Miracle-dz/UniFAR-FTUs huggingface dataset:
Type I CRISPR-Cas provides robust immunity but incomplete attenuation of phage-induced cellular stress

Abstract During infection, phages manipulate bacteria to redirect metabolism towards viral proliferation. To counteract phages, some bacteria employ CRISPR-Cas systems that provide adaptive immunity. While CRISPR-Cas mechanisms have been studied extensively, their effects on both the phage and the host during phage infection remains poorly understood. Here, we analysed the infection of Serratia by a siphovirus (JS26) and the transcriptomic response with, or without type I-E or I-F CRISPR-Cas immunity. In non-immune Serratia, phage infection altered bacterial metabolism by upregulating anaerobic respiration and amino acid biosynthesis genes, while flagella production was suppressed. Furthermore, phage proliferation required a late-expressed viral Cas4 homologue, which did not influence CRISPR adaptation. While type I-E and I-F immunity provided robust defence against phage infection, phage development still impacted the bacterial host. Moreover, DNA repair and SOS response pathways were upregulated during type I immunity. We also discovered that the type I-F system is controlled by a positive autoregulatory feedback loop that is activated upon phage targeting during type I-F immunity, leading to a controlled anti-phage response. Overall, our results provide new insight into phage-host dynamics and the impact of CRISPR immunity within the infected cell.
What ‘Omics can tell us about antifungal adaptation

ABSTRACT Invasive candidiasis, the most frequent healthcare-associated invasive fungal infection, is commonly caused by Candida albicans. However, in recent years other antifungal-resistant Candida species—namely Candida glabrata and Candidaauris—have emerged as a serious matter of concern. Much of our understanding of the mechanisms regulating antifungal resistance and tolerance relies on studies utilizing C. albicans, C. glabrataand the model yeast Saccharomyces cerevisiae. ‘Omics studies have been used to describe alterations in metabolic, genomic and transcriptomic expression profiles upon antifungal treatment of fungal cells. The physiological changes identified by these approaches could significantly affect fungal fitness in the host and survival during antifungal challenge, as well as provide further understanding of clinical resistance. Thus, this review aims to comparatively address ‘omics data for C. albicans, C. glabrata andS. cerevisiae published from 2000 to 2021 to identify what these technologies can tell us regarding cellular responses to antifungal therapy. We will also highlight possible effects on pathogen survival and identify future avenues for antifungal research.
Non-strategic detection of identity-threatening information: Epistemic validation and identity defense may share a common cognitive basis

Readers use prior knowledge to evaluate the validity of statements and detect false information without effort and strategic control. The present study expands this research by exploring whether people also non-strategically detect information that threatens their social identity. Participants (N = 77) completed a task in which they had to respond to a “True” or “False” probe after reading true, false, identity-threatening, or non-threatening sentences. Replicating previous studies, participants reacted more slowly to a positive probe (“True”) after reading false (vs. true) sentences. Notably, participants also reacted more slowly to a positive probe after reading identity-threatening (vs. non-threatening) sentences. These results provide first evidence that identity-threatening information, just as false information, is detected at a very early stage of information processing and lends support to the notion of a routine, non-strategic identity-defense mechanism.
Twelve-Month Follow-up of Early COVID-19 Cases in the United States: Cellular and Humoral Immune Longevity

Abstract We quantify antibody and memory B-cell responses to severe acute respiratory syndrome coronavirus 2 at 6 and 12 months postinfection among 7 unvaccinated US coronavirus disease 2019 cases. All had detectable S-specific memory B cells and immunoglobulin G at both time points, with geometric mean titers of 117.2 BAU/mL and 84.0 BAU/mL at 6 and 12 months, respectively.
Relationship between Personality Traits and the Inner Strengths.

