Miracle-dz/UniFAR-FTUs huggingface dataset:
A systematic review of policy and clinical guidelines on positive risk management

Abstract Background National policies and guidelines advocate that mental health practitioners employ positive risk management in clinical practice. However, there is currently a lack of clear guidance and definitions around this technique. Policy reviews can clarify complex issues by qualitatively synthesising common themes in the literature. Aims To review and thematically analyse national policy and guidelines on positive risk management to understand how it is conceptualised and defined. Method The authors completed a systematic review (PROSPERO: CRD42019122322) of grey literature databases (NICE, NHS England, UK Government) to identify policies and guidelines published between 1980 and April 2019. They analysed the results using thematic analysis. Results The authors screened 4999 documents, identifying 7 eligible policies and 19 guidelines. Qualitative synthesis resulted in three main themes: i) the conflicting aims of positive risk management; ii) conditional positive risk management; and iii) responsible positive risk management. Conclusions Analysis highlighted discrepancies and tensions in the conceptualisation of positive risk management both within and between policies. Documents described positive risk management in different and contradictory terms, making it challenging to identify what it is, when it should be employed, and by whom. Five policies offered only very limited definitions of positive risk management.
Integrated sensing of host stresses by inhibition of a cytoplasmic two-component system controls M. tuberculosis acute lung infection

Bacterial pathogens that infect phagocytic cells must deploy mechanisms that sense and neutralize host microbicidal effectors. For Mycobacterium tuberculosis, the causative agent of tuberculosis, these mechanisms allow the bacterium to rapidly adapt from aerosol transmission to initial growth in the lung alveolar macrophage. Here, we identify a branched signaling circuit in M. tuberculosis that controls growth in the lung through integrated direct sensing of copper ions and nitric oxide by coupled activity of the Rip1 intramembrane protease and the PdtaS/R two-component system. This circuit uses a two-signal mechanism to inactivate the PdtaS/PdtaR two-component system, which constitutively represses virulence gene expression. Cu and NO inhibit the PdtaS sensor kinase through a dicysteine motif in the N-terminal GAF domain. The NO arm of the pathway is further controlled by sequestration of the PdtaR RNA binding response regulator by an NO-induced small RNA, controlled by the Rip1 intramembrane protease. This coupled Rip1/PdtaS/PdtaR circuit controls NO resistance and acute lung infection in mice by relieving PdtaS/R-mediated repression of isonitrile chalkophore biosynthesis. These studies identify an integrated mechanism by which M. tuberculosis senses and resists macrophage chemical effectors to achieve pathogenesis
Ligustrum Robustum Alleviates Atherosclerosis by Decreasing Serum TMAO, Modulating Gut Microbiota and Decreasing Bile acid and Cholesterol Absorption in Mice.

SCOPE Atherosclerosis (AS) is closely related to gut microbiota. Our previous studies demonstrated that Ligustrum robustum (LR), a flavonoid-rich tea like plant, could mitigate several AS-related risk factors and modulate gut microbiota in animal models and human subjects. But its anti-AS effect and mechanisms remain unclear. Therefore, in this study, we investigated impacts of LR on AS development and explored the potential underlying mechanisms in C57BL/6J and Apoe-/- mice. METHODS AND RESULTS Female C57BL/6J and Apoe-/ - mice were fed a chow diet or high-choline diet, supplemented with vehicle (water) or LR water extract (700 mg/kg) by gavage for 17 weeks. We found that LR attenuated diet-induced AS by reducing serum trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) levels likely by modulating gut microbiota. Moreover, LR increased the abundance of the genus Bifidobacterium, which generated bile salt hydrolase, and thus presumably enhanced bile acid (BA) deconjugation and increased fecal BA excretion. Meanwhile, LR increased fecal cholesterol excretion, decreased the levels of serum and hepatic cholesterol, but did not affect short-chain fatty acids (SCFAs) in feces. CONCLUSION LR attenuated AS development presumably by decreasing serum TMAO levels and increasing fecal BA excretion likely via gut microbial modulation. These effects were accompanied by increases in fecal cholesterol excretion, decreases in serum and hepatic cholesterol. This article is protected by copyright. All rights reserved.
Implantable Peripheral Nerve Stimulation for Trigeminal Neuropathic Pain: A Systematic Review and Meta‐Analysis

