Miracle-dz/UniFAR-FTUs huggingface dataset:
Low Cytoplasmic Magnesium Increases the Specificity of the Lon and ClpAP Proteases

The bacterium Salmonella enterica serovar Typhimurium narrows down the spectrum of substrates degraded by the proteases Lon and ClpAP in response to low cytoplasmic Mg2+, a condition that decreases protein synthesis. This control is exerted by PhoP, a transcriptional regulator activated in low cytoplasmic Mg2+ that governs proteostasis and is conserved in enteric bacteria. The uncovered mechanism enables bacteria to control the abundance of preexisting proteins. ABSTRACT Proteolysis is a fundamental property of all living cells. In the bacterium Salmonella enterica serovar Typhimurium, the HspQ protein controls the specificities of the Lon and ClpAP proteases. Upon acetylation, HspQ stops being a Lon substrate and no longer enhances proteolysis of the Lon substrate Hha. The accumulated HspQ protein binds to the protease adaptor ClpS, hindering proteolysis of ClpS-dependent substrates of ClpAP, such as Oat, a promoter of antibiotic persistence. HspQ is acetylated by the protein acetyltransferase Pat from acetyl coenzyme A (acetyl-CoA) bound to the acetyl-CoA binding protein Qad. We now report that low cytoplasmic Mg2+ promotes qad expression, which protects substrates of Lon and ClpSAP by increasing HspQ amounts. The qad promoter is activated by PhoP, a regulatory protein highly activated in low cytoplasmic Mg2+ that also represses clpS transcription. Both the qad gene and PhoP repression of the clpS promoter are necessary for antibiotic persistence. PhoP also promotes qad transcription in Escherichia coli, which shares a similar PhoP box in the qad promoter region with S. Typhimurium, Salmonella bongori, and Enterobacter cloacae. Our findings identify cytoplasmic Mg2+ and the PhoP protein as critical regulators of protease specificity in multiple enteric bacteria. IMPORTANCE The bacterium Salmonella enterica serovar Typhimurium narrows down the spectrum of substrates degraded by the proteases Lon and ClpAP in response to low cytoplasmic Mg2+, a condition that decreases protein synthesis. This control is exerted by PhoP, a transcriptional regulator activated in low cytoplasmic Mg2+ that governs proteostasis and is conserved in enteric bacteria. The uncovered mechanism enables bacteria to control the abundance of preexisting proteins.
The decomposition process and nutrient release of invasive plant litter regulated by nutrient enrichment and water level change

Wetlands are vulnerable to plant invasions and the decomposition of invasive plant litter could make impacts on the ecosystem services of wetlands including nutrient cycle and carbon sequestration. However, few studies have explored the effects of nutrient enrichment and water level change on the decomposition of invasive plant litter. In this study, we conducted a control experiment using the litterbag method to compare the decomposition rates and nutrient release in the litter of an invasive plant Alternanthera philoxeroides in three water levels and two nutrient enrichment treatments. This study found that the water level change and nutrient enrichment showed significant effects on the litter decomposition and nutrient dynamic of A. philoxeroides. The increase of water level significantly reduced the decomposition rate and nutrient release of litter in the nutrient control treatment, whereas no clear relationship was observed in the nutrient enrichment treatment, indicating that the effect of water level change on litter decomposition might be affected by nutrient enrichment. At the late stage of decomposition, the increase of phosphorus (P) concentration and the decrease of the ratio of carbon to P suggested that the decomposition of invasive plant litter was limited by P. Our results suggest that controlling P enrichment in water bodies is essential for the management of invasive plant and carbon sequestration of wetlands. In addition, the new index we proposed could provide a basis for quantifying the impact of invasive plant litter decomposition on carbon cycle in wetlands.
Clinicians’ experiences of inquiries following mental health related homicide: a qualitative study

Objectives: This aim of this qualitative study was to explore the experiences of clinicians involved with inquiries into the mental health care of patients who were perpetrators of homicide in New Zealand. Methods: Our purposive sample comprised ten clinicians working in New Zealand district health board mental health services. These clinicians were individually interviewed. Interviews were audio-recorded, transcribed and thematically analysed. The coding framework was checked and peer reviewed by an independent researcher. Results: Five themes were identified: the inquiry process; emotional burden; impact on team dynamics; changes to individual clinical practice; and perceptions of inquiries being influenced by organisational culture. Clinicians involved with inquiries reported significant anxiety and disrupted multidisciplinary team dynamics. Some participants found inquiries led to changes to their clinical practice and perceived that a punitive organisational culture limited learning. Conclusions: Clinicians perceived inquiries as threatening, anxiety provoking and primarily concerned with protecting organisational interests. Communication of the inquiry process and ensuring inquiry findings are disseminated may enhance clinicians’ experiences of inquiries and facilitate their participation and their reflection on changes to clinical practice that could contribute to improving services. Support for clinicians and multidisciplinary teams should be emphasised by the commissioning agency.
Locus-Specific Characterization of Human Endogenous Retrovirus Expression in Prostate, Breast, and Colon Cancers