BACKGROUND Zuckerman-Kuhlman-Aluja Personality questionnaire (ZKA-PQ) measures five psychobiologically based personality factors (activity, aggression, extraversion, neuroticism, and sensation seeking). The inner strength (from the ten perfections based on Theravada Buddhism) deems positive character, which includes truthfulness, perseverance, wisdom, generosity, morality (five precepts), mindfulness and meditation, patience and endurance, equanimity, determination, and loving kindness measured by the strength-based inventory (SBI). Our aim was to unfold the relationship between ZKA factors and SBI. METHODS 642 Thai (age mean = 28.27, SD = 10.61) individuals (males 26.2%, females 73.8%) filled out our questionnaire battery: (1) Zuckerman-Kuhlman-Aluja Personality questionnaire - 200 items, 20 facets, five factors: Aggressiveness, Sensation Seeking, Activity, Extraversion, Neuroticism. (Cronbach alphas: 0.88, 0.81, 0.83, 0.89, 0.91 for AG, SS, AC, EX, NEU, respectively). (2) Strength-based inventory - 10 items, measuring 10 inner strength (Cronbach alpha: 0.68). Pearson correlation, neural network modelling and person-oriented methodology (model-based clustering) were conducted for analysis. RESULTS Our correlational results revealed that inner strengths are negatively related to Aggression (r=-0.44**), Neuroticism (r=-0.43**), Sensation seeking (r=-0.16**), whereas positively related to Extraversion (r=0.37**) and Activity (r=0.24**). Highest correlations were found between AG and patience (-0.43**) and NEU and perseverance (r=-0.40**), both with negative sign. According to neural network modelling Activity was most related to Perseverance, Aggression to lack of Patience, Neuroticism to lack of Perseverance and Equanimity, Sensation Seeking to lack of Morality. Extraversion was most weakly related to inner strengths, but it was related to all other personality dimensions. Model based clustering revealed four typical personality profiles: resilients (41.8%), extraverted undercontrollers (29.0%), introverted undercontrollers (10.6%) and overcontrolled (18.6%). Results showed that resilients had highest inner strength levels, whereas overcontrolled ones had the lowest. CONCLUSION Negative traits are, as expected, conversely related with strength, while positive traits (extraversion and activity) are positively related with strength. Our results confirm that resilient personality pattern can be linked to the inner strengths measured by SBI scale, which was based on 10 Buddhist perfections. Further results should be addressed how increase in inner strength can be related to changes in biologically based personality dimensinos towards the resilient pattern.
Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort

Abstract Background Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion. Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid. Methods Multicentre (16 countries), prospective, observational study reporting incidence and frequency of clinically relevant adverse events of special interest (AESIs) among patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent. Results Among 2296 patients, the most common clinically relevant AESIs were peripheral neuropathy (26.4%), electrolyte depletion (26.0%), and hearing loss (13.2%) with an incidence per 1000 person months of treatment, 1000 person-months of treatment 21.5 (95% confidence interval [CI]: 19.8–23.2), 20.7 (95% CI: 19.1–22.4), and 9.7 (95% CI: 8.6–10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4–2.3)/1000 person-months of treatment. Patients receiving injectables (N = 925) and linezolid (N = 1826) were most likely to experience events during exposure. Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95% CI: 66.0–80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis, and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9–24.8) times/1000 patient-months of linezolid exposure. Conclusions AEs often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring and drug durations should reflect expected safety profiles of drug combinations. Clinical Trials Registration NCT03259269.
Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation

Women have higher prevalence of asthma compared with men. In asthma, allergic airway inflammation is initiated by IL-33 signaling through ST2, leading to increased IL-4, IL-5, and IL-13 production and eosinophil infiltration. Foxp3+ Tregs suppress and ST2+ Tregs promote allergic airway inflammation. Clinical studies showed that the androgen dehydroepiandrosterone (DHEA) reduced asthma symptoms in patients, and mouse studies showed that androgen receptor (AR) signaling decreased allergic airway inflammation. Yet the impact of AR signaling on lung Tregs remains unclear. Using AR-deficient and Foxp3 fate-mapping mice, we determined that AR signaling increased Treg suppression during Alternaria extract (Alt Ext; allergen) challenge by stabilizing Foxp3+ Tregs and limiting the number of ST2+ ex-Tregs and IL-13+ Th2 cells and ex-Tregs. AR signaling also decreased Alt Ext–induced ST2+ Tregs in mice by limiting expression of Gata2, a transcription factor for ST2, and by decreasing Alt Ext–induced IL-33 production from murine airway epithelial cells. We confirmed our findings in human cells where 5α-dihydrotestosterone (DHT), an androgen, decreased IL-33–induced ST2 expression in lung Tregs and decreased Alt Ext–induced IL-33 secretion in human bronchial epithelial cells. Our findings showed that AR signaling stabilized Treg suppressive function, providing a mechanism for the sex difference in asthma.
Epigenetic comparison of CHO hosts and clones reveals divergent methylation and transcription patterns across lineages

In this study, we examined DNA methylation and transcription profiles of recombinant clones derived from two different Chinese hamster ovary hosts. We found striking epigenetic differences between the clones, with global hypomethylation in the host 1 clones that produce bispecific antibody with higher productivity and complex assembly efficiency. Whereas the methylation patterns were found mostly inherited from the host, the host 1 clones exhibited continued demethylation reflected by the hypomethylation of newly emerged differential methylation regions (DMRs) even at the clone development stage. Several interconnected biological functions and pathways including cell adhesion, regulation of ion transport, and cholesterol biosynthesis were significantly altered between the clones at the RNA expression level and contained DMR in the promoter and/or gene‐body of the transcripts, suggesting epigenetic regulation. Indeed, expression changes of epigenetic regulators were observed including writers (Dnmt1, Setdb1), readers (Mecp2), and erasers (Tet3, Kdm3a, Kdm1b/5c) involved in CpG methylation, histone methylation, and heterochromatin maintenance. In addition, we identified putative transcription factors that may be readers or effectors of the epigenetic regulation in these clones. By combining transcriptomics with DNA methylation data, we identified potential processes and factors that may contribute to the variability in cell physiology between different production hosts.
Diagnostic value of calcaneal quantitative ultrasound in the evaluation of osteoporosis in middle-aged and elderly patients

Abstract To study the correlation between calcaneal quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA), and analyze the diagnostic value of calcaneal QUS in the evaluation of middle-aged and elderly osteoporosis. We assessed bone mineral density (BMD) at the femoral neck and intertrochanteric of left hip and lumbar spine (L1–L4) sites with DXA and QUS parameters of the right and left calcanei in a cohort of 82 patients over the age of 50 years. Using DXA parameters as the gold standard for the diagnosis of osteoporosis, the correlation coefficient between BMD and QUS parameters was calculated. Receiver operating characteristic curve was generated and areas under the curves were evaluated. Cut-off values for QUS were defined. In men, there was a moderate correlation between calcaneal QUS and proximal femoral BMD (P < .05), but no significant correlation between calcaneal QUS and lumbar BMD (P > .05). In women, calcaneal QUS were moderately correlated with lumbar spine and proximal femoral BMD (P < .05). Using DXA as the gold standard, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of calcaneal QUS in the diagnosis of osteoporosis were 90.2%, 89.2%, 100%, 100%, and 50.0%, respectively. According to the receiver operating characteristic curve, when the QUS T-score of calcaneum was –1.8, the area under the curve was 0.888, the sensitivity was 73.21%, and the specificity was 92.31% (P < .05). When the QUS T-score of calcaneum was –2.35, the sensitivity was 37.2% and the specificity was 100%. Calcaneal QUS can be used to predict proximal femoral BMD in middle-aged and elderly people, as well as lumbar BMD in women. As a screening method for osteoporosis, calcaneal QUS has good specificity, so it can be recommended to use it as a pre-screening tool to reduce the number of DXA screening. When the QUS T-score of calcaneum is –1.8, it has the greatest diagnostic efficiency for osteoporosis; when the QUS T-score of calcaneum is ≤–2.35, it can be diagnosed as osteoporosis.
The current state of patient-to-provider communication of childhood adversity in primary care

