Miracle-dz/UniFAR-FTUs huggingface dataset:
Doxorubicin delivery systems based on doped CaCO3 cores and polyanion drug conjugates

Abstract In order to prolong the release and reduce the toxicity of anticancer drug – doxorubicin (DOX), delivery systems (DS) using different polyanions have been developed. Structural (size, morphological stability) and functional (encapsulation efficiency, DOX release) characteristics of three types of DS are compared: CaCO3 porous vaterites doped with polyanions by co-precipitation and coating techniques, and DOX-polyanion conjugates. Using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS), it was shown that the doping enhances the morphological stability of CaCO3-based DS during the DOC loading. Doping of CaCO3 cores by co-precipitation reduces its sizes (up to 1 µm) and DOX encapsulation efficiency. Polyanion-coated CaCO3 cores and polyanion drug conjugates show about 98 w/w% DOX encapsulation. For the first time, it was shown that the release of DOX from developed DS into human blood plasma is more intense (from 1.3 to 3.0 times for different DS) than into model tumour environment.
Vancomycin Intoxication and Cefepime-induced Encephalopathy Treated by Abdominal Drainage of Massive Ascites in Addition to Online Hemodiafiltration

A patient with recurrent plasmacytoma with massive ascites exhibited vancomycin intoxication and cefepime-induced encephalopathy due to renal dysfunction. The ascitic accumulation of these drugs was suspected because of the refractory intoxicated state. To remove these drugs that had accumulated in the blood and ascites, abdominal drainage was performed in addition to online hemodiafiltration. If patients with renal dysfunction and massive ascites develop vancomycin intoxication and cefepime-induced encephalopathy that cannot be improved by drug discontinuation, physicians should suspect ascitic accumulation and evaluate the ascitic concentration. Furthermore, if a high accumulation in massive ascites occurs, physicians should perform abdominal drainage along with blood purification.
Lynch Syndrome: Its Impact on Urothelial Carcinoma

Lynch syndrome, known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal-dominant familial cancer syndrome with an increased risk for urothelial cancer (UC). Mismatch repair (MMR) deficiency, due to pathogenic variants in MLH1, MSH2, MSH6, and PMS2, and microsatellite instability, are known for development of Lynch syndrome (LS) associated carcinogenesis. UC is the third most common cancer type in LS-associated tumors. The diversity of germline variants in the affected MMR genes and their following subsequent function loss might be responsible for the variation in cancer risk, suggesting an increased risk of developing UC in MSH2 mutation carriers. In this review, we will focus on LS-associated UC of the upper urinary tract (UUT) and bladder, their germline profiles, and outcomes compared to sporadic UC, the impact of genetic testing, as well as urological follow-up strategies in LS. In addition, we present a case of metastatic LS-associated UC of the UUT and bladder, achieving complete response during checkpoint inhibition since more than 2 years.
ECCO Topical Review Optimising reporting in surgery, endoscopy, and histopathology.

BACKGROUND AND AIMS Diagnosis and management of inflammatory bowel diseases (IBD) requires a lifelong multidisciplinary approach. The quality of medical reporting is essential in this context. The present topical review addresses the need for optimised reporting in endoscopy, surgery, and histopathology. METHODS A consensus expert panel consisting of gastroenterologists, surgeons, and pathologists convened by the European Crohn's and Colitis Organisation performed a systematic literature review. Following topics were covered: In endoscopy: (i) general IBD endoscopy; (ii) disease activity and surveillance; (iii) endoscopy treatment in IBD. In surgery: (iv) medical history with surgical relevance, surgical indication and strategy; (v) operative approach; (vi) intraoperative disease description; (vii) operative steps. In pathology: (viii) macroscopic assessment and interpretation of resection specimens; (ix) IBD histology, including biopsies, surgical resections, and neoplasia; (x) IBD histology conclusion and report. Statements were developed using a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when >80% of participants agreed on a recommendation. RESULTS Thirty practice positions established a standard terminology for optimal reporting in endoscopy, surgery, and histopathology. Assessment of disease activity, surveillance recommendations, advice to surgeons for operative indication and strategies, including margins and extent of resection, and diagnostic criteria of IBD, as well as guidance for the interpretation of dysplasia and cancer were handled. A standardized report including a core set of items to include in each speciality report, was defined. CONCLUSIONS Interdisciplinary high-quality care requires thorough and standardised reporting across specialities. This topical review offers an actionable framework and practice recommendations to optimise reporting in endoscopy, surgery, and histopathology.
An evidence review of face masks against COVID-19

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people (“source control”) with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.
Peer Support for Post Intensive Care Syndrome Self-Management (PS-PICS): Study protocol for peer mentor training.

