Miracle-dz/UniFAR-FTUs huggingface dataset:
Extra-hepatopulmonary cystic echinococcosis in Bulgaria: frequency, management and outcome of the disease

Abstract In the endemic countries, human cystic echinococcosis (CE) poses a serious medical and social problem. Because it most often affects the liver and lungs we aimed to define the proportion of cases with different organ localization, the diagnostic and therapeutic approaches in such cases, and the outcome of them. For a period 2010–2019, a total of 2863 cases of CE were registered in Bulgaria, of which 148 (5.17%) with organ localization other than liver and/or lung. The majority of patients with extra-hepatopulmonary localization of CE were adults. The distribution by gender showed predominance of female patients (57.43%) over those of males and primary cases (85.14%) exceeded the cases of recurrence. According to our study most common is the spleen involvement, followed by involvement of the abdominal cavity, kidneys and muscle/subcutaneous tissue. Other extra-hepatopulmonary organ localizations are significantly less common. This study shows that the extra-hepatopulmonary localization of CE is not so rare, and in most cases it is a primary disease. In respect of this, clinicians should consider hydatidosis in the differential diagnosis when cystic formation(s) is found, regardless of the organ involved.
Fibrinogen‐related protein, FGL2, of hamster cauda epididymal fluid: Purification, kinetic analysis of its prothrombinase activity, and its role in segregation of nonviable spermatozoa

Although the epididymal environment promotes the maturation and survival of spermatozoa, not all spermatozoa remain viable during passage through the epididymis. Does the epididymis has a protective mechanism(s) to segregate the viable sperm from defective spermatozoa? Previously, we identified 260/280 kDa oligomers (termed eFGL—Epididymal Fibrinogen‐Like oligomer) are composed of two disulfide‐linked subunits: a 64 kDa polypeptide identified as fibrinogen‐like protein‐2 (FGL2) and a 33 kDa polypeptide identified as fibrinogen‐like protein‐1 (FGL1). Our morphological studies demonstrated that the eFGL, secreted from the principal cells of the cauda epididymis, is polymerized into a death cocoon‐like complex (DCF), masking defective luminal spermatozoa but, not the viable sperm population. In the present study, we purified FGL2 from hamster cauda epididymal fluid toward homogeneity and its prothrombinase catalytic activity was examined. Time‐course conversion studies revealed that all prothrombin was converted to thrombin by purified hamster FGL2. Our biochemical studies demonstrate that FGL2 is a lipid‐activated serine protease and functions as a lectin by binding specific carbohydrate residues. Co‐immunoprecipitation analysis demonstrated that FGL2 of cauda epididymal fluid is ubiquitinated but not the FGL1. We propose that FGL2/FGL1 oligomers represent a novel and unique mechanism to shield the viable sperm population from degenerating spermatozoa contained within the tubule lumen.
Biogeographical and Altitudinal Distribution of Cataract: A Nine-Year Experience Using Electronic Medical Record-Driven Big Data Analytics in India

ABSTRACT Purpose: To use electronic medical record data to study the altitude, UV exposure, and biogeographical distribution of senile cataract in India. Methods: This is a hospital-based, cross-sectional study of patients over 40 years old with an ophthalmologist-confirmed diagnosis of senile cataract (cortical, nuclear, posterior subcapsular, or a combination) in either or both eyes. Electronic medical record data entered between August 2010 to December 2019 were extracted from a large multi-tiered ophthalmology network in India. Residential districts were classified into their respective biogeographical zone based on nationally reported boundaries, and altitude at the geographic centroid was determined using Google Earth. Occupations were classified as low UV exposure and high UV exposure. Descriptive statistics, hypothesis testing, and multiple logistic regression analysis were done. Results: In the 1,127,232 eligible patients, associations were found between high UV exposure (OR = 1.47, 95%CI: 1.45–1.49), low socioeconomic status (OR = 1.54, 95%CI: 1.52–1.55), rural geographies (OR = 1.32), female gender (OR = 1.33, 95%CI: 1.32–1.34), and older age (OR ) with cataract. This Indian patient population did not demonstrate increased formation of cataracts at higher altitudes (OR ). Patients residing in the Deccan Peninsula (OR ) and those with high UV exposures within each increasing altitude category, except >750 m, (OR had higher odds of senile cataract comparatively. Conclusion: Female gender, occupations with high UV exposure, rural geography and increasing age were observed to have greater odds of developing senile cataract. Increased likelihood of cataracts in populations residing at low altitudes and within the Deccan Peninsula may be attributed to greater hospital development in those areas.
Disease Ionomics: Understanding the Role of Ions in Complex Disease

