Miracle-dz/UniFAR-FTUs huggingface dataset:
Central Venous Catheter Failures: Nowhere Near Zero.

2054 www.ccmjournal. org December 2018 • Volume 46 • Number 12 REFERENCES 1. Altman DG: The scandal of poor medical research. BMJ 1994; 308:283–284 2. Kyriacou DN: The enduring evolution of the p value. JAMA 2016; 315:1113–1115 3. Goodman S: A dirty dozen: Twelve p-value misconceptions. Semin Hematol 2008; 45:135–140 4. Schulz KF, Altman DG, Moher D; CONSORT Group: CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. BMJ 2010; 340:c332 5. Wasserstein RL, Lazar NA: The ASA’s statement on p-values: Context, process, and purpose. Am Stat 2016; 70:129–133 6. Chavalarias D, Wallach JD, Li AH, et al: Evolution of reporting p values in the biomedical literature, 1990–2015. JAMA 2016; 315:1141–1148 7. Gates S: New England Journal of Medicine for the last time. Reducing Uncertainty: clinical trials and statistics, mostly. 2018. Available at: https://simongates.com/2018/08/01/new-england-journal-of-medicinefor-the-last-time/. Accessed September 5, 2018 8. The New England Journal of Medicine: New Manuscripts: Guidelines for Statistical Methods. 2018. Available at: https://www.nejm. org/ author-center/new-manuscripts. Accessed August 4, 2018 9. Ioannidis JPA: The proposal to lower p value thresholds to.005. JAMA 2018; 319:1429–1430 10. Blume JD, D’Agostino McGowan L, Dupont WD, et al: Secondgeneration p-values: Improved rigor, reproducibility, & transparency in statistical analyses. PLoS One 2018; 13:e0188299 11. Begley CG, Ellis LM: Drug development: Raise standards for preclinical cancer research. Nature 2012; 483:531–533 12. McCullough JPA, Lipman J, Presneill JJ: The Statistical Curriculum Within Randomized Controlled Trials in Critical Illness. Crit Care Med 2018; 46:1985–1990 13. Windish DM, Huot SJ, Green ML: Medicine residents’ understanding of the biostatistics and results in the medical literature. JAMA 2007; 298:1010–1022 14. Lewis RJ, Angus DC, Laterre PF, et al: Rationale and design of an adaptive phase 2b/3 clinical trial of selepressin for adults in septic shock. Selepressin evaluation programme for sepsis-induced shockadaptive clinical trial. Ann Am Thorac Soc 2018; 15:250–257 15. REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia, 2016. Available at: https:// clinicaltrials.gov/ct2/show/NCT02735707. Accessed August 4, 2018
Differences in multiple immune parameters between Indian and U.S. infants

To compare immune phenotypes across two geographic and ethnic communities, we examined umbilical cord blood by flow cytometry and Luminex in parallel cohorts of 53 newborns from New Delhi, India, and 46 newborns from Stanford, California. We found that frequencies of a B cell subset suggested to be B-1-like, and serum IgM concentration were both significantly higher in the Stanford cohort, independent of differences in maternal age. While serum IgA levels were also significantly higher in the Stanford cohort, IgG1, IgG2, and IgG4 were significantly higher in the New Delhi samples. We found that neutrophils, plasmacytoid dendritic cells, CD8+ T cells, and total T cells were higher in the U.S. cohort, while dendritic cells, patrolling monocytes (CD14dimCD16+), natural killer cells, CD4+ T cells, and naïve B cells were higher in the India cohort. Within the India cohort, we also identified cell types whose frequency was positively or negatively predictive of occurrence of infection(s) in the first six months of life. Monocytes, total T cells, and memory CD4+ T cells were most prominent in having an inverse relationship with infection. We suggest that these data provide impetus for follow-up studies linking phenotypic differences to environmental versus genetic factors, and to infection outcomes.
Imaging functional motor connectivity in hemiparetic children with perinatal stroke

