Miracle-dz/UniFAR-FTUs huggingface dataset:
Nutrition and the gut microbiome during critical illness: A new insight of nutritional therapy

Changes in the microbiome in response to environmental influences can affect the overall health. Critical illness is considered one of the major environmental factors that can potentially influence the normal gut homeostasis. It is associated with pathophysiological effects causing damage to the intestinal microbiome. Alteration of intestinal microbial composition during critical illness may subsequently compromise the integrity of the intestinal epithelial barrier and intestinal mucosa absorptive function. Many factors can impact the microbiome of critically ill patients including ischemia, hypoxia and hypotension along with the iatrogenic effects of therapeutic agents and the lack of enteral feeds. Factors related to disease state and medication are inevitable and they are part of the intensive care unit (ICU) exposure. However, a nutritional intervention targeting gut microbiota might have the potential to improve clinical outcomes in the critically ill population given the extensive vascular and lymphatic links between the intestines and other organs. Although nutrition is considered an integral part of the treatment plan of critically ill patients, still the role of nutritional intervention is restricted to improve nitrogen balance. What is dismissed is whether the nutrients we provide are adequate and how they are processed and utilised by the host and the microbiota. Therefore, the goal of nutrition therapy during critical illness should be extended to provide good quality feeds with balanced macronutrient content to feed up the entire body including the microbiota and host cells. The main aim of this review is to examine the current literature on the effect of critical illness on the gut microbiome and to highlight the role of nutrition as a factor affecting the intestinal microbiome-host relationship during critical illness.
Unbiased High-Throughput Drug Combination Pilot Screening Identifies Synergistic Drug Combinations Effective against Patient-Derived and Drug-Resistant Melanoma Cell Lines

We describe the development, optimization, and validation of 384-well growth inhibition assays for six patient-derived melanoma cell lines (PDMCLs), three wild type (WT) for BRAF and three with V600E-BRAF mutations. We conducted a pilot drug combination (DC) high-throughput screening (HTS) of 45 pairwise 4×4 DC matrices prepared from 10 drugs in the PDMCL assays: two B-Raf inhibitors (BRAFi), a MEK inhibitor (MEKi), and a methylation agent approved for melanoma; cytotoxic topoisomerase II and DNA methyltransferase chemotherapies; and drugs targeting the base excision DNA repair enzyme APE1 (apurinic/apyrimidinic endonuclease-1/redox effector factor-1), SRC family tyrosine kinases, the heat shock protein 90 (HSP90) molecular chaperone, and histone deacetylases. Pairwise DCs between dasatinib and three drugs approved for melanoma therapy—dabrafenib, vemurafenib, or trametinib—were flagged as synergistic in PDMCLs. Exposure to fixed DC ratios of the SRC inhibitor dasatinib with the BRAFis or MEKis interacted synergistically to increase PDMCL sensitivity to growth inhibition and enhance cytotoxicity independently of PDMCL BRAF status. These DCs synergistically inhibited the growth of mouse melanoma cell lines that either were dabrafenib-sensitive or had acquired resistance to dabrafenib with cross resistance to vemurafenib, trametinib, and dasatinib. Dasatinib DCs with dabrafenib, vemurafenib, or trametinib activated apoptosis and increased cell death in melanoma cells independently of their BRAF status or their drug resistance phenotypes. These preclinical in vitro studies provide a data-driven rationale for the further investigation of DCs between dasatinib and BRAFis or MEKis as candidates for melanoma combination therapies with the potential to improve outcomes and/or prevent or delay the emergence of disease resistance.
Sequence analysis in Bos taurus reveals pervasiveness of X–Y arms races in mammalian lineages

Studies of Y Chromosome evolution have focused primarily on gene decay, a consequence of suppression of crossing-over with the X Chromosome. Here, we provide evidence that suppression of X–Y crossing-over unleashed a second dynamic: selfish X–Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of Bos taurus (bull) and find it to be dominated by massive, lineage-specific amplification of testis-expressed gene families, making it the most gene-dense Y Chromosome sequenced to date. As in mice, an X-linked homolog of a bull Y-amplified gene has become testis-specific and amplified. This evolutionary convergence implies that lineage-specific X–Y coevolution through gene amplification, and the selfish forces underlying this phenomenon, were dominatingly powerful among diverse mammalian lineages. Together with Y gene decay, X–Y arms races molded mammalian sex chromosomes and influenced the course of mammalian evolution.
Technical and Methodological Aspects of Cell-Free Nucleic Acids Analyzes

