Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum thymosin alpha 1 levels in normal and pathological conditions

ABSTRACT Introduction: Thymosin alpha 1 (Ta1) is a natural occurring peptide hormone that is crucial for the maintenance of the organism homeostasis. It has been chemically synthesized and used in diseases where the immune system is hindered or malfunctioning. Areas covered: Many clinical trials investigate the Ta1 effects in patients with cancer, infectious diseases and as a vaccine enhancer. The number of diseases that could benefit from Ta1 treatment is increasing. To date, questions remain about the physiological basal levels of Ta1 and the most effective dose and schedule of treatment. Evidence is growing that diseases characterized by deregulation of immune and/or inflammatory responses are associated with serum levels of Ta1 significantly lower than those of healthy individuals: to date, B hepatitis, psoriatic arthritis, multiple sclerosis and sepsis. The sputum of cystic fibrosis patients contains lower levels of Ta1 than healthy controls. These data are consistent with the role of Ta1 as a regulator of immunity, tolerance and inflammation. Expert opinion: Low serum Ta1 levels are predictive and/or associated with different pathological conditions. In case of Ta1 treatment, it is crucial to know the patient’s baseline serum Ta1 level to establish effective treatment protocols and monitor their effectiveness over time.
Theory of Mind after Severe Acquired Brain Injury: Clues for Interpretation

Background. Recently, increased interest has been shown in Theory of Mind (ToM) abilities of individuals with severe acquired brain injury (sABI). ToM impairment following sABI can be associated with altered executive functioning and/or with difficulty in decoding and elaborating emotions. Two main theoretical models have been proposed to explain the mechanisms underlying ToM in the general population: Theory Theory and Simulation Theory. This review presents and discusses the literature on ToM abilities in individuals with sABI by examining whether they sustain the applicability of the Theory Theory and/or Simulation Theory to account for ToM deficits in this clinical population. We found 32 papers that are directly aimed at investigating ToM in sABI. Results did not show the univocal predominance of one model with respect to the other in explaining ToM deficits in sABI. We hypothesised that ToM processes could be explained by coinvolvement of the two models, i.e., according to personal experience, cognitive features, or the emotional resources of the persons with sABI.
Quantifying excess deaths related to heatwaves under climate change scenarios: A multicountry time series modelling study

Background Heatwaves are a critical public health problem. There will be an increase in the frequency and severity of heatwaves under changing climate. However, evidence about the impacts of climate change on heatwave-related mortality at a global scale is limited. Methods and findings We collected historical daily time series of mean temperature and mortality for all causes or nonexternal causes, in periods ranging from January 1, 1984, to December 31, 2015, in 412 communities within 20 countries/regions. We estimated heatwave–mortality associations through a two-stage time series design. Current and future daily mean temperature series were projected under four scenarios of greenhouse gas emissions from 1971–2099, with five general circulation models. We projected excess mortality in relation to heatwaves in the future under each scenario of greenhouse gas emissions, with two assumptions for adaptation (no adaptation and hypothetical adaptation) and three scenarios of population change (high variant, median variant, and low variant). Results show that, if there is no adaptation, heatwave-related excess mortality is expected to increase the most in tropical and subtropical countries/regions (close to the equator), while European countries and the United States will have smaller percent increases in heatwave-related excess mortality. The higher the population variant and the greenhouse gas emissions, the higher the increase of heatwave-related excess mortality in the future. The changes in 2031–2080 compared with 1971–2020 range from approximately 2,000% in Colombia to 150% in Moldova under the highest emission scenario and high-variant population scenario, without any adaptation. If we considered hypothetical adaptation to future climate, under high-variant population scenario and all scenarios of greenhouse gas emissions, the heatwave-related excess mortality is expected to still increase across all the countries/regions except Moldova and Japan. However, the increase would be much smaller than the no adaptation scenario. The simple assumptions with respect to adaptation as follows: no adaptation and hypothetical adaptation results in some uncertainties of projections. Conclusions This study provides a comprehensive characterisation of future heatwave-related excess mortality across various regions and under alternative scenarios of greenhouse gas emissions, different assumptions of adaptation, and different scenarios of population change. The projections can help decision makers in planning adaptation and mitigation strategies for climate change.
Telepsychiatry for stable Chinese psychiatric out-patients in custody in Hong Kong: a case-control pilot study.

