Miracle-dz/UniFAR-FTUs huggingface dataset:
Vasopressin Versus Norepinephrine for the Management of Septic Shock in Cancer Patients: The VANCS II Randomized Clinical Trial.

OBJECTIVES Previous trials suggest that vasopressin may improve outcomes in patients with vasodilatory shock. The aim of this study was to evaluate whether vasopressin could be superior to norepinephrine to improve outcomes in cancer patients with septic shock. DESIGN Single-center, randomized, double-blind clinical trial, and meta-analysis of randomized trials. SETTING ICU of a tertiary care hospital. PATIENTS Two-hundred fifty patients 18 years old or older with cancer and septic shock. INTERVENTIONS Patients were assigned to either vasopressin or norepinephrine as first-line vasopressor therapy. An updated meta-analysis was also conducted including randomized trials published until October 2018. MEASUREMENTS AND MAIN RESULTS The primary outcome was all-cause mortality at 28 days after randomization. Prespecified secondary outcomes included 90-days all-cause mortality rate; number of days alive and free of advanced organ support at day 28; and Sequential Organ Failure Assessment score 24 hours and 96 hours after randomization. We also measure the prevalence of adverse effects in 28 days. A total of 250 patients were randomized. The primary outcome was observed in 71 patients (56.8%) in the vasopressin group and 66 patients (52.8%) in the norepinephrine group (p = 0.52). There were no significant differences in 90-day mortality (90 patients [72.0%] and 94 patients [75.2%], respectively; p = 0.56), number of days alive and free of advanced organ support, adverse events, or Sequential Organ Failure Assessment score. CONCLUSIONS In cancer patients with septic shock, vasopressin as first-line vasopressor therapy was not superior to norepinephrine in reducing 28-day mortality rate.
Conservative Oxygen Therapy during Mechanical Ventilation in the ICU.

BACKGROUND Patients who are undergoing mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation). METHODS We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2. The primary outcome was the number of ventilator-free days from randomization until day 28. RESULTS The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of -0.3 days (95% confidence interval [CI], -2.1 to 1.6; P = 0.80). The conservative-oxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37). CONCLUSIONS In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days. (Funded by the New Zealand Health Research Council; ICU-ROX Australian and New Zealand Clinical Trials Registry number, ACTRN12615000957594.).
In planta colonization and role of T6SS in two rice Kosakonia endophytes.

Endophytes live inside plants and are often beneficial. Kosakonia is a novel bacterial genus including many diazotrophic plant-associated isolates. Plant-bacteria studies on two rice endophytic Kosakonia beneficial strains were performed including comparative genomics, secretome profiling, in-planta tests and a field release trial. The strains are efficient rhizoplane and root endosphere colonizers and localized in the root cortex. Secretomics revealed 144 putative secreted proteins including type VI secretory system (T6SS) proteins. A Kosakonia T6SS genomic knock-out mutant showed a significant decrease in rhizoplane and endosphere colonization ability. A field trial using rice seeds inoculated with Kosakonia sp. showed no effect on plant growth promotion upon nitrogen stress and microbiome studies revealed that Kosakonia was significantly more present in the inoculated rice. Comparative genomics evidenced that several protein domains were enriched in plant-associated Kosakonia. This study highlights that Kosakonia is an important recently classified genus involved in plant-bacteria interaction.
Genomic epidemiology of penicillin-non-susceptible Streptococcus pneumoniae

Penicillin-non-susceptible Streptococcus pneumoniae (PNSP) were first detected in the 1960s, and are now common worldwide, predominantly through the international spread of a limited number of strains. Extant PNSP are characterized by mosaic pbp2x, pbp2b and pbp1a genes generated by interspecies recombinations, with the extent of these alterations determining the range and concentrations of β-lactams to which the genotype is non-susceptible. The complexity of the genetics underlying these phenotypes has been the subject of both molecular microbiology and genome-wide association and epistasis analyses. Such studies can aid our understanding of PNSP evolution and help improve the already highly-performing bioinformatic methods capable of identifying PNSP from genomic surveillance data.
Posttransplant Calcineurin Inhibitors Levels and Intrapatient Variability Are Not Associated With Long-term Outcomes Following Liver Transplantation