Implantable peripheral nerve stimulation has been increasingly used to treat neuropathic pain. This neuromodulation strategy may be an alternative option for intractable trigeminal neuropathic pain; however, evidence for this treatment approach remains limited. A systematic review was conducted to identify studies of patients that underwent peripheral nerve stimulation implantation for trigeminal neuropathic pain.
Impact of the COVID-19 pandemic and related control measures on cancer diagnosis in Catalonia: a time-series analysis of primary care electronic health records covering about five million people

Objective Cancer care has been disrupted by the response of health systems to the COVID-19 pandemic, especially during lockdowns. The objective of our study is to evaluate the impact of the pandemic on the incidence of cancer diagnoses in primary care. Design Time-series study of malignant neoplasms and diagnostic procedures, using data from the primary care electronic health records from January 2014 to September 2020. Setting Primary care, Catalonia, Spain. Participants People older than 14 years and assigned in one of the primary care practices of the Catalan Institute of Health with a new diagnosis of malignant neoplasm. Main outcome measures We obtained the monthly expected incidence of malignant neoplasms using a temporary regression, where the response variable was the incidence of cancer from 2014 to 2018 and the adjustment variables were the trend and seasonality of the time series. Excess or lack of malignant neoplasms was defined as the number of observed minus expected cases, globally and stratified by sex, age, type of cancer and socioeconomic status. Results Between March and September 2020 we observed 8766 (95% CI 4135 to 13 397) fewer malignant neoplasm diagnoses, representing a reduction of 34% (95% CI 19.5% to 44.1%) compared with the expected. This underdiagnosis was greater in individuals aged older than 64 years, men and in some types of cancers (skin, colorectal, prostate). Although the reduction was predominantly focused during the lockdown, expected figures have not yet been reached (40.5% reduction during the lockdown and 24.3% reduction after that). Conclusions Reduction in cancer incidence has been observed during and after the lockdown. Urgent policy interventions are necessary to mitigate the indirect effects of the COVID-19 pandemic and related control measures on other diseases and some strategies must be designed in order to reduce the underdiagnosis of cancer.
Transgelin-2 and phosphoregulation of the LIC2 subunit of dynein govern mitotic spindle orientation

ABSTRACT The molecular motor dynein is essential for mitotic spindle orientation, which defines the axis of cell division. The light intermediate chain subunits, LIC1 and LIC2, define biochemically and functionally distinct vertebrate dynein complexes, with LIC2-dynein playing a crucial role in ensuring spindle orientation. We reveal a novel, mitosis-specific interaction of LIC2-dynein with the cortical actin-bundling protein transgelin-2. Transgelin-2 is required for maintaining proper spindle length, equatorial metaphase chromosome alignment, spindle orientation and timely anaphase onset. We show that transgelin-2 stabilizes the cortical recruitment of LGN-NuMA, which together with dynein is required for spindle orientation. The opposing actions of transgelin-2 and LIC2-dynein maintain optimal cortical levels of LGN-NuMA. In addition, we show that the highly conserved serine 194 phosphorylation of LIC2 is required for proper spindle orientation, by maintaining mitotic centrosome integrity to ensure optimal astral microtubule nucleation. The work reveals two specific mechanisms through which LIC2-dynein regulates mitotic spindle orientation; namely, through a new interactor transgelin-2, which is required for engagement of LGN-NuMA with the actin cortex, and through mitotic phosphoregulation of LIC2 to control microtubule nucleation from the poles. This article has an associated First Person interview with the first author of the paper. Summary: The dynein motor regulates mitotic spindle orientation through two novel mechanisms: through the cortical interactor transgelin-2 and through mitotic phosphoregulation of the dynein motor itself.
Hypertonic saline for goal-directed therapy guided by Capstesia in gastrointestinal surgery: a randomized controlled study

