Miracle-dz/UniFAR-FTUs huggingface dataset:
A Linear and Non-Linear Mendelian Randomization Analysis of the Association Between Diastolic Blood Pressure and Cardiovascular Events: The J Curve Revisited.

Background: Recent clinical guidelines support intensive blood pressure (BP) treatment targets. However, observational data suggest that excessive diastolic BP (DBP) lowering might increase the risk of myocardial infarction (MI); reflecting a J- or U-shaped relationship. Methods: We analyzed 47,407 participants from 5 cohorts (median age 60 years). First, to corroborate prior observational analyses, we used traditional statistical methods to test the shape of association between DBP and CVD. Second, we created polygenic risk scores (PRS) of DBP and SBP and generated linear Mendelian randomization (MR) estimates for the effect of DBP on CVD. Third, using novel non-linear MR approaches, we evaluated for non-linearity in the genetic relationship between DBP and CVD. Comprehensive MR interrogation of DBP required us to also model SBP, given the two are strongly correlated. Results: Traditional observational analysis of our cohorts suggested a J-shaped association between DBP and MI. By contrast, linear MR analyses demonstrated an adverse effect of increasing DBP increments on CVD outcomes, including MI (MI Hazard ratio = 1.07 per unit mmHg increase in DBP, p<0.001). Furthermore, non-linear MR analyses found no evidence for a J-shaped relationship, instead confirming that MI risk decreases consistently per unit decrease in DBP, even among individuals with low values of baseline DBP. Conclusions: In this analysis of the genetic effect of DBP, we found no evidence for a non-linear J- or U-shaped relationship between DBP and adverse CVD outcomes; including MI.
COVID-19 severity in kidney transplant recipients is similar to nontransplant patients with similar comorbidities

Higher rates of severe COVID‐19 have been reported in kidney transplant recipients (KTRs) compared to nontransplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score‐matching method to compare survival and severe disease‐free survival (defined as death and/or need for intensive care unit [ICU]) incidence in hospitalized KTRs and nontransplant control patients between February 26 and May 22, 2020. Patients were matched for risk factors of severe COVID‐19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease, and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3–73.1) in three French transplant centers. After a median follow‐up of 13 days (7–30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow‐up of 8.5 days (2–14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched nontransplant patients with respective 30‐day survival of 62.9% and 71% (p = .38) and severe disease‐free 30‐day survival of 50.6% and 47.5% (p = .91). These findings suggest that severity of COVID‐19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression.
Adaptivity and dynamics in type III secretion systems

The type III secretion system is the common core of two bacterial molecular machines: the flagellum and the injectisome. The flagellum is the most widely distributed prokaryotic locomotion device, whereas the injectisome is a syringe‐like apparatus for inter‐kingdom protein translocation, which is essential for virulence in important human pathogens. The successful concept of the type III secretion system has been modified for different bacterial needs. It can be adapted to changing conditions, and was found to be a dynamic complex constantly exchanging components. In this review, we highlight the flexibility, adaptivity, and dynamic nature of the type III secretion system.
Antibiofilm and antifungal activities of medium‐chain fatty acids against Candida albicans via mimicking of the quorum‐sensing molecule farnesol

Candida biofilms are tolerant to conventional antifungal therapeutics and the host immune system. The transition of yeast cells to hyphae is considered a key step in C. albicans biofilm development, and this transition is inhibited by the quorum‐sensing molecule farnesol. We hypothesized that fatty acids mimicking farnesol might influence hyphal and biofilm formation by C. albicans. Among 31 saturated and unsaturated fatty acids, six medium‐chain saturated fatty acids, that is, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid and lauric acid, effectively inhibited C. albicans biofilm formation by more than 75% at 2 µg ml−1 with MICs in the range 100–200 µg ml−1. These six fatty acids at 2 µg ml−1 and farnesol at 100 µg ml−1 inhibited hyphal growth and cell aggregation. The addition of fatty acids to C. albicans cultures decreased the productions of farnesol and sterols. Furthermore, down‐regulation of several hyphal and biofilm‐related genes caused by heptanoic or nonanoic acid closely resembled the changes caused by farnesol. In addition, nonanoic acid, the most effective compound diminished C. albicans virulence in a Caenorhabditis elegans model. Our results suggest that medium‐chain fatty acids inhibit more effectively hyphal growth and biofilm formation than farnesol.
What are the factors affecting postoperative nausea and vomiting following breast cancer surgery with inhalation anesthesia?