INTRODUCTION In Hong Kong, persons in custody receive primary medical care within the institutions of the Correctional Services Department (CSD). However, for psychiatric care, persons in custody must attend specialist out-patient clinics (SOPCs), which may cause embarrassment and stigmatisation. The aim of this interventional pilot study was to compare teleconsultations with face-to-face consultations for a group of stable Chinese psychiatric out-patients in custody. METHODS A total of 86 stable Chinese male out-patients in custody were recruited for psychiatric teleconsultations. They were compared with 249 age-matched Chinese male out-patients in custody attending standard face-to-face psychiatric consultations at other SOPCs. The two groups had comparable baseline characteristics including age, education level, and 12-item Chinese General Health Questionnaire (C-GHQ-12) score. A satisfaction survey of patients towards the teleconsultation was also carried out. RESULTS Compared with the face-to-face consultation group, the teleconsultation group showed a significantly better result in the difference in C-GHQ-12 scores before and after consultations (P=0.023). The correlation between the first and second teleconsultations also showed a moderate positive relationship (r=0.309). The satisfaction survey showed a favourable response to teleconsultations. No significant adverse events were identified for the teleconsultation group. CONCLUSIONS The results suggest that teleconsultations are a sustainable and safe alternative to face-to-face consultations for stable Chinese psychiatric out-patients in custody.
Reaching Independence Through Forced Learning: Learning Processes and Illness Management in Parents of Children Affected by Hemophilia

Hemophilia is a complex condition to manage, especially for parents to newly diagnosed children. This grounded theory study explores parents’ learning processes and illness management in daily life during the first year after the start of their child’s treatment. Using a longitudinal qualitative design, eight parents of four children were interviewed repeatedly during 12 to 14 months. The core category, reaching independence through forced learning, reflected the parents’ learning process and their experiences of the challenges during the first year after start of treatment. Incentives for learning were characterized by a longing to reach independence and regain control of one’s life situation. The emerging key incentive for learning was a desire to become independent of health care professionals. Early home treatment reduced the impact of the illness, and by supporting parents in different ways during the learning process, health care professionals can promote the parents’ trajectory toward independency.
Cognitive Impairment and Celiac Disease: Is Transcranial Magnetic Stimulation a Trait d’Union between Gut and Brain?

Celiac disease is a systemic disorder with multifactorial pathogenesis and multifaceted symptomatology. In response to gluten exposure, a significant part of the general population produces antibodies that have been hypothesized to be deleterious to the brain. Among the well-known neurological manifestations, adult celiac patients often complain cognitive symptoms, ranging from the so-called “brain fog” till an overt dementia. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that can contribute to the assessment and monitoring of celiac patients, even in those without a clear neurological involvement. The studies here reviewed seem to converge on an impaired central motor conductivity and a “hyperexcitable celiac brain” to TMS, which partially reverts back after a long-term gluten restriction. Notably, a clear hyperexcitability is a stably reported feature of both degenerative and vascular dementia. Therefore, given its potential neuroprotective effect, the gluten-free diet should be introduced as early as possible, although the overall response of neurological symptoms (and cognition in particular) is still controversial. Identifying new and possibly modifiable risk factors may be of crucial importance for patients, clinicians, and researchers.
An automated identification and analysis of ontological terms in gastrointestinal diseases and nutrition-related literature provides useful insights

