccine-preventable diseases (VPDs). However, vaccination of young adults may not have drawn adequate attention. In Asia, adensely populated region with ahigh proportion of low-income countries, VPDs impose more of an economic and social burden than in western countries. However, knowledge about attitudes toward vaccines among young Asians is limited. This study aims to fill that gap by describing attitudes toward vaccines and how well they are accepted among young Asian adults through asystematic review of relevant Chinese and English publications. Methods: A three-stage searching strategy was adopted to identify eligible studies published during 2009–2019 according to the selection criteria, resulting in 68 articles being included. Results: The review finds that vaccination coverage among young Asians is generally lower than among their western peers, and there is a lack of relevant study in many Asian countries. Factors influencing young Asians’ attitudes toward vaccines are categorized into contextual level, individual and social level, and vaccine-specific level. Conclusion: These suggest that there is a need to strengthen young adults’ vaccination programs and to promote vaccine-related information and government.
A Sentence Repetition Task for Early Language Assessment in Spanish

Abstract Sentence repetition tasks have been widely used in the last years as a diagnostic tool in developmental language disorders. However in Spanish there are few (if any) of these instruments, especially for younger children. In this context, we develop a new Sentence Repetition Task for assessing language (morphosyntactic) abilities of very young Spanish children. A list of 33 sentences of different length and complexity was created and included in the task. A total of 130 typical developing children from 2 to 4 years of age were engaged in a play situation and asked to repeat the sentences. Children’s answers were scored for accuracy at sentence and word level and error analysis at the word level was undertaken. Besides a subsample of 92 children completed a non-word repetition task. First results show its adequacy to children from 2 to 4 years of age, its capacity to discriminate between different developmental levels, and its concurrent validity with the nonword repetition task.
Explanatory variables and nomogram of a clinical prediction model to estimate the risk of caesarean section after term induction

Abstract The aims of this study were to identify the explanatory variables associated with failure of induction of labour (IOL) and to designate nomograms that predict probability. This retrospective study included 1328 singleton term pregnant women (37–42 weeks). The penalised maximum likelihood estimation (PMLE) method was used instead of traditional logistic regression. Of the 25,678 deliveries that occurred during the study period, 1328 (5.1%) women underwent term delivery. Of those, 1125 (84.7%) had successful vaginal deliveries and 203 (15.3%) had failed vaginal deliveries following use of a dinoprostone slow-release vaginal insert. Explanatory variables were discovered that were associated with delivery failure in term pregnancy undergoing induction of labour with an unfavourable cervix, and a nomogram that predicted probability was developed. IMPACT STATEMENT What is already known on this subject? The caesarean rate has continued to climb worldwide over the past decade. Most caesarean sections are performed because of suspected foetal distress or failure to progress. In absolute numbers, most caesarean deliveries are performed in women with a term pregnancy with a foetus in cephalic presentation. Despite these numbers, predicting the mode of delivery by which these women will deliver remains a challenge. What do the results of this study add? Five explanatory variables were strongly associated with failure of dinoprostone delivery of term pregnancies: nulliparity, induction time, premature rupture of membranes, Bishop score and foetal gender What are the implications of these findings for clinical practice and further research? The developed nomograms enable fast and easy implementation in clinical practice. After external validation and proof of generalisability, the present model could be used in obstetric clinical management.
Early predictors for mechanical ventilation in COVID-19 patients