Analyzes of cell-free nucleic acids (cfNAs) have shown huge potential in many biomedical applications, gradually entering several fields of research and everyday clinical care. Many biological properties of cfNAs can be informative to gain deeper insights into the function of the organism, such as their different types (DNA, RNAs) and subtypes (gDNA, mtDNA, bacterial DNA, miRNAs, etc.), forms (naked or vesicle bound NAs), fragmentation profiles, sequence composition, epigenetic modifications, and many others. On the other hand, the workflows of their analyzes comprise many important steps, from sample collection, storage and transportation, through extraction and laboratory analysis, up to bioinformatic analyzes and statistical evaluations, where each of these steps has the potential to affect the outcome and informational value of the performed analyzes. There are, however, no universal or standard protocols on how to exactly proceed when analyzing different cfNAs for different applications, at least according to our best knowledge. We decided therefore to prepare an overview of the available literature and products commercialized for cfNAs processing, in an attempt to summarize the benefits and limitations of the currently available approaches, devices, consumables, and protocols, together with various factors influencing the workflow, its processes, and outcomes.
Settleable Dust and Bioburden in Portuguese Dwellings

Monitoring campaigns in several buildings have shown that occupants exposed to contaminated indoor air generally exhibit diverse health symptoms. This study intends to assess settleable dust loading rates and bioburden in Portuguese dwellings by passive sampling onto quartz fiber filters and electrostatic dust cloths (EDCs), respectively. Settled dust collected by EDCs was analyzed by culture-based methods (including azole-resistance screening) and qPCR, targeting four different toxigenic Aspergillus sections (Flavi, Fumigati, Circumdati, and Nidulantes). Dust loading rates and bioburden showed higher variability in the summer season. In both seasons, Penicillium sp. was the one with the highest prevalence (59.1% winter; 58.1% summer), followed by Aspergillus sp. in winter (13.0%). Fungal contamination increased in the winter period, while bacterial counts decreased. Aspergillus sections Circumdati and Nidulantes, detected in voriconazole supplemented media, and Aspergillus sections Fumigati and Nidulantes, detected by molecular tools, were found in the winter samples. This study reinforces the importance of applying: (a) Passive sampling methods in campaigns in dwellings; (b) two different culture media (MEA and DG18) to assess fungi; (c) in parallel, molecular tools targeting the most suitable indicators of fungal contamination; and (d) azole resistance screening to unveil azole resistance detection in fungal species.
Online Proximal Learning Over Jointly Sparse Multitask Networks With $\ell _{\infty, 1}$ Regularization

Modeling relations between local optimum parameter vectors to estimate in multitask networks has attracted much attention over the last years. This work considers a distributed optimization problem with jointly sparse structure among nodes, that is, the local solutions have the same sparse support set. Several mixed norm have been proposed to address the jointly sparse structure in the literature. Among several candidates, the (reweighted) <inline-formula><tex-math notation="LaTeX">$\ell _{\infty,1}$</tex-math></inline-formula>-norm is element-wise separable, it is more convenient to evaluate their approximate proximal operators. Thus by introducing a (reweighted) <inline-formula><tex-math notation="LaTeX">$\ell _{\infty,1}$</tex-math></inline-formula>-norm penalty term at each node, and using a proximal gradient method to minimize the regularized cost, we devise a proximal multitask diffusion LMS algorithm which can promote joint-sparsity. Analyses are provided to characterize the algorithm behavior in the mean and mean-square sense. Simulation results are presented to show its effectiveness, as well as the accuracy of the theoretical findings.
A Review of Wood Biomass-Based Fatty Acids and Rosin Acids Use in Polymeric Materials