AIMS The primary aim of the Peer Support for Post Intensive Care Syndrome Self-Management (PS-PICS) peer mentor training trial is to determine the feasibility for peer mentor training to connect new ICU survivors with survivors who have made successful recoveries. Secondary aims are to also examine peer mentor eligibility, recruitment and retention rates and assess changes in participant knowledge of Post Intensive Care Syndrome (PICS), reported symptoms and health-related quality of life. DESIGN Prospective clinical feasibility trial. METHODS This study received funding from the National Institutes of Health funded P30 Center for Excellence (2014-2020). Up to 20 adult patients who have had an ICU stay of 3 days or longer more than 3 months ago will be enrolled into the study. Participants will undergo a 6-week peer mentor training program to learn how to promote healthy self-management behaviours, social connections, and well-being using motivational interviewing (MI). Participants will complete surveys about their recovery at 3 points during the study: prior to training, 6 weeks post-training and 3 months post-training. Survey questions will be used to assess trends in participant social isolation, depression, functional status, and self-management behaviours. DISCUSSION Enrollment closes by December 2020. As a feasibility trial, power sufficient for hypothesis testing will not be available. However, study operations and intervention fidelity contribute to future research knowledge and participant characteristics and longitudinal outcomes will yield data on intervention feasibility. This study is the first use of embedding peer-led motivational interviewing training into a peer support intervention for ICU survivors. IMPACT Current self-management interventions are limited for ICU survivors and do not sufficiently address barriers to promoting self-management behaviours or improving their health status, well-being and cost of health. This study will provide data to develop and implement interventions for the self-management of PICS-related symptoms and sequelae.
Cold-Shock Domains—Abundance, Structure, Properties, and Nucleic-Acid Binding

Simple Summary Proteins are composed of compact domains, often of known three-dimensional structure, and natively unstructured polypeptide regions. The abundant cold-shock domain is among the set of canonical nucleic acid-binding domains and conserved from bacteria to man. Proteins containing cold-shock domains serve a large variety of biological functions, which are mostly linked to DNA or RNA binding. These functions include the regulation of transcription, RNA splicing, translation, stability and sequestration. Cold-shock domains have a simple architecture with a conserved surface ideally suited to bind single-stranded nucleic acids. Because the binding is mostly by non-specific molecular interactions which do not involve the sugar-phosphate backbone, cold-shock domains are not strictly sequence-specific and do not discriminate reliably between DNA and RNA. Many, but not all functions of cold shock-domain proteins in health and disease can be understood based of the physical and structural properties of their cold-shock domains. Abstract The cold-shock domain has a deceptively simple architecture but supports a complex biology. It is conserved from bacteria to man and has representatives in all kingdoms of life. Bacterial cold-shock proteins consist of a single cold-shock domain and some, but not all are induced by cold shock. Cold-shock domains in human proteins are often associated with natively unfolded protein segments and more rarely with other folded domains. Cold-shock proteins and domains share a five-stranded all-antiparallel β-barrel structure and a conserved surface that binds single-stranded nucleic acids, predominantly by stacking interactions between nucleobases and aromatic protein sidechains. This conserved binding mode explains the cold-shock domains’ ability to associate with both DNA and RNA strands and their limited sequence selectivity. The promiscuous DNA and RNA binding provides a rationale for the ability of cold-shock domain-containing proteins to function in transcription regulation and DNA-damage repair as well as in regulating splicing, translation, mRNA stability and RNA sequestration.
Studies on the Digraph-Based Approach for Fault-Tree Synthesis. 2. The Trip Systems

The digraph-based fault-tree synthesis procedures for feedforward and feedback trip systems are presented. The proposed techniques are suitable for assessing risks associated with all possible top events in a unified framework. This feature is potentially useful in automating the fault-tree construction process and thus represents an improvement of the conventional method. Two application examples are also provided to demonstrate the feasibility of the approach
Structural vaccinology of malaria transmission-blocking vaccines

ABSTRACT Introduction: The development of effective vaccines remains a major health priority to combat the global burden of malaria, a life-threatening disease caused by Plasmodium parasites. Transmission-blocking vaccines (TBVs) elicit antibodies that neutralize the sexual stages of the parasite in blood meals ingested by the Anopheles mosquito, interrupting parasite development in the vector host and preventing disease spread to other individuals. Areas covered: The P. falciparum gametocyte surface antigens Pfs230, Pfs48/45, and Pfs47, the parasite ookinete surface protein Pfs25, and the male gametocyte specific protein PfHAP2 are leading TBV candidates, some of which are in clinical development. The recent expansion of methodology to study monoclonal antibodies isolated directly from humans and animal models, coupled with effective measures for parasite neutralization, has provided unprecedented insight into TBV efficacy and development. Expert opinion: Available structural and functional data on antigen-monoclonal antibody (Ag-mAb) complexes, as well as epitope classification studies, have identified neutralizing epitopes that may aid vaccine development and improve protection. Here, we review the clinical prospects of TBV candidates, progress in the development of novel vaccine strategies for TBVs, and the impact of structural vaccinology in TBV design.
Ectopic Expression of CrPIP2;3, a Plasma Membrane Intrinsic Protein Gene from the Halophyte Canavalia rosea, Enhances Drought and Salt-Alkali Stress Tolerance in Arabidopsis

