Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery and genomic analyses of hybridization between divergent lineages of Trypanosoma congolense, causative agent of Animal African Trypanosomiasis

Hybrid populations and introgressive hybridization remain poorly documented in pathogenic micro‐organisms, as such that genetic exchange has been argued to play a minor role in their evolution. Recent work demonstrated the existence of hybrid microsatellite profiles in Trypanosoma congolense, a parasitic protozoan with detrimental effects on livestock productivity in sub‐Saharan Africa. Here, we present the first population genomic study of T. congolense, revealing a remarkable number of single nucleotide polymorphisms (SNPs), small insertions/deletions (indels) and gene deletions among 56 parasite genomes from ten African countries. One group of parasites from Zambia was particularly diverse, displaying a substantial number of heterozygous SNP and indel sites compared to T. congolense parasites from the nine other sub‐Saharan countries. Genomewide 5‐kb phylogenetic analyses based on phased SNP data revealed that these parasites were the product of hybridization between phylogenetically distinct T. congolense lineages. Other parasites within the same region in Zambia presented a mosaic of haplotypic ancestry and genetic variability, indicating that hybrid parasites persisted and recombined beyond the initial hybridization event. Our observations challenge traditional views of trypanosome population biology and encourage future research on the role of hybridization in spreading genes for drug resistance, pathogenicity and virulence.
Factors Affecting Trypanosome Maturation in Tsetse Flies

Trypanosoma brucei brucei infections which establish successfully in the tsetse fly midgut may subsequently mature into mammalian infective trypanosomes in the salivary glands. This maturation is not automatic and the control of these events is complex. Utilising direct in vivo feeding experiments, we report maturation of T. b. brucei infections in tsetse is regulated by antioxidants as well as environmental stimuli. Dissection of the maturation process provides opportunities to develop transmission blocking vaccines for trypanosomiasis. The present work suggests L-cysteine and/or nitric oxide are necessary for the differentiation of trypanosome midgut infections in tsetse.
High-dose oral amoxicillin plus probenecid is highly effective for syphilis in patients with HIV infection.

BACKGROUND Intramuscular benzathine penicillin G (BPG) is widely used for the treatment of syphilis. However, BPG is not available in some countries. This study examined the effectiveness and safety of high-dose oral amoxicillin plus probenecid for the treatment of syphilis in patients with human immunodeficiency virus type 1 (HIV-1). METHODS This retrospective observational study included 286 HIV-infected male patients with syphilis (median age, 36 years; median CD4 count, 389 cells/µL) who were treated with oral amoxicillin 3 g plus probenecid. Syphilis was diagnosed by both serum rapid plasma reagin (RPR) titers ≥8 and positive Treponema pallidum hemagglutination test. Patients with neurosyphilis diagnosed by cerebrospinal fluid examination were excluded. Successful treatment was defined as a at least 4-fold decrement in RPR titer. RESULTS The overall treatment efficacy was 95.5% (95% confidence interval [CI], 92.4%-97.7%; 273/286 patients), and efficacy for primary, secondary, early latent, late latent, and unknown duration syphilis was 93.8% (95% CI, 68.1%-99.8%; 15/16), 97.3% (95% CI, 92.9%-99.2%; 142/146), 100% (95% CI, 90.5%-100%; 37/37), 85.7% (95% CI, 58.6%-96.4%; 18/21), and 92.4% (95% CI, 81.9%-97.3%; 61/66), respectively. Treatment duration was mostly 14-16 days (49.7%) or 28-30 days (34.3%), with efficacy of 94.4% (134/142) and 95.9% (94/98), respectively; 96.3% of successfully treated patients achieved a ≥4-fold decrement in RPR titer within 12 months. Adverse events were noted in 28 (9.8%) patients, and 25 of these (89.3%) were successfully treated. Only 6% of patients underwent lumbar puncture. CONCLUSIONS The combination of oral amoxicillin 3 g plus probenecid was highly effective and tolerable for the treatment of syphilis in patients with HIV-1 infection.
High Resolution Population Maps for Low Income Nations: Combining Land Cover and Census in East Africa

