Miracle-dz/UniFAR-FTUs huggingface dataset:
Does Natural Killer Cell Deficiency (NKD) Increase the Risk of Cancer? NKD May Increase the Risk of Some Virus Induced Cancer

Natural killer cell deficiency (NKD) is a primary immunodeficiency where the main defect lies in CD56+CD3− natural killer (NK) cells which mediate cytotoxicity against tumors. Most cases are observed in children and adolescents with recurrent viral infections and cancer. GATA2 and MCM4 mutations are found in NKD patients with cancer. However, the question remains unclear whether NKD increases the risk of cancer. Mutations in the second zinc finger of GATA2 cause both NKD and haematopoietic malignancies. MCM4 splice site mutations are found in NKD patients and they increase susceptibility to DNA instability during replication. IRF8, RTEL1, and FCGR3A mutations are associated with NKD but their associations with cancer are unknown. Based on the studies, it is hypothesized that genetic mutations alone are sufficient to cause cancer. However, a number of NKD patients developed oncogenic viral infections which progressed into cancer. Here, we review the evidence of genetic mutations responsible for both NKD and cancer to identify whether NKD contributes to development of cancer. The findings provide insights into the role of NK cells in the prevention of cancer and the significance of assessing NK cell functions in susceptible individuals.
Systematic Review on the Involvement of the Kynurenine Pathway in Stroke: Pre-clinical and Clinical Evidence

Background: Stroke is the second leading cause of death after ischemic heart disease and the third leading cause of disability-adjusted life-years lost worldwide. There is a great need for developing more effective strategies to treat stroke and its resulting impairments. Among several neuroprotective strategies tested so far, the kynurenine pathway (KP) seems to be promising, but the evidence is still sparse. Methods: Here, we performed a systematic review of preclinical and clinical studies evaluating the involvement of KP in stroke. We searched for the keywords: (“kynurenine” or “kynurenic acid” or “quinolinic acid”) AND (“ischemia” or “stroke” or “occlusion) in the electronic databases PubMed, Scopus, and Embase. A total of 1,130 papers was initially retrieved. Results: After careful screening, forty-five studies were included in this systematic review, being 39 pre-clinical and six clinical studies. Despite different experimental models of cerebral ischemia, the results are concordant in implicating the KP in the pathophysiology of stroke. Preclinical evidence also suggests that treatment with kynurenine and KMO inhibitors decrease infarct size and improve behavioral and cognitive outcomes. Few studies have investigated the KP in human stroke, and results are consistent with the experimental findings that the KP is activated after stroke. Conclusion: Well-designed preclinical studies addressing the expression of KP enzymes and metabolites in specific cell types and their potential effects at cellular levels alongside more clinical studies are warranted to confirm the translational potential of this pathway as a pharmacological target for stroke and related complications.
Heterogeneities in Cognitive and Socio-Emotional Development in Children With Autism Spectrum Disorder and Severe Intellectual Disability as a Comorbidity