Ionomics is a novel multidisciplinary field that uses advanced techniques to investigate the composition and distribution of all minerals and trace elements in a living organism and their variations under diverse physiological and pathological conditions. It involves both high-throughput elemental profiling technologies and bioinformatic methods, providing opportunities to study the molecular mechanism underlying the metabolism, homeostasis, and cross-talk of these elements. While much effort has been made in exploring the ionomic traits relating to plant physiology and nutrition, the use of ionomics in the research of serious diseases is still in progress. In recent years, a number of ionomic studies have been carried out for a variety of complex diseases, which offer theoretical and practical insights into the etiology, early diagnosis, prognosis, and therapy of them. This review aims to give an overview of recent applications of ionomics in the study of complex diseases and discuss the latest advances and future trends in this area. Overall, disease ionomics may provide substantial information for systematic understanding of the properties of the elements and the dynamic network of elements involved in the onset and development of diseases.
Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis

Background: The objective of this systematic review was to evaluate the efficacy and safety profiles of sodium-glucose co-transporter 2 (SGLT-2) inhibitors for treatment of diabetes mellitus (DM) among kidney transplant patients. Methods: We conducted electronic searches in Medline, Embase, Scopus, and Cochrane databases from inception through April 2020 to identify studies that investigated the efficacy and safety of SGLT-2 inhibitors in kidney transplant patients with DM. Study results were pooled and analyzed utilizing random-effects model. Results: Eight studies with 132 patients (baseline estimated glomerular filtration rate (eGFR) of 64.5 ± 19.9 mL/min/1.73 m2) treated with SGLT-2 inhibitors were included in our meta-analysis. SGLT-2 inhibitors demonstrated significantly lower hemoglobin A1c (HbA1c) (WMD = −0.56% [95%CI: −0.97, −0.16]; p = 0.007) and body weight (WMD = −2.16 kg [95%CI: −3.08, −1.24]; p < 0.001) at end of study compared to baseline level. There were no significant changes in eGFR, serum creatinine, urine protein creatinine ratio, and blood pressure. By subgroup analysis, empagliflozin demonstrated a significant reduction in body mass index (BMI) and body weight. Canagliflozin revealed a significant decrease in HbA1C and systolic blood pressure. In terms of safety profiles, fourteen patients had urinary tract infection. Only one had genital mycosis, one had acute kidney injury, and one had cellulitis. There were no reported cases of euglycemic ketoacidosis or acute rejection during the treatment. Conclusion: Among kidney transplant patients with excellent kidney function, SGLT-2 inhibitors for treatment of DM are effective in lowering HbA1C, reducing body weight, and preserving kidney function without reporting of serious adverse events, including euglycemic ketoacidosis and acute rejection.
In utero exposure to protease inhibitor-based antiretroviral regimens delays growth and developmental milestones in mice

Antiretroviral therapy (ART) in pregnancy has dramatically reduced HIV vertical transmission rates. Consequently, there is a growing number of children that are HIV exposed uninfected (CHEUs). Studies suggest that CHEUs exposed in utero to ART may experience developmental delays compared to their peers. We investigated the effects of in utero ART exposure on perinatal neurodevelopment in mice, through assessment of developmental milestones. Developmental milestone tests (parallel to reflex testing in human infants) are reflective of brain maturity and useful in predicting later behavioral outcomes. We hypothesized that ART in pregnancy alters the in utero environment and thereby alters developmental milestone outcomes in pups. Throughout pregnancy, dams were treated with boosted-atazanavir combined with either abacavir/lamivudine (ATV/r/ABC/3TC), or tenofovir/emtricitabine (ATV/r/TDF/FTC), or water as control. Pups were assessed daily for general somatic growth and on a battery of tests for primitive reflexes including surface-righting, negative-geotaxis, cliff-aversion, rooting, ear-twitch, auditory-reflex, forelimb-grasp, air-righting, behaviors in the neonatal open field, and olfactory test. In utero exposure to either ART regimen delayed somatic growth in offspring and evoked significant delays in the development of negative geotaxis, cliff-aversion, and ear-twitch reflexes. Exposure to ATV/r/ABC/3TC was also associated with olfactory deficits in male and forelimb grasp deficits in female pups. To explore whether delays persisted into adulthood we assessed performance in the open field test. We observed no significant differences between treatment arm for males. In females, ATV/r/TDF/FTC exposure was associated with lower total distance travelled and less ambulatory time in the centre, while ATV/r/ABC/3TC exposure was associated with higher resting times compared to controls. In utero PI-based ART exposure delays the appearance of primitive reflexes that involve vestibular and sensory-motor pathways in a mouse model. Our findings suggest that ART could be disrupting the normal progress/maturation of the underlying neurocircuits and encourage further investigation for underlying mechanisms.
Altered Auditory Self-recognition in People with Schizophrenia