Background Between 2005 and 2050, the human population is forecast to grow by 2.7 billion, with the vast majority of this growth occurring in low income countries. This growth is likely to have significant social, economic and environmental impacts, and make the achievement of international development goals more difficult. The measurement, monitoring and potential mitigation of these impacts require high resolution, contemporary data on human population distributions. In low income countries, however, where the changes will be concentrated, the least information on the distribution of population exists. In this paper we investigate whether satellite imagery in combination with land cover information and census data can be used to create inexpensive, high resolution and easily-updatable settlement and population distribution maps over large areas. Methodology/Principal Findings We examine various approaches for the production of maps of the East African region (Kenya, Uganda, Burundi, Rwanda and Tanzania) and where fine resolution census data exists, test the accuracies of map production approaches and existing population distribution products. The results show that combining high resolution census, settlement and land cover information is important in producing accurate population distribution maps. Conclusions We find that this semi-automated population distribution mapping at unprecedented spatial resolution produces more accurate results than existing products and can be undertaken for as little as $0.01 per km2. The resulting population maps are a product of the Malaria Atlas Project (MAP: http://www.map.ox.ac.uk) and are freely available.
A case of pulmonary cryptococcosis with large pericardial effusion diagnosed using cervical lymph node biopsy

Pulmonary cryptococcosis (PC) is a relatively rare infectious disease. It mainly involves the lungs; however, in some patients, the infection could spread to other parts of the body. PC mostly occurs in patients with immune deficiencies. However, PC infections have been reported in non‐immunocompromised patients. The diagnosis of PC is challenging in patients without immune deficiencies. Here, the case of a 27‐year‐old immunocompetent woman who was diagnosed with PC was report. She had unexplained fever and a history of close contact with poultry feathers. Lesions were observed in the lungs, pleural cavity, pericardium, and cervical lymph nodes. Biopsy of the cervical lymph nodes helped in the pathological diagnosis of PC. She was treated with fluconazole, and the lesions disappeared. They present this case to encourage detailed inquiry of medical history in such patients, improve the diagnostic awareness of clinicians, and help reduce the likelihood of misdiagnosis.
Acute traumatic coagulopathy: The elephant in a room of blind scientists

ABSTRACT Acute traumatic coagulopathy (ATC) is the failure of coagulation homeostasis that can rapidly arise following traumatic injury, hemorrhage, and shock; it is associated with higher injury severity, coagulation abnormalities, and increased blood transfusions. Acute traumatic coagulopathy has historically been defined by a prolonged prothrombin time, although newer, more informative measurements of hemostatic function have been used to improve diagnosis and support clinical decision making. The underlying biochemical mechanisms of and best practice therapeutics for ATC remain under active investigation because of its significant correlation to poor outcomes. The wide range of hypothesized mechanisms for ATC results from the large number of symptoms, phenotypes, and altered states in these patients as observed by multiple research groups. Much like the ancient fable of blind men describing an elephant from their limited perspectives, the limited nature of clinical and laboratory tools used to diagnose coagulopathy or evaluate hemostatic function has made finding causation difficult. The prolonged prothrombin time, degree of fibrinolysis, depletion of coagulation factors and inhibitors, and general failure of the blood have all been identified as being primary indicators for ATC. Therapeutic interventions including recombinant coagulation factors, antifibrinolytics, and blood products have been used with varying degrees of success as they are used to address specific symptoms. To truly understand the causes of ATC, research efforts must recognize the complexity of the hemostatic system and get to the heart of the matter by answering the question: “Is ATC a pathological condition that develops from the observed deficiencies in coagulation, fibrinolysis, and autoregulation, or is ATC an adaptive response generated as the body attempts to restore perfusion and avoid massive organ failure? ” Because patient management must proceed without definitive answers regarding the entire causative chain, the current therapeutic focus should be on using what knowledge has been gained to the patient’s advantage: control hemorrhage, maintain appropriate homeostatic balances of coagulation proteins, and restore oxygen perfusion.
Phosphorylation of MDMX Mediated by Akt Leads to Stabilization and Induces 14-3-3 Binding*

