Miracle-dz/UniFAR-FTUs huggingface dataset:
TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment

Variants in the microglial receptor TREM2 confer risk for multiple neurodegenerative diseases. However, it remains unknown how this receptor functions on microglia to modulate these diverse neuropathologies. To understand the role of TREM2 on microglia more generally, we investigated changes in microglial function in Trem2−/− mice. We found that loss of TREM2 impairs normal neurodevelopment, resulting in reduced synapse number across the cortex and hippocampus in 1‐month‐old mice. This reduction in synapse number was not due directly to alterations in interactions between microglia and synapses. Rather, TREM2 was required for microglia to limit synaptic engulfment by astrocytes during development. While these changes were largely normalized later in adulthood, high fat diet administration was sufficient to reinitiate TREM2‐dependent modulation of synapse loss. Together, this identifies a novel role for microglia in instructing synaptic pruning by astrocytes to broadly regulate appropriate synaptic refinement, and suggests novel candidate mechanisms for how TREM2 and microglia could influence synaptic loss in brain injury and disease.
LC-ESI/MS/MS analysis of neonicotinoids in urine of very low birth weight infants at birth

Objectives Neonicotinoid insecticides are widely used systemic pesticides with nicotinic acetylcholine receptor agonist activity that are a concern as environmental pollutants. Neonicotinoids in humans and the environment have been widely reported, but few studies have examined their presence in fetuses and newborns. The objective of this study is to determine exposure to neonicotinoids and metabolites in very low birth weight (VLBW) infants. Methods An analytical method for seven neonicotinoids and one neonicotinoid metabolite, N-desmethylacetamiprid (DMAP), in human urine using LC-ESI/MS/MS was developed. This method was used for analysis of 57 urine samples collected within 48 hours after birth from VLBW infants of gestational age 23–34 weeks (male/female = 36/21, small for gestational age (SGA)/appropriate gestational age (AGA) = 6/51) who were admitted to the neonatal intensive care unit of Dokkyo Hospital from January 2009 to December 2010. Sixty-five samples collected on postnatal day 14 (M/F = 37/22, SGA/AGA = 7/52) were also analyzed. Results DMAP, a metabolite of acetamiprid, was detected in 14 urine samples collected at birth (24.6%, median level 0.048 ppb) and in 7 samples collected on postnatal day 14 (11.9%, median level 0.09 ppb). The urinary DMAP detection rate and level were higher in SGA than in AGA infants (both p<0.05). There were no correlations between the DMAP level and infant physique indexes (length, height, and head circumference SD scores). Conclusion These results provide the first evidence worldwide of neonicotinoid exposure in newborn babies in the early phase after birth. The findings suggest a need to examine potential neurodevelopmental toxicity of neonicotinoids and metabolites in human fetuses.
Carriage of carbapenemase‐ and extended‐spectrum cephalosporinase‐producing Escherichia coli and Klebsiella pneumoniae in humans and livestock in rural Cambodia; gender and age differences and detection of bla OXA‐48 in humans

This study investigates the frequency and characteristics of carbapenemase‐producing Escherichia coli/Klebsiella pneumoniae (CPE/K) and extended‐spectrum cephalosporinase‐producing E. coli/K. pneumoniae (ESCE/K) in healthy humans and livestock in rural Cambodia. Additionally, household practices as risk factors for faecal carriage of ESCE/K are identified.
The effect of saffron on weight and lipid profile: A systematic review, meta‐analysis, and dose–response of randomized clinical trials