Aquaporins are channel proteins that facilitate the transmembrane transport of water and other small neutral molecules, thereby playing vital roles in maintaining water and nutrition homeostasis in the life activities of all organisms. Canavalia rosea, a seashore and mangrove-accompanied halophyte with strong adaptability to adversity in tropical and subtropical regions, is a good model for studying the molecular mechanisms underlying extreme saline-alkaline and drought stress tolerance in leguminous plants. In this study, a PIP2 gene (CrPIP2;3) was cloned from C. rosea, and its expression patterns and physiological roles in yeast and Arabidopsis thaliana heterologous expression systems under high salt-alkali and high osmotic stress conditions were examined. The expression of CrPIP2;3 at the transcriptional level in C. rosea was affected by high salinity and alkali, high osmotic stress, and abscisic acid treatment. In yeast, the expression of CrPIP2;3 enhanced salt/osmotic and oxidative sensitivity under high salt/osmotic and H2O2 stress. The overexpression of CrPIP2;3 in A. thaliana could enhance the survival and recovery of transgenic plants under drought stress, and the seed germination and seedling growth of the CrPIP2;3 OX (over-expression) lines showed slightly stronger tolerance to high salt/alkali than the wild-type. The transgenic plants also showed a higher response level to high-salinity and dehydration than the wild-type, mostly based on the up-regulated expression of salt/dehydration marker genes in A. thaliana plants. The reactive oxygen species (ROS) staining results indicated that the transgenic lines did not possess stronger ROS scavenging ability and stress tolerance than the wild-type under multiple stresses. The results confirmed that CrPIP2;3 is involved in the response of C. rosea to salt and drought, and primarily acts by mediating water homeostasis rather than by acting as an ROS transporter, thereby influencing physiological processes under various abiotic stresses in plants.
Neutron radiation hardening of polycrystalline iron

Abstract The dependence of the yield stress of vacuum-annealed and hydrogen-purified iron polycrystals on neutron dose and annealing temperature and the influence of these two parameters on the effect of static strain-ageing has been investigated. The radiation hardening was found to depend sensitively on the interstitial impurities N and C. This may be explained by both a nucleation of precipitation and a trapping of the impurities at radiation produced intrinsic defects. The radiation enhanced precipitation predominates in the relatively impure iron samples at low doses and may be eliminated by annealing at 190 °C. The trapping becomes effective at higher doses or in higher purity iron. Below 400 °C two recovery stages for the yield stress are observed, one between 200 and 260 °C and the other between 320 and 400°C; these may be explained by the detrapping of N and C respectively. The static strain-ageing was found to be reduced by neutron irradiation. It reappears after annealing at temperatures at whi.
Elbasvir and grazoprevir for the treatment of hepatitis C

ABSTRACT Introduction: Hepatitis C is one of the leading causes of chronic liver disease. The direct-acting-antivirals has revolutionized the chronic hepatitis C treatment. DAAs can achieve a sustained virological response rate >95% in different populations. Area covered: This review summarizes the pharmacokinetics, pharmacodynamics, efficacy, and safety of Elbasvir/Grazoprevir (EBR/GZR). Expert opinion: EBR/GZR is a combination of NS5A and NS3/4A inhibitors. The performance in the EBR/GZR combination’s safety and tolerability is appreciated in clinical treatment. EBR/GZR also has a higher barrier to resistance-associated substitutions. Based on clinical trials and real-world experience, elbasvir/grazoprevir is effective in the HCV GT1, 4 infections.
Next-Generation Wearable Biosensors Developed with Flexible Bio-Chips