The critical tumor suppressor p53 is mutated or functionally inactivated in nearly all cancers. We have shown previously that the MDM2-MDMX complex functions as an integral unit in targeting p53 for degradation. Here we identify the small protein 14-3-3 as a binding partner of MDMX, which binds at the C terminus (Ser367) in a phosphorylation-dependent manner. Importantly, we demonstrate that the serine/threonine kinase Akt mediates phosphorylation of MDMX at Ser367. This phosphorylation leads to stabilization of MDMX and consequent stabilization of MDM2. Previous studies have shown that Akt phosphorylates and stabilizes MDM2. Our data suggest that stabilization of MDMX by Akt may be an alternative mechanism by which Akt up-regulates MDM2 protein levels and exerts its oncogenic effects on p53 in tumor cells.
Belatacept‐Resistant Rejection Is Associated With CD28+ Memory CD8 T Cells

Recently, newer therapies have been designed to more specifically target rejection in an effort to improve efficacy and limit unwanted toxicity. Belatacept, a CD28‐CD80/86 specific reagent, is associated with superior patient survival and graft function compared with traditional therapy, but its adoption as a mainstay immunosuppressive therapy has been tempered by increased rejection rates. It is essential that the underlying mechanisms associated with this rejection be elucidated before belatacept is more widely used. To that end, we designed a study in a nonhuman primate kidney transplant model where animals were treated with either a belatacept‐ or a tacrolimus‐based immunosuppressive regimen. Interestingly, we found that elevated pretransplant frequencies of CD28+CD8+TEMRA cells are associated with rejection on belatacept but not tacrolimus treatment. Further analysis showed that the CD28+CD8+TEMRA cells rapidly lose CD28 expression after transplant in those animals that go on to reject with the allograft infiltrate being predominantly CD28−. These data suggest that CD28+ memory T cells may be resistant to belatacept, capable of further differentiation including loss of CD28 expression while maintaining effector function. The unique signaling requirements of CD28+ memory T cells provide opportunities for the development of targeted therapies, which may synergize with belatacept to prevent costimulation‐independent rejection.
Efficacy and safety of combined immunosuppressive therapy plus umbilical cord blood infusion in severe aplastic anemia patients: A cohort study

The present study aimed to evaluate the efficacy and safety of combined immunosuppressive therapy (IST) plus umbilical cord blood infusion (UCBI) in severe aplastic anemia (SAA) patients. A total of 68 patients with SAA were enrolled in the current prospective cohort study and divided into the IST (n=35; positive control) and IST+UCBI (n=33; experimental) groups according to the treatment conditions. Patients in the IST group were treated with rabbit antithymocyte globulin (r-ATG) at a dose of 2.5 mg/kg through intravenous infusion once a day for five days. This was combined with oral cyclosporine A (CsA) at a dose of 3–5 mg/kg twice a day for 2 years. Patients in the IST+UBCI group were treated with r-ATG and CsA at the same doses and frequencies as the IST group plus one UCBI 1 day after the final treatment with r-ATG. At 6 months post treatment, the complete response and overall response rate (ORR) of the IST+UCBI group were markedly higher compared with those in the IST group. Furthermore, patients in the IST+UCBI group achieved absolute neutrophil count (ANC) and platelet count responses more rapidly as compared with the IST group. However, no difference in the hemoglobin (Hb) response was identified between the two groups. In addition, SAA patients achieved responses in the ANC and platelet count more rapidly in comparison with very severe aplastic anemia (VSAA) patients, while the number of days to Hb responses were similar in the SAA and VSAA patients. Multivariate logistic regression analysis also revealed that IST+UCBI treatment was an independent predicting factor for patients achieving complete response or partial response, whereas VSAA was an independent predictor of a worse ORR. Platelet and reticulocyte were also independent predicting factors. Finally, the survival of patients was similar between the groups, and no difference in the safety of the treatment was observed. In conclusion, combined IST plus UCBI treatment may be applied as an effective and safe therapy for SAA patients.
Mutations in the IMD Pathway and Mustard Counter Vibrio cholerae Suppression of Intestinal Stem Cell Division in Drosophila