Plant derivatives such as carotenoids and phytosterols enrich foods have been shown to reduce plasma triglyceride (TG), low‐density lipoprotein (LDL) cholesterol, and cholesterol concentrations. The aim of this systematic review and meta‐analyses study was to investigate the effects of saffron on lipid profiles, reported in randomized controlled trials (RCTs). We performed a systematic electronic search in PubMed/MEDLINE, Cochrane, and SCOPUS to identify RCTs and screening of relevant articles references up to October 12, 2018. There were no language restrictions. We performed this systematic review and meta‐analysis according to the Preferred Items for Reporting of Systematic Reviews and Meta‐Analyses guidelines. We identified and analyzed 14 eligible studies in this meta‐analysis. Our study found a significant reduction in cholesterol and TG following saffron intervention (weighted mean difference [WMD]: −6.36 mg/dl, 95% confidence interval, CI, [−10.58, −2.18] and WMD: −5.37 mg/dl, 95% CI [−10.25, −0.48], respectively). There was no significant effect on weight and LDL concentration. A meta‐regression analysis showed that long‐term saffron intervention can increase the high‐density lipoprotein (HDL) levels. In conclusions, our study findings indicate some benefits of saffron on cholesterol, HDL, and TG compared with placebo. However, we recommend the conduct of adequately powered, high‐quality RCTs with short‐ and long‐term follow‐up, evaluating relevant clinical outcomes to allow for making definitive recommendations.
Photolytic Aging of Secondary Organic Aerosol: Evidence for a Substantial Photo-Recalcitrant Fraction.

Photolytic aging has been proposed as a major mass loss mechanism for atmospheric secondary organic aerosol (SOA). However, estimated mass loss rates vary by orders of magnitude, and their impacts on modeled SOA loadings and properties are highly uncertain. In this study, photolysis rates and composition changes of α-pinene SOA are analyzed in-situ over multiple days in an environmental chamber. After an initial exponential decay (τ~22 hrs), the mass loss rate slows dramatically, with more than ~70-90% of the SOA particulate mass undergoing an essentially negligible photolytic degradation. Scaled to ambient conditions, SOA undergoes rapid photolysis over only its first day in the atmosphere; beyond this the remaining SOA is photo-recalcitrant, and photolysis ceases to be a major sink compared to wet deposition timescales. Thus, extrapolation of the initial photolysis loss rate to the entire aerosol mass may significantly overestimate the role of photolysis in the removal of atmospheric SOA.
Controlled Drug Delivery Systems for Oral Cancer Treatment—Current Status and Future Perspectives

Oral squamous cell carcinoma (OSCC), which encompasses the oral cavity-derived malignancies, is a devastating disease causing substantial morbidity and mortality in both men and women. It is the most common subtype of the head and neck squamous cell carcinoma (HNSCC), which is ranked the sixth most common malignancy worldwide. Despite promising advancements in the conventional therapeutic approaches currently available for patients with oral cancer, many drawbacks are still to be addressed; surgical resection leads to permanent disfigurement, altered sense of self and debilitating physiological consequences, while chemo- and radio-therapies result in significant toxicities, all affecting patient wellbeing and quality of life. Thus, the development of novel therapeutic approaches or modifications of current strategies is paramount to improve individual health outcomes and survival, while early tumour detection remains a priority and significant challenge. In recent years, drug delivery systems and chronotherapy have been developed as alternative methods aiming to enhance the benefits of the current anticancer therapies, while minimizing their undesirable toxic effects on the healthy non-cancerous cells. Targeted drug delivery systems have the potential to increase drug bioavailability and bio-distribution at the site of the primary tumour. This review confers current knowledge on the diverse drug delivery methods, potential carriers (e.g., polymeric, inorganic, and combinational nanoparticles; nanolipids; hydrogels; exosomes) and anticancer targeted approaches for oral squamous cell carcinoma treatment, with an emphasis on their clinical relevance in the era of precision medicine, circadian chronobiology and patient-centred health care.
Healthcare resource utilization, expenditures, and productivity in patients with asthma with and without allergies