With an unprecedented growth in the biomedical literature, keeping up to date with the new developments presents an immense challenge. Publications are often studied in isolation of the established literature, with interpretation being subjective and often introducing human bias. With ontology-driven annotation of biomedical data gaining popularity in recent years and online databases offering metatags with rich textual information, it is now possible to automatically text-mine ontological terms and complement the laborious task of manual management, interpretation, and analysis of the accumulated literature with downstream statistical analysis. In this paper, we have formulated an automated workflow through which we have identified ontological information, including nutrition-related terms in PubMed abstracts (from 1991 to 2016) for two main types of Inflammatory Bowel Diseases: Crohn’s Disease and Ulcerative Colitis; and two other gastrointestinal (GI) diseases, namely, Coeliac Disease and Irritable Bowel Syndrome. Our analysis reveals unique clustering patterns as well as spatial and temporal trends inherent to the considered GI diseases in terms of literature that has been accumulated so far. Although automated interpretation cannot replace human judgement, the developed workflow shows promising results and can be a useful tool in systematic literature reviews. The workflow is available at https://github.com/KociOrges/pytag.
Prevalence and antibiotic utilization pattern of uropathogens causing community-acquired urinary tract infection in Kerala, India

Abstract Background: A prospective observational study was carried out over a period of 6 months among the inpatients and outpatients in the departments of general medicine, urology, obstetrics, and gynecology of a tertiary level referral hospital in south Malabar region of Kerala to assess the prevalence of various bacterial isolates and their changing susceptibility to antimicrobial agents and to evaluate the pattern of antibiotic utilization in urinary tract infection (UTI). Methods: A total of 680 samples were analyzed from December 2015 to May 2016; among them, only 74 patients met the inclusion criteria. Of the 74 patients, 53 were female and 21 were male. Female patients were found to be significantly higher in number in the age group of 61–70years. The maximum number of UTI cases was reported from the general medicine department. Results: The disease was more significantly portrayed in suburbans (47%) and rural (38%) population compared with urbans (15%). Fever (60.81%) and dysuria (48.64%) were the most common symptoms. Diabetes (34%) was found to be the major predisposing factor followed by postmenopausal factors (24%), previous UTI (14%), renal disease (9%), benign prostatic hypertrophy (8%), smoking (7%), and oral contraceptives (4%). Escherichia coli was the major isolate (n=36) followed by Klebsiella (n=13), Citrobacter (n=8), Enterococcus (n=7), Enterobacter (n=4), Pseudomonas (n=3), coagulase-negative Staphylococcus (n=2), and Proteus (n=1). Majority of patients were prescribed with cefoperazone+sulbactum (n=28) followed by levofloxacin (n=25) and nitrofurantoin (n=10). Cumulative antibiogram was prepared as the final step of the study using the WHONET 5.6 software. Gram-negative organisms such as E. coli, Klebsiella, and Citrobacter showed higher susceptibility toward piperacillin-tazobactum, cefoperazone-sulbactam, imipenem, meropenem, amikacin, and netilmicin. Gram-positive organisms such as Enterococcus showed higher susceptibility toward piperacillin-tazobactum, cefoperazone-sulbactam, amoxicillin-clavulanic acid, vancomycin, and linezolid. Conclusions: In our setting, routine culture may be necessary as treatment failure with empirical therapy is likely to occur.
The natural plant compound carvacrol as an antimicrobial and anti-biofilm agent: mechanisms, synergies and bio-inspired anti-infective materials

Abstract Carvacrol (5-isopropyl-2-methyl phenol) is a natural compound that occurs in the leaves of a number of plants and herbs including wild bergamot, thyme and pepperwort, but which is most abundant in oregano. The aim of this review is to analyse the scientific data from the last five years (2012-2017) on the antimicrobial and anti-biofilm activities of carvacrol, targeting different bacteria and fungi responsible for human infectious diseases. The antimicrobial and anti-biofilm mechanisms of carvacrol and its synergies with antibiotics are illustrated. The potential of carvacrol-loaded anti-infective nanomaterials is underlined. Carvacrol shows excellent antimicrobial and anti-biofilm activities, and is a very interesting bioactive compound against fungi and a wide range of Gram-positive and Gram-negative bacteria, and being active against both planktonic and sessile human pathogens. Moreover, carvacrol lends itself to being combined with nanomaterials, thus providing an opportunity for preventing biofilm-associated infections by new bio-inspired, anti-infective materials.
Dynamic NBTI Management Using a 45 nm Multi-Degradation Sensor

