Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical considerations on posaconazole administration and therapeutic drug monitoring in allogeneic hematopoietic cell transplant recipients.

There is a paucity of data on posaconazole (PCZ) dosing and therapeutic-drug-monitoring (TDM) in allogeneic hematopoietic cell transplant recipients (allogeneic-HCTr). This was a 3-year retrospective multicenter study (January 1, 2016 to December 31, 2018) in adult allogeneic-HCTr who received PCZ (intravenously, IV and/or as delayed-release tablet, DRT) as prophylaxis or treatment for ≥7 consecutive days (D) with at least 1-PCZ-level available using data of the Swiss Transplant Cohort Study. The primary objective was to describe the distribution of PCZ-level and identify predictors of therapeutic PCZ-level and associations between PCZ-dosing and PCZ-level. A total of 288 patients were included: 194 (67.4%) and 94 (32.6%) received PCZ as prophylaxis and treatment, respectively, for a median of 90 days (interquartile range, IQR: 42-188.5). There were 1944 PCZ-level measurements performed, with a median PCZ level of 1.3 mg/L (IQR: 0.8-1.96). PCZ-level was <0.7 mg/L in 383/1944 (19.7%) and <1.0 mg/L in 656/1944 (33.7%) samples. PCZ-level was <0.7 mg/L in 260/1317 (19.7%) and <1.0 mg/L in 197/627 (31.4%) in patients who received PCZ-prophylaxis versus treatment, respectively. There were no significant differences in liver function tests between baseline and end-of-treatment. There were nine (3.1%) breakthrough invasive fungal infections (bIFI), with no difference in PCZ levels between patients with or without bIFI. Despite a very intensive PCZ-TDM, PCZ-levels remain below target levels in up to one-third of allogeneic-HCTr. Considering the low incidence of bIFI observed among patients with PCZ levels in the targeted range, our data challenge the clinical utility of routine universal PCZ-TDM.
PathFinder: Bayesian inference of clone migration histories in cancer

Summary Metastases form by dispersal of cancer cells to secondary tissues. They cause a vast majority of cancer morbidity and mortality. Metastatic clones are not medically detected or visible until later stages of cancer development. Thus, clone phylogenies within patients provide a means of tracing the otherwise inaccessible dynamic history of migrations of cancer cells. Here we present a new Bayesian approach, PathFinder, for reconstructing the routes of cancer cell migrations. PathFinder uses the clone phylogeny and the numbers of mutational differences among clones, along with the information on the presence and absence of observed clones in different primary and metastatic tumors. In the analysis of simulated datasets, PathFinder performed well in reconstructing migrations from the primary tumor to new metastases as well as between metastases. However, it was much more challenging to trace migrations from metastases back to primary tumors. We found that a vast majority of errors can be corrected by sampling more clones per tumor and by increasing the number of genetic variants assayed. We also identified situations in which phylogenetic approaches alone are not sufficient to reconstruct migration routes. Conclusions We anticipate that the use of PathFinder will enable a more reliable inference of migration histories, along with their posterior probabilities, which is required to assess the relative preponderance of seeding of new metastasis by clones from primary tumors and/or existing metastases. Availability PathFinder is available on the web at https://github.com/SayakaMiura/PathFinder. Contact s.kumar@temple.edu
Vegetarian Diets and Eating Disorders in Adolescents and Young Adults: A Systematic Review

Background: Eating disorders are more common among adolescents and young adults. An increase in the rates of these disorders has been reported during the last years. Meanwhile, vegetarianism is becoming more popular in these age groups. The purpose of the present paper is to evaluate the association between eating disorders and vegetarian diets in adolescents and young adults. Methods: Systematic review of related articles published in PubMed, PsycInfo and Google Scholar up to 30 May 2019. Results: A total of 20 studies (14,391 subjects) were deemed eligible for this systematic review. The majority of the studies reported significant correlations between vegetarianism and eating disorders. However, due to the cross-sectional design, a causal link between eating disorders and vegetarian status cannot be established. Conclusions: Vegetarianism seems to be associated with eating disorders. Longitudinal studies are needed to establish temporal patterns between vegetarianism and the emergence of disordered eating.
Semi-Destructive and Non-Destructive Tests of Timber Structure of Various Moisture Contents