Introduction: Intellectual disability (ID) is frequently associated as a comorbidity in autism spectrum disorders (ASD). This study investigated a) how similar the heterogeneity in the cognitive and socio-emotional developmental profiles was for children with ASD and ID, b) the difference between the subjects’ profiles and those of typically developing children (TD) matched for developmental levels, c) the skills existing with the lowest and highest developmental levels, and d) the relationship between developmental profiles in ASD and the severity of autism, ID, and the overall developmental level. Participants: The sample was comprised of 119 children (101 boys and 18 girls) who ranged in chronological age (CA) from 21 months to 14 years (M = 5 years 2 months; SD = 2 years 6 months) with developmental levels lower than 24 months. They came from three countries (France = 40, Brazil = 40, and Algeria = 39). The control group was comprised of 40 TD children from these same countries who ranged in CA from 4 to 24 months (M = 1 year 3 months; SD = 5 months). The ASD diagnosis was carried out according to International Statistical Classification of Diseases and Related Health Problems-10th Edition (ICD-10), Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR), Diagnostic and Statistical Manual of Mental Disorders-5th ed (DSM-5) criteria and the Childhood Autism Rating Scale (CARS). Measures: Children were tested using the Social Cognitive Evaluation Battery (SCEB; Adrien, 2007) by trained psychologists from public and private institutions specialized in the diagnosis of autism and interventions in this field. The SCEB explores 16 functional abilities, in both cognitive and socio-emotional areas, and allows the calculation of domain and area developmental levels and heterogeneity indices for the global, cognitive, and socio-emotional areas. Results: Children with ASD developmental profiles show very high heterogeneity as opposed to TD children. Regardless of the country of origin, there are similarities between the heterogeneous cognitive and socio-emotional developmental profiles of the children with ASD, whose profiles are characterized by lower developmental levels of language and vocal imitation skills, and a relationship between these developmental heterogeneities and the degree of severity of autistic symptomatology, intellectual disability, and overall development level. The implications of this study are presented for clinical assessment and intervention purposes in ASD and ID.
Topological Disruption of Structural Brain Networks in Patients With Cognitive Impairment Following Cerebellar Infarction

Cerebellar lesions can lead to a series of cognitive and emotional disorders by influencing cerebral activity via cerebro-cerebellar loops. To explore changes in cognitive function and structural brain networks in patients with posterior cerebellar infarction, we conducted the current study using diffusion-weighted MRI (32 cerebellar infarction patients, 29 controls). Moreover, a series of neuropsychological tests were used to assess the subject's cognitive performance. We found cognitive impairment following cerebellar infarction involving multiple cognitive domains, including memory, executive functions, visuospatial abilities, processing speed and language functions, and brain topological abnormalities, including changes in clustering coefficients, shortest path lengths, global efficiency, local efficiencies, betweenness centrality and nodal efficiencies. Our results indicated that measures of local efficiency, mainly in the precuneus, cingulate gyrus and frontal-temporal cortex, were significantly reduced with posterior cerebellar infarction. At the same time, The correlation analysis suggested thatthe abnormal alterations in the right PCG, bilateral DCG, right PCUN may play a core role in the cognitive impairment following cerebellar infarctions. The differences in topological features of the structural brain networks within the cerebro-cerebellar circuits may provide a new approach to explore the pathophysiological mechanisms of cognitive impairment following cerebellar infarction.
Understanding the relationship between family planning method choices and modern contraceptive use: an analysis of geographically linked population and health facilities data in Haiti

Introduction This study linked data from the 2012 Haiti Demographic and Health Survey (DHS) and the 2013 Haiti Service Provision Assessment (SPA) to estimate the extent to which women’s contraceptive use is associated with the method choices available in Haiti’s health facilities. Methods Using Global Positioning System (GPS) data for DHS clusters and for health facilities, we linked each DHS cluster to all of the family planning facilities located within a specified distance, and then measured the cluster’s level of contraceptive method choice based on the number of facilities within the buffer zone that offered three or more modern contraceptive methods. Random intercept logistic regressions were used to model the variation in individual modern contraceptive use and the availability of multiple method choices at the cluster level. Results Limited number of family planning facilities in Haiti offered at least three modern contraceptive methods (51% in urban and 23% in rural). Seventeen percent of both rural and urban women lived in an area with low availability of multiple methods—meaning that no facility in the specified buffer zone offered three or more contraceptive methods. Another 29% of rural women and 41% of urban women had medium availability—that is, only one facility in the buffer zone offered three or more methods. In rural areas, compared with women living in a cluster with low availability of multiple methods, the odds of using a modern method are 73% higher for women living in a cluster with medium availability, and over twice as high for women living in a cluster with high availability. A similar positive relationship was also found in urban areas. Conclusions Women in Haiti have only limited proximity to a health facility offering a variety of contraceptive methods. Improving access to a range of methods available at health facilities near where people live is critical for increasing contraceptive use in both urban and rural areas of Haiti.
CD90low MSCs modulate intratumoral immunity to confer antitumor activity in a mouse model of ovarian cancer

