Miracle-dz/UniFAR-FTUs huggingface dataset:
Two-component systems required for virulence in Pseudomonas aeruginosa

Abstract Pseudomonas aeruginosa is a versatile opportunistic pathogen capable of infecting a broad range of hosts, in addition to thriving in a broad range of environmental conditions outside of hosts. With this versatility comes the need to tightly regulate its genome to optimise its gene expression and behaviour to the prevailing conditions. Two-component systems (TCSs) comprising sensor kinases and response regulators play a major role in this regulation. This minireview discusses the growing number of TCSs that have been implicated in the virulence of P. aeruginosa, with a special focus on the emerging theme of multikinase networks, which are networks comprising multiple sensor kinases working together, sensing and integrating multiple signals to decide upon the best response. The networks covered in depth regulate processes such as the switch between acute and chronic virulence (GacS network), the Cup fimbriae (Roc network and Rcs/Pvr network), the aminoarabinose modification of lipopolysaccharide (a network involving the PhoQP and PmrBA TCSs), twitching motility and virulence (a network formed from the Chp chemosensory pathway and the FimS/AlgR TCS), and biofilm formation (Wsp chemosensory pathway). In addition, we highlight the important interfaces between these systems and secondary messenger signals such as cAMP and c-di-GMP.
Primary Care Interventions to Support Breastfeeding: US Preventive Services Task Force Recommendation Statement.

Importance There is convincing evidence that breastfeeding provides substantial health benefits for children. However, nearly half of all US mothers who initially breastfeed stop doing so by 6 months, and there are significant disparities in breastfeeding rates among younger mothers and in disadvantaged communities. Objective To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on primary care interventions to promote breastfeeding. Evidence Review The USPSTF reviewed the evidence on the effectiveness of interventions to support breastfeeding on breastfeeding initiation, duration, and exclusivity. The USPSTF also briefly reviewed the literature on the effects of these interventions on child and maternal health outcomes. Findings The USPSTF found adequate evidence that interventions to support breastfeeding, including professional support, peer support, and formal education, change behavior and that the harms of these interventions are no greater than small. The USPSTF concludes with moderate certainty that interventions to support breastfeeding have a moderate net benefit. Conclusions and Recommendation The USPSTF recommends providing interventions during pregnancy and after birth to support breastfeeding. (B recommendation).
Intelligent Decision Support System in Diabetic eHealth Care-From the perspective of Elders

This thesis proposes intelligent decision support System in diabetes eHealth care in order to improve the quality of life of Diabetes patients. Diabetes is one of the chronic diseases that can cause the serious health complication. Patients of diabetes especially elder people need more care than others as well as regularity in medicine. Only patients themselves or doctors cannot provide the care that patient needs. To improve the quality of daily life of patient a team of care providers work together. This thesis covers the different fields of intelligent decision support system for the diabetes type2 patients. The proposed intelligent decision support system is 24-hours accessible for the patients and care providers. The system stores the patients’ information and gives them optimal advices according to their condition entered by them. It also provides adequate and detail information about the patient to the health-care providers that help them to take an optimal decision about the patients. If system analyzes any alarming condition of the patient, it generates automatic alarming message for the health-care providers to help the patients. We validate our study by conducting interviews with diabetes health-care providers and perform questionnaires filled from diabetes type2 patients.
Determination of normal values for eye protrusion in Bushehr port population

Background: Exophthalmos is the protrusion of eye from the orbital cavity. It may be due to inflammation, infection, tumors and thyroid disorders.Normal value of ocular protrusion is different in each population. It is related to age, gender and ethnicity. The measurement of eye protrusion is helpful in the diagnosis and management of exophthalmos. The aim of this study is to determine the normal values for eye protrusion in Bushehr port population. Materials and Methods: In this study, 1303 subjects of healthy population (15-75 years old) in Bushehr were randomly selected from eccompannies persons of patients that referred to our endocrine clinic. Subjects with previous history of orbital surgery, eye trauma, strabismus, myopia (>-2 Diopter), orbital inflammatory disease, skull and face abnormality were excluded. Extent of eye protrusion was measured by one endocrinologist using Hertel exophthalmometry. Results : The mean protrusion values for right eye and left eye were 17.9±11.55 and 18.08±1.5mm, respectively. The exophthalmometric measurements were lower in right eye than left eye (p<0.0001). Also the mean eye protrusion decreased with increasing in age (p<0.0001). The upper limit of eye protrusion in healthy adult was 21.11 mm. Conclusion: The eye protrusion more than 21.11 mm should be considered as exophthalmos in Bushehr port population.
Insulin degludec: overview of a novel ultra long‐acting basal insulin

