Miracle-dz/UniFAR-FTUs huggingface dataset:
Ending neglect: providing effective childhood tuberculosis training for health care workers in Tanzania.

SETTING Health care facilities in Dar es Salaam, Pwani, and Arusha, Tanzania. OBJECTIVE To assess health care worker (HCW) knowledge and practices 1 year after specialized training in childhood tuberculosis (TB). DESIGN Using a standardized survey, we interviewed a convenience sample of HCWs providing both general and specialized care to children. RESULTS We interviewed 117 HCWs in TB clinics, maternal and child health clinics, human immunodeficiency virus (HIV) clinics, out-patient departments, and pediatric in-patient wards at 12 facilities. A total of 81 HCWs (62% of nurses, 74% of clinicians) reported having attended the national childhood TB training course. Most HCWs responded correctly to questions on childhood TB diagnosis, treatment, and TB-HIV co-management, regardless of training history. Most HCWs reported that they routinely obtain chest radiographs, HIV testing, and a TB contact history when evaluating children for TB. Less than half of HCWs reported routinely obtaining sputum for mycobacterial culture or performing a tuberculin skin test. Three times as many trained as untrained HCWs reported having ever prescribed isoniazid preventive therapy (IPT) to a child (P < 0.05). CONCLUSION In general, levels of childhood TB knowledge were high and practices were in accordance with national guidance. Specific gaps in diagnosis, treatment and use of IPT were identified for future focused training.
A Founder Mutation in Artemis, an SNM1-Like Protein, Causes SCID in Athabascan-Speaking Native Americans1

Athabascan SCID (SCIDA) is an autosomal recessive disorder found among Athabascan-speaking Native Americans and is manifested by the absence of both T and B cells (T−B−NK+ SCID). We previously mapped the SCIDA gene to a 6.5-cM interval on chromosome 10p. SCIDA fibroblasts were found to have defective coding joint and reduced, but precise signal joint formation during V(D)J recombination. After excluding potential candidate genes, we conducted a combined positional candidate and positional cloning approach leading to the identification of nine novel transcripts in the refined SCIDA region. One of the transcripts showed significant homology with the mouse and yeast SNM1/PSO2 and was recently reported (Artemis) to be responsible for another T−B−NK+ SCID condition (radiation sensitive SCID) in 13 patients of primarily European origin. In our evaluation of this gene, we have identified a unique nonsense mutation in 21 SCIDA patients that is closely correlated to the founder haplotypes that we had previously identified. This nonsense founder mutation results in the truncation of the deduced protein product. The wild-type construct of the primary transcript can effectively complement the defective coding joint and reduced signal joint formation in SCIDA fibroblasts. The above results indicate that this SNM1-like gene (Artemis) is the gene responsible for SCIDA. We also discovered three additional alternative exons and detected at least six alternatively spliced SCIDA variants (SCIDA-V1, 2, 3, 4, 5, and 6) coexisting with the primary transcript in trace amounts. Finally, we found that the SCIDA primary transcript (Artemis) encodes a nuclear protein.
Dose Dependency of Pharmacokinetics and Therapeutic Efficacy of Pegylated Liposomal Doxorubicin (DOXIL) in Murine Models

Stealth (pegylated) liposomal doxorubicin (Doxil) has been extensively studied at the pre-clinical and clinical level in recent years. However, one issue not yet addressed is the effect of dose on tumor localization and therapeutic efficacy of Doxil. Although it has been reported that the pharmacokinetics of drug-free Stealth liposomes is independent of dose within a certain range, clinical pharmacokinetic analysis of Doxil suggests a dose-dependent clearance saturation phenomenon when a broad dose range is examined. In addition, liposome-encapsulated doxorubicin can exert toxic effects on the liver macrophage population in the form of impairment of the phagocytic function and reduced ability of colloid particle clearance. In studies with tumor-bearing mice in which the dose of Doxil was escalated from 2.5 to 20 mg/kg, we demonstrate that dose escalation results in a saturation of Doxil clearance and a disproportional increase of the amount of liposomal drug accumulating in tumor. Experiments with radiolabeled highly negatively-charged liposomes injected into mice previously treated with Doxil are consistent with a partial blockade of the reticulo-endothelial system with relative reduction of liver uptake and greater prolongation of liposome circulation time. The clearance saturation effect is seen after Doxil in a dose-dependent fashion, and not after a similar free doxorubicin dose or similar phospholipid dose in drug-free liposomes. A trend to superior therapeutic efficacy for treatments based on larger doses as compared to smaller split doses, while maintaining an equivalent dose intensity, was also observed. These observations may be relevant to the choice of dose-schedule of Doxil to ensure optimal anti-tumor activity. Therefore, dose-dependent liposomal doxorubicin blockade of the reticulo-endothelial system may prolong liposome circulation time and enhance significantly drug delivery to tumors.
O-Linked N-Acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Interact with Mi2β Protein at the Aγ-Globin Promoter*

