Miracle-dz/UniFAR-FTUs huggingface dataset:
Network meta‐analysis of His bundle, biventricular, or right ventricular pacing as a primary strategy for advanced atrioventricular conduction disease with normal or mildly reduced ejection fraction

Although right ventricular pacing (RVP) may impair ventricular function, it is commonly used for advanced atrioventricular block (AVB) and normal or mildly reduced ejection fraction (EF). We aimed to compare His bundle pacing (HBP), biventricular pacing (BiVP), and RVP for advanced AVB in patients with normal or mildly reduced EF.
Draft Whole-Genome Sequences of Ciprofloxacin-Resistant Derivatives of a Bacillus anthracis ΔANR Strain Lacking pXO1 and pXO2 Plasmids

Mutants of an attenuated Bacillus anthracis (ΔANR) strain conferring increasing levels of ciproﬂoxacin resistance have been described. Here, we report the draft genome sequences of the parent strain (ΔANR pXO1−, pXO2−) and its derivatives conferring low (step 1; 0.5 μg/ml), medium (step 2; 8 to 16 μg/ml), and high (step 3; 32 to 64 μg/ml) levels of ciprofloxacin resistance. ABSTRACT Mutants of an attenuated Bacillus anthracis (ΔANR) strain conferring increasing levels of ciproﬂoxacin resistance have been described. Here, we report the draft genome sequences of the parent strain (ΔANR pXO1−, pXO2−) and its derivatives conferring low (step 1; 0.5 μg/ml), medium (step 2; 8 to 16 μg/ml), and high (step 3; 32 to 64 μg/ml) levels of ciprofloxacin resistance.
Race and Personal Exposure to AD Influence Projected Memory Failure Attributions and Help-Seeking Behaviors

ABSTRACT Objectives Examine race and personal exposure to Alzheimer’s Disease (AD) on projected memory failure attributions and medical help-seeking thresholds of pre-morbid adults. The goal is to better understand race discrepancies in help-seeking for those potentially at risk for early-onset AD. Methods 498 adults aged 40 to 65 (M = 52.27), screened for current memory failure, completed an online questionnaire exploring their help-seeking intentions and threshold, attributions of hypothetical memory failures, and level of AD concern. Results Non-Hispanic Whites (n = 248) were significantly more concerned about AD than African Americans (n = 250) (p =.027). Personal exposure to AD moderated the impact of race on memory failure attributions (p =.036), so that personal exposure was more influential for African Americans. Those who were more likely to attribute hypothetical memory failures to AD had lower projected thresholds for seeking a medical evaluation (p =.010). Memory failure attribution emerged as a potential mediator of the impact of race on projected help-seeking behaviors (p =.057). Conclusions African Americans were more influenced by personal experience when considering the causes of hypothetical memory failures. Clinical Implications Healthcare providers should emphasize to African American families the value of early AD detection and treatment in terms of quality of life for both patient and caregiver.
Polarized Raman spectroscopy for studying two-dimensional materials

Raman spectroscopy has been established as one of the core experimental tools to study two-dimensional materials (2DMs) including graphene, black phosphorus, transitional metal chalcogenides, and other layered materials. If the polarization of the incident photons and the scattered photons are carefully controlled, the selection rules for the Raman scattering from phonon modes allow accurate mode assignments, which is not always possible in Raman scattering measurements using unpolarized light. Furthermore, polarized Raman spectroscopy can be used to determine the crystallographic orientation of isotropic 2DMs with in-plane strain or anisotropic 2DMs. This review explains the basics of polarized Raman spectroscopy, especially in the context of 2DMs research, and survey some of the most important applications of polarized Raman spectroscopy in isotropic and anisotropic 2DMs studies.
Alveolar wars: The rise of in vitro models to understand human lung alveolar maintenance, regeneration, and disease

Diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and bronchopulmonary dysplasia injure the gas‐exchanging alveoli of the human lung. Animal studies have indicated that dysregulation of alveolar cells, including alveolar type II stem/progenitor cells, is implicated in disease pathogenesis. Due to mouse‐human differences, there has been a desperate need to develop human‐relevant lung models that can more closely recapitulate the human lung during homeostasis, injury repair, and disease. Here we discuss how current single‐cell RNA sequencing studies have increased knowledge of the cellular and molecular composition of human lung alveoli, including the identification of molecular heterogeneity, cellular diversity, and previously unknown cell types, some of which arise specifically during disease. For functional analysis of alveolar cells, in vitro human alveolar organoids established from human pluripotent stem cells, embryonic progenitors, and adult tissue from both healthy and diseased lungs have modeled aspects of the cellular and molecular features of alveolar epithelium. Drawbacks of such systems are highlighted, along with possible solutions. Organoid‐on‐a‐chip and ex vivo systems including precision‐cut lung slices can complement organoid studies by providing further cellular and structural complexity of lung tissues, and have been shown to be invaluable models of human lung disease, while the production of acellular and synthetic scaffolds hold promise in lung transplant efforts. Further improvements to such systems will increase understanding of the underlying biology of human alveolar stem/progenitor cells, and could lead to future therapeutic or pharmacological intervention in patients suffering from end‐stage lung diseases.
Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

ABSTRACT Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders.
Food Safety and COVID-19.

CAN I GET SICK WITH COVID19 FROM TOUCHING FOOD, THE FOOD PACKAGING, OR FOOD CONTACT SURFACES IF THE CORONAVIRUS WAS PRESENT ON IT? • Currently there is no evidence of food or food packaging being associated with transmission of COVID19. Like other viruses, it is possible that the virus that causes COVID-19 can survive on surfaces or objects. • For that reason, it is critical to follow safe food handling procedures FOOD HANDLING BEST PRACTICES • As always, following good hygiene and food safety practices are the key to keeping food safe • Wash hands frequently, when arriving at work, when changing tasks, after touching money or anything handed to you from a customer, before and after eating, after going to the bathroom, • Use only single-use paper towels for drying hands and use that paper towel to turn the spigot off • Clean and sanitize food contact surfaces and equipment regularly • Do not allow customers to handle produce
Reference values for thrombin dynamics in platelet rich plasma

Abstract Thrombin generation (TG) is a better determinant of the overall function of the hemostatic system than routinely used clotting time-based assays and can be studied more in detail by thrombin dynamics analysis. Platelet poor plasma is often used to measure TG, however, measuring the contribution of the platelets is also important as patients with a low platelet count or with dysfunctional platelets have an increased risk of developing bleeding. In this study, platelet rich plasma (PRP) was collected from 117 healthy individuals. PRP was measured undiluted and diluted to a varying platelet concentration of 10*109/L to 400*109/L. Prothrombin conversion and thrombin inactivation were calculated from the data obtained by the TG parameters and coagulation factor levels (antithrombin, α2Macroglobulin (α2M) and fibrinogen). Reference ranges of TG and thrombin dynamics in PRP of 117 healthy individuals were established. Peak, velocity index and the maximum rate of prothrombin conversion increased linearly with platelet count, but endogenous thrombin potential reached a maximum at 150*109/L as seen in a subset population (n = 20). More extensive analysis revealed that a platelet count below 50*109/L did not affect TG parameters (except for the ETP). Correlation analysis indicated that the platelet count mainly affected the rate of prothrombin conversion. Inhibition of thrombin by antithrombin and α2M increased with increasing TG, but the ratio of inhibition by antithrombin or α2M remained the same independently of the total thrombin formed. In conclusion, TG and thrombin dynamics were assessed in PRP of healthy donors to provide reference values for future TG studies in PRP. Increasing the platelet count mainly affected the rate of prothrombin conversion and TG, rather than the total amount of thrombin formed.
Combined deletion of Bap1, Nf2, and Cdkn2ab causes rapid onset of malignant mesothelioma in mice