ABSTRACT Vibrio cholerae is an estuarine bacterium and an intestinal pathogen of humans that causes severe epidemic diarrhea. In the absence of adequate mammalian models in which to study the interaction of V. cholerae with the host intestinal innate immune system, we have implemented Drosophila melanogaster as a surrogate host. We previously showed that immune deficiency pathway loss-of-function and mustard gain-of-function mutants are less susceptible to V. cholerae infection. We find that although the overall burden of intestinal bacteria is not significantly different from that of control flies, intestinal stem cell (ISC) division is increased in these mutants. This led us to examine the effect of V. cholerae on ISC division. We report that V. cholerae infection and cholera toxin decrease ISC division. Because IMD pathway and Mustard mutants, which are resistant to V. cholerae, maintain higher levels of ISC division during V. cholerae infection, we hypothesize that suppression of ISC division is a virulence strategy of V. cholerae and that accelerated epithelial regeneration protects the host against V. cholerae. Extension of these findings to mammals awaits the development of an adequate experimental model. IMPORTANCE Here we show that Vibrio cholerae and cholera toxin suppress intestinal stem cell (ISC) division. This is the first evidence of manipulation of ISC division by V. cholerae and demonstrates the utility of the Drosophila model in generating novel hypotheses regarding the interaction of V. cholerae with the intestinal epithelium. Furthermore, we add to the body of data suggesting that the IMD pathway and the Mustard protein modulate ISC division independently of the overall load of commensal intestinal bacteria. Here we show that Vibrio cholerae and cholera toxin suppress intestinal stem cell (ISC) division. This is the first evidence of manipulation of ISC division by V. cholerae and demonstrates the utility of the Drosophila model in generating novel hypotheses regarding the interaction of V. cholerae with the intestinal epithelium. Furthermore, we add to the body of data suggesting that the IMD pathway and the Mustard protein modulate ISC division independently of the overall load of commensal intestinal bacteria.
MIMO-OFDM with Enhanced Channel Estimation based on DFT Interpolation

In practical wireless communication systems, the transmitter send the information out through a multipath fading channel. At the receiver side, the received information distorted by the channel characteristic (due to multipath fading). So, in order to recover the transmitted information accurately, the channel effect must be known at the receiver. In this paper channel estimation for STBC-MIMO-OFDM system has been investigated by implementing the most popular channel estimators least Square (LS) and Minimum Mean Error Square (MMSE) both based on comb type pilot arrangement to estimate the channel effect at pilot locations, and channel interpolation between pilot locations was done using linear interpolation. The performance of LS and MMSE estimators can be improved by using DFT-based estimation technique. LS and MMSE estimator have been implemented with and without DFT-based estimation technique to estimate the channel effect for STBC-MIMO-OFDM system and compare their performance by measuring the bit error rate BER with QAM as modulation scheme and for different MIMO antenna configurations, also the channel between each antenna pair is assumed to be multipath Rayleigh Slow fading channel based on Clark's model. General Terms Channel estimation, communication, DFT algorithms.
Coupled electrodynamical and thermal processes induced by picosecond and femtosecond laser pulses on a rough dielectric surface

This paper is devoted to electrodynamical aspects of laser conditioning of rough dielectric surface. Points of interest are (1) space distribution of scattered radiation near the surface; (2) space distribution of light pressure; (3) laser- induced evolution of surface roughness under action of light pressure. The problems under consideration are of great importance for investigation of surface modification by femtosecond pulses, in particular, formation of periodic ripples. The problems are studied making use of modified finite-difference time-domain technique.
Identifiability of Nonparametric Mixture Models and Bayes Optimal Clustering

