Miracle-dz/UniFAR-FTUs huggingface dataset:
Leveraging HIV Care Infrastructures for Integrated Chronic Disease and Pandemic Management in Sub-Saharan Africa

In Sub-Saharan Africa, communicable and other tropical infectious diseases remain major challenges apart from the continuing HIV/AIDS epidemic. Recognition and prevalence of non-communicable diseases have risen throughout Africa, and the reimagining of healthcare delivery is needed to support communities coping with not only with HIV, tuberculosis, and COVID-19, but also cancer, cardiovascular disease, diabetes, and depression. Many non-communicable diseases can be prevented or treated with low-cost interventions, yet implementation of such care has been limited in the region. In this Perspective piece, we argue that deployment of an integrated service delivery model is an urgent next step, propose a South African model for integration, and conclude with recommendations for next steps in research and implementation. An approach that is inspired by South African experience would build on existing HIV-focused infrastructure that has been developed by Ministries of Health with strong support from the U.S. President’s Emergency Response for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis and Malaria. An integrated chronic healthcare model holds promise to sustainably deliver infectious disease and non-communicable disease care. Integrated care will be especially critical as health systems seek to cope with the unprecedented challenges associated with COVID-19 and future pandemic threats.
Borreliae Part 1: Borrelia Lyme Group and Echidna-Reptile Group

Simple Summary Borreliae are spirochaetes, which represent a heterogeneous phylum within bacteria. Spirochaetes are indeed distinguished from other bacteria for their spiral shape, which also characterizes Borreliae. This review describes briefly the organization of the phylum Spirocheteales with a digression about its pathogenicity and historical information about bacteria isolation and characterization. Among spirochaetes, Borrelia genus is here divided into three groups, namely the Lyme group (LG), the Echidna-Reptile group (REPG) and the Relapsing Fever group (RFG). Borreliae Part 1 deals with Lyme group and Echidna-Reptile group Borreliae, while the subject of Borreliae Part 2 is Relapsing Fever group and unclassified Borreliae. Lyme group Borreliae is organized here in sections describing ecology, namely tick vectors and animal hosts, epidemiology, microbiology, and Borrelia genome organization and antigen characterization. Furthermore, the main clinical manifestations in Lyme borreliosis are also described. Although included in the Lyme group due to their particular clinical features, Borrelia causing Baggio Yoshinari syndrome and Borrelia mayonii are described in dedicated paragraphs. The Borrelia Echidna-Reptile group has been recently characterized including spirochaetes that apparently are not pathogenic to humans, but infect reptiles and amphibians. The paragraph dedicated to this group of Borreliae describes their vectors, hosts, geographical distribution and their characteristics. Abstract Borreliae are divided into three groups, namely the Lyme group (LG), the Echidna-Reptile group (REPG) and the Relapsing Fever group (RFG). Currently, only Borrelia of the Lyme and RF groups (not all) cause infection in humans. Borreliae of the Echidna-Reptile group represent a new monophyletic group of spirochaetes, which infect amphibians and reptiles. In addition to a general description of the phylum Spirochaetales, including a brief historical digression on spirochaetosis, in the present review Borreliae of Lyme and Echidna-Reptile groups are described, discussing the ecology with vectors and hosts as well as microbiological features and molecular characterization. Furthermore, differences between LG and RFG are discussed with respect to the clinical manifestations. In humans, LG Borreliae are organotropic and cause erythema migrans in the early phase of the disease, while RFG Borreliae give high spirochaetemia with fever, without the development of erythema migrans. With respect of LG Borreliae, recently Borrelia mayonii, with intermediate characteristics between LG and RFG, has been identified. As part of the LG, it gives erythema migrans but also high spirochaetemia with fever. Hard ticks are vectors for both LG and REPG groups, but in LG they are mostly Ixodes sp. ticks, while in REPG vectors do not belong to that genus.
A National Population Cohort Study Showed That Exposure to General Anesthesia in Early Childhood Is Associated with an Increase in the Risk of Developmental Delay