Background Goal-directed fluid therapy (GDT) aims to increase stroke volume and cardiac output and improve gut perfusion. Hypertonic saline (HS) can restore the macro-and micro-circulation, increase myocardial contractility, and reduce tissue edema. Therefore, we aimed to investigate the efficacy of intraoperative HS administration in GDT during gastrointestinal (GI) surgery. Methods Forty patients who underwent GI surgery under general anesthesia were enrolled in this randomized controlled study. Patients received boluses of either lactated Ringer’s (LR) solution, or 3% HS solution guided by an algorithm dependent on a smartphone application for estimations of pulse pressure variation (PPV). The primary outcome was the total amount of administered intraoperative crystalloid fluids in both groups. Serum sodium and time to first bowel movement after surgery were also recorded. Results In the HS group, patients received 1262.50 ± 318.25 mL of crystalloids compared to 2667.50 ± 670.29 mL received by patients in the LR group (P < 0.001). The mean time of first bowel movement in hours was 44.40 (± 14.09) in the HS group compared to 55.80 (± 18.38) in the LR group, but the P-value was > 0.05. Conclusions The use of HS solution for GDT in GI surgery resulted in a beneficial reduction in positive fluid balance and possibly earlier resumption of bowel movements.
Fe-S coordination defects in the replicative DNA polymerase delta cause deleterious DNA replication in vivo and subsequent DNA damage in the yeast Saccharomyces cerevisiae

Abstract B-type eukaryotic polymerases contain a [4Fe-4S] cluster in their C-terminus domain, whose role is not fully understood yet. Among them, DNA polymerase delta (Polδ) plays an essential role in chromosomal DNA replication, mostly during lagging strand synthesis. Previous in vitro work suggested that the Fe-S cluster in Polδ is required for efficient binding of the Pol31 subunit, ensuring stability of the Polδ complex. Here, we analyzed the in vivo consequences resulting from an impaired coordination of the Fe-S cluster in Polδ. We show that a single substitution of the very last cysteine coordinating the cluster by a serine is responsible for the generation of massive DNA damage during S phase, leading to checkpoint activation, requirement of homologous recombination for repair, and ultimately to cell death when the repair capacities of the cells are overwhelmed. These data indicate that impaired Fe-S cluster coordination in Polδ is responsible for aberrant replication. More generally, Fe-S in Polδ may be compromised by various stress including anti-cancer drugs. Possible in vivo Polδ Fe-S cluster oxidation and collapse may thus occur, and we speculate this could contribute to induced genomic instability and cell death, comparable to that observed in pol3-13 cells.
Decoupling the bridge helix of Cas12a results in a reduced trimming activity, increased mismatch sensitivity and impaired conformational transitions

Abstract The widespread and versatile prokaryotic CRISPR–Cas systems (clustered regularly interspaced short palindromic repeats and associated Cas proteins) constitute powerful weapons against foreign nucleic acids. Recently, the single-effector nuclease Cas12a that belongs to the type V CRISPR–Cas system was added to the Cas enzymes repertoire employed for gene editing purposes. Cas12a is a bilobal enzyme composed of the REC and Nuc lobe connected by the wedge, REC1 domain and bridge helix (BH). We generated BH variants and integrated biochemical and single-molecule FRET (smFRET) studies to elucidate the role of the BH for the enzymatic activity and conformational flexibility of Francisella novicida Cas12a. We demonstrate that the BH impacts the trimming activity and mismatch sensitivity of Cas12a resulting in Cas12a variants with improved cleavage accuracy. smFRET measurements reveal the hitherto unknown open and closed state of apo Cas12a. BH variants preferentially adopt the open state. Transition to the closed state of the Cas12a-crRNA complex is inefficient in BH variants but the semi-closed state of the ternary complex can be adopted even if the BH is deleted in its entirety. Taken together, these insights reveal that the BH is a structural element that influences the catalytic activity and impacts conformational transitions of FnCas12a.
Residual cardiovascular risk reduction guided by lifetime benefit estimation in patients with symptomatic atherosclerotic disease: effectiveness and cost-effectiveness.