In recent decades, vegetable oils as a potential replacement for petrochemical materials have been extensively studied. Tall oil (crude tall oil, distilled tall oil, tall oil fatty acids, and rosin acids) is a good source to be turned into polymeric materials. Unlike vegetable oils, tall oil is considered as lignocellulosic plant biomass waste and is considered to be the second-generation raw material, thus it is not competing with the food and feed chain. The main purpose of this review article is to identify in what kind of polymeric materials wood biomass-based fatty acids and rosin acids have been applied and their impact on the properties.
Analysis of predictors of response to ruxolitinib in patients with myelofibrosis in the phase 3b expanded-access JUMP study

Abstract Data from the large, prospective, multinational, phase 3b JUMP study were analyzed to identify factors predictive of spleen and symptom responses in myelofibrosis patients receiving ruxolitinib. Factors associated with higher spleen response rates included International Prognostic Scoring System (IPSS) low/intermediate-1 risk vs intermediate-2/high risk (43.1% vs 30.6%; adjusted OR [aOR] 0.65 [95% CI 0.44–0.95]), ruxolitinib as first- vs second- or later-line therapy (40.2% vs 31.5%; aOR 0.53 [95% CI 0.38–0.75]), and a ruxolitinib total daily dose at Week 12 of >20 mg/day vs ≤20 mg/day (41.3% vs 30.4%; aOR 0.47 [95% CI 0.33–0.68]). No association was seen between baseline characteristics or total daily dose at Week 12 and symptom response. Ruxolitinib led to higher spleen response rates in patients with lower IPSS risk, and when used earlier in treatment. Higher doses of ruxolitinib were associated with higher spleen response rates, but not with symptom improvement. Trial registration INC424 for patients with primary myelofibrosis, post polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis (JUMP). 2010-024473-39; NCT01493414 Date of registration: 16 December 2011 https://www.clinicaltrialsregister. eu/ctr-search/search? query=2010-024473-39 https://clinicaltrials.gov/ct2/show/NCT01493414
Mediterranean Lifestyle to Promote Physical, Mental, and Environmental Health: The Case of Chile

Chile is currently experiencing a progressive epidemiological transition towards chronic diseases. In this country, >50% of annual deaths are attributed to cardiovascular disease and cancer. Moreover, health surveys have shown high prevalence of obesity, diabetes, hypertension, and elevated cardiovascular disease risk. In addition, mental health issues are also frequent among Chilean adults. On the other hand, the agri-food system contributes to 21–37% of greenhouse gases emissions worldwide. Overall, current health and food chain situation calls out for design and implementation of evidence-based feasible and effective nutritional interventions needed to promote physical and mental health along with addressing food sustainability in Chile. Nowadays, the Mediterranean diet is recognized as one of the healthiest dietary patterns based on observational and interventional studies linked to a wide variety of health outcomes. However, a Mediterranean lifestyle goes well beyond food intake: it includes promotion of psychosocial resources, community life as well as cultural traditions. Indeed, Mediterranean lifestyle is a true modus vivendi that integrally promotes physical, mental, and social well-being. In addition, the Mediterranean diet stands out for its environmental sustainability because it is characterized mainly as a plant-based dietary pattern with low carbon and water footprints. Remarkably, Central Chile has a Mediterranean-like setting with plant and animal food production and availability patterns comparable to those present in countries located around the Mediterranean Sea. Therefore, this article reviews how promotion of Mediterranean lifestyle adherence in Chile offers great potential for management of the ongoing epidemiological transition to chronic diseases as well to promote psychological well-being within a unique food system and dietary sustainability vision for this Latin American country.
Role of EEG in Predicting Outcome of Hepatic Encephalopathy Patients