Badhai et al. describe a mouse model of mesothelioma with combined deletion of Bap1, Nf2, and Cdkn2ab that shows rapid onset and recapitulates human mesothelioma including its response to the standard treatment. This autochthonous model is well suited for testing cancer immunotherapies.
Detection of Circulating Tumor Cells in the Diagnostic Leukapheresis Product of Non-Small-Cell Lung Cancer Patients Comparing CellSearch® and ISET

Circulating tumor cells (CTCs) detected by CellSearch are prognostic in non-small-cell lung cancer (NSCLC), but rarely found. CTCs can be extracted from the blood together with mononuclear cell populations by diagnostic leukapheresis (DLA), therefore concentrating them. However, CellSearch can only process limited DLA volumes (≈2 mL). Therefore, we established a protocol to enumerate CTCs in DLA products with Isolation by SizE of Tumor cells (ISET), and compared CTC counts between CellSearch® and ISET. DLA was performed in NSCLC patients who started a new therapy. With an adapted protocol, ISET could process 10 mL of DLA. CellSearch detected CTCs in a volume equaling 2 × 108 leukocytes (mean 2 mL). CTC counts per mL were compared. Furthermore, the live cell protocol of ISET was tested in eight patients. ISET successfully processed all DLA products—16 with the fixed cell protocol and 8 with the live cell protocol. In total, 10–20 mL of DLA was processed. ISET detected CTCs in 88% (14/16), compared to 69% (11/16, p < 0.05) with CellSearch. ISET also detected higher number of CTCs (ISET median CTC/mL = 4, interquartile range [IQR] = 2–6, CellSearch median CTC/mL = 0.9, IQR = 0–1.8, p < 0.01). Cells positive for the epithelial cell adhesion molecule (EpCAM+) per mL were detected in similar counts by both methods. Eight patients were processed with the live cell protocol. All had EpCAM+, CD45−, CD235- cells isolated by fluorescence-activated cell sorting (FACS). Overall, ISET processed larger volumes and detected higher CTC counts compared to CellSearch. EpCAM+ CTCs were detected in comparable rates.
Problematic Social-Networks-Use in German Children and Adolescents—The Interaction of Need to Belong, Online Self-Regulative Competences, and Age

Adolescents nowadays spend much time communicating via social networks. Recent investigations also report a noticeable proportion showing a problematic usage behavior, underlining the importance of better understanding its development and maintenance in young individuals. Theoretical views on Internet-use disorders assume that specific predispositions and needs can contribute to addictive behaviors in interaction with further aspects including Internet-related cognitive biases. This study focuses on vulnerable individuals due to their age and investigates interactions between possible risk (need to belong, NTB) and protective factors (online self-regulative competences, OSRC). Participants (N = 466) between 10 and 17 years answered questionnaires assessing social-networks-use disorder symptoms, NTB, and OSRC. Moderated regression analysis revealed significant effects of age, NTB, and OSRC. Three-way interaction was also significant (potentially mainly caused by females), with highest social-networks-use disorder symptoms found for individuals with high NTB and low OSRC, especially when older. With high OSRC, symptoms were significantly lower for both younger and older individuals having high NTB. However, even if NTB was low, older individuals showed high social-networks-use disorder symptoms if their OSRC were low. The results highlight the importance of improving specific competences to prevent problematic usage behaviors, which should be considered in youth-tailored prevention and intervention programs.
Synthesis and Biological Evaluation of New Antitubulin Agents Containing 2-(3′,4′,5′-trimethoxyanilino)-3,6-disubstituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine Scaffold