This paper proposes a low power unified oxide and negative bias temperature instability (NBTI) degradation sensor designed in 45 nm process node. The cell power consumption is 105 lower than a previously proposed sensor. The unified nature enables efficient reliability monitoring with reduced sensor deployment effort and area overhead. Using the sensor dynamic NBTI management (DNM) has been implemented for the first time. DNM trades the excess “reliability margin” present in the design, due to better than worst case operating conditions, with performance. For the typical case shown in this paper, DNM allows for an average boost of 90 mV in accelerated supply voltage while bringing down the excess NBTI margin of 22.5 mV to 8 mV where the total budget for NBTI was 66 mV.
Past year and prior incarceration and HIV transmission risk among HIV-positive men who have sex with men in the US*

ABSTRACT Three quarters of new HIV infections in the US are among men who have sex with men (MSM). In other populations, incarceration is a social determinant of elevations in viral load and HIV-related substance use and sex risk behavior. There has been limited research on incarceration and these HIV transmission risk determinants in HIV-positive MSM. We used the Veterans Aging Cohort Study (VACS) 2011-2012 follow-up survey to measure associations between past year and prior (more than one year ago) incarceration and HIV viral load and substance use and sex risk behavior among HIV-positive MSM (N = 532). Approximately 40% had ever been incarcerated, including 9% in the past year. In analyses adjusting for sociodemographic factors, past year and prior incarceration were strongly associated with detectable viral load (HIV-1 RNA >500 copies/mL) (past year adjusted odds ratio (AOR): 3.50 95% confidence interval (CI): 1.59, 7.71; prior AOR: 2.48 95% CI: 1.44, 4.29) and past 12 month injection drug use (AORs > 6), multiple sex partnerships (AORs > 1.8), and condomless sex in the context of substance use (AORs > 3). Past year incarceration also was strongly associated with alcohol and non-injection drug use (AOR > 2.5). Less than one in five HIV-positive MSM recently released from incarceration took advantage of a jail/prison re-entry health care program available to veterans. We need to reach HIV-positive MSM leaving jails and prisons to improve linkage to care and clinical outcomes and reduce transmission risk upon release.
Oribatid mites (Acari, Oribatida) from the Oumé region (Côte d’Ivoire): list of taxa, new findings, description of a new species

The present study is based on oribatid mite material (Acari, Oribatida) collected from the Oumé region (Côte d’Ivoire, West Africa) in 2007. A list of identified taxa, including 67 species from 50 genera and 31 families, is presented; all species, genera and families are registered in this country for the first time; Kalloia simpliseta, Scheloribates latoincisus and Pergalumna paraelongata are recorded in the Ethiopian region for the first time. One new species of the genus Arcoppia (Oppiidae) is described; A. goulikaoensis Ermilov sp. n. differs from A. robusta Mahunka, 1988 by the well-developed bothridial heads (versus not developed), barbed branches on the bothridial setae (versus smooth) and smooth notogaster surface (versus lineolate).
Engineering Cocrystals of Poorly Water-Soluble Drugs to Enhance Dissolution in Aqueous Medium