Abstract Objective: To compare healthcare resource utilization (HCRU), healthcare expenditures, and work productivity and activity impairment within a general asthma population with persistent asthma and evidence of allergy (PA-EA) and persistent asthma with no evidence of allergy (PA-NEA). Methods: We conducted a retrospective analysis of survey responses and claims from the Observational Study of Asthma Control and Outcomes (OSACO) study. Eligible patients with persistent asthma aged ≥12 years were sent four surveys over 15 months. Regression models were used to assess the association between: (1) PA-EA (defined as a positive response to a survey question about hay fever/seasonal allergies AND ≥1 diagnostic code for atopic conditions) and HCRU and expenditures; and (2) PA-EA and Work Productivity and Activity Impairment (WPAI)-Asthma questionnaire scores (vs. PA-NEA). Results: Adjusted data showed that, vs. PA-NEA (n = 312), patients with PA-EA (n = 971) incurred 1.34-times more all-cause prescriptions (95% confidence interval [CI], 1.20–1.48), $132.79 higher prescription costs (95% CI, $22.03–243.56), and $926.11 higher all-cause total healthcare costs (95% CI, $279.67–1572.54), per 4-month period. Patients with PA-EA were 4.1% less productive while working (95% CI, 3.75–4.48%) and experienced a 6.5% reduction in all activities (95% CI, 6.11–6.88%) vs. those with PA-NEA. Conclusions: Patients with PA-EA had greater HCRU, healthcare expenditures, and lower productivity compared with those patients with PA-NEA. These results highlight the burden of atopy in patients with persistent asthma and underscore the importance of allergic endotype identification for more vigilant disease management.
Decoding Immune Heterogeneity of Triple Negative Breast Cancer and Its Association with Systemic Inflammation

Triple negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options. New opportunities are emerging from current comprehensive characterization of tumor immune infiltration and fitness. Therefore, effectiveness of current chemotherapies and novel immunotherapies are partially dictated by host inflammatory and immune profiles. However, further progress in breast cancer immuno-oncology is required to reach a detailed awareness of the immune infiltrate landscape and to determine additional reliable and easily detectable biomarkers. In this study, by analyzing gene expression profiles of 54 TNBC cases we identified three TNBC clusters displaying unique immune features. Deep molecular characterization of immune cells cytolytic-activity and tumor-inflammation status reveled variability in the local composition of the immune infiltrate in the TNBC clusters, reconciled by tumor-infiltrating lymphocytes counts. Platelet-to-lymphocyte ratio (PLR), a blood systemic parameter of inflammation evaluated using pre-surgical blood test data, resulted negatively correlated with local tumoral cytolytic activity and T cell–inflamed microenvironment, whereas tumor aggressiveness score signature positively correlated with PLR values. These data highlighted that systemic inflammation parameters may represent reliable and informative markers of the local immune tumor microenvironment in TNBC patients and could be exploited to decipher tumor infiltrate properties and consequently to select the most appropriate therapies.
The Human Brain Project—Synergy between neuroscience, computing, informatics, and brain-inspired technologies

The Human Brain Project (HBP) is a European flagship project with a 10-year horizon aiming to understand the human brain and to translate neuroscience knowledge into medicine and technology. To achieve such aims, the HBP explores the multilevel complexity of the brain in space and time; transfers the acquired knowledge to brain-derived applications in health, computing, and technology; and provides shared and open computing tools and data through the HBP European brain research infrastructure. We discuss how the HBP creates a transdisciplinary community of researchers united by the quest to understand the brain, with fascinating perspectives on societal benefits.
Citryl ornithine is an intermediate in a three-step biosynthetic pathway for rhizoferrin in Francisella.

The Gram-negative bacterium Francisella tularensis secretes the siderophore rhizoferrin to scavenge necessary iron from the environment. Rhizoferrin, also produced by a variety of fungi and bacteria, comprises two citrate molecules linked by amide bonds to a central putrescine (diaminobutane) moiety. Genetic analysis has determined that rhizoferrin production in F. tularensis requires two enzymes: FslA, a siderophore synthetase of the non-ribosomal peptide synthetase-independent siderophore synthetase (NIS) family and a pyridoxal-phosphate dependent decarboxylase, FslC. To discern the steps in the biosynthetic pathway, we tested cultures of F. tularensis strain LVS and its Δ fslA and Δ fslC mutants for the ability to incorporate potential precursors into rhizoferrin. Unlike putrescine supplementation, supplementation with ornithine greatly enhanced siderophore production by LVS. Radioactivity from [L-U-14C] ornithine, but not from [1-14C] ornithine, was efficiently incorporated into rhizoferrin by LVS. Although neither the Δ fslA nor the Δ fslC mutant produced rhizoferrin, a putative siderophore intermediate labeled by both [U-14C] ornithine and [1-14C] ornithine was secreted by the Δ fslC mutant. Rhizoferrin was identified by liquid chromatography and mass spectrometry in LVS culture supernatants, while citryl-ornithine was detected as the siderophore intermediate in the culture supernatant of the Δ fslC mutant. Our findings support a three-step pathway for rhizoferrin production in Francisella; unlike the fungus Rhizopus delemar, where putrescine functions as a primary precursor for rhizoferrin, biosynthesis in Francisella preferentially starts with ornithine as the substrate for FslA-mediated condensation with citrate. Decarboxylation of this citryl ornithine intermediate by FslC is necessary for a second condensation reaction with citrate to produce rhizoferrin.
Asthma Hospitalizations Among Homeless Children in New York State