AIMS To determine the (cost)-effectiveness of blood pressure lowering, lipid-lowering, and antithrombotic therapy guided by predicted lifetime benefit compared to risk factor levels in patients with symptomatic atherosclerotic disease. METHODS AND RESULTS For all patients with symptomatic atherosclerotic disease in the UCC-SMART cohort (1996-2018; n = 7697) two treatment strategies were compared. The lifetime benefit-guided strategy was based on individual estimation of gain in cardiovascular disease (CVD)-free life with the SMART-REACH model. In the risk factor-based strategy, all patients were treated the following: low-density lipoprotein cholesterol (LDL-c) < 1.8 mmol/L, systolic blood pressure <140 mmHg, and antithrombotic medication. Outcomes were evaluated for the total cohort using a microsimulation model. Effectiveness was evaluated as total gain in CVD-free life and events avoided, cost-effectiveness as incremental cost-effectivity ratio (ICER). In comparison to baseline treatment, treatment according to lifetime benefit would lead to an increase of 24 243 CVD-free life years [95% confidence interval (CI) 19 980-29 909] and would avoid 940 (95% CI 742-1140) events in the next 10 years. For risk-factor based treatment, this would be an increase of 18 564 CVD-free life years (95% CI 14 225-20 456) and decrease of 857 (95% CI 661-1057) events. The ICER of lifetime benefit-based treatment with a treatment threshold of ≥1 year additional CVD-free life per therapy was €15 092/QALY gained and of risk factor-based treatment €9933/QALY gained. In a direct comparison, lifetime benefit-based treatment compared to risk factor-based treatment results in 1871 additional QALYs for the price of €36 538/QALY gained. CONCLUSION Residual risk reduction guided by lifetime benefit estimation results in more CVD-free life years and more CVD events avoided compared to the conventional risk factor-based strategy. Lifetime benefit-based treatment is an effective and potentially cost-effective strategy for reducing residual CVD risk in patients with clinical manifest vascular disease.
Inter‐Individual versus Inter‐Population Variability of Calendula suffruticosa subsp. algarbiensis Hexane Extracts

Calendula suffruticosa subsp. algarbiensis (Boiss.) Nyman is very common on the Portuguese coast, but it has only recently begun to be studied chemically and belongs to a genus of difficult taxonomic classification. To improve the knowledge on the chemical variability of this taxon and evaluate the possible use of this tool for taxonomical purposes, the aim of this work was to determine the extent of chemical variation between individuals collected in the same geographic region, and to compare with samples mixing fragments of several individuals each (populations) from different local environments. Overall, hexane extract analysis by GC/MS allowed to identify 42 compounds, eight fatty acids, 24 terpenoids, three alcohols, five alkanes, and two pollutants. Greater chemical differences were found between individuals, grown in the same region, than were found between population samples from different regions. Additionally, 25 phytochemicals were identified for this taxon for the first time and may be used for taxonomic classification, even to distinguish between subspecies of C. suffruticosa. Furthermore, plants collected near urban areas accumulated pollutants, indicating the importance of controlling local environmental conditions when C. suffruticosa cultivation is for human consumption.
Safety and Efficacy of Nano‐Pulse Stimulation Treatment of Non‐Genital, Cutaneous Warts (Verrucae)

This study describes the effects of nano‐pulse stimulation (NPS) technology on the common verruca with the objectives of demonstrating efficacy and safety. NPS technology applies nanosecond pulses of non‐thermal electrical energy to induce highly localized regulated cell death in the cellular structures of the targeted zone with negligible effects on surrounding non‐cellular structures. Previous clinical studies applying NPS to common, benign skin lesions have demonstrated safety and efficacy in clearing seborrheic keratoses and sebaceous hyperplasia.
Changes of epicardial fat thickness after laparoscopic sleeve gastrectomy: a prospective study