BACKGROUND The incidence and risk factors of postoperative nausea and vomiting (PONV) and early PONV (ePONV) was evaluated in patients who underwent breast surgery with volatile anesthesia. METHODS In this retrospective study, we used a multivariate logistic regression to investigate the incidence and risk factors of PONV. RESULTS Among 928 patients, 166 (18%) and 220 (24%) had ePONV and PONV, respectively. In the multivariate analysis, the anesthesia duration and the use of desflurane were independent risk factors for ePONV. For PONV, the anesthesia duration and Apfel score were the independent risk factors. CONCLUSIONS Although many previous studies have shown that PONV is a multifactorial event, our results indicate that desflurane use can be considered a main cause of ePONV. However, in the delayed phase, a higher Apfel score was the main predictor. In the early and delayed phases, a long duration of anesthesia was related to a high risk of PONV. Accordingly, avoiding a long duration of anesthesia and desflurane use is recommended for patients at a high risk of developing PONV, particularly for those with high Apfel scores.
The integration of Gaussian noise by long-range amygdala inputs in frontal circuit promotes fear learning in mice

Survival depends on the ability of animals to select the appropriate behavior in response to threat and safety sensory cues. However, the synaptic and circuit mechanisms by which the brain learns to encode accurate predictors of threat and safety remain largely unexplored. Here, we show that frontal association cortex (FrA) pyramidal neurons of mice integrate auditory cues and basolateral amygdala (BLA) inputs non-linearly in a NMDAR-dependent manner. We found that the response of FrA pyramidal neurons was more pronounced to Gaussian noise than to pure frequency tones, and that the activation of BLA-to-FrA axons was the strongest in between conditioning pairings. Blocking BLA-to-FrA signaling specifically at the time of presentation of Gaussian noise (but not 8 kHz tone) between conditioning trials impaired the formation of auditory fear memories. Taken together, our data reveal a circuit mechanism that facilitates the formation of fear traces in the FrA, thus providing a new framework for probing discriminative learning and related disorders.
Are We Getting What We Really Want? A Systematic Review of Concordance Between Physician Orders for Life-Sustaining Treatment (POLST) Documentation and Subsequent Care Delivered at End-of-Life

Background: Physician Orders for Life-Sustaining Treatments (POLST) is an advance care planning (ACP) tool that is designed to facilitate End-of-Life (EoL) care discussions between a medical provider and a terminally ill patient. It is often used as a tool to translate care wishes into a medical order, which can be honored across healthcare settings. With an increased utilization of the POLST paradigm in various healthcare settings along with continued dissemination across the nation, it is critical to examine whether documented wishes on POLST are concordant with subsequent care delivered. Purpose of this article was to examine concordance rate between POLST and subsequent care delivered in any care settings and communities. Design: Systematic review. Results: Of 1,406 articles identified, 10 articles met inclusion criteria. Together, included studies represent 5,688 POLST forms reviewed from individuals residing in a total of 126 nursing care facilities, 9 elderly care centers, 4 community settings, and 2 hospitals. Preference for cardiopulmonary resuscitation and actual delivery/ withholding of resuscitation was the most observed intervention in study of concordance (n = 8). It is also where highest concordance rate (97.5%) was reported. Seven studies compared care provided during EoL and the level of medical intervention requested on POLST forms (91.17% concordance). Preference to use artificial nutrition/ hydration, and actual delivery was 93.0% (n = 4 studies), and antibiotics use preference and delivery was 96.5% (reported in 4 studies). Conclusion: Published literature evidence suggests that EoL care wishes documented on POLST forms were largely concordant with subsequent care delivered. Additional research is needed to evaluate concordance between POLST documentation and care received among POLST users, who experienced multiple care transitions across healthcare settings, or across state during EoL care journey.
Cell therapy for cytomegalovirus infection