Supplemental Digital Content is Available in the Text. ABSTRACT Background: There is a wealth of literature focused on the task of adverse childhood experiences (ACEs) screening; however, little literature exists describing the broader process of ACE-related communication, specifically between nurse practitioners (NPs) and adult primary care patients. Consequently, there is no standardized process for communicating about ACEs in primary care and significant gaps remain related to how, when, and where these conversations occur. Objectives: To systematically examine peer-reviewed published literature from 2011 to 2021 to describe the current state of patient-to-provider communication about ACEs in primary care. Data sources: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a focused literature search for the dates January 1, 2011 through January 1, 2021 using the search engines CINAHL, PubMed, Ovid, and PsycINFO with inclusion criteria of “adverse childhood experiences,” “communication,” and “primary care” provided boundaries for this systematic review. Conclusions: Findings revealed that effective communication about childhood adversity is an integral and understated element when addressing ACE exposure among adult primary care patients. Further research focused on how primary care NPs apply the concepts of effective communication while providing clinical care to adults with histories of childhood adversity is warranted. Implications for practice: This systematic review will serve as a catalyst for informing future research, theory development, and curricular initiatives focused on enhancing communication between primary care NPs and adult patients with histories of childhood adversity. From a clinical perspective, this will illuminate opportunities to develop NP-centered approaches that emphasize identification, interpretation, documentation, and development of individual, ACE-specific interventions among adults with ACE exposure in primary care.
Smartphone Ownership and Interest in Mobile Health Smartphone Ownership and Interest in Mobile Health Technologies for Self-care Among Patients With Chronic Heart Technologies for Self-care Among Patients With Chronic Heart Failure: Cross-sectional Survey Study Failure: Cross-sectional Survey Study

Background: Heart failure (HF) is a highly prevalent chronic condition that places a substantial burden on patients, families, and health care systems worldwide. Recent advances in mobile health (mHealth) technologies offer great opportunities for supporting many aspects of HF self-care. There is a need to better understand patients’ adoption of and interest in using mHealth for self-monitoring and management of HF symptoms. Objective: The purpose of this study is to assess smartphone ownership and patient attitudes toward using mHealth technologies for HF self-care in a predominantly minority population in an urban clinical setting. Methods: We conducted a cross-sectional survey of adult outpatients (aged ≥ 18 years) at an academic outpatient HF clinic in the Midwest. The survey comprised 34 questions assessing patient demographics, ownership of smartphones and other mHealth devices, frequently used smartphone features, use of mHealth apps, and interest in using mHealth technologies for vital sign and HF symptom self-monitoring and management. Results: A total of 144 patients were approached, of which 100 (69.4%) participated in the study (63/100, 63% women). The participants had a mean age of 61.3 (SD 12.25) years Conclusions: Most patients with HF have smartphones and are interested in using commercial mHealth apps and connected health devices to self-monitor their condition. Thus, there is a great opportunity to capitalize on the high smartphone ownership among racial and ethnic minority patients to increase reach and enhance HF self-management through mHealth interventions.
An analysis of Public Health England’s vaccination data for care home workers immediately preceding a ‘Roadmap out of COVID-19 Lockdown’