Abstract Purpose Epicardial fat thickness is an interesting parameter of early atherosclerosis. We prospectively assessed whether weight loss following laparoscopic sleeve gastrectomy (LSG) leads to a significant reduction in the epicardial fat thickness (EFT) and the correlation between the decline in the epicardial fat thickness with other clinical parameters. Methods A prospective analysis of 98 cases that were scheduled to undergo LSG and followed up for 12 months was conducted. EFT was assessed using two-dimensional (2 D) echocardiography. Results A total of 98 cases and 70 controls were enrolled. EFT demonstrated a significant reduction at follow-up in the whole group (median 8.9 (1.95) versus 7.65 (1.67) mm, respectively). The degree of reduction was higher in the LSG cohort compared to control cohort 1.3 (0.4) versus 1 (0.4), respectively; p < . 001). The univariate regression analysis demonstrated a notable correlation of the EFT with the weight, body mass index (BMI), fasting blood glucose (FBG), and creatinine with a p-value of <. 0001, . 001, . 022, and . 018, respectively while the multivariate analysis showed a strong correlation between EFT and weight and creatinine with a p-value of <. 0001 and . 033 respectively. Conclusion LSG can have a favourable impact on metabolic syndrome aspects, namely EFT, as it can decrease it considerably.
O Teste do Degrau de Seis Minutos como Preditor de Capacidade Funcional de Acordo com o Consumo de Oxigênio de Pico em Pacientes Cardíacos

Resumo Fundamento: O teste do degrau de seis minutos (TD6) é uma forma simples de avaliar a capacidade funcional, embora tenha sido pouco estudado em pacientes com doença arterial coronariana (DAC) ou insuficiência cardíaca (IC). Objetivo: Analisar a associação entre o TD6 e o consumo de oxigênio de pico (VO2pico) e desenvolver uma equação que estime o VO2pico com base no TD6, bem como determinar um ponto de corte para o TD6 que preveja um VO2pico ≥ 20 mL.kg-1.min-1 Métodos: Nos 171 pacientes submetidos ao TD6 e a um teste de exercício cardiopulmonar, análises da curva ROC, de regressão e de correlação foram usadas, e um p < 0,05 foi admitido como significativo. Resultados: A idade média foi 60±14 anos, e 74% eram do sexo masculino. A média da fração de ejeção ventricular esquerda foi 57±16%; 74% apresentavam DAC, e 28%, IC. A média do VO2pico foi 19±6 mL.kg-1.min-1, e o desempenho médio do TD6 foi 87±45 passos. A associação entre o TD6 e o VO2pico foi r 0,69 (p < 0,001). Os modelos VO2pico = 19,6 + (0,075 x TD6) – (0,10 x idade) para homens e VO2pico = 19,6 + (0,075 x TD6) – (0,10 x idade) – 2 para mulheres poderiam prever o VO2pico com base nos resultados do TD6 (R ajustado 0,72; R2 ajustado 0,53). O ponto de corte mais acurado para que o TD6 preveja um VO2pico ≥ 20 mL.kg-1.min-1 foi de > 105 passos [área sob a curva 0,85; intervalo de confiança de 95% 0,79 - 0,90; p < 0,001]. Conclusão: Uma equação que preveja o VO2pico com base nos resultados do TD6 foi derivada, e foi encontrada uma associação significativa entre o TD6 e o VO2pico. O ponto de corte do TD6, que prevê um VO2pico ≥ 20 mL.kg-1.min-1, foi > 105 passos. (Arq Bras Cardiol. 2021; 116(5):889-895)
Use of Motor Learning Strategies in Occupational Therapy for Children and Youth with Acquired Brain Injury

Abstract Motor learning strategies (MLS) can be used to promote motor skills acquisition in children and youth with acquired brain injury (ABI). While occupational therapists (OTs) likely use MLS in clinical practice, research has not investigated the extent and variety of their application. Aims: This study explored MLS use by OTs in pediatric ABI and factors influencing their application. Method: Individual video-recorded occupational therapy sessions for a sample of eight children/youth (ages 4-16) with ABI were evaluated via mixed methods approach. The Motor Learning Strategies Rating Instrument (MLSRI-22) quantified the extent of MLS use in each video. Directed content analysis of the videos explored the factors influencing how and when MLS were applied. Results: The most frequently used MLS were promoting problem solving, encouragement, directing attention to the body, permitting errors as part of learning, repetitive practice, and whole practice. Three themes described how and when the OTs used MLS: 1) Getting buy-in, 2) Going with the flow, and 3) Movement and thinking go hand-in-hand. Conclusions: The OTs frequently used MLS with children with ABI, appearing to select MLS based on factors related to the child, task, and environment. These findings are fundamental to future exploration of OT decision-making and evaluation of MLS effectiveness.