In this study, using 2009–2014 statewide inpatient data from New York, we provide compelling new insight on levels of health care use among homeless children with asthma. BrightcoveDefaultPlayer10.1542/6138642836001PEDS-VA_2018-2769 Video Abstract BACKGROUND AND OBJECTIVES: Asthma is widely prevalent among US children, particularly in homeless children, who often lack proper medication storage or the ability to avoid environmental triggers. In this study, we assess asthma-attributed health care use among homeless youth. We hypothesize that asthma hospitalization rates, symptom severity, and admission through the emergency department (ED) will be higher among homeless youth compared with nonhomeless youth. METHODS: This secondary data analysis identified homeless and nonhomeless pediatric patients (<18 years old) with a primary diagnosis of asthma from New York statewide inpatient databases between 2009 and 2014. Hospitalization rate, readmission rate, admission through the ED, ventilation use, ICU admittance, hospitalization cost, and length of stay were measured. RESULTS: We identified 71 837 asthma hospitalizations, yielding 73.8 and 2.3 hospitalizations per 1000 homeless and nonhomeless children, respectively. Hospitalization rates varied by nonhomeless income quartile, with low-income children experiencing higher rates (5.4) of hospitalization. Readmissions accounted for 16.0% of homeless and 12.5% of nonhomeless hospitalizations. Compared with nonhomeless patients, homeless patients were more likely to be admitted from the ED (odds ratio 1.96; 95% confidence interval: 1.82–2.12; P < .01), and among patients >5 years old, homeless patients were more likely to receive ventilation (odds ratio 1.45; 95% confidence interval: 1.01–2.09; P = .04). No significant differences were observed in ICU admittance, cost, or length of stay. CONCLUSIONS: Homeless youth experience an asthma hospitalization rate 31 times higher than nonhomeless youth, with higher rates of readmission. Homeless youth live under uniquely challenging circumstances. Tailored asthma control strategies and educational intervention could greatly reduce hospitalizations.
Construct validity of the Mechanical Restraint – Confounders, Risk, Alliance Score (MR-CRAS): a new risk assessment instrument

Abstract Background: A new short-term risk assessment instrument, the Mechanical Restraint – Confounders, Risk, Alliance Score (MR – CRAS) checklist, including three subscales with altogether 18 items, has been developed in close collaboration with forensic mental health nurses, psychiatrists’ etc., and shows evidence of being comprehensible, relevant, comprehensive and easy to use for assessing the patient’s readiness to be released from mechanical restraint. Aim: The aim of this study was to investigate whether the subscales: confounders, risk and parameters of alliance constituted separate subscales and needed further revisions. Materials and methods: MR – CRAS was field-study tested among nurses, nurse assistants and social and health care assistants in 13 Danish closed forensic mental health inpatient units, and a Mokken analysis of scalability and a Spearman correlation analysis were performed. Results: MR – CRAS was completed by clinicians in 143 episodes of mechanical restraint, representing 88 patients, with a mean duration of 63.25 hours. Most patients were younger men, diagnosed within the schizophrenia spectrum. One-third of the patients had repeated mechanical restraint episodes ranging between 2 and 8 episodes. MR – CRAS and especially the parameters of alliance were perceived as usable for assessment of the patient’s readiness to be released from mechanical restraint. The psychometric analyses showed that the three subscales were unidimensional. Conclusions: The study shows evidence of the construct validity of MR – CRAS among clinicians at closed forensic mental health inpatient units. MR – CRAS contributes with a common language and structured, systematic and transparent observations and assessments on an hour by hour basis during mechanical restraint
CCR5 Promoter Polymorphism −2459G > A: Forgotten or Ignored?