Expressed human endogenous retroviruses are mapped at locus-specific resolution and linked to specific pathways to identify potential biomarkers and therapeutic targets in prostate, breast, and colon cancers. Human endogenous retroviruses (HERV) have been implicated in a variety of diseases including cancers. Recent research implicates HERVs in epigenetic gene regulation. Here we utilize a recently developed bioinformatics tool for identifying HERV expression at the locus-specific level to identify differential expression of HERVs in matched tumor-normal RNA-sequencing (RNA-seq) data from The Cancer Genome Atlas. Data from 52 prostate cancer, 111 breast cancer, and 24 colon cancer cases were analyzed. Locus-specific analysis identified active HERV elements and differentially expressed HERVs in prostate cancer, breast cancer, and colon cancer. In addition, differentially expressed host genes were identified across prostate, breast, and colon cancer datasets, respectively, including several involved in demethylation and antiviral response pathways, supporting previous findings regarding the pathogenic mechanisms of HERVs. A majority of differentially expressed HERVs intersected protein coding genes or lncRNAs in each dataset, and a subset of differentially expressed HERVs intersected differentially expressed genes in prostate, breast, and colon cancers, providing evidence towards regulatory function. Finally, patterns in HERV expression were identified in multiple cancer types, with 155 HERVs differentially expressed in all three cancer types. This analysis extends previous results identifying HERV transcription in cancer RNA-seq datasets to a locus-specific level, and in doing so provides a foundation for future studies investigating the functional role of HERV in cancers and identifies a number of novel targets for cancer biomarkers and immunotherapy. Significance: Expressed human endogenous retroviruses are mapped at locus-specific resolution and linked to specific pathways to identify potential biomarkers and therapeutic targets in prostate, breast, and colon cancers.
Effect of education on the readiness levels of primigravida women to hygienic care practices of the newborn with the use of QR code

Abstract The researcers planned this study to determine the effect of the education on the hygienic care of the newborn with the use of QR Code on readiness levels of primigravida women to hygienic care practices of the newborn. A total of 68 primigravida women constituted of this interventional study. After the intervention group completed their education on newborn care, mobile application and QR codes were introduced to the pregnant women. The control group received routine newborn care training. It was observed that the education of hygienic care to the newborn, which was provided to pregnant women with the use of QR Code, was effective on their readiness to care. Pediatric nurses can provide QR code supported training to prepare pregnant women for the hygienic care of the newborn.
Dialyzer Performance During Hemodialysis Without Systemic Anticoagulation Using a Heparin-Grafted Dialyzer Combined With a Citrate-Enriched Dialysate: Results of the Randomized Crossover Noninferiority EVOCIT Study.

RATIONALE AND OBJECTIVE The EVOCIT study was designed to evaluate dialyzer performance during hemodialysis with and without systemic anticoagulation. STUDY DESIGN Randomized, crossover, non-inferiority trial. Noninferiority was defined as a difference of ≤10% for the primary outcome. SETTING AND PARTICIPANTS Single hemodialysis center; 26 prevalent patients treated with 617 hemodialysis sessions. INTERVENTIONS Hemodialysis using a heparin-grafted dialyzer combined with a 1.0 mmol/L citrate-enriched dialysate ("Evocit") without systemic anticoagulation was compared to hemodialysis performed with a heparin-grafted dialyzer with systemic heparin ("Evohep"). Patients were randomly allocated to a first period of 4 weeks and crossed over to the alternative strategy for a second period of 4 weeks. OUTCOMES The primary end point was the difference in Kt/Vurea between Evocit and Evohep. Secondary end points were urea reduction ratio (RR), middle molecule removal, treatment time, thrombin generation and reduction in dialyzer blood compartment volume. RESULTS The estimated difference in Kt/Vurea between Evocit and Evohep was -0.03 (95%CI, -0.06 to -0.007) establishing non-inferiority with mean Kt/Vurea of 1.47±0.05 (SE) for Evocit and 1.50±0.05 for Evohep. Non-inferiority was also established for urea RR and beta-2 microglobulin RR. Premature discontinuation of dialysis was required for 4.2% of sessions among 6 patients during Evocit and no sessions during Evohep. Effective treatment time was 236±5 minutes for Evocit and 238±1 minutes for Evohep. Thrombin generation was increased, and there was greater reduction in dialyzer blood compartment volume after treatments with Evocit compared with Evohep. LIMITATIONS The effects of avoiding systemic anticoagulation on clinical outcomes were not evaluated. CONCLUSIONS Evocit is non-inferior to Evohep with respect to solute clearance but results in a greater number of shortened treatments, more membrane clotting and greater thrombin generation.
COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters

SARS-CoV-2 infects the olfactory epithelium of hamsters and humans and persists in it in individuals with COVID-19 for several months after infection. Sticking the nose into COVID-19 Patients with COVID-19 can develop loss of smell and/or taste. Unfortunately, the pathophysiology of these alterations remains unclear. Here, de Melo et al. examined the olfactory mucosa in patients with COVID-19 reporting loss of smell and detected SARS-CoV-2 viral particles and inflammation in multiple cell types in the olfactory neuroepithelium, including olfactory sensory neurons. Hamster infected with SARS-CoV-2 developed loss of smell that was associated with dissemination of the virus in the olfactory mucosa and CNS and with neuroinflammation. In four patients who developed persistent loss of smell, the authors detected lasting SARS-CoV-2 presence in the olfactory mucosa, suggesting that the prolonged relapsing anosmia in patients with COVID-19 could be due to persistent viral infection. Whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung pathogenesis, the pathophysiology of neurological disorders in coronavirus disease 2019 (COVID-19) remains poorly understood. Olfactory and taste dysfunction are common in COVID-19, especially in mildly symptomatic patients. Here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patients with COVID-19 presenting with acute loss of smell. We report evidence that the olfactory neuroepithelium is a major site of SARS-CoV2 infection with multiple cell types, including olfactory sensory neurons, support cells, and immune cells, becoming infected. SARS-CoV-2 replication in the olfactory neuroepithelium was associated with local inflammation. Furthermore, we showed that SARS-CoV-2 induced acute anosmia and ageusia in golden Syrian hamsters, lasting as long as the virus remained in the olfactory epithelium and the olfactory bulb. Last, olfactory mucosa sampling from patients showing long-term persistence of COVID-19–associated anosmia revealed the presence of virus transcripts and of SARS-CoV-2–infected cells, together with protracted inflammation. SARS-CoV-2 persistence and associated inflammation in the olfactory neuroepithelium may account for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management of this disease.
Retrospective Detection of SARS-CoV-2 in Symptomatic Patients prior to Widespread Diagnostic Testing in Southern California

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused one of the worst pandemics in recent history. Few reports have revealed that SARS-CoV-2 was spreading in the United States as early as the end of January. In this study, we aimed to determine if SARS-CoV-2 had been circulating in the Los Angeles (LA) area at a time when access to diagnostic testing for coronavirus disease 2019 (COVID-19) was severely limited. Methods We used a pooling strategy to look for SARS-CoV-2 in remnant respiratory samples submitted for regular respiratory pathogen testing from symptomatic patients from November 2019 to early March 2020. We then performed sequencing on the positive samples. Results We detected SARS-CoV-2 in 7 specimens from 6 patients, dating back to mid-January. The earliest positive patient, with a sample collected on January 13, 2020 had no relevant travel history but did have a sibling with similar symptoms. Sequencing of these SARS-CoV-2 genomes revealed that the virus was introduced into the LA area from both domestic and international sources as early as January. Conclusions We present strong evidence of community spread of SARS-CoV-2 in the LA area well before widespread diagnostic testing was being performed in early 2020. These genomic data demonstrate that SARS-CoV-2 was being introduced into Los Angeles County from both international and domestic sources in January 2020.
Young adults suffering from mental illness: Evaluation of the family-centred support conversation intervention from the perspective of mental healthcare professionals.

AIMS AND OBJECTIVES To explore how mental healthcare professionals' experience and evaluate the use of Family-Centred Support Conversation Intervention. BACKGROUND Mental health professionals working in the community mental health service provide treatment, care and support to young adults suffering from mental illness. Young adults suffering from mental illness are dependent on other family members and live close to the family. The Family-Centred Support Conversation promotes healing and alleviates the suffering of the family. DESIGN AND METHODS A qualitative explorative design was used. Individual interviews with health professionals (n = 13) were conducted in Norway and analysed using a phenomenographic approach. The COREQ checklist was used. RESULTS Three descriptive categories emerged: A new tool in the toolbox, the family as a conversational partner and Implementing the intervention, with seven conceptions. The mental health professionals had no previous routine for family support. The conversations helped them to structure the involvement of family members. Having the family as a conversational partner together with the patients was considered both somewhat new and rewarding but also challenging. The mental health professionals described a need to adjust the intervention. CONCLUSIONS The Family-Centred Support Conversation was described as a complement to care, as usual, structuring the involvement of families. The knowledge exchange between the families and the mental health professionals may create a context of changing beliefs, strengths and resources. RELEVANCE TO CLINICAL PRACTICE Clinical practice is challenged to work on establishing a mindset; whereby, the family is regarded as a resource with important skills and life experience. The family should be offered individualised support and follow-up, and FCSC may be a relevant intervention.
Tempering hope with Intimate Knowledge: Contrasting emergences of the concept 'uninfectious' in HIV.