This study investigated the relationship between exposure to general anesthesia (GA) and the risk of cognitive and mental disorders. This study has thus investigated the relationships between exposure to GA before the age of 3 and subsequent cognitive and mental disorders in a national-wide research sample. We obtained our subjects from the National Health Insurance Research Database (NHIRD) of Taiwan, which was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Children in the hospital aged less than 3 years old were included if there was GA exposure or not during the period of year 1997 to 2008. Cox proportional hazard regression models adjusted for potential confounding factors were used to estimate the relative magnitude of the risk associated with GA exposure. The cohort contained 2261 subjects with GA and 4522 children without GA as a comparison group. GA exposure group had a higher rate of developmental delay than in the without GA group (hazard ratio 1.46, p < 0.0001). There was no significant difference in the overall incidence of ADHD, autism and intellectual disability between the GA-exposed group and the comparison cohort. In conclusion, this study reported that children exposed to GA early before the age of three had a small association with increased risk of development delay thereafter.
The Combination of Solid-State Chemistry and Medicinal Chemistry as the Basis for the Synthesis of Theranostics Platforms

This review presents the main patterns of synthesis for theranostics platforms. We examine various approaches to the interpretation of theranostics, statistics of publications drawn from the PubMed database, and the solid-state and medicinal chemistry methods used for the formation of nanotheranostic objects. We highlight and analyze chemical methods for the modification of nanoparticles, synthesis of spacers with functional end-groups, and the immobilization of medicinal substances and fluorophores. An overview of the modern solutions applied in various fields of medicine is provided, along with an outline of specific examples and an analysis of modern trends and development areas of theranostics as a part of personalized medicine.
Biomarkers in Small Intestine NETs and Carcinoid Heart Disease: A Comprehensive Review

Simple Summary Neuroendocrine tumors (NET), a heterogeneous group of tumors arising from neuroendocrine cells, often pose a diagnostic and therapeutic challenge for the clinician. Biomarkers can serve as a useful diagnostic, prognostic, and predictive tool in the management of these rare tumors. For years the field of NET biomarkers was mainly based on products se-creted by neuroendocrine tumor cells, however, during the last decade the development of nov-el multianalyte biomarkers has rapidly evolved the field. The aim of this review is to summa-rize the literature on the use and limitations of available NET biomarkers for the diagnosis and management of small intestine neuroendocrine tumors (SI-NETs) and carcinoid heart disease. Abstract Biomarkers remain a valuable tool for the diagnosis and management of Neuroendocrine tumors (NETs). Traditional monoanalyte biomarkers such as Chromogranin A (CgA) and 5-Hydrocyondoleacetic acid (5-HIAA) have been widely used for many years as diagnostic, predictive and prognostic biomarkers in the field of NETs. However, the clinical utility of these molecules often has limitations, mainly inherent to the heterogeneity of NETs and the fact that these tumors can often be non-secretory. The development of new molecular multianalyte biomarkers, especially the mRNA transcript based “NETest”, has rapidly evolve the field and gives the ability for a “liquid biopsy” which can reliably assess disease status in real time. In this review we discuss the use of established and novel biomarkers in the diagnosis and management of small intestine NETs and carcinoid heart disease.
Early Effects of HTLV-1 Infection on the Activation, Exhaustion, and Differentiation of T-Cells in Humanized NSG Mice

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy of CD4+ T-cells associated with HTLV-1 infection. In this study, we used the model of immunodeficient NSG mice reconstituted with a functional human immune system (HIS) to investigate early events in HTLV-1 pathogenesis. Upon infection, human T-cells rapidly increased in the blood and lymphoid tissues, particularly CD4+CD25+ T-cells. Proliferation of CD4+ T-cells in the spleen and mesenteric lymph nodes (MLN) correlated with HTLV-1 proviral load and CD25 expression. In addition, splenomegaly, a common feature of ATLL in humans, was also observed. CD4+ and CD8+ T-cells predominantly displayed an effector memory phenotype (CD45RA−CCR7−) and expressed CXCR3 and CCR5 chemokine receptors, suggesting the polarization into a Th1 phenotype. Activated CD8+ T-cells expressed granzyme B and perforin; however, the interferon-γ response by these cells was limited, possibly due to elevated PD-1 expression and increased frequency of CD4+FoxP3+ regulatory T-cells in MLN. Thus, HTLV-1-infected HIS-NSG mice reproduced several characteristics of infection in humans, and it may be helpful to investigate ATLL-related events and to perform preclinical studies. Moreover, aspects of chronic infection were already present at early stages in this experimental model. Collectively, we suggest that HTLV-1 infection modulates host immune responses to favor viral persistence.
Tanshinone IIa Induces Autophagy and Apoptosis via PI3K/Akt/mTOR Axis in Acute Promyelocytic Leukemia NB4 Cells