Background On March 8th 2021, a Roadmap out of COVID-19 Lockdown was activated, informed by Public Health England’s (PHE) surveillance and open access reporting of infection and vaccination rates. The PHE open dataset used for the Roadmap was published on 25th February 2021, and included total number of first and second vaccinations in England and vaccination count of all older adult care home workers. Children returned to school, based on the government’s impression that vaccination rates for people in the priority levels were sufficient. Acknowledging the vulnerability of older adult care home residents to COVID19, the Scientific Advisory Group (SAGE) recommended an 80% vaccine uptake in older adult care home workers. While the rationale behind the 80% remains largely unreported, it was felt to be a critical factor in achieving the aims of the vaccination programme, namely: to open up society; to prevent healthcare from becoming overwhelmed; and to reduce severe illness. By 25th February, all older adult care home workers had been offered a first vaccination and a decision had been made to proceed with the Roadmap. An assumption could therefore be made that >80% of older adult care home workers in all regions, regardless of the infection rate, had at this point been vaccinated with at least a single vaccination. It is, however, plausible that care home workers in regions of high infection rates, particularly in the North West and Midlands, may have a vaccination rate in excess of 80%. In this commentary, we analyse the 25th February data from PHE to test these theories and explore the following questions (Q): Q1. What was the percentage first vaccine uptake by older adult care home staff across England immediately ahead of the Roadmap out of COVID-19 Lockdown? Q2. Did this consistently achieve 80% in all regions of England? Q3. Was there a difference in vaccine uptake across regions in England?
Transcranial Direct Current Stimulation Combined With or Without Caffeine: Effects on Training Volume and Pain Perception

ABSTRACT Purpose: This study aimed to investigate the acute effects of tDCS combined with caffeine intake on training volume and pain perception in the bench press in resistance-trained males. The correlation between training volume and pain perception was also assessed in all interventions. Methods: Sixteen healthy males (age = 25.2 ± 4.7 years, body mass = 82.8 ± 9.1 kg, and height = 178.3 ± 5.7 cm), advanced in RT, were randomized and counterbalanced for the following experimental conditions: Sham tDCS with placebo intake (Sham+Pla), Sham tDCS with caffeine intake (Sham+Caff), anodal tDCS with placebo intake (a-tDCS+Pla), and anodal tDCS with caffeine intake (a-tDCS+Caff). The caffeine or placebo ingestion (both with 5 mg.kg−1) occurred 40 minutes before the tDCS sessions. The tDCS was applied over the left DLPFC for 20 minutes, with a 2 mA current intensity. After the tDCS sessions, participants performed the bench press with an 80% of 1RM load, where training volume and pain perception were measured. Results: Training volume was higher in the 1st and 2nd sets in both a-tDCS+Caff and Sham+Caff conditions, compared to the Sham+Pla condition (P < .05). Both a-tDCS+Caff and a-tDCS+Pla showed an increased pain perception during the third set compared to the first set. Also, no correlation was found between the number of repetitions and pain perception in any condition (P > .05). Conclusion: This research revealed that caffeine intake alone could be used as an ergogenic aid during resistance training programs in resistance-trained males.
Blockchain Technology: Principles and Applications

This paper expounds the main principles behind blockchain technology and some of its cutting-edge applications. Firstly, we present the core concepts at the heart of the blockchain, and we discuss the potential risks and drawbacks of public distributed ledgers, and the shift toward hybrid solutions. Secondly, we expose the main features of decentralized public ledger platforms. Thirdly, we show why the blockchain is a disruptive and foundational technology, and fourthly, we sketch out a list of important applications, bearing in mind the most recent evolutions.
Smart Meter Analytics to Pinpoint Opportunities for Reducing Household Water Use

AbstractKnowledge of when, how, and by whom water is being used is crucial for planning ways to conserve drinking water. The goal of this paper is to identify groups of similar households (whom) based on their regular high-magnitude behaviors (RHMBs) of water consumption (when and how). RHMBs are frequent recurrences of high water use with regular timing. Household RHMBs are promising targets for behavior change. A two-stage data analytics approach is proposed. First, smart meter data is analyzed to identify RHMBs automatically. Second, salient features of the RHMBs are used to group households with similar behaviors. The approach is evaluated on two contrasting towns from low-rainfall regions of Australia. RHMBs accounted for 2 to 10 times more water than the traditional water efficiency target of continuous flows. For one group of 220 households, 60% of peak-hour demand was RHMBs. This paper demonstrates how RHMBs can be used to pinpoint opportunities for tailored demand management. Targets for substant.