Both anti-tumoral and pro-tumoral effects of mesenchymal stem cells (MSCs) in preclinical treatment of ovarian cancer have been controversially demonstrated. In this study, we profiled the phenotypes of mouse compact bone-derived MSCs (CB-MSCs) and bone marrow-derived MSCs (BM-MSCs) and found that CB-MSCs expressed lower CD90 compared to BM-MSCs. We examined gene expression of immune regulating cytokines of CB-MSCs in 2D and 3D culture and under stimulation with TLR4 agonist LPS or immune activator VIC-008. Our data showed that when CB-MSCs were cultured in simulated in vivo 3D condition, CD90 expression was further decreased. Moreover, gene expressions of immune activating cytokines IL-12, IL-21, IFNγ and a pro-inflammatory cytokine CXCL10 in CB-MSCs were increased in 3D culture whereas gene expression of anti-inflammatory cytokines IL-10 and CCL5 were downregulated. Stimulation of CB-MSCs by LPS or VIC-008 presented similar profile of the cytokine gene expressions to that in 3D culture which might benefit the anti-tumor efficacy of CD90low MSCs. The anti-tumor effects of CD90low CB-MSCs alone or in combination with VIC-008 were evaluated in a syngeneic orthotopic mouse model of ovarian cancer. Treatment that combines CB-MSCs and VIC-008 significantly decreased tumor growth and prolonged mouse survival. This was associated with the increase of activated anti-tumoral CD4+ and CD8+ T cells and the decrease of Treg cells in the tumor microenvironment. Taken together, our study demonstrates the synergistic anti-tumoral efficacy by application of CB-MSCs combined with immune activator VIC-008 and provides new insight into CD90low MSCs as a new anti-tumor arsenal.
Role of computed tomography scan in assessment of skull fracture patterns among motorcycle road traffic accident patients in South Western Nigeria

Background: Commercial motorcycling is a common means of transportation in Nigeria, and motorcycle road traffic accidents (MCRTAs) are commonly associated with multiple skull fractures. Cranial computed tomography (CT) scan is the standard imaging modality of patients with head injury. Aim: The aim of this study is to describe the pattern of skull fractures on cranial CT scan in patients with head injury following MCRTA. Patients and Methods: This was a descriptive cross-sectional study conducted at the University College Hospital, Ibadan, between June and October 2016. Noncontrast cranial CT scan was performed on 190 patients who presented with head injury following MCRTAs. Results: Over half (n = 59.8%) of the patients were within the ages of 20–39 years with a mean age of 33 ± 14.37 years. A total of 183 patients did not use crash helmet at the time of accident, out of which 168 (n = 88.4%) sustained skull fractures. Six different skull fracture patterns were identified on cranial CT scan of these patients. The most common fracture pattern seen was the combined calvarial, facial, and base of skull fractures representing 22.1% while the least fracture pattern was the base of skull fracture (n = 4.7%). Most of the patients with calvarial fractures were without helmet at the time of injury (n = 98.3%) compared to 1.7% of patients who wore helmet at the time of injury. This was statistically significant (P = 0.040). Conclusion: This study further underscores the usefulness of cranial CT scan in identifying and evaluating patients with skull fractures following MCRTA in our environment, thus guiding proper medical and surgical management of such patients in a low-resource setting.
DISCOVERY OF THE FIRST B[e] SUPERGIANTS IN M 31