Objective: To identify potential predictors for invasive and non-invasive mechanical ventilation in coronavirus disease 2019 (COVID-19) patients. Methods: This study retrospectively analyzes data of 516 patients with confirmed COVID-19, who were categorized into three groups based on which mechanical ventilation method was used during the hospitalization period. Results: Among 516 confirmed cases with COVID-19, 446 patients did not receive mechanical ventilation, 38 patients received invasive mechanical ventilation (IMV) and 32 received non-invasive mechanical ventilation (NIMV). The median age of the included patients was 61 years old (interquartile range, 52–69). A total of 432 patients had one or more coexisting illnesses. The main clinical symptoms included fever (79.46%), dry cough (66.47%) and shortness of breath (46.90%). IMV and NIMV patients included more men, more coexisting illnesses and received more medication. Patients in the IMV group and NIMV had higher leukocyte and neutrophil count, lower lymphocyte count, higher aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin (PCT) and D-dimer levels and lower albumin (ALB) level. The univariate and multiple logistic regression analysis showed that the use of glucocorticoid, increased neutrophil count and LDH had a predictive role as indicators for IMV, and the use of glucocorticoid, increased neutrophil count and PCT had a predictive role as indicators for NIMV. The area under the curve (AUC) of use of glucocorticoid, increased neutrophil count and LDH was 0.885 (95% confidence interval (CI) 0.838–0.933, p < 0.0001), which provided the specificity and sensitivity 77.7% and 90.9%, respectively. AUC of the use of glucocorticoid, increased neutrophil count and PCT for NIMV was 0.888 (95% CI 0.825–0.952, p < 0.0001), which provided the specificity and sensitivity 70.3% and 96.4%, respectively. Conclusion: Glucocorticoid, increased neutrophil and LDH were predictive indicators for IMV, whereas glucocorticoid, increased neutrophil and PCT were predictive indicators for NIMV. In addition, the above-mentioned mediators had the most predictive meaning for mechanical ventilation when combined. The reviews of this paper are available via the supplemental material section.
COVID-19 Emergency Sick Leave Has Helped Flatten The Curve In The United States.

This paper tests whether the coronavirus disease 2019 (COVID-19) emergency sick leave provision of the bipartisan Families First Coronavirus Response Act (FFCRA) reduced the spread of the virus. Using a difference-in-differences strategy, we compare pre-post FFCRA changes in newly reported COVID-19 cases in states where workers gained the right to take paid sick leave (treatment group) to states where workers already had access to paid sick leave (control group). We adjust for differences in testing, day-of-the-week reporting, structural state differences, general virus dynamics, and policies such as stay-at-home orders (SHO). Compared to the control group and relative to the pre-FFCRA period, states that gained access to paid sick leave through FFCRA saw a statistically significant 400 fewer confirmed cases per day. This estimate translates into roughly 1 prevented COVID-19 case per day, per 1300 workers who newly gained the option to take up to two weeks of paid sick leave. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs. ].
Genetic evidence for Amh modulation of gonadotropin actions to control gonadal homeostasis and gametogenesis in zebrafish and its noncanonical signaling through Bmpr2a receptor

ABSTRACT Anti-Müllerian hormone (Amh) plays an important role in gonadal function. Amh deficiency causes severe gonadal dysgenesis and dysfunction in zebrafish, with gonadal hypertrophy in both sexes. However, its mechanism of action remains unknown. Intriguingly, the Amh cognate type II receptor (Amhr2) is missing in the zebrafish genome, in sharp contrast to other species. Using a series of zebrafish mutants (amh, fshb, fshr and lhcgr), we provided unequivocal evidence for actions of Amh, via modulation of gonadotropin signaling, on both germ cell proliferation and differentiation. The gonadal hypertrophy in amh mutants was abolished in the absence of Fshr in females or Fshr/Lhcgr in males. Furthermore, we demonstrated that knockout of bmpr2a, but not bmpr2b, phenocopied all phenotypes of the amh mutant in both sexes, including gonadal hypertrophy, hyperproliferation of germ cells, retarded gametogenesis and reduced fshb expression. In summary, the present study provided comprehensive genetic evidence for an intimate interaction of gonadotropin and Amh pathways in gonadal homeostasis and gametogenesis and for Bmpr2a as the possible missing link for Amh signaling in zebrafish. Summary: Amh controls gametogenesis in zebrafish by inhibiting gonadotropin stimulation of germ cell proliferation but promoting its action on germ cell differentiation.
Prediction of Energetic Material Properties from Electronic Structure Using 3D Convolutional Neural Networks