Perinatal stroke causes lifelong disability, particularly hemiparetic cerebral palsy. Arterial ischemic strokes (AIS) are large, cortical, and subcortical injuries acquired near birth due to acute occlusion of the middle cerebral artery. Periventricular venous infarctions (PVI) are smaller, subcortical strokes acquired prior to 34 weeks gestation involving injury to the periventricular white matter. Both stroke types can damage motor pathways, thus, we investigated resulting alterations in functional motor networks and probed function. We measured blood oxygen level dependent (BOLD) fluctuations at rest in 38 participants [10 arterial patients (age = 14.7 ± 4.1 years), 10 venous patients (age = 13.5 ± 3.7 years), and 18 typically developing controls (TDCs) (age = 15.3 ± 5.1 years)] and explored strength and laterality of functional connectivity in the motor network. Inclusion criteria included MRI‐confirmed, unilateral perinatal stroke, symptomatic hemiparetic cerebral palsy, and 6–19 years old at time of imaging. Seed‐based functional connectivity analyses measured temporal correlations in BOLD response over the whole brain using primary motor cortices as seeds. Laterality indices based on mean z‐scores in lesioned and nonlesioned hemispheres explored laterality. In AIS patients, significant differences in both strength and laterality of motor network connections were observed compared with TDCs. In PVI patients, motor networks largely resembled those of healthy controls, albeit slightly weaker and asymmetric, despite subcortical damage and hemiparesis. Functional connectivity strengths were not related to motor outcome scores for either stroke group. This study serves as a foundation to better understand how resting‐state fMRI can assess motor functional connectivity and potentially be applied to explore mechanisms of interventional therapies after perinatal stroke.
Lipid Metabolic Reprogramming in Hepatocellular Carcinoma

Metabolic reprogramming for adaptation to the local environment has been recognized as a hallmark of cancer. Although alterations in fatty acid (FA) metabolism in cancer cells have received less attention compared to other metabolic alterations such as glucose or glutamine metabolism, recent studies have uncovered the importance of lipid metabolic reprogramming in carcinogenesis. Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC), and individuals with these conditions exhibit an increased intake of dietary FAs accompanied by enhanced lipolysis of visceral adipose tissue due to insulin resistance, resulting in enormous exogenous FA supplies to hepatocytes via the portal vein and lymph vessels. This “lipid-rich condition” is highly characteristic of obesity- and NASH-driven HCC. Although the way in which HCC cells adapt to such a condition and exploit it to aid their progression is not understood, we recently obtained new insights into this mechanism through lipid metabolic reprogramming. In addition, accumulating evidence supports the importance of lipid metabolic reprogramming in various situations of hepatocarcinogenesis. Thus, in this review, we discuss the latest findings regarding the role of FA metabolism pathways in hepatocarcinogenesis, focusing on obesity- and NASH-driven lipid metabolic reprogramming.
Impact of direct-acting antivirals on leukocytic DNA telomere length in hepatitis C virus-related hepatic cirrhosis

Background Direct-acting antiviral (DAAs) represent advancement in the management of hepatitis C virus (HCV)-related hepatic cirrhosis. A high proportion of patients achieve a sustained virologic response; eradication of HCV is coupled with a decreased risk of hepatocellular carcinoma. Recent evidence suggests that shortening of the DNA telomere may be linked to cellular senescence as well as predisposition to malignant transformation. Objective This study aimed to assess pretreatment leukocytic DNA telomere length in HCV-related cirrhosis and post viral eradication using DAAs. Patients and methods This study included 24 patients with HCV-related cirrhosis, Child–Pugh A. Whole-blood samples were obtained from patients before treatment and 12 weeks after the end of treatment, as well as from 24 healthy controls. Terminal restriction fragment, corresponding to telomere length, was measured using a nonradioactive Southern blot technique, detected by chemiluminescence. Results DNA telomere length was significantly shorter before treatment compared with 12 weeks after end of treatment in HCV-related cirrhotic patients. Also, it was significantly shorter in patients before treatment compared with healthy individuals. Conclusion Telomere elongation in blood leukocytes can be considered a marker of recovery of inflammation after DAAs-induced HCV eradication. Still, the possibility of activation by cancer initiation cannot be excluded.
Immunotherapy: A Novel Era of Promising Treatments for Multiple Myeloma