ABSTRACT Introduction Cytomegalovirus (CMV) infection is widely prevalent but mostly harmless in immunocompetent individuals. In the post hematopoietic stem cell transplant (HSCT) setting unrestricted viral replication can cause end-organ damage (CMV disease) and, in a small proportion, mortality. Current management strategies are based on sensitive surveillance programmes, with the more recent introduction of an effective prophylactic antiviral drug, letermovir, but all aim to bridge patients until reconstitution of endogenous immunity is sufficient to constrain viral replication. Areas covered Over the past 25 years, the adoptive transfer of CMV-specific T-cells has developed from the first proof of concept transfer of CD 8 + T-cell clones, to the development of ‘off the shelf’ third party derived Viral-Specific T-cells (VSTs). In this review, we cover the current management of CMV, and discuss the developments in CMV adoptive cellular therapy. Expert opinion Due to the adoption of letermovir as a prophylaxis in standard therapy, the incidence of CMV reactivation is likely to decrease, and any widely adopted cellular therapy needs to be economically competitive. Current clinical trials will help to identify the patients most likely to gain the maximum benefit from any form of cell therapy.
Response of summer okra (cv. Phule Utkarsha) to iron, zinc and boron in inceptisol.

A field experiment was conducted to study the response of summer okra (cv. Phule Utkarsha) to iron, zinc and boron in Inceptisol at Regional Fruit Research Station, Ganeshkhind, Pune (M.S.) during 2007-08. The objective of experiment was to study the effect of iron, zinc and boron on growth, yield, quality, nutrient uptake of okra and soil properties after harvest of okra. There were twelve treatments viz., water spray, foliar spray FeSO4 (0.5 %), foliar spray ZnSO4 (0.5 %), foliar spray boric acid (0.2 %), foliar spray FeSO4+ ZnSO4 (0.5 % each), foliar spray FeSO4 (0.5 %) + boric acid (0.2 %), foliar spray ZnSO4 (0.5 %) + boric acid (0.2 %), foliar spray FeSO4 + ZnSO4 (0.5 % each) + boric acid (0.2%), soil application of FeSO4@ 20 kg ha-1, soil application of ZnSO4@ 20 kg ha-1, soil application of FeSO4+ ZnSO4@ 20 kg ha-1 each and soil application of FeSO4 + ZnSO4@ 20 kg ha-1 each + borax @ 5 kg ha-1. The experiment was laid in Randomized Block Design with three replications. The foliar sprays of micronutrients were done at 30 days and 45 days after sowing of okra. The soil application of micronutrients were done at the time of sowing. The results of experiment indicated that the soil application of FeSO4+ ZnSO4@ 20 kg ha-1each + borax @ 5 kg ha-1 registered significantly higher plant height (155.64cm), higher number of nodes per plant (24.96), higher number of days to 50 % flowering (43.67). The higher average fruit diameter (1.60 cm), higher fruit length (11.30 cm) and average fruit weight (11.67 g) were found in T11. The micronutrient application to okra helped to improve yield parameters. The soil application of FeSO4+ ZnSO4@ 20 kg ha-1 each + borax @ 5 kg ha-1 yielded significantly higher yield (205.8 q ha-1) and was at par with foliar spray FeSO4 + ZnSO4 (0.5 % each) + boric acid (0.2%) (196.4 q ha-1), soil application of FeSO4 + ZnSO4@ 20 kg ha-1 each (191.2 q ha-1) and foliar spray FeSO4 + ZnSO4 (0.5 % each) (191.2 q ha-1). In general the combined application of FeSO4+ ZnSO4@ 20 kg ha-1 each + borax@ 5 kg ha-1 as soil application and foliar sprays of FeSO4 (0.5 %) + ZnSO4 (0.5 %) + boric acid (0.2%), both treatments were found significantly effective in increasing the yield of okra and maintained soil properties. The uptake of nitrogen was significantly higher due to soil application of FeSO4 + ZnSO4 + borax (48.03 kg ha-1) and at par with foliar spray FeSO4 + ZnSO4+ boric acid (45.84 kg ha-1) and soil application of FeSO4+ ZnSO4@ 20 kg ha-1each (45.61 kg ha-1). The similar treatment showed significantly higher uptake of phosphorus and potassium. The application of FeSO4, ZnSO4 and borax either alone or in combination helped to increase the uptake of iron, zinc, boron, manganese and copper by okra.
Transvenous lead extraction outcomes using a novel hand-powered bidirectional rotational sheath as a first-line extraction tool in a low-volume centre.