We develop a convolutional neural network capable of directly parsing the 3D electronic structure of a molecule described by spatial point data for charge density and electrostatic potential represented as a 4D tensor. This method effectively bypasses the need to construct complex representations, or descriptors, of a molecule. This is beneficial because the accuracy of a machine learned model depends on the input representation. Ideally, input descriptors encode the essential physics and chemistry that influence the target property. Thousands of molecular descriptors have been proposed, and proper selection of features requires considerable domain expertise or exhaustive and careful statistical downselection. In contrast, deep learning networks are capable of learning rich data representations. This provides a compelling motivation to use deep learning networks to learn molecular structure-property relations from "raw" data. The convolutional neural network model is jointly trained on over 20,000 molecules that are potentially energetic materials (explosives) to predict dipole moment, total electronic energy, Chapman-Jouguet (C-J) detonation velocity, C-J pressure, C-J temperature, crystal density, HOMO-LUMO gap, and solid phase heat of formation. This work demonstrates the first use of complete 3D electronic structure for machine learning of molecular properties.
Prevention of acute rejection after rescue with Belatacept by association of low-dose Tacrolimus maintenance in medically complex kidney transplant recipients with early or late graft dysfunction

Background Increased acute rejection risk in rescue protocols with Belatacept may limit its use particularly in medically complex patients where preexisting increased risk of rejection couples with CNI toxicity. Methods Retrospective analysis was performed in 19 KTs shifted to a Belatacept-based immunosuppression with low-dose Tacrolimus (2–3 ng/mL) after evidence of allograft disfunction, including patients with primary non-function (PNF), chronic-active antibody-mediated rejection (cAMR), history of previous KTs and/or other concomitant transplants (liver, pancreas). Evaluation of CD28+ CD4+ effector memory T cell (TEM) before conversion was performed in 10/19. Results Kidney function significantly improved (median eGFR 16.5 ml/min/1.73m2 before vs 25 ml/min after; p = 0.001) at a median time after conversion of 12.5 months (9.1–17.8). Overall graft and patient survival were 89.5% and 100% respectively. Definitive weaning from dialysis in 5/5 KTs with PNF was observed, whereas 7/8 patients lost their graft within first year in a control group. eGFR significantly ameliorated in re-trasplants (p = 0.001) and stabilized in KTs with other organ transplants or cAMR. No acute rejection episodes occurred, despite the significant risk suggested by high frequency of CD28+ CD4+ TEM in most patients. Opportunistic infections were limited and most common in early vs late-converted. Conclusions Rescue association of Belatacept with low-dose Tacrolimus in medically complex KTs is a feasible option that allows prevention of acute rejection and amelioration of graft function.
Can Emotional Awareness of Liars Influence Deception Detection Effectiveness?

Abstract Emotional awareness is defined as the ability to cognitively process emotional arousal and the expression thereof. When telling a lie, emotional awareness comes into play: the most important objective is to conceal one’s true emotions and fabricate false ones; simultaneously, however, one must control for the affective state of those who are to believe the falsehood; via such efforts, one can assess the potential for success in the deceit. With this in mind, we hypothesized that emotional awareness may play a vital role in the process of creating a convincing lie. Study participants (Group A, N = 40) were asked to complete the Polish adaptation of the Levels of Emotional Awareness Scale (LEAS) and record videos consisting of plotting some truth or lie, which were then rated as true or false by 400 volunteers (Group B). Both samples (Group A and Group B) were recruited among students attending Polish universities. The results allowed us to confirm correlational relationships between emotional awareness (general, self-awareness, and awareness of others’ emotions) and the effectiveness of the deception. We were also able to confirm previous studies’ results about the truth bias in detecting lies and gender differences in emotional awareness.
Understanding of Health-related Decision-making Terminology Among Cancer Caregivers

Research on understanding health-related decision-making terminology among family caregivers of adults living with advanced cancer is lacking. The purpose of this study was to examine interpretations of the meaning of health-related decision-making terminology such as quality-of-life and end-of-life among caregivers of adults living with advanced cancer as a basis for improved understanding of caregiver decision support needs. Interviews were conducted with a purposive sub-sample of 10 caregivers of adults diagnosed with advanced cancer who completed a longitudinal, descriptive study (NRO14856) of factors influencing cancer care decisions. Audio transcripts were analyzed using qualitative descriptive methods. Caregivers described interpretations of the meaning and process of decision-making and decision-related distress. Caregivers were uncertain about the meaning of end-of-life-related terminology, and a placed high value on quality-of-life and faith/spirituality in the decision-making process. Improvements in information and decision support interventions are needed to better support caregivers and subsequently patients towards informed cancer care decisions.