Supplemental Digital Content is available in the text. Background. There is an interest in understanding the association between early calcineurin inhibitors exposure post-liver transplantation (LT) and long-term outcomes. We aimed to analyze this association exploring median calcineurin inhibitor levels and intrapatient variability (IPV) in a multicenter, retrospective cohort. Methods. Tacrolimus (Tac) and Cyclosporine (CsA) levels obtained during the first 15 days post-LT were collected. High immunosuppression (IS) was considered as a median of Tac, CsA blood trough levels 12 hours after drug administration, or blood levels 2 hours after drug administration higher than 10, 250, or 1200 ng/mL, respectively, or a peak of Tac >20 ng/mL. Optimal IS was defined as a median of Tac, CsA blood trough levels 12 hours after drug administration, or blood levels 2 hours after drug administration levels between 7 and 10, 150 and 250, or 800 and 1200 ng/mL. Low IS was defined as below the thresholds of optimal IS. IPV was estimated during the first 15 days post-LT. Results. The study included 432 patients with a median follow-up of 8.65 years. IS regimen was based on either Tac or CsA in 243 (56.3%) and 189 (43.8%), respectively. There were no differences in terms of graft loss among low versus optimal and high IS groups (P = 0.812 and P = 0.451) nor in high versus low IPV (P = 0.835). Only viral hepatitis and arterial hypertension were independently associated with higher graft loss (hazard ratio = 1.729, P = 0.029 and hazard ratio = 1.570, P = 0.021). Conclusions. In contrast to what has previously been reported, no association was found between very early postoperative over IS or high IPV and long-term outcome measures following LT. Strategies aimed at reducing these long-term events should likely focus on other factors or on a different IS time window.
Local Governance System for Management of Public Health Facilities: Functioning of Rogi Kalyan Samiti in North Eastern States of India

In India, the National Rural Health Mission envisaged of having committees with civil society representation at all publicly financed hospitals known as Rogi Kalyan Samiti (RKS), with mandate to enhance governance in hospitals. There are limited evidences about functioning of these committees in many states, especially in North Eastern (NE) states. This paper analyses the perspective of RKS members and relate to changing community- health system structure for improved governance. The study was conducted in three states Manipur, Meghalaya, and Tripura of NE Region of India. Using stratified sampling design, 14 RKS/facilities were selected from Manipur, 15 from Meghalaya and 11 from Tripura. Two key informants (mainly, president/secretary of RKS) were interviewed using a semi-structured pre-tested questionnaire in local language. The major areas of RKS operationalization identified include; constitution, finance management and activities related to health systems strengthening. RKS was constituted during 2006-07 with governing body following issuance of government of India guidelines. The funds (grants and User Fee) were utilized for purchase of furniture, bio-medical waste management etc. The governing body meetings focused mainly on ensuring services; in Tripura 72% of RKS had regular meetings and have shown improvement in functioning of facilities.Formation of RKS model paved way to a new beginning for strengthening health system with involvement of local leaders, civil society to improve governance. The functioning is derived by availability of resources, capacity of committee members and the bureaucratic process. Revision in functioning of RKS model is essential towards self-sustainability and bridge between community-health systems. South East Asia Journal of Public Health Vol.4(2) 2014: 16-22
Neural Network Fixed-Time Control of a Robotic System under Output Constraint

A fixed-time robotic system control method is proposed with input deadzone under a delayed time constraint. Radial basis function neural networks (RBFNN) is employed, and an error-driven adaptive law is designed. The stability of the system is achieved by introducing a new error shifting function, and by the Lyapunov stability theory convergent tracking error to a small set near zero has been observed. Simulation results proved the method effectiveness.
Near-infrared dual bioluminescence imaging in mouse models of cancer using infraluciferin

Bioluminescence imaging (BLI) is ubiquitous in scientific research for the sensitive tracking of biological processes in small animal models. However, due to the attenuation of visible light by tissue, and the limited set of near-infrared bioluminescent enzymes, BLI is largely restricted to monitoring single processes in vivo. Here we show, that by combining stabilised colour mutants of firefly luciferase (FLuc) with the luciferin (LH2) analogue infraluciferin (iLH2), near-infrared dual BLI can be achieved in vivo. The X-ray crystal structure of FLuc with a high-energy intermediate analogue, 5’-O-[N-(dehydroinfraluciferyl)sulfamoyl] adenosine (iDLSA) provides insight into the FLuc-iLH2 reaction leading to near-infrared light emission. The spectral characterisation and unmixing validation studies reported here established that iLH2 is superior to LH2 for the spectral unmixing of bioluminescent signals in vivo; which led to this novel near-infrared dual BLI system being applied to monitor both tumour burden and CAR T cell therapy within a systemically induced mouse tumour model.
Association of Socioeconomic Status With Ischemic Stroke Survival.