Two novel series of compounds based on the 4,5,6,7-tetrahydrothieno[2,3-c]pyridine and 4,5,6,7-tetrahydrobenzo[b]thiophene molecular skeleton, characterized by the presence of a 3′,4′,5′-trimethoxyanilino moiety and a cyano or an alkoxycarbonyl group at its 2- or 3-position, respectively, were designed, synthesized, and evaluated for antiproliferative activity on a panel of cancer cell lines and for selected highly active compounds, inhibition of tubulin polymerization, and cell cycle effects. We have identified the 2-(3′,4′,5′-trimethoxyanilino)-3-cyano-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivative 3a and its 6-ethoxycarbonyl homologue 3b as new antiproliferative agents that inhibit cancer cell growth with IC50 values ranging from 1.1 to 4.7 μM against a panel of three cancer cell lines. Their interaction with tubulin at micromolar levels leads to the accumulation of cells in the G2/M phase of the cell cycle and to an apoptotic cell death. The cell apoptosis study found that compounds 3a and 3b were very effective in the induction of apoptosis in a dose-dependent manner. These two derivatives did not induce cell death in normal human peripheral blood mononuclear cells, suggesting that they may be selective against cancer cells. Molecular docking studies confirmed that the inhibitory activity of these molecules on tubulin polymerization derived from binding to the colchicine site.
Expression-Invariant Age Estimation

In this paper, we investigate and exploit the influence of facial expressions on automatic age estimation. Different from existing approaches, our method jointly learns the age and expression by introducing a new graphical model with a latent layer between the age/expression labels and the features. This layer aims to learn the relationship between the age and expression and captures the face changes which induce the aging and expression appearance, and thus obtaining expression-invariant age estimation. Conducted on two age-expression datasets (FACES and Lifespan), our experiments illustrate the improvement in performance when the age is jointly learnt with expression in comparison to expression-independent age estimation. The age estimation error is reduced by 14.43% and 37.75% for the FACES and Lifespan datasets respectively. Furthermore, the results obtained by our graphical model, without prior-knowledge of the expressions of the tested faces, are better that the best reported ones for both datasets.
Age- and Organ-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

Mitochondria play a central role in energy homeostasis and act as regulatory checkpoints for downstream metabolic responses and cell senescence processes during an entire life span. Acute or chronic environmental toxicant exposures have shown deleterious organ-specific human health issues at various life stages. Since mitochondria are a prime target for ensuing cellular bioenergetics responses and senescence, it is essential to understand mitochondrial bioenergetic responses in different organs over multiple life stages. Therefore, in the present study, we evaluated mitochondrial bioenergetic parameters in the liver, lung, and heart in four diverse age groups (young: 1 month; adult: 4 months; middle-aged: 12 months; old-aged: 24 month) using male Brown Norway rats as a model of aging (n = 5 sample size/organ/age group) and compared them with our previously published results on brain. Real-time mitochondrial bioenergetic parameters (i.e., State III, State IV, and State V) were measured using the Seahorse Extracellular Flux Analyzer. Additionally, mitochondrial enzyme pyruvate dehydrogenase complex (PDHC), Complex I, Complex II, and Complex IV activities were measured using Synergy HT plate reader. Our results indicated that nearly in all parameters, significant age- and organ-specific interactions were observed. We observed age-specific declines in State III (i.e., ATP synthesis rate) responses in both the heart and lung, where opposite was observed in the liver as age advances. Across the age, the heart has highest enzyme activities than the liver and lung. Interestingly, heart and liver mitochondrial bioenergetic rates and enzyme activities remain higher than the lung, which specifies their higher metabolic capabilities than the lung. Amongst all, bioenergetic rates and enzyme activities in the lung remain lowest suggesting the lung may display higher vulnerability and lower resilience to environmental toxicants during aging than other organs tested here. Overall, these age- and organ-specific findings may facilitate a more contextualized understanding of mitochondrial bioenergetic outcomes when considering the interactions of age-related sensitivities with exposure to chemical stressors from the environment.
Plant based extracts show novel sanitising effects against Escherichia coli on romaine lettuce and cucumber