In this paper, we contrast two emergences of the concept of 'uninfectious' (that pharmaceuticals can render someone living with HIV non-infectious) in HIV. First, using Novas' framing of 'political economies of hope', we describe the deployment of 'uninfectious' as part of global health campaigns. Second, we draw on Raffles' (International Social Science Journal, 2002, 54, 325) concept of 'intimate knowledge' to theorise our own account of 'uninfectious' through a re-analysis of qualitative data comprising the intimate experiences of people living with or around HIV collected at various points over the last 25 years. Framed as intimate knowledge, 'uninfectious' becomes known through people's multiple engagements with and developing understandings of HIV over a prolonged period. As contingent and specific, intimate knowledge does not register within the biomedical/scientific ontological system that underpins discourses of hope employed in global campaigns. The concept of intimate knowledge offers the potential to critique discourses of hope in biomedicine problematising claims to universality whilst enriching biomedical understandings with accounts of affective, embodied experience. Intimate knowledge may also provide a bridge between different epistemological traditions in the sociology of health and illness.
Women’s experiences of cultural and traditional health beliefs about pregnancy and childbirth in Zambia: An ethnographic study

Abstract Zambian women's pregnancy and childbirth are linked to a variety of cultural and traditional practices, activities and beliefs. These existential events affect the women's health and the newborn's care. In this study we used an interpretative ethnographic design. Individual deep interviews with eight Zambian women were carried out. The formation of family, pregnancy and childbirth are important for strengthening generational traditions and preserving culture. Having many children is especially important for Zambian men as it increases their status in the society. Family continuity is related to the legacy of generations through the spirits of the ancestors.
Dynamic risk allows us to adequately select patients with differentiated thyroid cancer who do not require radioiodine treatment.

Objective The treatment of patients with differentiated thyroid cancer (DTC) was modified in the last decade towards a more individualized approach according to the risk of recurrence (RR). We compared the outcomes of patients with low and intermediate RR (LRR and IRR) who received or did not receive radioiodine remnant ablation (RRA) after assessing the dynamic risk. Methods We included 307 DTC patients with LRR and IRR submitted to total thyroidectomy. All patients were reclassified according to the dynamic risk stratification (low or high). Patients with high dynamic risk received RRA (141 patients). Results LRR patients who received RRA presented a frequency of structural incomplete response (SIR) of 5% at the end of the follow-up, compared to 2% in those who did not receive it (p=0.353). IRR patients treated with RRA had a frequency of SIR of 22%, compared to 5% in patients without RRA (p=0.008). Conclusion This study demonstrates the usefulness of dynamic risk assessment to decide RRA in a cohort with a long-term follow-up. The lower prevalence of SIR at the end of the follow-up in patients who did not receive RRA highlights the adequate selection of those who would not benefit from RRA, even with an intermediate risk of recurrence.
Enhancement of endothelialization by topographical features is mediated by PTP1B-dependent endothelial adherens junctions remodeling

Rationale Failure of small synthetic vascular grafts is largely due to late endothelialization and has been an ongoing challenge in the treatment of cardiovascular diseases. Objective Previous strategies developed to promote graft endothelialization include surface topographical modulation and biochemical modifications. However, these have been met with limited success. Importantly, although the integrity of Endothelial Cell (EC) monolayer is crucial for endothelialization, the crosstalk between surface topography and cell-cell connectivity is still not well understood. Here we explored a combined strategy that utilizes both topographical features and pharmacological perturbations. Methods and result We characterized EC behaviors in response to micron-scale grating topography in conjunction with pharmacological perturbations of endothelial adherens junctions (EAJ) regulators. We studied the EA.hy 926 cell-cell junctions and monolayer integrity using the junctional markers upon the inhibitory effect of EAJ regulator on both planar and grating topographies substrates. We identified a protein tyrosine phosphatase, PTP1B, as a potent regulator of EAJ stability. Next, we studied the physiologically relevant behaviors of EC using primary human coronary arterial endothelial cells (HCAEC). Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration to promote endothelialization. Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration and proliferation. Conclusion The synergistic effect of PTP1B inhibition and grating topographies could be useful for the promotion of endothelialization by enhancing EC migration and proliferation.