Background and Purpose- The aim of the study was to determine the impact of individuals' socioeconomic status and their Primary Care Service Area Socioeconomic Index on survival after ischemic stroke. Methods- We conducted a nationwide population-based cohort study in Catalonia, Spain. We included all patients with first ischemic stroke admitted to a public hospital between January 1, 2015, and December 31, 2016. We measured both individual socioeconomic status (categorized as exempts, <€18 000 [$US 20 468] income per year, and >€18 000 income per year) and Primary Care Service Area Socioeconomic Index (from 0 to 100 categorized in quartiles). We used mixed-effects logistic and survival models to estimate odds ratios and hazard ratios for the short- (30 days) and the long-term (3 years) all-cause case fatality rates by individuals' socioeconomic status groups. Results- The cohort consisted of 16 344 ischemic stroke patients with 24 638 person-years of follow-up. We did not find an association between the lowest socioeconomic individual status and short-term survival (odds ratio, 1.03; 95% CI, 0.76-1.40), although we found it in patients with <€18 000 income/year (odds ratio, 1.26; 95% CI, 1.10-1.45). At long-term, after adjustment, we observed a gradient in mortality risk with decreasing individual socioeconomic status (hazard ratio, 1.52; 95% CI, 1.30-1.77). The Primary Care Service Area Socioeconomic Index had only an influence on short-term survival (odds ratio, 1.19; 95% CI, 1.03-1.37). Conclusions- Individuals' socioeconomic status was associated with short- and long-term survival in patients with ischemic stroke. Conversely, Primary Care Service Area Socioeconomic Index measures had an influence only in short-term survival. A small fraction of this association is due to differences in comorbidity and cardiovascular risk factors. Interventions addressing both individuals' and primary care service socioeconomic aspects might eventually affect differently short- and long-term survival.
Use of High-Cost Cancer Treatments in Academic and Nonacademic Practice.

BACKGROUND Academic physicians, such as those affiliated with National Cancer Institute (NCI)-designated Comprehensive Cancer Centers, may have different practice patterns regarding the use of high-cost cancer drugs than nonacademic physicians. MATERIALS AND METHODS For this cohort study, we linked cancer registry, administrative, and demographic data for patients with newly diagnosed cancer in North Carolina from 2004 to 2011. We selected cancer types with multiple U.S. Food and Drug Administration-approved, National Comprehensive Cancer Network-recommended treatment options and large differences in reimbursement between higher-priced and lower-priced options (stage IV colorectal, stage IV lung, and stage II-IV head-and-neck cancers). We assessed whether provider's practice setting-NCI-designated Comprehensive Cancer Center ("NCI") versus other location ("non-NCI")-was associated with use of higher-cost treatment options. We used inverse probability of exposure weighting to control for patient characteristics. RESULTS Of 800 eligible patients, 79.6% were treated in non-NCI settings. Patients treated in non-NCI settings were more likely to receive high-cost treatment than patients treated in NCI settings (36.0% vs. 23.2%), with an unadjusted prevalence difference of 12.7% (95% confidence interval [CI], 5.1%-20.0%). After controlling for potential confounding factors, non-NCI patients remained more likely to receive high-cost treatment, although the strength of association was attenuated (adjusted prevalence difference, 9.6%; 95% CI -0.1%-18.7%). Exploratory analyses suggested potential heterogeneity across cancer type and insurance status. CONCLUSION Use of higher-cost cancer treatments may be more common in non-NCI than NCI settings. This may reflect differential implementation of clinical evidence, local practice variation, or possibly a response to the reimbursement incentives presented by chemotherapy billing. IMPLICATIONS FOR PRACTICE Oncology care delivery and practice patterns may vary between care settings. By comparing otherwise similar patients treated in National Cancer Institute (NCI)-designated Comprehensive Cancer Centers with those treated elsewhere, this study suggests that patients may be more likely to receive treatment with certain expensive cancer drugs if treated in the non-NCI setting. These practice differences may result in differences in patient costs and outcomes as a result of where they receive treatment.
Environmental entrainment demonstrates natural circadian rhythmicity in the cnidarian Nematostella vectensis