The condition of heritage and historic timber constructions depends on how they are exploited. Numerous environmental factors degrade the physical and mechanical properties of timber and hence, affect the load-bearing capacity of constructions. As a result, frequent evaluations of their technical condition become necessary. Currently, modern technologies allow for extensive diagnostics of timber constructions using non-destructive and semi-destructive methods; yet, in contrast to classical laboratory tests, there is insufficient knowledge of the impact of individual factors on the results of such studies. This article presents an assessment of the influence of the moisture content of timber elements on the results of ultrasonic stress wave, sclerometric, and resistance drilling tests. Additionally, computed tomography scans were performed on selected samples to demonstrate the destruction mechanism occurring during the semi-destructive tests. The research involved three types of wood: pine, spruce, and fir of different moisture contents. The results reveal a strong relation between the moisture of timber and all the tests conducted in terms of both hygroscopic and capillary moisture.
Incidence of septicemia. Etiology and antimicrobial susceptibility testing among patients admitted to tertiary care hospital.

INTRODUCTION Septicemia is considered as an important cause of life-threating infections. The study was aimed at determining the incidence of septicemia considering different age groups and gender among suspected patients admitted to a tertiary care hospital in Iraq. METHODOLOGY A total of 168 blood samples were collected and cultured using BacT/Alert 3D automated system. The isolated pathogens were identified and subjected to antimicrobial susceptibility testing using automated Vitek 2 Compact system. RESULTS Out of 168 blood samples, 53 (31.5%) gave positive microbial growth. Thirty-three samples (62.3%) came from male patients and 20 (37.7%) from female ones, both gender and microbial growth were significantly related (P < 0.05). Age group (21 year - 30 year) was found to have the highest percentage of positive growth (26.4%) while age group (51 year - 60 year) the lowest percentage (5.7%) of positive growth. Both microbial growth and age group were found to be associated to a significant level (P < 0.05). 36 isolates (67.9%) were Gram negative, 15 isolates (28.3%) were Gram-positive and 2 isolates (3.8%) were fungi. Salmonella typhi (41.7%) represented the most common pathogen isolated followed by Acinetobacter baumannii (22.2%). An isolate of Pseudomonas aeruginosa showed resistance to all antibiotics used. CONCLUSION Community-acquired septicemia occurred mainly in male than female. Salmonella typhi and Acinetobacter baumannii represented the most frequent causative agents of community-acquired septicemia. Antimicrobial susceptibility testing should be performed to detect the antibiotic of choice for each pathogen causing community-acquired septicemia.
The modern management of Barrett’s oesophagus and related neoplasia: role of pathology

Modern management of Barrett’s oesophagus and related neoplasia essentially focuses upon surveillance to detect early low‐risk neoplastic lesions and offering organ‐preserving advanced endoscopic therapies, while traditional surgical treatments of oesophagectomy and lymph node clearance with or without chemoradiation are preserved only for high‐risk and advanced carcinomas. With this evolution towards figless invasive therapy, the choice of therapy hinges upon the pathological assessment for risk stratifying patients into those with low risk for nodal metastasis who can continue with less invasive endoscopic therapies and others with high risk for nodal metastasis for which surgery or other forms of treatment are indicated. Detection and confirmation of neoplasia in the first instance depends upon endoscopic and pathological assessment. Endoscopic examination and biopsy sampling should be performed according to the recommended protocols, and endoscopic biopsy interpretation should be performed applying standard criteria using appropriate ancillary studies by histopathologists experienced in the pathology of Barrett’s disease. Endoscopic resections (ERs) are both diagnostic and curative and should be performed by clinicians who are skilled with advanced endoscopic techniques. Proper preparation and handling of ERs are essential to assess histological parameters that dictate the curative nature of the procedure. Those parameters are adequacy of resection and risk of lymph node metastasis. The risk of lymph node metastasis is determined by depth invasion and presence of poor differentiation and lymphovascular invasion. Those adenocarcinomas with invasion up to muscularis mucosae (pT1a) and those with superficial submucosal invasion (pT1b) up to 500 µ with no poor differentiation and lymphovascular invasion and negative margins may be considered cured by endoscopic resections.
A Comprehensive Review of Coronavirus Disease 2019: Epidemiology, Transmission, Risk Factors, and International Responses