C-C chemokine receptor 5 (CCR5) polymorphisms, particularly a 32-base pair deletion (∆32) in the open reading frame and −2459G > A in the promoter, are well known for their associations with HIV-1 infection and/or disease progression in a variety of studies. In this era of an HIV cure, where all the emphasis is on ∆32, it seems that −2459G > A has been forgotten or ignored. There is significant importance in the incorporation of the CCR5 −2459G > A genotype information into studies evaluating new immunologic and chemotherapeutic strategies, and those designing and implementing better treatment strategies with current antiretroviral therapy, doing so would enable a better understanding of the response to the intervention, due to a mechanistic or constitutive explanation. Until we find a strategy, whether a stem-cell transplantation or CCR5 editing approach or something else, that delivers a cure to the millions, we should make use of every piece of information that may help curtail HIV/AIDS as a threat to public health.
Body weight and subcutaneous fat patterning in elite judokas

Body weight and fat are major performance variables in many sports. Extreme weight reduction can lead to severe medical problems. Accurate body composition measurements are fundamental for both medical and performance optimization. Relative body weight in terms of mass index (MI1 = 0.53 M/(hs)), and in terms of body mass index (BMI = M/h2) were determined (h:stature, s:sitting height, M:body mass). Subcutaneous adipose tissue (SAT) was measured using a recently standardized ultrasound (US) method. US thickness sums from eight body sites were measured in 26 female and 35 male judokas of various weight classes. Comparisons of US and skinfold results indicate that the latter can be severely misleading in competitive judokas. Mean MI1 of females was 22.8 kg m−2 (BMI:22.9 kg m−2), males: 26.7 kg m−2 (BMI:26.5 kg m−2), but individual differences MI1‐BMI were larger than 0.5 kg m−2 in 13 and larger than 1.0 kg m−2 in three cases. Medians of SAT thickness sums DI were three‐times higher in females (66.1 mm) than in males (21.8 mm), and the fat patterning differed significantly. Females had 8.6% (median) fibrous structures embedded in SAT, and males 20.2%. Both MI and BMI were not correlated with SAT. Mean pre‐competition weight loss was 4.3% (ie, 3.0 kg), and maximum was 9.2% (7.4 kg), indicating that modifications of weigh‐in procedures are urgently needed. DI‐values mirror the athletes' potential to reduce ballast fat instead of short‐term weight reduction by dehydration; however, weight loss and SAT measured some weeks before the competitions were not correlated. Further, US measurements and medical longitudinal observations are required for discussing the large individual variations and possible fat minimum demands.
The Impact of the Adipose Organ Plasticity on Inflammation and Cancer Progression

Obesity is characterized by chronic and low-grade systemic inflammation, an increase of adipose tissue, hypertrophy, and hyperplasia of adipocytes. Adipose tissues can be classified into white, brown, beige and pink adipose tissues, which display different regulatory, morphological and functional characteristics of their adipocyte and immune cells. Brown and white adipocytes can play a key role not only in the control of energy homeostasis, or through the balance between energy storage and expenditure, but also by the modulation of immune and inflammatory responses. Therefore, brown and white adipocytes can orchestrate important immunological crosstalk that may deeply impact the tumor microenvironment and be crucial for cancer establishment and progression. Recent works have indicated that white adipose tissues can undergo a process called browning, in which an inducible brown adipocyte develops. In this review, we depict the mechanisms involved in the differential role of brown, white and pink adipocytes, highlighting their structural, morphological, regulatory and functional characteristics and correlation with cancer predisposition, establishment, and progression. We also discuss the impact of the increased adiposity in the inflammatory and immunological modulation. Moreover, we focused on the plasticity of adipocytes, describing the molecules produced and secreted by those cells, the modulation of the signaling pathways involved in the browning phenomena of white adipose tissue and its impact on inflammation and cancer.