Multiple myeloma (MM) remains an incurable hematological malignancy characterized by clonal proliferation of malignant plasma cells in bone marrow. In the last 20 years, the introduction of autologous stem cell transplantation, followed by proteasome inhibitors and immunomodulatory agents, increased the survival of MM patients by 50%. However, still a high proportion of patients relapse and become refractory, especially, high-risk patients with adverse cytogenetics where these treatment combinations have shown limited benefit. Therefore, novel strategies, such as immunotherapy, have been developed in the last few years to help improve the survival of these patients. Immunotherapy treatments include a high number of different strategies used to attack the tumor cells by using the immune system. Here, we will review the most successful immunotherapy strategies published up to date in patients with relapsed or refractory (R/R) MM, including monoclonal antibodies targeting specific antigens on the tumor cells, antibodies combined with cytotoxic drugs or Antibodies Drug Conjugates, immune checkpoint inhibitors which eliminate the barriers that damper immune cells and prevent them from attacking tumor cells, bi-specific T-cell engagers antibodies (BiTEs), bi-specific antibodies and the infusion of chimeric antigen receptor-modified T cells. We overview the results of clinical studies that have been presented up to date and also review pre-clinical studies describing potential novel treatments for MM.
Identification of metabolites involved in the aerobic degradation of 1 estrogen A/B-rings

Various bacteria, mainly actinobacteria and proteobacteria, are capable of aerobic estrogen 22 degradation. In a previous study, we used the obligate aerobic alphaproteobacterium, 23 Sphingomonas sp. strain KC8 as a model microorganism to identify initial metabolites 24 involved in the oxygenolytic cleavage of the estrogen A-ring: 4-hydroxyestrone, a 25 meta -cleavage product, and a dead-end product pyridinestrone acid. In this study, we 26 managed to identify the downstream metabolites of this aerobic degradation pathway using 27 UPLC-HRMS. 4-Norestrogen-5(10)-en-3-oyl-CoA and its closely related deconjugated 28 (non-CoA) structure, 4-norestrogenic acid, were detected in the estrone-grown strain KC8 29 cultures. The structure of 4-norestrogenic acid was elucidated using NMR spectroscopy. The 30 extracellular distribution and the accumulation of 4-norestrogenic acid in the bacterial 31 cultures indicate that the estrogen-degrading bacteria cannot degrade this deconjugated 32 product. We also observed temporal accumulation and subsequent consumption of a common 33 steroid metabolite, 3a α - H -4 α (3'-propanoate)-7a β -methylhexahydro-1,5-indanedione (HIP), in 34 the bacterial cultures. The metabolite profile and genomic analyses shed light on the 35 biochemical mechanisms involved in the degradation of the A/B-rings of natural estrogens. In 36 this proposed aerobic pathway, C-4 of the meta -cleavage product is removed by a 2-oxoacid 37 oxidoreductase through an oxidative decarboxylation to produce the 38 4-norestrogen-5(10)-en-3-oyl-CoA. Subsequently, the B-ring is cleaved through hydrolysis. The resulting A/B-rings cleaved product is transformed into a common steroid metabolite 40 HIP through β-oxidation reactions. Accordingly, the A/B-rings of different steroids are 41 degraded through at least three peripheral pathways, which converge at HIP, and HIP is then 42 degraded through a common central pathway. Estrogens, often detected in surface waters worldwide, have been classified as endocrine 45 disrupting chemicals and carcinogens. Bacterial degradation is crucial for removing natural 46 estrogens from natural and engineered ecosystems; however, current knowledge regarding 47 biochemical mechanisms and catabolic enzymes involved in estrogen biodegradation is very 48 limited. Our estrogen metabolite profile and genomic analyses on estrone-degrading bacteria 49 enabled us to characterize the aerobic estrogen degradation pathway. The results greatly 50 expand our understanding of microbial steroid degradation. In addition, the characteristic 51 metabolites, dead-end products, and degradation genes can be used as biomarkers to 52 investigate fate and biodegradation potential of estrogens in the environment. 53
Protein tyrosine phosphatase 1B inhibitors from a marine-derived fungal strain aspergillus sp. SF-5929