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide pandemic. The first reports of patients with COVID-19 were provided to World Health Organization on December 21, 2019 and were presumably associated with seafood markets in Wuhan, China. As of October 25, 2020, more than 42 million cases have been confirmed worldwide, with more than 1.1 million deaths. Asymptomatic transmission contributes significantly to transmission, and clinical features are non-specific to the disease. Thus, the diagnosis of COVID-19 requires specific viral RNA testing. The disease demonstrates extensive human-to-human transmissibility and has infected healthcare workers at high rates. Clinical awareness of the epidemiology and the risk factors for nosocomial transmission of COVID-19 is essential to preventing infection. Moreover, effective control measures should be further identified by comprehensive evaluation of hospital and community responses. In this review, we provide a comprehensive update on the epidemiology, presentation, transmission, risk factors, and public health measures associated with COVID-19. We also review past insights from previous coronavirus epidemics [i.e., severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)] to suggest measures to reduce transmission.
A Formulation for the Static Permittivity of Water and Steam at Temperatures from 238 K to 873 K at Pressures up to 1200 MPa, Including Derivatives and Debye–Hückel Coefficients

A new formulation is presented of the static relative permittivity or dielectric constant of water and steam, including supercooled and supercritical states. The range is from 238 K to 873 K, at pressures up to 1200 MPa. The formulation is based on the ITS-90 temperature scale. It correlates a selected set of data from a recently published collection of all experimental data. The set includes new data in the liquid water and the steam regions that have not been part of earlier correlations. The physical basis for the formulation is the so-called g-factor in the form proposed by Harris and Alder. An empirical 12-parameter form for the g-factor as a function of the independent variables temperature and density is used. For the conversion of experimental pressures to densities, the newest formulation of the equation of state of water on the ITS-90, prepared by Wagner and Pruss, has been used. All experimental data are compared with the formulation. The reliability of the new formulation is assessed in all su.
Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota

ABSTRACT Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.
Randomised clinical trial comparing concomitant and hybrid therapy for eradication of Helicobacter pylori infection.

BACKGROUND The primary objective of this study was to compare concomitant and hybrid therapy in the first line eradication treatment of Helicobacter pylori infection in Split-Dalmatia County, Croatia, in which clarithromycin resistance is above 20%. The secondary objective of the study was to determine and compare compliance and adverse events rate between these therapeutic protocols. MATERIALS AND METHODS In an open-label, randomised clinical trial 140 patients total with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 g, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or hybrid (esomeprazole 40 mg and amoxicillin 1 g twice daily during 14 days with adding metronidazole 500 mg and clarithromycin 500 mg twice daily, in the last 7 days,) treatment group. RESULTS Eradication rates for concomitant group and hybrid therapy group were 84.1% (58/69) and 83.1% (59/71) respectively in the intention-to-treat analysis and 96.7% (58/60) and 95.2% (59/62) in per-protocol analysis. There was no significant difference between the groups (ITT analysis: P = 0.878; PP analysis: P = 0.675). Adverse events were more frequent in the concomitant group (33.3% vs 18.3%, P = 0.043). There was no difference among groups regarding compliance rate. CONCLUSION Hybrid therapy has similar eradication rate as concomitant therapy, with lower adverse events rate. In the era of increasing antibiotic resistance, eradication regime with less antibiotic's usage, as hybrid therapy, should be reasonable first line treatment choice for H. pylori infection. Clinical Trials, gov: NCT03572777.
Toll-like receptor 4/nuclear factor-kappa B pathway is involved in radicular pain by encouraging spinal microglia activation and inflammatory response in a rat model of lumbar disc herniation

Background Lumbar disc herniation (LDH) is a common cause of radicular pain, but the mechanism is not clear. In this study, we investigated the engagement of toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) in radicular pain and its possible mechanisms. Methods An LDH model was induced by autologous nucleus pulposus (NP) implantation, which was obtained from coccygeal vertebra, then relocated in the lumbar 4/5 spinal nerve roots of rats. Mechanical and thermal pain behaviors were assessed by using von Frey filaments and hotplate test respectively. The protein level of TLR4 and phosphorylated-p65 (p-p65) was evaluated by western blotting analysis and immunofluorescence staining. Spinal microglia activation was evaluated by immunofluorescence staining of specific relevant markers. The expression of pro- and anti-inflammatory cytokines in the spinal dorsal horn was measured by enzyme linked immunosorbent assay. Results Spinal expression of TLR4 and p-NF-κB (p-p65) was significantly increased after NP implantation, lasting up to 14 days. TLR4 was mainly expressed in spinal microglia, but not astrocytes or neurons. TLR4 antagonist TAK242 decreased spinal expression of p-p65. TAK242 or NF-κB inhibitor pyrrolidinedithiocarbamic acid alleviated mechanical and thermal pain behaviors, inhibited spinal microglia activation, moderated spinal inflammatory response manifested by decreasing interleukin (IL)-1β, IL-6, tumor necrosis factor-α expression and increasing IL-10 expression in the spinal dorsal horn. Conclusions The study revealed that TLR4/NF-κB pathway participated in radicular pain by encouraging spinal microglia activation and inflammatory response.
Terahertz Broadband Polarization Conversion for Transmitted Waves Based on Graphene Plasmon Resonances