Tanshinone IIa (TanIIa), an ingredient of Radix Salviae Miltiorrhizae, has an anticancer effect on various solid tumors with high efficiency and low toxicity. Nonetheless, the underlying role of TanIIa in acute promyelocytic leukemia (APL) remains unclear. Here, we revealed that TanIIa drastically inhibited NB4 cell viability with an IC50 value of 31.25 μmol/L. Using flow cytometry apoptosis assay, we identified that TanIIa dose-dependently exacerbated NB4 cell apoptosis. Mechanistically, TanIIa upregulated apoptotic factor levels, namely, cleaved-caspase 9, cleaved-caspase 3, and cleaved-PARP-1. Moreover, we noticed that TanIIa dose-dependently suppressed the PI3K/Akt/mTOR axis. This axis not only functions as an essential antiapoptotic modulator but also serves as a suppressant regulator of autophagy. Correspondingly, we detected the levels of autophagic marker, namely, LC3B, which were increased after the TanIIa treatment. Furthermore, the autophagy inhibitor Baf-A1 could effectively reverse the TanIIa-induced apoptosis, manifesting that TanIIa eliminated NB4 cells in an autophagy-dependent manner. In conclusion, tanshinone IIa exerts anti-APL effects through triggering autophagy and apoptosis in NB4 cells.
Regulation of Tumor Metabolism and Extracellular Acidosis by the TIMP-10–CD63 Axis in Breast Carcinoma

A hallmark of malignant solid tumor is extracellular acidification coupled with metabolic switch to aerobic glycolysis. Using the human MCF10A progression model of breast cancer, we show that glycolytic switch and extracellular acidosis in aggressive cancer cells correlate with increased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), known to induce intracellular signal transduction through the interaction with its cell surface receptor CD63, independent of its metalloproteinase inhibitory function. We found that, in aggressive breast carcinoma, the TIMP-1–CD63 signaling axis induced a metabolic switch by upregulating the rate of aerobic glycolysis, lowering mitochondrial respiration, preventing intracellular acidification, and inducing extracellular acidosis. Carbonic anhydrase IX (CAIX), a regulator of cellular pH through the hydration of metabolically released pericellular CO2, was identified as a downstream mediator of the TIMP-1–CD63 signaling axis responsible for extracellular acidosis. Consistently with our previous study, the TIMP-1–CD63 signaling promoted survival of breast cancer cells. Interestingly, breast carcinoma cell survival was drastically reduced upon shRNA-mediated knockdown of CAIX expression, demonstrating the significance of CAIX-regulated pH in the TIMP-1–CD63-mediated cancer cell survival. Taken together, the present study demonstrates the functional significance of TIMP-1–CD63–CAXI signaling axis in the regulation of tumor metabolism, extracellular acidosis, and survival of breast carcinoma. We propose that this axis may serve as a novel therapeutic target.
Hiding in Plain Sight: Modern Thiamine Deficiency