One mode of γ-globin gene silencing involves a GATA-1·FOG-1·Mi2β repressor complex that binds to the −566 GATA site relative to the Aγ-globin gene cap site. However, the mechanism of how this repressor complex is assembled at the −566 GATA site is unknown. In this study, we demonstrate that the O-linked N-acetylglucosamine (O-GlcNAc) processing enzymes, O-GlcNAc-transferase (OGT) and O-GlcNAcase (OGA), interact with the Aγ-globin promoter at the −566 GATA repressor site; however, mutation of the GATA site to GAGA significantly reduces OGT and OGA promoter interactions in β-globin locus yeast artificial chromosome (β-YAC) bone marrow cells. When WT β-YAC bone marrow cells are treated with the OGA inhibitor Thiamet-G, the occupancy of OGT, OGA, and Mi2β at the Aγ-globin promoter is increased. In addition, OGT and Mi2β recruitment is increased at the Aγ-globin promoter when γ-globin becomes repressed in postconception day E18 human β-YAC transgenic mouse fetal liver. Furthermore, we show that Mi2β is modified with O-GlcNAc, and both OGT and OGA interact with Mi2β, GATA-1, and FOG-1. Taken together, our data suggest that O-GlcNAcylation is a novel mechanism of γ-globin gene regulation mediated by modulating the assembly of the GATA-1·FOG-1·Mi2β repressor complex at the −566 GATA motif within the promoter.
Internal and External Hiring

Using large-scale, linked, employer–employee, Finnish panel data, the authors examine firms’ internal versus external hiring decisions more comprehensively than has prior literature. The results show that vacancies in job hierarchies are filled more often by horizontal moves than by promotions. Most horizontal moves are external and within the same job functions, so that internally promoted workers face external competitors occupying higher job levels. Compared to internally promoted workers, external and internal horizontal hires have stronger observable ability indicators (e.g., education, experience, prior work history) but weaker job performance in the year preceding the transfer. Internal and external horizontal hires have similar job histories.
Cervical Epidermal Growth Factor‐Receptor (EGF‐R) and Serum Insulin‐Like Growth Factor II (IGF‐II) Levels are Potential Markers for Cervical Cancer 1

PROBLEM: To ascertain if cervical epithelial epidermal growth factor receptor (EGF‐R) and serum insulin‐like growth factor II (IGF‐II) levels are potential markers for cervical cancer. METHOD OF STUDY: We tested cervical biopsies obtained from 18 controls, 3 women with cervical intraepithelial neoplasia (CIN) I, 17 women with CIN II and III, and 12 women with cervical cancer for EGF‐R using a quantitative immunofluorescent antibody assay. We measured serum IGF‐II levels using an enzyme‐linked immunosorbent assay in 20 controls, 26 CIN patients, 12 with cervical cancer before therapy, 5 with cervical cancer for <1 year, and 9 others ≥1 year after therapy. RESULTS: The levels of cervical EGF‐R in women with CIN and cervical cancer were significantly higher (P<0.05 for CIN I; P<0.001 for patients with CIN II and III or cervical cancer) than in controls. Women with cervical cancer (P<0.001 vs. controls) or advanced CIN (P=0.03) had elevated levels of serum IGF‐II, while the women with CIN I had levels similar to controls. Women with cervical cancer in the post‐therapy period had significantly lower serum IGF‐II levels than the women with cervical cancer before therapy (P<0.001). CONCLUSION: Cervical epithelial EGF‐R and serum IGF‐II levels may be used for the diagnosis and prognosis of cervical cancer.
Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis.

A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages became large, vacuolated foamy cells, and containing numerous bacilli with immunoreactivity to mycobacterial lipids and lipoarabinomannan (LAM). These macrophages displayed poor and scarce TNF-alpha and IL-1 alpha immunostaining but still strong immunoreactivity to TGF-beta. These cytokine production kinetics and the spatial relationship between immunostained cells and lung lesions corroborate the important role of TNF-alpha and IL-1 alpha in the constitution of granulomas and immune protection during the early phase of the infection, and also suggest an important if not primary role for TGF-beta in the immunopathogenesis of the advanced forms of pulmonary tuberculosis.
Local Reactive Power Control Methods for Overvoltage Prevention of Distributed Solar Inverters in Low-Voltage Grids