Abstract In the course of our continuing investigation of bioactive secondary metabolites from marine-derived fungal strains, a racemate of a novel diphenolic derivative named (±)-tylopilusin D (1) along with ten previously known secondary metabolites (2–11) were isolated from a marine-derived fungal strain Aspergillus sp. SF-5929. Their structures were elucidated mainly by analysis of NMR and MS data. In addition, the inhibitory effects of the isolated compounds against protein tyrosine phosphatase 1B (PTP1B) activity were evaluated, and compounds 1, 2, and 5–7 inhibited PTP1B activity with IC50 values ranging from 3.3 to 8.1 µM. Kinetics studies suggested that compounds 1, 2, and 5 had noncompetitive inhibitory effects against PTP1B.
“Being in Control of My Asthma Myself” Patient Experience of Asthma Management: A Qualitative Interpretive Description

Asthma control can be achieved with effective and safe medication use; however, many patients are not controlled. Patients’ perceptions of asthma, asthma treatment, and pharmacist roles can impact patient outcomes. The purpose of this study was to explore patients’ experiences and patient–pharmacist relationships in asthma care. Qualitative Interpretive Description method guided the study. Semi-structured individual interviews were conducted with 11 patients recruited from personal contacts, pharmacies, and asthma clinics. Categories and themes were identified using inductive constant comparison. Themes indicated patients had a personalized common sense approach to asthma management, “go-to” health care provider, and prioritized patient–pharmacist relationships. Patients described their illness experiences and asthma control based on personal markers similar to the common sense model of self-regulation. Patients chose a family physician, asthma specialist, respiratory therapist, or pharmacist as an expert resource for asthma management. Patient perceived pharmacists’ roles as information provider, adviser, or care provider. Pharmacists who develop a collaborative relationship with their asthma patients are better positioned to provide tailored education and self-management support. Inviting patients to share their perspective could increase patient engagement and uptake of personalised asthma action plans to achieve asthma control.
Perceived barriers and facilitators in the assessment of occupational diseases.

Background Information is collected worldwide on the diagnosis and assessment of occupational diseases (ODs) by occupational physicians (OPs). However, information on perceived facilitators and barriers to assessment is scarce. Aims To evaluate the perceived barriers and facilitators in the assessment of ODs by OPs. Methods We conducted a qualitative study, using interviews and focus groups. We held 12 interviews and two focus groups with Dutch OPs, to identify barriers and facilitators in the assessment of ODs. Results Case definition, exposure assessment, attribution to work, guidelines and decision tools, external expertise, individual motivation and consequences were identified as themes. Barriers and facilitators were mainly reported regarding assessing work attribution, e.g. how to assess multifactorial causes or the need for training, and individual motivation such as the perceived lack of usefulness or the need for monitoring suspected OD cases. Within the theme of consequences, only barriers to the assessment of ODs were reported, including the liability of employers. Conclusions Perceived facilitators in the assessment of ODs were practical assessment tools, multifaceted education, ability to assess work exposures and professional independence. Perceived barriers were lack of usefulness, lack of urgency, complexity of assessment and concerns about liability issues.
Single Cylinder-Type Piezoelectric Actuator with Two Active Kinematic Pairs

There is an ever-increasing demand for small-size, low-cost, and high-precision positioning systems. Therefore, investigation in this field is performed to search for various solutions that can meet technical requirements of precise multi-degree-of-freedom (DOF) positioning systems. This paper presents a new design of a piezoelectric cylindrical actuator with two active kinematic pairs. This means that a single actuator is used to create vibrations that are transformed into the rotation of the sphere located on the top of the cylinder and at the same time ensure movement of the piezoelectric cylinder on the plane. Numerical and experimental investigations of the piezoelectric cylinder have been performed. A mathematical model of contacting force control was developed to solve the problem of positioning of the rotor when it needs to be rotated or moved according to a specific motion trajectory. The numerical simulation included harmonic response analysis of the actuator to analyze the trajectories of the contact points motion. A prototype actuator has been manufactured and tested. Obtained results confirmed that such a device is suitable for both positioning and movement of the actuator in the plane.
Global change and climate‐driven invasion of the Pacific oyster (Crassostrea gigas) along European coasts: a bioenergetics modelling approach