OBJECTIVES Extraction of cardiovascular implantable electronic devices in low-volume medical centres with limited clinical experience and an evolving lead extraction programme may be challenging. We aimed to evaluate the safety and efficacy of stepwise transvenous lead extraction (TLE) using a novel type of hand-powered rotational sheath as a first-line tool for extraction of chronically implanted devices in a single, low-volume centre. METHODS Sixty-seven consecutive patients undergoing a TLE procedure using the novel Evolution® RL rotational sheath as the first-line extraction tool between 2015 and 2019 at our institution were enrolled in the study. Their short-term and 30-day outcomes were observed. RESULTS Sixty-nine devices and 131 leads were explanted. Procedural and clinical success rates were 92.4% and 98.5%, respectively. Two procedures were classified as failures due to lead remnants >4 cm remaining in patients' vascular systems. One major (1.5%) and 3 minor (4.4%) adverse events and no deaths were observed. CONCLUSIONS TLE procedures, performed in a stepwise manner, using the Evolution RL sheath as a first-line extraction device and conducted by an experienced, surgically well-trained operator, offer excellent results with clinical and procedural success rates comparable to those, achieved in dedicated, high-volume institutions. Opting for optimal lead extraction approach in low-volume centres or institutions with evolving TLE programmes, a stepwise extraction strategy using the Evolution RL sheath by skilled operator may provide the optimal scheme with an excellent ratio between clinical and/or procedural success and complications.
Knowledge of 5-aminosalicylic acid nephrotoxicity and adherence to kidney function monitoring of patients with inflammatory bowel disease

Supplemental Digital Content is available in the text. Background and aim 5-Aminosalicylic acid (5-ASA) nephrotoxicity is a rare and idiosyncratic condition in patients with inflammatory bowel disease (IBD), which may lead to end-stage kidney failure. Kidney function monitoring is recommended in clinical practice to prevent this complication. However, no data is available regarding the knowledge and adherence of patients with IBD to this monitoring. Methods As a part of routine practice, patients with IBD under treatment or previously treated with 5-ASA were systematically interviewed about knowledge of 5-ASA nephrotoxicity and adherence to kidney function monitoring. We reported here the experience among the first 103 consecutive patients seen in a French referral center. Results A total of 103 patients (93.2% ulcerative colitis, 5.8% Crohn’s disease, and 1% unclassified colitis) were analyzed. Among them, 70% were informed about the need for kidney function monitoring, and in most cases, information was provided by their gastroenterologist (94.4%). The adherence rate to monitoring was very high (84.7%). Monitoring consisted of serum creatinine and estimated glomerular filtration rate in most cases (97.2%), while 24-h proteinuria was less frequently used (69.4%). These tests were performed twice or ≥3 times per year by 44.4 and 41.7% of patients, respectively. One case of isolated elevation of proteinuria related to 5-ASA treatment was observed. Conclusion We reported for the first time that patients with IBD are well informed and adherent to kidney function monitoring of treatment with 5-ASA. The monitoring performed by their treating physician was generally in accordance with current recommendations.
Multisystem inflammatory syndrome in children and SARS-CoV-2: A scoping review.