We applied the harmonic oscillator model combined with the transfer matrix method to study the polarization conversion for transmitted waves in metallic grating/plasmon-excitation layer/metallic grating structure in the terahertz (THz) region. By comparing the calculated spectra and the simulated (by the finite-difference-time-domain method) ones, we found that they correspond well with each other. Both methods show that the Drude background absorption and the excited plasmon resonances are responsible for polarization conversion. The transmission is close to 0 when the distance between the top/bottom metallic gratings and gated graphene is an integer multiple of half the wavelength of the incident wave (in the dielectrics), at which points the plasmon resonances are greatly suppressed by the destructive interference between the backward/forward electromagnetic waves and that reflected by the top/bottom metallic gratings. Away from these points, the transmission can be higher than 80%. The electron density and the excitation efficiency of the plasmon-excitation layer were found to be important for the bandwidth of the polarization conversion window, while the scattering rate was found to influence mainly the polarization conversion rate. Multi-broadband polarization conversion is realized by exciting plasmon modes between the 0 transmission points in the THz region.
Implant functionalization with mesoporous silica: A promising antibacterial strategy, but does such an implant osseointegrate?

New strategies for implant surface functionalization in the prevention of peri‐implantitis while not compromising osseointegration are currently explored. The aim of this in vivo study was to assess the osseointegration of a titanium‐silica composite implant, previously shown to enable controlled release of therapeutic concentrations of chlorhexidine, in the Göttingen mini‐pig oral model.
Serum Adipocytokines Levels and Their Association with Insulin Sensitivity in Morbidly Obese Individuals Undergoing Bariatric Surgery

Background Obese adipose tissue secretes a variety of adipocytokines that act as metabolic regulators with complex mechanisms. Our objective was to compare serum concentration of a panel of adipocytokines between obese and non-obese individuals and identify any distinct patterns correlating with insulin sensitivity in obesity. Methods We designed a cross-sectional study among obese (body mass index [BMI] ≥30 kg/m2, n=62) and non-obese (BMI <25 kg/m2, n=32) individuals to compare circulating levels of the adipokines, such as adiponectin and resistin in conjunction with the measurement of the levels of inflammatory cytokines including C-reactive protein (CRP), interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α using Luminex multiplex immunoassay with drop array technology. Correlations between circulating adipocytokine levels and those of multiple well-established markers of insulin resistance including homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β) and quantitative insulin sensitivity check index were also established. Results CRP, IL-8, MCP-1, and TNF-α levels were higher in obese than non-obese individuals; the CRP and IL-8 differences were statistically significant. CRP correlated significantly with markers of insulin resistance (fasting plasma insulin, HOMA-IR, and QUICKI), and adiponectin correlated with HOMA-β in obese individuals. We divided the group of obese individuals on the basis of HOMA-IR levels into insulin-resistant (IR; HOMA-IR ≥2.5) and insulin-sensitive (IS; HOMA-IR <2.5) groups; and 43 out of 62 participants were IR despite comparable BMIs. An overall proinflammatory profile was compared between IR and IS obese, though the values were higher in IR obese but the difference was not significant. Conclusion Obesity is associated with a general inflammatory milieu and a crosstalk between adipocytokines and insulin resistance is complex as well as multifactorial.
Flap Failure and Salvage in Head and Neck Reconstruction

Abstract With advanced head and neck ablative surgery comes the challenge to find an ideal reconstructive option that will optimize functional and aesthetic outcomes. Contemporary microvascular reconstructive surgery with free tissue transfer has become the standard for complex head and neck reconstruction. With continued refinements in surgical techniques, larger surgical volumes, and technological advancements, free flap success rates have exceeded 95%. Despite these high success rates, postoperative flap loss is a feared complication requiring the surgeon to be aware of potential options for successful salvage. The purpose of this article is to review free flap failure and ways to optimize surgical salvage in the scenario of flap compromise.