Motivated by problems in data clustering, we establish general conditions under which families of nonparametric mixture models are identifiable by introducing a novel framework for clustering overfitted \emph{parametric} (i.e. misspecified) mixture models. These conditions generalize existing conditions in the literature, and are flexible enough to include for example mixtures of Gaussian mixtures. In contrast to the recent literature on estimating nonparametric mixtures, we allow for general nonparametric mixture components, and instead impose regularity assumptions on the underlying mixing measure. As our primary application, we apply these results to partition-based clustering, generalizing the well-known notion of a Bayes optimal partition from classical model-based clustering to nonparametric settings. Furthermore, this framework is constructive in that it yields a practical algorithm for learning identified mixtures, which is illustrated through several examples. The key conceptual device in the analysis is the convex, metric geometry of probability distributions on metric spaces and its connection to optimal transport and the Wasserstein convergence of mixing measures. The result is a flexible framework for nonparametric clustering with formal consistency guarantees.
Diabetic Foot Infections: A Need for Innovative Assessments

Foot wounds are the most common diabetes-related cause of hospitalization and frequently result in amputation. Although generally diagnosed clinically based on signs and symptoms of inflammation, empirical antibiotic treatment should be based on tissue cultures until resolution of infection. Advances in molecular detection over the past decade, including rapid chromogenic agar and real-time polymerase chain reaction, have improved diagnostic capabilities. However, chronic wounds may host biofilm bacteria not adequately detected by current microbiological testing. Enhanced DNA testing is required to identify these pathogens as well as evolving and previously underdiagnosed bacteria. Two options, nucleic acid fluorescent in situ hybridization and rDNA sequencing, are on the horizon for clinical use. Wound biofilms also necessitate more complex clinical management including debridement, augmenting host defenses, suppression of biofilms, and wound closure. Adopting these advances in diagnosis and treatment may help with overall prognosis and reduce health care costs.
Impact of Conventional Stroke Risk Factors on Stroke in Women: An Update

Stroke is a disease that affects all populations, but women bear a greater disease burden compared with men. Because of increasing stroke risk with age and a longer life expectancy, women experience more strokes and more death from stroke over the lifetime.1,2 In addition, recent data show that age-adjusted stroke risk in women may not be declining to the same extent that it is in men, potentially resulting in similar age-adjusted stroke incidence rates between the sexes.3 Finally, women have worse functional outcomes after stroke,2 adding to the negative impact that stroke has on women. Optimizing stroke prevention in women is critical to reducing the number of strokes, the personal and societal costs of long-term disability from stroke, and stroke deaths. In 2014, guidelines published by the American Heart Association and American Stroke Association highlighted aspects of stroke prevention that should be tailored for women.4 The objective of this article is to summarize recent evidence on stroke risk factors in women and to identify possible sex differences in these risk factors. We aim to review current literature (2013 to present) to determine whether (1) there are sex differences in the prevalence of key risk factors for ischemic stroke; (2) there is a sex difference in the strength of associations between key risk factors and ischemic stroke; and (3) there is evidence for disparities in treatment or control of stroke risk factors between women and men. We chose to focus on ischemic stroke because the risk factors and pathophysiology differ from those relevant to hemorrhagic stroke. Risk factors included in the current review include hypertension, atrial fibrillation (AF), dyslipidemia, diabetes mellitus, migraine, and cognitive impairment. This article was designed as a narrative review. Pubmed was searched using the following terms: women, sex differences, or gender …
Do adults make scale errors too? How function sometimes trumps size.

Scale errors-futile attempts to use impossibly sized items as though they were appropriately scaled-have been thought to exist only in young children. Here, we document a similar version of the underlying phenomenon among adults. When asked to select 1 of 2 tools to achieve an instrumental goal, adults in Study 1 frequently selected, via keypress, a tool that was "for" the goal despite the tool being clearly ill sized in the given instance. In doing so, adults ignored an alternative tool that was perfectly sized for the task. Study 2 revealed this outcome did not emerge from a shape bias. Study 3 confirmed findings using a reaching task. Results support proposals that teleofunctional (purpose-based) reasoning is a highly powerful influence on categorization and behavior across development. Toddlers' scale errors may not be a symptom of immature thinking, but reflect a type of reasoning apparent in mature cognition.