All the basal insulin products currently available have suboptimal pharmacokinetic (PK) properties, with none reliably providing a reproducible and peakless pharmacodynamic (PD) effect that endures over 24 h from once‐daily dosing. Insulin degludec is a novel acylated basal insulin with a unique mechanism of protracted absorption involving the formation of a depot of soluble multihexamer chains after subcutaneous injection. PK/PD studies show that insulin degludec has a very long duration of action, with a half‐life exceeding 25 h. Once‐daily dosing produces a steady‐state profile characterized by a near‐constant effect, which varies little from injection to injection in a given patient. Clinically, insulin degludec has been shown consistently to carry a lower risk of nocturnal hypoglycaemia than once‐daily insulin glargine, in both basal+bolus and basal‐only insulin regimens. The constancy of the steady‐state profile of insulin degludec also means that day‐to‐day irregularities at the time of injection have relatively little PD influence, thereby offering the possibility of greater treatment flexibility for patients.
JUPITER clinical directions--polling results.

In November 2008, we published the results of the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER; ClinicalTrials.gov number, NCT00239681),1 along with a new online Clinical Directions interactive feature that allowed readers to vote and comment on two questions related to this major trial. We asked whether the results of JUPITER should change the approach to laboratory screening of apparently healthy adults or the therapeutic use of statins in apparently healthy adults. Over 18 days, 2553 people voted, and the votes were split almost evenly between the two choices. In all, 49% of .
Anti-ulcerogenic effect of ginger (rhizome of Zingiber officinale Roscoe) hydroalcoholic extract on acetic acid-induced acute colitis in rats

Spasmolytic, antioxidant, anti-inflammatory and immuno-modulatory properties of ginger (rhizome of Zingiber officinale Roscoe) suggest that it may has beneficial effects on inflammatory bowel diseases. In the present study, the effect of this herbal extract on a model of acute colitis was evaluated. Ginger hydroalcoholic extract with doses of 150, 350, 700 mg/kg, prednisolone (2 mg/kg), or vehicle were administered orally to groups of male Wistar rats (n=6) for 5 days. Other four groups received two doses of vehicle, extract (350, 700 mg/kg), or hydrocortisone acetate enema (10 mg/kg) rectally, 15 and 2 h prior to ulcer induction (2 ml of acetic acid 4% was instilled via the anus). All rats were sacrificed 24 h later and the tissue injuries were assessed macroscopically and pathologically. Extracts with all doses used were effective to reduce colon weight/length ratio similar to the reference drugs (corticosteroids). Higher oral doses of extracts (350 and 700 mg/kg) were effective to reduce ulcer severity, area and index as well as mucosal inflammation severity, extent and total colitis index compared to controls. Rectally administered extract, only at high dose (700 mg/kg) was effective to reduce ulcer index and total colitis index. It is concluded that ginger hydroalcoholic extract was effective to protect against experimental colitis, and the efficacy was greater when higher doses of extract were administered orally and in a prolonged period.
CCR2 antagonism in patients with type 2 diabetes mellitus: a randomized, placebo‐controlled study

Macrophage recruitment through C‐C motif chemokine receptor‐2 (CCR2) into adipose tissue is believed to play a role in the development of insulin resistance and type 2 diabetes mellitus (T2DM). The objective of this Phase 2 proof‐of‐concept study was to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of JNJ‐41443532, an orally bioavailable CCR2 antagonist, in patients with T2DM.
Spatial clustering of high load ocular Chlamydia trachomatis infection in trachoma: a cross-sectional population-based study

&NA; Chlamydia trachomatis (Ct) is the most common cause of bacterial sexually transmitted infection and infectious cause of blindness (trachoma) worldwide. Understanding the spatial distribution of Ct infection may enable us to identify populations at risk and improve our understanding of Ct transmission. In this study, we sought to investigate the spatial distribution of Ct infection and the clinical features associated with high Ct load in trachoma‐endemic communities on the Bijagós Archipelago (Guinea Bissau). We collected 1507 conjunctival samples and corresponding detailed clinical data during a cross‐sectional population‐based geospatially representative trachoma survey. We used droplet digital PCR to estimate Ct load on conjunctival swabs. Geostatistical tools were used to investigate clustering of ocular Ct infections. Spatial clusters (independent of age and gender) of individuals with high Ct loads were identified using local indicators of spatial association. We did not detect clustering of individuals with low load infections. These data suggest that infections with high bacterial load may be important in Ct transmission. These geospatial tools may be useful in the study of ocular Ct transmission dynamics and as part of trachoma surveillance post‐treatment, to identify clusters of infection and thresholds of Ct load that may be important foci of re‐emergent infection in communities. &NA; Graphical Abstract Figure. One sentence summary: We identified clusters of high load Ct infections suggesting that high load infections may be important in transmission, which may have implications in trachoma elimination strategies and surveillance.
Circadian rhythm‐related genes: implication in autoimmunity and type 1 diabetes