B[e] supergiants (B[e]SGs) are transitional objects in the post-main sequence evolution of massive stars. The small number of B[e]SGs known so far in the Galaxy and the Magellanic Clouds indicates that this evolutionary phase is short. Nevertheless, the strong aspherical mass loss occurring during this phase, which leads to the formation of rings or disk-like structures, and the similarity to possible progenitors of SN1987 A emphasize the importance of B[e]SGs for the dynamics of the interstellar medium as well as stellar and galactic chemical evolution. The number of objects and their mass-loss behavior at different metallicities are essential ingredients for accurate predictions from stellar and galactic evolution calculations. However, B[e]SGs are not easily identified, as they share many characteristics with luminous blue variables (LBVs) in their quiescent (hot) phase. We present medium-resolution near-infrared K-band spectra for four stars in M 31, which have been assigned a hot LBV (candidate) status. Applying diagnostics that were recently developed to distinguish B[e]SGs from hot LBVs, we classify two of the objects as bonafide LBVs; one of them currently in outburst. In addition, we firmly classify the two stars 2MASS J00441709+4119273 and 2MASS J00452257+4150346 as the first B[e]SGs in M 31 based on strong CO band emission detected in their spectra, and infrared colors typical for this class of stars.
Medication regimen complexity and its impact on medication adherence and glycemic control among patients with type 2 diabetes mellitus in an Ethiopian general hospital

Background Different studies reported that higher diabetes-specific Medication Regimen Complexity Index (MRCI) has a negative impact on glycemic control potentially by decreasing medication adherence. However, information about regimen complexity and its association with adherence and glycemic control in Ethiopian patients with diabetes is unknown. Aim To evaluate medication regimen complexity and to assess its impact on medication adherence and glycemic control among patients with type 2 diabetes Mellitus (T2DM). Methods A hospital-based cross-sectional design was conducted at Debre Tabor General Hospital from 1 May 2018 to 30 June 2018. Medication regimen complexity was evaluated using the 65-item validated tool called Medication Complexity Index (MRCI). Adherence was measured using Morisky Medication Adherence Scale while patients were classified as having poor or good glycemic control based on the recent record of their fasting blood glucose. Multivariable logistic regression analysis was applied to determine the association between predictive variables and outcome variables. Results A total of 275 patients with T2DM who meet the inclusion criteria were included in the final analysis. About 22.2% of the participants were classified as having high diabetes-specific MRCI, whereas 35.6% of the participants were classified as having high patient-level MRCI. The majority (70.5%) of the respondents were adherent to their medications, and 42.9% of the total population were categorized as having good glycemic control. According to the result of the multivariate analysis, patients with low-level and moderate-level MRCI of both diabetes-specific and patient-level MRCI were more adherent to their medication compared with patients with high MRCI. High diabetes medication regimen complexity was associated with poor glycemic control in the adjusted analyses (adjusted OR = 0.276; 95% CI = 0.100 o 0.759). Conclusion The prevalence of high MRCImedication regimen complexity index is high among patients with T2DM. Patients with low and moderate regimen complexity had improved adherence. High diabetes-specific medication regimen complexity was associated with poor glycemic control. Simplification of a complex medication regimen for patients with diabetes should be sought by physicians and pharmacists to improve medication adherence and subsequent improvement in glycemic control.
Bacillus pumilus increases boron uptake and inhibits rapeseed growth under boron supply irrespective of phosphorus fertilization

Abstract The present study was carried out to investigate how plant growth-promoting bacteria (PGPB) influence plant growth and uptake of boron (B) and phosphorus (P) in rapeseed (Brassica napus). Rapeseed was subjected to control, B, P and B + P treatments, either with or without B. pumilus (PGPB) inoculation, and grown in pot culture for 6 weeks. In the absence of B. pumilus, the addition of B, P or both elements improved the growth of rapeseed compared with the control. Interestingly, B. pumilus inoculation inhibited plant growth and enhanced B uptake under B and B + P but not under control and P conditions. In addition, B. pumilus inoculation decreased the pH of soil under B and B + P supplies. Bacillus pumilus inoculation thus increased rapeseed B uptake and inhibited growth under B supply, which suggests that the effects of PGPB on rapeseed growth depend on the addition of B to soil. Bacillus pumilus inoculation may therefore be recommended for the enhancement of rapeseed B levels in B-deficient soils but not in B-sufficient ones.
Intermediate Monocytes and Cytokine Production Associated With Severe Forms of Chagas Disease