The development of biosensors that measure various biosignals from our body is an indispensable research field for health monitoring. In recent years, as the demand to monitor the health conditions of individuals in real time have increased, wearable-type biosensors have received more attention as an alternative to laboratory equipment. These biosensors have been embedded into smart watches, clothes, and accessories to collect various biosignals in real time. Although wearable biosensors attached to the human body can conveniently collect biosignals, there are reliability issues due to noise generated in data collection. In order for wearable biosensors to be more widely used, the reliability of collected data should be improved. Research on flexible bio-chips in the field of material science and engineering might help develop new types of biosensors that resolve the issues of conventional wearable biosensors. Flexible bio-chips with higher precision can be used to collect various human data in academic research and in our daily lives. In this review, we present various types of conventional biosensors that have been used and discuss associated issues such as noise and inaccuracy. We then introduce recent studies on flexible bio-chips as a solution to these issues.
Structural phase transitions in solids with applied stresses and fields, and effect of isotopic impurities on the free energy

Subject to the assumptions described in the text, we obtain the following expression for the transition temperature Tc associated with a structural phase transition: Tc = α (ΔU + JiPiΔai)/kB, α ≡ 2/ln(‖Φ‖/‖Φ′‖). Here ΔU is the change in energy, the Pi are given by the pressure, stresses, and applied fields, the Δai are given by the changes in volume, strains, and dipole moments, and ‖Φ‖ is the determinant of the force constant matrix. We also give a result which may be useful for solids containing isotopic impurities: At high temperatures and in the harmonic approximation, ΔG = −(3/2) kBT Jkln(mk′/mk), where ΔG is the change in Gibbs free energy when some of the particle masses are changed from mk to mk′.
Associations between Social Determinants and Hypertension, Stage 2 Hypertension and Controlled Blood Pressure among Men and Women in the US.

BACKGROUND Social determinants influence the development and control of hypertension. METHODS National Health and Nutrition Examination Survey (2011-2018) data for adults aged ≥18 included education, income, employment, race/ethnicity, healthcare access, marital status, and nativity status. Outcomes were hypertension (blood pressure (BP) ≥130/80 mm Hg or self-reported hypertension medication use), stage 2 hypertension (BP ≥140/90 mm Hg), and controlled BP (BP <130/80 mm Hg among those with hypertension). Poisson regression with robust variance estimates was used to examine associations between social determinants and outcomes, by sex. RESULTS The analysis included 21,664 adults (mean age 47.1 years), of whom 51% were women. After adjustment, hypertension and stage 2 hypertension prevalence remained higher among Black and Asian than White adults, regardless of sex. Blacks had lower prevalence of controlled BP than Whites. Compared to college graduates, men and women with less education had a higher prevalence of hypertension and stage 2 hypertension. Men (Prevalence Ratio [P.R.]: 0.28, 95% confidence interval [CI]: 0.16-0.49) and women (PR: 0.44, 0.24-0.78) with no routine place for healthcare had lower prevalence of controlled BP than those who had a routine place for healthcare. Uninsured men (PR: 0.66, 0.44-0.99) and women (PR: 0.67, 0.51-0.88) had lower prevalence of controlled BP than those insured. Unemployed or unmarried women were more likely to have controlled BP than employed or married women. CONCLUSIONS Social determinants were independently associated with hypertension outcomes in US adults. Policy interventions are urgently needed to address healthcare access and education, and eliminate racial disparities.
The Impact of Olive Oil Compounds on the Metabolic Reprogramming of Cutaneous Melanoma Cell Models

Cutaneous melanoma is the deadliest type of skin cancer, characterized by a high molecular and metabolic heterogeneity which contributes to therapy resistance. Despite advances in treatment, more efficient therapies are needed. Olive oil compounds have been described as having anti-cancer properties. Here, we clarified the cytotoxic potential of oleic acid, homovanillyl alcohol, and hydroxytyrosol on melanoma cells. Metabolic viability was determined 48 h post treatment of A375 and MNT1 cells. Metabolic gene expression was assessed by qRT-PCR and Mitogen-Activated Protein Kinase (MAPK) activation by Western blot. Hydroxytyrosol treatment (100 and 200 µM) significantly reduced A375 cell viability (p = 0.0249; p < 0.0001) which, based on the expression analysis performed, is more compatible with a predominant glycolytic profile and c-Jun N-terminal kinase (JNK) activation. By contrast, hydroxytyrosol had no effect on MNT1 cell viability, which demonstrates an enhanced oxidative metabolism and extracellular signal-regulated kinase (ERK) activation. This compound triggered cell detoxification and the use of alternative energy sources in A375 cells, inhibiting JNK and ERK pathways. Despite oleic acid and homovanillyl alcohol demonstrating no effect on melanoma cell viability, they influenced the MNT1 glycolytic rate and A375 detoxification mechanisms, respectively. Both compounds suppressed ERK activation in MNT1 cells. The distinct cell responses to olive oil compounds depend on the metabolic and molecular mechanisms preferentially activated. Hydroxytyrosol may have a cytotoxic potential in melanoma cells with predominant glycolytic metabolism and JNK activation.