Biopharmaceutics Classification System (BCS) Class II and IV drugs suffer from poor aqueous solubility and hence low bioavailability. Most of these drugs are hydrophobic and cannot be developed into a pharmaceutical formulation due to their poor aqueous solubility. One of the ways to enhance the aqueous solubility of poorlywater-soluble drugs is to use the principles of crystal engineering to formulate cocrystals of these molecules with water-soluble molecules (which are generally called coformers). Many researchers have shown that the cocrystals significantly enhance the aqueous solubility of poorly water-soluble drugs. In this review, we present a consolidated account of reports available in the literature related to the cocrystallization of poorly water-soluble drugs. The current practice to formulate new drug cocrystals with enhanced solubility involves a lot of empiricism. Therefore, in this work, attempts have been made to understand a general framework involved in successful (and unsuccessful) cocrystallization events which can yield different solid forms such as cocrystals, cocrystal polymorphs, cocrystal hydrates/solvates, salts, coamorphous solids, eutectics and solid solutions. The rationale behind screening suitable coformers for cocrystallization has been explained based on the rules of five i.e., hydrogen bonding, halogen bonding (and in general non-covalent bonding), length of carbon chain, molecular recognition points and coformer aqueous solubility. Different techniques to screen coformers for effective cocrystallization and methods to synthesize cocrystals have been discussed. Recent advances in technologies for continuous and solvent-free production of cocrystals have also been discussed. Furthermore, mechanisms involved in solubilization of these solid forms and the parameters influencing dissolution and stability of specific solid forms have been discussed. Overall, this review provides a consolidated account of the rationale for design of cocrystals, past efforts, recent developments and future perspectives for cocrystallization research which will be extremely useful for researchers working in pharmaceutical formulation development.
Concurrent HER or PI3K Inhibition Potentiates the Antitumor Effect of the ERK Inhibitor Ulixertinib in Preclinical Pancreatic Cancer Models

Effective treatment for pancreatic ductal adenocarcinoma (PDAC) is an urgent, unmet medical need. Targeting KRAS, the oncogene that is present in >95% of PDAC, is a heavily pursued strategy, but remains unsuccessful in the clinic. Therefore, targeting key effector cascades of KRAS oncoprotein, particularly the mitogenic RAF–MEK–ERK pathway, represents the next best strategy. However, RAF or MEK inhibitors have failed to show clinical efficacy in PDAC. Several studies have shown that cancer cells treated with RAF or MEK inhibitors adopt multiple mechanisms to reactivate ERK signaling. Therefore, development of ERK-specific inhibitors carries the promise to effectively abrogate this pathway. Ulixertinib (or BVD-523) is a first-in-class ERK-specific inhibitor that has demonstrated promising antitumor activity in a phase I clinical trial for advanced solid tumors with NRAS and BRAF mutations, providing a strong rationale to test this inhibitor in PDAC. In this study, we show that ulixertinib effectively inhibits in vitro growth of multiple PDAC lines and potentiates the cytotoxic effect of gemcitabine. Moreover, we found that PDAC cells treated with ulixertinib upregulates the parallel PI3K–AKT pathway through activating the HER/ErbB family proteins. Concurrent inhibition of PI3K or HER proteins synergizes with ulixertinib in suppressing PDAC cell growth in vitro and in vivo. Overall, our study provides the preclinical rationale for testing combinations of ulixertinib with chemotherapy or PI3K and HER inhibitors in PDAC patients. Mol Cancer Ther; 17(10); 2144–55. ©2018 AACR.
Ecto-F0/F1 ATPase as a novel candidate of prothymosin α receptor

ABSTRACT Objectives: Prothymosin α (ProTα) was reported to inhibit the neuronal necrosis by facilitating the plasma membrane localization of endocytosed glucose transporter 1/4 through an activation of putative Gi-coupled receptor. The present study aims to identify a novel ProTα target, which may lead to an activation of Gi-coupled receptor. Methods: We used Gi-rich lipid rafts fraction of retinal cell line N18-RE-105 cells for affinity cross-linking. The biological confirmation that F0/F1 ATPase is a target protein complex was performed by cell-free experiments using ELISA-based binding assay, surface plasmon resonance assay and quartz crystal microbalance assay, and cell-based experiments to measure extracellular ATP level in the HUVECs culture. Results: From the cross-linking study and above-mentioned protein-protein interaction assays, ATP5A1 and ATP5B, F1 ATPase subunits were found to ProTα binding target proteins. In the culture of HUVEC cells, furthermore, ProTα increased the extracellular ATP levels in a reversible manner by anti-ATP5A1- and ATP5B-antibodies. Conclusion: The present study suggests that ProTα may activate ecto-F0/F1 ATPase and produced ATP. This study leads to next subjects whether produced ATP and its metabolites, ADP or adenosine may activate corresponding Gi-coupled receptors.