Monocytes are classified according to their CD14 and CD16 expression into classical (reparative), intermediate (inflammatory), and non-classical. This study assessed the frequency of monocyte and the relationship between monocyte subset percentages and the levels of blood cytokines in Colombian chagasic patients with different clinical forms. This study included chagasic patients in different clinical stages: indeterminate (IND) n = 14, chronic chagasic cardiomyopathy (CCC) n = 14, and heart transplant chagasic (HTCC) n = 9; controls with non-chagasic cardiopathy (NCC) n = 15, and healthy individuals (HI) n = 15. Peripheral blood mononuclear cells (PBMCs) were isolated, labeled for CD14, CD16, and HLA-DR, and analyzed by flow cytometry. Cytokines were measured with a bead-based immunoassay. Percentages of total CD14+ CD16+ and CD14+ HLA-DR+ monocytes were higher in patients with heart involvement (CCC, HTCC, and NCC) than controls. Percentages of intermediate monocytes increased in symptomatic chagasic patients (CCC and HTCC) compared to asymptomatic chagasic patients (IND) and controls (HI). Asymptomatic chagasic patients (IND) had higher percentages of classical monocytes, an increased production of CCL17 chemokine compared to chagasic symptomatic patients (CCC), and their levels of CCL17 was positively correlated with the percentage of classical monocyte subset. In CCC, the percentages of intermediate and classical monocytes were positively correlated with IL-6 levels, which were higher in this group compared to HI, and negatively with IL-12p40 concentration, respectively. Remarkably, there also was an important increased of classical monocytes frequency in three chronic chagasic patients who underwent cardiac transplant, of which one received anti-parasitic treatment. Our findings suggest that cardiac chagasic patients have an increased percentage of inflammatory monocytes and produce more IL-6, a biomarker of heart failure and left ventricular dysfunction, whereas asymptomatic chagasic individuals present a higher percentage of reparative monocytes and CCL17.
Impact of the Time to Initiation of Parenteral Nutrition on Patient Outcomes in Critically Ill Adults

Background: The optimal time to initiate parenteral nutrition (PN) in critically ill adults in whom enteral nutrition is not feasible is controversial. Objective: The objectives were to compare in-hospital mortality and hospital length of stay in patients initiated on PN within 7 days or after 7 days of poor nutrient intake. Methods: This single-center, retrospective study included critically ill adult patients who received at least 2 consecutive days of PN during hospitalization from May 2014 to July 2016. Results: The median duration of PN (interquartile range) was 8 (5-13) days. In total, 110 patients received PN within 7 days of poor nutrient intake while 49 patients received PN after 7 days of poor nutrient intake. There was no statistically significant difference in in-hospital mortality between groups (29.09% vs 18.37%, P = .1535). Patients initiated within 7 days had a significantly shorter median hospital length of stay than patients initiated after 7 days (20 days vs 27 days, P = .0013). There were 69 patients who were classified as obese. Obese patients initiated within 7 days had a significantly shorter median hospital length of stay than obese patients initiated after 7 days (17 days vs 33 days, P = .0007). Conclusions: Time to initiation of PN did not impact in-hospital mortality. However, there was an association between early initiation of PN and a shorter hospital length of stay that was most pronounced among obese patients.
PEG-Derivatized Dual-Functional Nanomicelles for Improved Cancer Therapy

Polymeric micelles have attracted considerable attention for effective delivery of poorly water-soluble cancer drugs. Polyethylene glycol (PEG), which has been approved for human use by the US Food and Drug Administration, is the most commonly used hydrophilic component of polymeric micelles because it is biocompatible and biodegradable. One disadvantage of traditional polymeric micelles is that they include a large amount of inert carrier materials, which do not contribute to therapeutic activity but increase cost and toxicity risk. A better alternative may be “dual-functional” micellar carriers, in which the hydrophobic carrier material (conjugated to PEG) has intrinsic therapeutic activity that complements, or even synergizes with, the antitumor activity of the drug cargo. This review summarizes recent progress in the development of PEG-derivatized dual-functional nanomicelles and surveys the evidence of their feasibility and promise for cancer therapy.