The spread of non‐indigenous species in marine ecosystems world‐wide is one of today's most serious environmental concerns. Using mechanistic modelling, we investigated how global change relates to the invasion of European coasts by a non‐native marine invertebrate, the Pacific oyster Crassostrea gigas.
Outcomes of Bronchial Artery Embolization in Massive Hemoptysis of Various Etiologies

Massive hemoptysis characterized by the expectoration of 300 ml to 600 ml of blood in 24 hours, can be life threatening and without any regards to the etiologic factors, emergency management of this condition is crucial in restoring the health of the patient. Bronchial artery embolization has been gaining popularity in controlling massive hemoptysis and recurrent hemoptysis due to different etiologies. Along with its soaring use in interventional radiology, bronchial artery embolization definitely has proved itself to be useful in achieving hemostasis with minimal invasion and fewerpost-procedure complications. This has especially been evident in the patients with other comorbid conditions that render them unfit for a surgical approach to hemostasis. Nevertheless, the benefits of this procedure have not yet been solidified. Low sample size and lack of longer duration of follow-ups may have played a significant role in this. This review compares and summarizes the immediate and long-term benefits achieved in various studies conducted around the world to conclude that bronchial artery embolization is extremely effective in achieving immediate hemostasis with the least amount of complications. In addition, the longterm outcomes of the procedure are also overwhelmingly successful with a lesser number of recurrences and longer overall survival. This work is licensed under the Creative Commons Attribution-Non Commercial 4.0 International License. Review Article August 2017 | Volume 5 | Issue 2 | Pages 138-145 Science Letters ISSN 2345-5463 – An International Triannually Journal
The multi-water-bag equations for collisionless kinetic modeling

In this paper we consider the multi-water-bag model for collisionless kinetic equations. The multi-water-bag representation of the statistical distribution function of particles can be viewed as a special class of exact weak solution of the Vlasov equation, allowing to reduce this latter into a set of hydrodynamic equations while keeping its kinetic character. After recalling the link of the multi-water-bag model with kinetic formulation of conservation laws, we derive different multi-water-bag (MWB) models, namely the Poisson-MWB, the quasineutral-MWB and the electromagnetic-MWB models. These models are very promising because they reveal to be very useful for the theory and numerical simulations of laser-plasma and gyrokinetic physics. In this paper we prove some existence and uniqueness results for classical solutions of these different models. We next propose numerical schemes based on Discontinuous Garlerkin methods to solve these equations. We then present some numerical simulations of non linear problems arising in plasma physics for which we know some analytical results.
Predation on propagules regulates regeneration in a high-density reforested mangrove plantation

Seedling recruitment underpins natural regeneration and contributes to the restocking of forest stands, which in the long term determines the structure and functioning of mangrove ecosys- tems. Propagule predation (among other factors) has been found to play an important role in deter- mining seedling distribution patterns in many mangrove stands. The role of propagule predation in influencing the observed regeneration in a Rhizophora mucronata reforested stand (9 yr old) with various spontaneously established mangrove species was investigated by looking at the effects of pruning, position (planted/vertical or prone/horizontal on the forest floor to simulate stranding) and species (Rhizophora mucronata, Ceriops tagal and Bruguiera gymnorrhiza) found to be sponta- neously growing in the plantation. Predation intensity was higher (p = 0.05) in the pruned part of the stand than in the unpruned part. Prone propagules were preyed on more (p = 0.05) than the planted category, while R. mucronata was the species least preyed on compared to C. tagal and B. gymnor- rhiza, suggesting that predation favors the recruitment of R. mucronata into this conspecific stand. Significant differences among prone and planted propagules suggest that predation is intense during the stranding phase, and this may play a critical role in limiting seedling establishment and subse- quent recruitment. Predation is suggested to be a regulator of competition in this high-density stand by eliminating or reducing potential competitors, alluding to a 'mutual relationship' between crab predators and mangrove trees.