Recent gene association and functional studies have proven the implication of several circadian rhythm‐related genes in diabetes. Diabetes has been related to variation in central circadian regulation and peripheral oscillation. Different transcriptional regulators have been identified. Circadian genes are clearly implicated in metabolic pathways, pancreatic function and in type 2 diabetes. Much less evidence has been shown for the link between circadian regulation and type 1 diabetes. The hypothesis that circadian genes are involved in type 1 diabetes is reinforced by findings that the immune system undergoes circadian variation and that several autoimmune diseases are associated with circadian genes. Recent findings in the non‐obese diabetic mouse model pinpoint to specific mechanisms controlling type 1 diabetes by the clock‐related gene Arntl2 in the immune system.
Colloidal and Pharmacological Activity of Albumin in Clinical Fluid Management:Recent Developments

Abstract : Human albumin is extensively used and investigated in clinical fluid management. Whether albumin confers sufficient benefit to justify its cost has been a subject of enduring controversy. A 2003 systematic review assembled evi-dence of benefit, but uncertainty has persisted. Abundant additional data have been newly reported, and this review pro-vides an update. Major recent developments include the largest ever single randomized trial in the field of fluid manage-ment as well as the largest ever meta-analysis of randomized trials in the field. The randomized trial confirmed the safety of albumin in intensive care unit patients, while the meta-analysis demonstrated that albumin administration reduces mor-bidity in broad populations of acutely ill hospitalized patients. In liver disease, new randomized trials have shown that al-bumin can reduce morbidity as an adjunct to paracentesis and improve circulatory function in spontaneous bacterial peri-tonitis. Large observational studies have provided evidence of a survival advantage among cardiac surgery patients receiv-ing albumin rather than artificial colloids. For extracorporeal circuit priming during cardiopulmonary bypass, albumin was found in a meta-analysis to maintain platelet counts and fluid balance more effectively than crystalloid. Randomized trials in both cardiac and noncardiac surgery indicated less impairment of coagulation by albumin than hydroxyethyl starch. Improved oxygenation, augmented loss of excess fluid and reduced morbidity after albumin supplementation were dem-onstrated in a randomized trial of hypoalbuminemic patients. A large-scale pharmacovigilance study showed serious ad-verse events in albumin recipients to be rare. Emerging evidence has further supported many of the current uses of albu-min in fluid management.
Practical preventive therapy for tuberculosis?

Every new episode of tuberculosis — there were 9 million in 20101 — follows a period of asymptomatic infection lasting from weeks to decades. These subclinical infections, which are detectable with a tuberculin skin test or interferon-γ release assay, offer a target for prophylactic treatment either with drugs or, potentially, a vaccine. Vaccination after infection is not yet an option, but drug treatment has been available for 60 years in the form of 6 to 12 months of isoniazid preventive therapy (IPT), which protects up to 90% of infected persons from active tuberculosis. And yet very few tuberculosis-control programs have .
Opposite effects of a glucokinase activator and metformin on glucose‐regulated gene expression in hepatocytes

Small molecule activators of glucokinase (GKAs) have been explored extensively as potential anti‐hyperglycaemic drugs for type 2 diabetes (T2D). Several GKAs were remarkably effective in lowering blood glucose during early therapy but then lost their glycaemic efficacy chronically during clinical trials.
Metformin‐associated lactic acidosis (MALA): Moving towards a new paradigm

Although metformin has been used for over 60 years, the balance between the drug's beneficial and adverse effects is still subject to debate. Following an analysis of how cases of so‐called “metformin‐associated lactic acidosis” (MALA) are reported in the literature, the present article reviews the pitfalls to be avoided when assessing the purported association between metformin and lactic acidosis. By starting from pathophysiological considerations, we propose a new paradigm for lactic acidosis in metformin‐treated patients. Metformin therapy does not necessarily induce metformin accumulation, just as metformin accumulation does not necessarily induce hyperlactatemia, and hyperlactatemia does not necessarily induce lactic acidosis. In contrast to the conventional view, MALA probably accounts for a smaller proportion of cases than either metformin‐unrelated lactic acidosis or metformin‐induced lactic acidosis. Lastly, this review highlights the need for substantial improvements in the reporting of cases of lactic acidosis in metformin‐treated patients. Accordingly, we propose a check‐list as a guide to clinical practice.
New evidence that cigarette smoking remains the most important health hazard.