The main objective of this study is to increase the penetration level of photovoltaic (PV) power production in low-voltage (LV) grids by means of solar inverters with reactive power control capability. This paper underlines weak points of standard reactive power strategies which are already imposed by certain grid codes, and then, the study introduces a new reactive power control method that is based on sensitivity analysis. The sensitivity analysis shows that the same amount of reactive power becomes more effective for grid voltage support if the solar inverter is located at the end of a feeder. Based on this fundamental knowledge, a location-dependent power factor set value can be assigned to each inverter, and the grid voltage support can be achieved with less total reactive power consumption. In order to prevent unnecessary reactive power absorption from the grid during admissible voltage range or to increase reactive power contribution from the inverters that are closest to the transformer during grid overvoltage condition, the proposed method combines two droop functions that are inherited from the standard cos φ(P) and Q(U) strategies. Its performance comparison in terms of grid losses and voltage variation with different reactive power strategies is provided by modeling and simulating a real suburban LV network.
Shared Epitope–Antagonistic Ligands: A New Therapeutic Strategy in Mice With Erosive Arthritis

The mechanisms underlying bone damage in rheumatoid arthritis (RA) are incompletely understood. We recently identified the shared epitope (SE), an HLA–DRB1–coded 5–amino acid sequence motif carried by the majority of RA patients as a signal transduction ligand that interacts with cell surface calreticulin and accelerates osteoclast (OC)–mediated bone damage in collagen‐induced arthritis (CIA). Given the role of the SE/calreticulin pathway in arthritis‐associated bone damage, we sought to determine the therapeutic targetability of calreticulin.
Interferon-gamma in cerebrospinal fluid of children with aseptic meningitis.

BACKGROUND Certain cytokines may contribute to the sequence of events that lead to meningeal inflammation in bacterial meningitis. However, their role in viral meningitis is not so less well defined. We determined the cytokines levels in the cerebrospinal fluid (CSF) of children with aseptic meningitis and discussed their relationship with clinical and laboratory findings. METHODS We determined the concentrations of interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the CSF of 62 patients with aseptic meningitis including 17 patients with culture-proved enteroviral meningitis, and from 19 control acute febrile patients without meningitis. RESULTS The GM-CSF in the cerebrospinal fluid was detected from one of the 62 patients with aseptic meningitis and none of the 19 controls. Fourteen (23%) of the 62 patients with aseptic meningitis and 2 (10.5%) of 19 controls had detectable IL-1 beta. There was no significant difference in IL-1 beta levels between patients with aseptic meningitis (4.4 +/- 11.4 pg/ml) and control group (2.4 +/- 7.7 pg/ml). The CSF IFN-gamma level was detectable in 40 (65%) of 62 patients and 6 (31.6%) of 19 controls. The mean CSF IFN-gamma concentration was significantly higher in patients with aseptic meningitis when compared with that in control group (37.9 +/- 48.8 pg/ml vs 17.5 +/- 29.7 pg/ml; p = 0.007). CONCLUSIONS IFN-gamma was detectable in the CSF in 65% of patients with aseptic meningitis and the role of interferon-gamma remains to be determined.
Assessment of the Association between Human Papillomavirus Infection and Breast Carcinoma.

BACKGROUND AND OBJECTIVES Breast cancer is the most common malignancy in women throughout the world. There are controversial reports on the role of human papillomavirus (HPV) infection in breast carcinogenesis. The aim of this study was to assess the presence of HPV-DNA in invasive breast carcinoma to determine the association between HPV infection and breast carcinoma. METHODS The study included formalin-fixed paraffin-embedded tissue samples of 100 cases with invasive ductal carcinoma of breast and 50 control tissues of mammoplasty specimens. HPV-DNA was purified and amplified through GP5+/GP6+ and MY09/MY11 primers. RESULTS All tested carcinomas as well as normal tissues were negative for all types of HPV in PCR assay. CONCLUSION Our results do not support the association between HPV infection and breast carcinoma. Further studies involving larger number of cases are required to elucidate the role of HPV infection in breast carcinogenesis.
Interhemispheric functional connectivity in anorexia and bulimia nervosa

The functional interplay between hemispheres is fundamental for behavioral, cognitive, and emotional control. Anorexia nervosa (AN) and bulimia nervosa (BN) have been largely studied with brain magnetic resonance imaging (MRI) in relation to the functional mechanisms of high‐level processing, but not in terms of possible inter‐hemispheric functional connectivity anomalies. Using resting‐state functional MRI (fMRI), voxel‐mirrored homotopic connectivity (VMHC) and regional inter‐hemispheric spectral coherence (IHSC) were studied in 15 AN and 13 BN patients and 16 healthy controls (HC). Using T1‐weighted and diffusion tensor imaging MRI scans, regional VMHC values were correlated with the left‐right asymmetry of corresponding homotopic gray matter volumes and with the white matter callosal fractional anisotropy (FA). Compared to HC, AN patients exhibited reduced VMHC in cerebellum, insula, and precuneus, while BN patients showed reduced VMHC in dorso‐lateral prefrontal and orbito‐frontal cortices. The regional IHSC analysis highlighted that the inter‐hemispheric functional connectivity was higher in the ‘Slow‐5’ band in all regions except the insula. No group differences in left–right structural asymmetries and in VMHC vs. callosal FA correlations were significant in the comparisons between cohorts. These anomalies, not explained by structural changes, indicate that AN and BN, at least in their acute phase, are associated with a loss of inter‐hemispheric connectivity in regions implicated in self‐referential, cognitive control and reward processing. These findings may thus gather novel functional markers to explore aberrant features of these eating disorders.
Extracerebellar progenitors grafted to the neurogenic milieu of the postnatal rat cerebellum adapt to the host environment but fail to acquire cerebellar identities