Thiamine or vitamin B1 is an essential, water-soluble vitamin required for mitochondrial energetics—the production of adenosine triphosphate (ATP). It is a critical and rate-limiting cofactor to multiple enzymes involved in this process, including those at the entry points and at critical junctures for the glucose, fatty acid, and amino acid pathways. It has a very short half-life, limited storage capacity, and is susceptible to degradation and depletion by a number of products that epitomize modern life, including environmental and pharmaceutical chemicals. The RDA for thiamine is 1.1–1.2 mg for adult females and males, respectively. With an average diet, even a poor one, it is not difficult to meet that daily requirement, and yet, measurable thiamine deficiency has been observed across multiple patient populations with incidence rates ranging from 20% to over 90% depending upon the study. This suggests that the RDA requirement may be insufficient to meet the demands of modern living. Inasmuch as thiamine deficiency syndromes pose great risk of chronic morbidity, and if left untreated, mortality, a more comprehensive understanding thiamine chemistry, relative to energy production, modern living, and disease, may prove useful.
The Coordinated KNR6–AGAP–ARF1 Complex Modulates Vegetative and Reproductive Traits by Participating in Vesicle Trafficking in Maize

The KERNEL NUMBER PER ROW6 (KNR6)-mediated phosphorylation of an adenosine diphosphate ribosylation factor (Arf) GTPase-activating protein (AGAP) forms a key regulatory module for the numbers of spikelets and kernels in the ear inflorescences of maize (Zea mays L.). However, the action mechanism of the KNR6–AGAP module remains poorly understood. Here, we characterized the AGAP-recruited complex and its roles in maize cellular physiology and agronomically important traits. AGAP and its two interacting Arf GTPase1 (ARF1) members preferentially localized to the Golgi apparatus. The loss-of-function AGAP mutant produced by CRISPR/Cas9 resulted in defective Golgi apparatus with thin and compact cisternae, together with delayed internalization and repressed vesicle agglomeration, leading to defective inflorescences and roots, and dwarfed plants with small leaves. The weak agap mutant was phenotypically similar to knr6, showing short ears with fewer kernels. AGAP interacted with KNR6, and a double mutant produced shorter inflorescence meristems and mature ears than the single agap and knr6 mutants. We hypothesized that the coordinated KNR6–AGAP–ARF1 complex modulates vegetative and reproductive traits by participating in vesicle trafficking in maize. Our findings provide a novel mechanistic insight into the regulation of inflorescence development, and ear length and kernel number, in maize.
Rational Pharmacotherapy in Infectious Diseases: Issues Related to Drug Residues in Edible Animal Tissues

Simple Summary Drug use is essential to treat diseases in food-producing animals. The most widely used drugs are antiparasitics and antimicrobials. They contribute to guaranteeing good-quality food in sufficient quantity for human consumption. When using veterinary medicines, it is essential to follow the instructions on the package label. Administering the correct dose by the indicated route in the animal species for which the drug is labeled is critical. After a pharmacological treatment is administered to livestock, a period (indicated on the label) must often elapse before the tissues from the treated animals can be consumed by humans. Veterinary drug residues are controlled by taking food samples to verify that drug concentrations do not exceed the permitted limits. This allows authorities to know if the medicine use is correct or if suitable corrective measures should be taken. When label’s directions are not followed, drug residues may appear in food. The residues exceeding the permitted limits established by the authorities can produce unfavorable consequences, mainly on the consumer’s health. The food trade and even the environment can be affected by drug residues in animal tissues. Therefore, the correct use of drugs in livestock is critical, which includes respecting the rules to avoid residues in food for human consumption. Abstract Drugs are used in veterinary medicine to prevent or treat animal diseases. When rationally administered to livestock following Good Veterinary Practices (GVP), they greatly contribute to improving the production of food of animal origin. Since humans can be exposed chronically to veterinary drugs through the diet, residues in food are evaluated for effects following chronic exposures. Parameters such as an acceptable daily intake (ADI), the no-observed-adverse-effect level (NOAEL), maximum residue limits (MRLs), and the withdrawal periods (WPs) are determined for each drug used in livestock. Drug residues in food exceeding the MRLs usually appear when failing the GVP application. Different factors related either to the treated animal or to the type of drug administration, and even the type of cooking can affect the level of residues in edible tissues. Residues above the MRLs can have a diverse negative impact, mainly on the consumer’s health, and favor antimicrobial resistance (AMR). Drug residue monitoring programmes are crucial to ensure that prohibited or authorized substances do not exceed MRLs. This comprehensive review article addresses different aspects of drug residues in edible tissues produced as food for human consumption and provides relevant information contributing to rational pharmacotherapy in food-producing animals.
Health-Promoting Properties of Borage Seed Oil Fractionated by Supercritical Carbon Dioxide Extraction