Everyone knows cigarette smoking is bad for you. Most people in the United States assume that smoking is on its way out. But the grim reality is that smoking still exerts an enormous toll on the health of Americans, as documented in two articles in this issue of the Journal.1,2 Both articles review mortality trends over time for men and women according to smoking status, and both confirm that smoking remains a huge threat to the public's health. Jha et al. review data from the U.S. National Health Interview Survey, which involved 113,752 women and 88,496 men 25 .
Genome Sequencing of Multiple Isolates Highlights Subtelomeric Genomic Diversity within Fusarium fujikuroi

Abstract Comparisons of draft genome sequences of three geographically distinct isolates of Fusarium fujikuroi with two recently published genome sequences from the same species suggest diverse profiles of secondary metabolite production within F. fujikuroi. Species- and lineage-specific genes, many of which appear to exhibit expression profiles that are consistent with roles in host–pathogen interactions and adaptation to environmental changes, are concentrated in subtelomeric regions. These genomic compartments also exhibit distinct gene densities and compositional characteristics with respect to other genomic partitions, and likely play a role in the generation of molecular diversity. Our data provide additional evidence that gene duplication, divergence, and differential loss play important roles in F. fujikuroi genome evolution and suggest that hundreds of lineage-specific genes might have been acquired through horizontal gene transfer.
Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone

Importance Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. Objective To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. Design, Setting, and Participants Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. Intervention Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcomes and Measures The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). Results Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, −27 Agatston units; 95% CI, −80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. Conclusions and Relevance Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding. Trial Registration clinicaltrials.gov Identifier: NCT00799617
Interpretation of Clinical Trials That Stopped Early.

Clinical trials require significant resources to complete in terms of patients, investigators, and time and should be carefully designed and conducted so that they use the minimum amount of resources necessary to answer the motivating clinical question. The size of a clinical trial is typically based on the minimum number of patients required to have high probability of detecting the anticipated treatment effect. However, it is possible that strong evidence could emerge earlier in the trial either in favor of or against the benefit of the novel treatment. If early trial results are compelling, stopping the trial before the maximum planned sample size is reached presents ethical advantages for patients inside and outside the trial and can save resources that can be redirected to other clinical questions. This advantage must be balanced against the potential for overestimation of the treatment effect and other limitations of smaller trials (eg, limited safety data, less information about treatment effects in subgroups).
No association between telomere length and blood cell counts in elderly individuals.

BACKGROUND Telomeres play a crucial role in maintaining the physical integrity of chromosomes. Telomere length (TL) is severely reduced in individuals with dyskeratosis congenita and a number of other bone marrow failure syndromes. The TL of healthy individuals is highly variable, but shortens with age. It is presently unclear if variations in TL observed in normal aging individuals affect significantly their hematopoietic reserve. Method We studied the correlation between leukocyte age-adjusted TL (aTL) and blood cell parameters (total leukocytes, neutrophils, monocytes, eosinophils, lymphocytes, hemoglobin, and platelets) in a large cohort (n=717) of women aged 38-100 years. Result We did not find any significant correlation between aTL and blood counts. CONCLUSION Our data suggest that the aTL of aging individuals is not significantly predictive of their hematopoietic reserve, which implies that TL measurement may not be clinically useful in the selection of hematopoietic stem cell transplantation donors.
I-SPY 2--Toward More Rapid Progress in Breast Cancer Treatment.

Clinical trials of systemic therapy for operable breast cancer are evolving. Our understanding of breast cancer as a family of biologically distinct diseases has implications for patient selection and the optimization of drug choices. In addition, there is a growing dissatisfaction with trials of adjuvant therapy that are large, take many years to complete, and often result in very small improvements in outcome. For these reasons, we must be thoughtful and rigorous in focusing the testing of promising agents in patients who could derive a meaningful benefit. These realities are in part responsible for the explosion of “neoadjuvant,” or preoperative, .