ABSTRACT Considerable advances in chronobiology have been made through controlled laboratory studies, but distinct temporal rhythms can emerge under natural environmental conditions. Lab-reared Nematostella vectensis sea anemones exhibit circadian behavioral and physiological rhythms. Given that these anemones inhabit shallow estuarine environments subject to tidal inputs, it was unclear whether circadian rhythmicity would persist following entrainment in natural conditions, or whether circatidal periodicity would predominate. Nematostella were conditioned within a marsh environment, where they experienced strong daily temperature cycles as well as brief tidal flooding around the full and new moons. Upon retrieval, anemones exhibited strong circadian (∼24 h) activity rhythms under a light–dark cycle or continuous darkness, but reduced circadian rhythmicity under continuous light. However, some individuals in each light condition showed circadian rhythmicity, and a few individuals showed circatidal rhythmicity. Consistent with the behavioral studies, a large number of transcripts (1640) exhibited diurnal rhythmicity compared with very few (64) with semidiurnal rhythmicity. Diurnal transcripts included core circadian regulators, and 101 of 434 (23%) genes that were previously found to be upregulated by exposure to ultraviolet radiation. Together, these behavioral and transcriptional studies show that circadian rhythmicity predominates and suggest that solar radiation drives physiological cycles in this sediment-dwelling subtidal animal. Summary: The subtidal anemone Nematostella vectensis exhibits strong circadian behavioral rhythms following entrainment in natural conditions. Corresponding transcriptional rhythms suggest that solar radiation drives physiological cycles in this sediment-dwelling animal.
Sugar as a therapeutic target for the cognitive restoration following traumatic brain injury.

PURPOSE OF REVIEW This review aims to discuss examples of changes in glucose (sugar) metabolism after traumatic brain injury (TBI). It will attempt to provide an understanding of what changes in glucose metabolism mean for the injured brain. It will further identify potential therapeutic target(s) emanating from our growing understanding of glucose pathways and their roles in TBI. RECENT FINDINGS Although a significant fraction of glucose is utilized for the energy production in the brain, a small fraction is utilized in other, often ignored pathways. Recent studies have unraveled unexpected biological effects of glucose through these pathways, including redox regulation, genetic and epigenetic regulation, glycation of proteins, nucleotide synthesis and amino acid synthesis. SUMMARY A number of regulatory players in minor glucose metabolic pathways, such as folate and chondroitin sulfate proteoglycans, have recently been identified as potential targets to restore cognitive functions. Targeting of these players should be combined with the supplementation of alternative energy substrates to achieve the maximal cognitive restoration after TBI. This multimodal therapeutic strategy deserves testing in various models of TBI. VIDEO ABSTRACT Supplemental digital video content 1: Video that demonstrates an effective therapeutic strategy for the cognitive restoration after TBI. http://links.lww. com/CONR/A46.
Causes of Infertility in Female Camels (Camelus dromedarius) in Middle of Saudi Arabia

The objective of this study was to investigate the common infertility forms in female camels (camelus dromedarius) in the Central Region of Saudi Arabia. Over two breeding seasons, a total of 447 female camels were examined for reproductive disorders. Based on history, animals were categorized as repeat breeder (RB syndrome, n=343), refused mating (RM syndrome, n=73) and early embryonic death (EED syndrome, n=31). Animals were then exposed to rectal examination, vaginal exploration and rectal ultrasonography. Results showed that endometritis and metritis were the major causes of infertility (57.1%). Vaginal adhesions were the second important infertility problem (16.1%) and recorded frequently in multipara than in nullipara animals (P< 0.01). Ovarian cysts (5.3%) and ovarian inactivity (3.6%) did not represent major infertility problems. Miscellaneous causes of infertility included anomalies of the genital tract (1.1%), hydrosalpinx (0.5%), and vaginal tumors (0.5%).
Allosteric discrimination at the NADH/ADP regulatory site of glutamate dehydrogenase

Glutamate dehydrogenase (GDH) is a target for treating insulin‐related disorders, such as hyperinsulinism hyperammonemia syndrome. Modeling native ligand binding has shown promise in designing GDH inhibitors and activators. Our computational investigation of the nicotinamide adenine diphosphate hydride (NADH)/adenosine diphosphate (ADP) site presented in this paper provides insight into the opposite allosteric effects induced at a single site of binding inhibitor NADH versus activator ADP to GDH. The computed binding free‐energy difference between NADH and ADP using thermodynamic integration is −0.3 kcal/mol, which is within the −0.275 and −1.7 kcal/mol experimental binding free‐energy difference range. Our simulations show an interesting model of ADP with dissimilar binding conformations at each NADH/ADP site in the GDH trimer, which explains the poorly understood strong binding but weak activation shown in experimental studies. In contrast, NADH showed similar inhibitory binding conformations at each NADH/ADP site. The structural analysis of the important residues in the NADH/ADP binding site presented in this paper may provide potential targets for mutation studies for allosteric drug design.