Borage (Borago officinalis L.) seed oil is an important source of γ–linolenic acid, which is normally used as a treatment against different pathologies. Since the fractionation of this interesting seed oil has many environmental, economic and biological benefits, two borage fractionation techniques after extraction with CO2 under supercritical conditions have been studied: precipitation in two cyclone separators and countercurrent extraction column. Both techniques have successfully collected free fatty acids in one fraction: (i) two separators set up in series obtained the highest concentration of free fatty acids in separator 2 at 90 bar/40 °C; (ii) when countercurrent extraction column was used, the acidity index of the raffinate stream was independent from the operating conditions (2.6 ± 0.5%). Furthermore, the composition of the fatty acids, as well as their antioxidant and cytotoxic activities, were determined. The profile of the fatty acids obtained by either of these two methods remained unaltered, so that the crude oil exhibited improved antioxidant and cytotoxic properties. All the extracts obtained in the two cyclone separators at the same pressure/temperature conditions displayed high tumouricidal activity against HL 60 promyelocytic leukaemia cells, even if the extracts at 50% concentration from separator 2 presented a lower inhibitory activity (IC50). The extracts from separator 2 at 90 bar/40 °C exhibited the highest anti-proliferative activity at low doses (IC50 of 0.3 μL/mL for the trypan blue exclusion test). To reach the lethal dose—IC50—with the product obtained through countercurrent column fractionation, a concentration of 2 μL/mL of crude borage oil raffinate was required.
Body Shape Indices in Adolescents Based on the 2009–2012 Korea National Health and Nutrition Examination Survey

A Body Shape Index (ABSI) is a recently proposed index for standardizing waist circumference (WC) for body mass index (BMI) and height in adults, using 2/3 and 1/2 as scaling exponents, respectively. However, ABSI has limited applicability to children and adolescents, as the relationship between height and weight changes with age and varies according to sex. This study aimed to investigate whether ABSI can be applied to adolescents and to analyze the relationships among BMI, WC, height, weight, and body shape index (BSI) in Korean adolescents. The data of 1023 adolescents aged 10–19 years from the 2009–2012 Korea National Health and Nutrition Examination Survey were collected. Body measurements (height, weight, WC, and BMI) were analyzed to estimate the BSI using log-linear regression. The scaling exponents for standardizing WC for weight and height were estimated according to age (per year) and sex. The scaling exponents for standardizing WC for weight and height were 0.698 and −1.090 for boys and 0.646 and −0.855 for girls, respectively. The exponents also differed according to age. BSI was negatively correlated with height, weight, and BMI in boys and girls, and these correlations differed in direction from those in adults. ABSI cannot be applied to adolescents. In adolescents, the BSI is dependent on age and sex and is associated with growth and puberty. Further studies are required to evaluate the association between BSI and other biomarkers, to improve its applicability as a parameter for predicting the risk of chronic diseases in adolescents.
Text Mining for Building Biomedical Networks Using Cancer as a Case Study

In the assembly of biological networks it is important to provide reliable interactions in an effort to have the most possible accurate representation of real-life systems. Commonly, the data used to build a network comes from diverse high-throughput essays, however most of the interaction data is available through scientific literature. This has become a challenge with the notable increase in scientific literature being published, as it is hard for human curators to track all recent discoveries without using efficient tools to help them identify these interactions in an automatic way. This can be surpassed by using text mining approaches which are capable of extracting knowledge from scientific documents. One of the most important tasks in text mining for biological network building is relation extraction, which identifies relations between the entities of interest. Many interaction databases already use text mining systems, and the development of these tools will lead to more reliable networks, as well as the possibility to personalize the networks by selecting the desired relations. This review will focus on different approaches of automatic information extraction from biomedical text that can be used to enhance existing networks or create new ones, such as deep learning state-of-the-art approaches, focusing on cancer disease as a case-study.