ABSTRACT Introduction: A retrospective analysis of 151 patients with hepatic encephalopathy (HE) who were admitted to the liver intensive care unit (LICU) and liver transplant intensive care unit (TICU) and underwent electroencephalographic (EEG) testing was performed. We describe a method of grading the EEGs of patients with HE and predicting their subsequent outcomes. Methods: All liver failure patients with HE who underwent routine EEG testing in the LICU or TICU between October 1, 2018 and March 31, 2019, at the Institute of Liver and Biliary Sciences (ILBS) were enrolled in this analysis. The data was analyzed using Statistical Package for the Social Sciences (SPSS). The patients were divided into four grades of HE based on established EEG criteria (HE-EEG). Results: One hundred fifty-one patients [127 Male (84%), 24 Female (16%)] with HE who underwent EEG testing were enrolled. Ages ranged from 3 to 74 years, with a mean age of 48.34 years and median interquartile range (IQR) of 49 years (38–60 years). Ninety-five patients (62.9%) had grade 1 and 2 hepatic encephalopathy, with a statistically significant, worse outcome seen in grades 3 and 4 HE patients. Seizures were seen in 30 (20.1%) of HE patients. Fifteen of 30 patients with seizures (50%) were in the ethanol and nonalcoholic steatohepatitis (NASH) groups. Forty-four of 59 (74.6%) MRIs and 35 of 60 (58.3%) CTs demonstrated some type of brain abnormality in these patients. Imaging abnormalities and the presence of seizures did not contribute to a statistically worse outcome. Conclusion: EEG has an important role in predicting the outcome and prognosis in HE. Patients with grade 3 or 4 HE-EEG, or with progressive worsening of HE-EEG grading were associated with the highest mortality rates.
Circulating tumor DNA as a potential prognostic and predictive biomarker during interventional therapy of unresectable primary liver cancer.

Background Imaging and alpha fetoprotein (AFP) measurement are used as surveillance methods during interventional therapy in patients with unresectable liver cancer, but their accuracy has been challenged in patients receiving drug perfusion therapy. Circulating tumor DNA (ctDNA) can reflect tumor load and treatment efficacy. Studies of the prognostic value of ctDNA in unresectable liver cancer are needed. Methods Forty-two patients with unresectable liver cancer were prospective enrolled in this study. Pre-treatment, in-treatment plasma samples and available matched tissue samples were collected. Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors. Results Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors revealed that the most frequently mutated genes in ctDNA were TP53 (52.4%) and TERT (35.7%). The ctDNA abundance was more closely correlated with tumor size than the AFP level and was also related to BCLC stage (P<0.001). Gene mutations profile in ctDNA with progressed disease. PD patients were enriched in TP53 mutation group compared with TP53 wildtype group (P=0.0221). Moreover, interventional therapy was more effective in patients without TP53 mutation (OS: P=0.0589; PFS: 0.0411). The dynamic change of ctDNA showed consistent or more sensitivity than imaging for evaluating treatment response. The tumor mutation burden was highly consistent between tissue and blood samples (P<0.0001). Conclusions ctDNA was a reliable biomarker to assist in diagnosis and evaluation of prognosis and treatment efficacy in advanced liver cancer. Considering that biopsy is unnecessary when advanced liver cancer is diagnosed, ctDNA may be an ideal biomarker for evaluating tumor mutation burden prior to immunotherapy.
Research Trends in Green Product for Environment: A Bibliometric Perspective

The term “green products” is used commonly to describe the products that seek to protect or enhance the environment during production, use, or disposal by conserving resources and minimizing the use of toxic agents, pollution, and waste. Hence, green products offer potential benefits to the environment and human health. Therefore, environmentally conscious consumers have shown an enhanced inclination for them. Consumer preferences, environmental activism, and stringent regulations have forced sustainability-oriented firms to shift their focus to producing green products. The present study uses bibliometric tools and various indicators to discern research progress in the field of green products over the period 1964–2019. Further, VOSviewer software is applied to map the main trends. A total of 1619 publications during the study period were extracted from the SCOPUS database using different keywords related to the green products. The data analysis indicates that the field of green products has experienced significant growth since 1964, especially in the last 14 years. In terms of publications and citations, the United States is the leading country. The field of research concerning green products has evolved from the early debates on sustainable design, green marketing, sustainable development, and sustainability. The topic seems to be advancing into a variety of green themes related to consumer trust and purchase intentions, branding and loyalty, and environmental and health consciousness.
Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability

Mitochondria are constantly subjected to stressful conditions due to their unique physiology and organization. The resulting damage leads to mitochondrial dysfunction, which underlies many pathophysiological conditions. Hence, constant surveillance is required to closely monitor mitochondrial health for sound maintenance of cellular metabolism and thus, for viability. In addition to internal mitochondrial chaperones and proteases, mitochondrial health is also governed by host cell protein quality control systems. The ubiquitin-proteasome system (UPS) and autophagy constitute the main pathways for removal of damaged or superfluous proteins in the cytosol, nucleus, and from certain organelles such as the Endoplasmic Reticulum (ER) and mitochondria. Although stress-induced ubiquitin-dependent degradation of mitochondrial outer membrane proteins has been widely studied, mechanisms of intramitochondrial protein ubiquitination has remained largely elusive due to the predominantly cytosolic nature of UPS components, separated from internal mitochondrial proteins by a double membrane. However, recent research has illuminated examples of intramitochondrial protein ubiquitination pathways and highlighted their importance under basal and stressful conditions. Owing to the dependence of mitochondria on the error-prone process of protein import from the cytosol, it is imperative that the cell eliminate any accumulated proteins in the event of mitochondrial protein import deficiency. Apparently, a significant portion of this activity involves ubiquitination in one way or another. In the present review article, following a brief introduction to mitochondrial protein quality control mechanisms, we discuss our recent understanding of intramitochondrial protein ubiquitination, its importance for basal function of mitochondria, metabolic implications, and possible therapeutic applications.
Risk Factors and Outcome of C. difficile Infection after Hematopoietic Stem Cell Transplantation

Patients who undergo hematopoietic stem cell transplants (HSCT) are at major risk of C. difficile (CD) infection (CDI), the most common cause of nosocomial diarrhea. We conducted a retrospective study, which enrolled 481 patients who underwent autologous (220) or allogeneic HSCT (261) in a 5-year period, with the aim of identifying the incidence, risk factors and outcome of CDI between the start of conditioning and 100 days after HSCT. The overall cumulative incidence of CDI based upon clinical evidence was 5.4% (95% CI, 3.7% to 7.8%), without any significant difference between the two types of procedures. The median time between HSCT and CDI diagnosis was 12 days. Out of 26 patients, 19 (73%) with clinical and symptomatic evidence of CDI were positive also for enzymatic or molecular detection of toxigenic CD; in particular, in 5 out of 26 patients (19%) CD binary toxin was also detected. CDI diagnoses significantly increased in the period 2018–2019, since the introduction in the microbiology lab unit of the two-step diagnostic test based on GDH immunoenzymatic detection and toxin B/binary toxin/027 ribotype detection by real-time PCR. Via multivariate analysis, abdominal surgery within 10 years before HSCT (p = 0.002), antibiotic therapy within two months before HSCT (p = 0.000), HCV infection (p = 0.023) and occurrence of bacterial or fungal infections up to 100 days after HSCT (p = 0.003) were significantly associated with a higher risk of CDI development. The 26 patients were treated with first-line vancomycin (24) or fidaxomicine (2) and only 2 patients needed a second-line treatment, due to the persistence of stool positivity. No significant relationship was identified between CDI and the development of acute graft versus host disease (GVHD) after allogeneic HSCT. At a median follow-up of 25 months (range 1–65), the cumulative incidence of transplant related mortality (TRM) was 16.6% (95% CI 11.7% to 22.4%) and the 3-year overall survival (OS) was 67.0% (95% CI 61.9% to 71.6%). The development of CDI had no significant impact on TRM and OS, which were significantly impaired in the multivariate analysis by gastrointestinal and urogenital comorbidities, severe GVHD, previous infections or hospitalization within two months before HSCT, active disease at transplant and occurrence of infections after HSCT. We conclude that 20% of all episodes of diarrhea occurring up to 100 days after HSCT were related to toxigenic CD infection. Patients with a history of previous abdominal surgery or HCV infection, or those who had received broad spectrum parenteral antibacterial therapy were at major risk for CDI development. CDIs were successfully treated with vancomycin or fidaxomicin after auto-HSCT as well as after allo-HSCT.