Stem or progenitor cells acquire specific regional identities during early ontogenesis. Nonetheless, there is evidence that cells heterotopically transplanted to neurogenic regions of the developing or mature central nervous system may switch their fate to adopt host‐specific phenotypes. Here, we isolated progenitor cells from different germinative sites along the neuraxis where GABAergic interneurons are produced (telencephalic subventricular zone, medial ganglionic eminence, ventral mesencephalon and dorsal spinal cord), and grafted them to the prospective white matter of the postnatal rat cerebellum, at the time when local interneurons are generated. The phenotype acquired by transplanted cells was assessed by different criteria, including expression of region‐specific transcription factors, acquisition of morphological and neurochemical traits, and integration in the cerebellar cytoarchitecture. Regardless of their origin, all the different types of donor cells engrafted in the cerebellar parenchyma and developed mature neurons that shared some morphological and neurochemical features with local inhibitory interneurons, particularly in the deep nuclei. Nevertheless, transplanted cells failed to activate cerebellar‐specific regulatory genes. In addition, their major structural features, the expression profiles of type‐specific markers and the laminar placement in the recipient cortex did not match those of endogenous interneurons generated during the same developmental period. Therefore, although exogenous cells are influenced by the cerebellar milieu and show remarkable capabilities for adapting to the foreign environment, they essentially fail to switch their fate, integrate in the host neurogenic mechanisms and adopt clear‐cut cerebellar identities.
Volatility and Informativeness

We explore the equilibrium relation between price volatility and price informativeness in financial markets, with the ultimate goal of characterizing the type of inferences that can be drawn about price informativeness by observing price volatility. We identify two different channels (noise reduction and equilibrium learning) through which changes in price informativeness are associated with changes in price volatility. We show that when informativeness is sufficiently high (low) volatility and informativeness positively (negatively) comove in equilibrium for any change in primitives. In the context of our leading application, we provide conditions on primitives that guarantee that volatility and informativeness always comove positively or negatively. We use data on U.S. stocks between 1963 and 2017 to recover stock-specific primitives and find that most stocks lie in the region of the parameter space in which informativeness and volatility comove negatively.
Pairwise Knockdowns of cdc2-Related Kinases (CRKs) in Trypanosoma brucei Identified the CRKs for G1/S and G2/M Transitions and Demonstrated Distinctive Cytokinetic Regulations between Two Developmental Stages of the Organism

ABSTRACT Expression of the cdc2-related kinase 3 (CRK3) together with expression of CRK1, -2, -4, or -6, were knocked down in pairs in the procyclic and bloodstream forms of Trypanosoma brucei, using the RNA interference technique. Double knockdowns of CRK3 and CRK2, CRK4, or CRK6 exerted significant growth inhibition and enriched the cells in G2/M phase, whereas a CRK3 plus CRK1 (CRK3 + CRK1) knockdown arrested cells in both G1/S and G2/M transitions. Thus, CRK1 and CRK3 are apparently the kinases regulating the G1/S and G2/M checkpoint passages, respectively, whereas the other CRKs are probably playing only minor roles in cell cycle regulation. A CRK1 + CRK2 knockdown in the procyclic form was found to cause aberrant posterior cytoskeletal morphogenesis (X. M. Tu and C. C. Wang, Mol. Biol. Cell 16:97-105, 2005). A CRK3 + CRK2 knockdown, however, did not lead to such a change, suggesting that CRK2 depletion can lead to the abnormal morphogenesis only when procyclic-form cells are arrested in the G1 phase. The G2/M-arrested procyclic form produces up to 20% stumpy anucleated cells (zoids) in the population, suggesting that cytokinesis and cell division are not blocked by mitotic arrest but are apparently driven to completion by the kinetoplast cycle. In the bloodstream form, however, G2/M arrest resulted in little zoid formation but, instead, enriched a population of cells each containing multiple kinetoplasts, basal bodies, and flagella and an aggregate of multiple nuclei, indicating failure in entering cytokinesis. The two different cytokinetic regulations between two distinct stage-specific forms of the same organism may provide an interesting and useful model for further understanding the evolution of cytokinetic control among eukaryotes.