PURPOSE The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 43 million people resulting in over 1 million deaths. Approximately 2% of cases in the United States are children, and in most cases the child is either asymptomatic or has mild symptoms. However, some pediatric cases can present with Multisystem Inflammatory Syndrome (MIS-C). Understanding the epidemiology, clinical presentation, and management of MIS-C related to SARS-CoV-2 will help to streamline early diagnosis and treatment, particularly in pediatric patients with complex medical conditions. METHODS This scoping review adopted methods from the Joanna Briggs Institute (JBI) manual for evidence synthesis and preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) guidelines. Primary studies of patients meeting the Centers for Disease Control and Prevention (CDC) criteria for MIS-C from December 31st, 2019 to Oct 5th, 2020 were identified using PubMed and Scopus. Articles were screened for eligibility, and data collection was conducted on those fulfilling inclusion criteria. RESULTS Of 417 studies identified, 57 met inclusion criteria, accounting for 875 patients from 15 countries. Globally, 57% of children affected with MIS-C were males. The median age was 9 years old, ranging from 6 months to 21 years. Forty-five percent of the patients had underlying comorbidities including obesity and lung disease. Fever, conjunctivitis and GI symptoms were common. Most MIS-C patients had high biomarkers including troponin I, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cells (WBCs), interleukin 6 (IL-6), procalcitonin, and ferritin. The treatment for most patients included IVIG and inotropic support. CONCLUSION MIS-C can be a unique and potentially life-threatening manifestation of SARS-CoV-2 in children and often requires medical intervention.
Prevalence of depression, anxiety, and their associations among end-stage renal disease patients on maintenance hemodialysis: a multi-center population-based study

ABSTRACT Depression and anxiety are the most common mood disorder among end-stage renal disease (ESRD) patients, which can negatively affect quality-of-life and treatment outcomes. This study aimed to estimate the prevalence of depression and anxiety symptoms among ESRD patients undergoing hemodialysis (HD) and test associations with several covariates. In across-sectional study, we collected data from 457 patients using Hospital Anxiety and Depression Scale (HADS). We used multinomial logistic regression to model the associations between depression/anxiety symptoms and several covariates. The prevalence of depression (anxiety) symptoms was 21.7%(21.4%). About 12.6% had both depression and anxiety. Males were significantly less likely to have anxiety (depression) compared to females. Married with children were significantly less likely to have anxiety compared to divorced/widowed. Patients with Glomerulonephritis were significantly more likely to have anxiety (depression) compared to other causes of dialysis. Depression and anxiety are prevalent among HD patients with their HADS scores significantly positively correlated. This requires regular screening for symptoms of anxiety/depression. Future interventions should target females, those on dialysis between one and three years, and those with glomerulonephritis as ESRD cause. Finally, HADS is ascreening tool for symptoms of anxiety and depression for which aspecialist should assess the definitive diagnosis clinically.
Cannabis Use among Persons with Dementia and Their Caregivers: Lighting up an Emerging Issue for Clinical Gerontologists

ABSTRACT Objectives: Our goal is to illuminate cannabis use among persons with dementia (PwD) and their informal caregivers relative to the use of evidence-based as well as other complementary and alternative care practices. Methods: We analyzed focus group (FG) narratives provided by 26 caregivers of PwD and identified five themes concerning the provision of cannabis to PwD and caregivers’ self-use. Results: Three of the 26 caregivers provided PwD cannabis and also used themselves, another 3 of the 26 used themselves only, and all but two of the remaining FG participants indicated they would consider providing cannabis to PwD or using for themselves. These caregivers expressed a desire to obtain more empirically-based information about cannabis and to discuss options with their clinical care providers. Conclusions: A small but significant proportion of caregivers are providing cannabis to PwD as a possible treatment for agitation, sleep disturbances and other problematic secondary symptoms and using for themselves as way to relieve stress. Many other caregivers may start using cannabis upon receiving information and guidance from a credible source. Clinical Implications: Notwithstanding the need for more research, clinical gerontologists and other dementia care specialists are being looked upon to provide information and guidance about the benefits and harms of cannabis use among PwD and their caregivers.