Background: Diarrhoeal diseases affect approximately 550 million people and account for 230,000 deaths every year globally. Children in particular are at risk of foodborne diarrhoeal diseases, with 220 million falling ill and 96,000 dying every year. In 2017, an outbreak of diarrhoea caused by Escherichia coli (E. coli) occurred as a result of consuming contaminated/ill-washed Romaine lettuce in the USA. Consumption of ready-to-eat vegetables (RTEV) is increasing around the globe. Objective: The current study sought to assess the efficacy of extracts of selected African medicinal plants [Lannea edulis (Sond.) Engl. var. Edulis (L. edulis), Cassia abbreviata Oliv. (C. abbreviata), Solanum incanum (S. incanum) and Grewia bicolor (G. bicolor)] on removal of E. coli, an indicator of faecal contamination from Lactuca sativa L. var. longifolia (L. sativa) (Romaine lettuce) leaves, and Cucumis sativa L. (C. sativa) (cucumber) surfaces. Methods: Two cm square sections of lettuce and cucumber epidemal tissues were soaked in extracts of the medicinal plants (10 -1 of original extracts) for 1 hr. Washing of the RTEV with sterile water caused significant reductions in E. coli loads on lettuce or cucumber (P < 0.01) surfaces compared to unwashed controls. Results: Extracts from the medicinal plants caused reductions in E. coli loads on all both RTEV (load reduction by at least 2 log colony forming units (CFU)/cm) (P < 0.01) without changes in surface morphology and colour. Use of extracts from L. edulis, C. abbreviata, S. incanum and G. bicolor have potential for use in sanitisation of RTEV, especially in killing, inhibiting or removing pathogenic E. coli that are transmitted via these fresh foods and products. While washing with G. bicolor resulted in significant reductions of E. coli on cucumber and lettuce surfaces, its efficacy was lowest compared to the rest of the treatments; hence, it is the least favourable of the selected medicinal plants. Soaking in the extract preparations did not lead to significant changes in odor, texture or taste of the vegetables. Conclusion: Use of extracts from these plants is suggested as a possible way to sanitise RTEV to reduce occurrence of, or contain outbreaks of diseases that are borne on these vegetables.
A neural model of hierarchical reinforcement learning: Supporting information

It is helpful to compare the hierarchical mechanisms of this model to the various computational approaches to HRL (e.g., [1–3]), as another way of elucidating the features of this model. Firstly, it is important to note that this model is not an exact recreation of any of those theories—the process of neural implementation requires many adaptations and modifications, as we have seen in previous sections. In addition, the hierarchical structure of this model is not fixed, and can combine aspects of the various HRL frameworks depending on how the hierarchical interactions are constructed. Rather than recreating any particular HRL approach, the goal in the hierarchical structure of this model was to preserve, as far as possible, the basic operation of the flat SMDP model. As it happens, that was also the goal of the authors of the “options” HRL framework [2]. As they put it, “What is the minimal extension of the reinforcement learning framework that allows a general treatment of temporally abstract knowledge and action? ” ( [2], pg. 182). For that reason, this model bears the strongest similarity to the options framework; for example, the SMDP learning update (Eq. 3 in main text) is almost identical to the options approach.
Pan drug-resistant Acinetobacter baumannii causing nosocomial infections among burnt children

Background: Nosocomial infection caused by Acinetobacter baumannii has emerged as a world-wide serious problem in the emergence of multidrug-resistant (MDR). Infections caused by antibiotic-resistant strains of A. baumannii cannot be completely eliminated among the infected patients. This study aimed to monitor antibiotic resistance among A. baumannii strains isolated from burnt children. Methods: After performing biochemical identification tests on 115 isolates, 62 were detected as A. baumannii . Minimum inhibitory concentration (MIC) was used to test susceptibility to colistin, and disk agar diffusion was used for the susceptibility of the isolates to the antibiotics Ciprofloxacin, Amikacin, Gentamicin, Cefepime, Meropenem, Imipenem, Ceftazidime, Levofloxacin and Piperacillin/Tazobactam. Bacterial species were isolated and identified as multidrug-resistant (MDR), extensively drug-resistant (XDR) and pan drug-resistant (PDR), based on the susceptibility patterns to elected antibiotics, deputing different classes of antimicrobial. Results: The antibiotic susceptibility pattern out of a total of 62 bacterial strains used in this study. Thirty-six (58%) strains were categorized as MDR, 17 (27.5%) as XDR, and nine (14.5%) as PDR. Conclusion: To reduce the threat of antimicrobial resistance, MDR, XDR and PDR A. baumannii strains must be evaluated by all clinical microbiology laboratories.