Abstract Self-recognition is of great significance to our sense of self. To date, disturbances in the processing of visual self-recognition are well studied in people with schizophrenia, whereas relatively few studies have focused on the processing of self in other domains, such as auditory. An investigation of auditory self-recognition contributes to delineate changes related to self and the potential roots of the described psychopathological aspects connoting schizophrenia. By applying unimodal task and multisensory test, this study investigated auditory self-recognition in people with schizophrenia under unimodal and bimodal circumstances. Forty-six adults diagnosed with schizophrenia and thirty-two healthy controls were involved in this study. Results suggested that people with schizophrenia seemed to have significantly lower perceptual sensitivity in detecting self-voice, and also showed stricter judgment criteria in self-voice decision. Furthermore, in the presentation of stimuli that combined the stimulation of others’ faces with one’s own voice, people with schizophrenia mistakenly attributed the voices of others as their own. In conclusion, altered auditory self-recognition in people with schizophrenia was found.
Management of Antiphospholipid Syndrome

Antiphospholipid syndrome (APS), is an acquired autoimmune disorder characterised by thrombosis, pregnancy morbidity, and the presence of antiphospholipid antibodies (aPL). Although venous thromboembolism is the most common manifestation, thrombotic events in APS may also occur in virtually any vascular bed, with cerebral circulation being the arterial territory most commonly affected. As APS is a heterogeneous condition, its management should be tailored with a patient-centred approach based on individual risk assessment, which includes the aPL profile, concomitant auto-immune diseases, and traditional cardiovascular risk factors. Although literature data are conflicting regarding primary prophylaxis, there is some evidence indicating that antiplatelet agents may reduce the risk of a first thrombotic event in individuals with a high-risk profile. In patients with thrombotic APS, current evidence-based guidelines recommend lifelong vitamin K antagonists (VKAs), preferably warfarin. The optimal intensity of anticoagulation following arterial thrombosis remains controversial. Arterial thrombosis should be treated either with high-intensity warfarin at a target INR > 3.0, or low-dose aspirin (LDA) combined with moderate-intensity warfarin (INR 2.0–3.0). It is recommended to avoid direct oral anticoagulants (DOACs) in patients with high-risk APS, mainly those with triple-positive PL and previous arterial events. They would only be used exceptionally in selected patients with low-risk venous thromboembolism (VTE). In low-risk VTE patients currently treated with a DOAC due to warfarin intolerance or a previous unstable International Normalized Ratio on warfarin, the decision of continuing DOACs would be taken in carefully selected patients. In women with obstetric APS, the combination therapy with LDA plus heparin remains the conventional strategy.
The small RNA locus map for Chlamydomonas reinhardtii

Small (s)RNAs play crucial roles in the regulation of gene expression and genome stability across eukaryotes where they direct epigenetic modifications, post-transcriptional gene silencing, and defense against both endogenous and exogenous viruses. It is known that Chlamydomonas reinhardtii, a well-studied unicellular green algae species, possesses sRNA-based mechanisms that are distinct from those of land plants. However, definition of sRNA loci and further systematic classification is not yet available for this or any other algae. Here, using data-driven machine learning approaches including Multiple Correspondence Analysis (MCA) and clustering, we have generated a comprehensively annotated and classified sRNA locus map for C. reinhardtii. This map shows some common characteristics with higher plants and animals, but it also reveals distinct features. These results are consistent with the idea that there was diversification in sRNA mechanisms after the evolutionary divergence of algae from higher plant lineages.
Evaluation of a New Topical Treatment for the Control of Cutaneous Leishmaniasis

Leishmania major (L. major) causes cutaneous leishmaniasis in the Old World. The infection mostly induces a localized lesion restricted to the sand fly bite. The costs and the side effects of current treatments render imperative the development of new therapies that are affordable and easy to administrate. Topical treatment would be the ideal option for the treatment of cutaneous leishmaniasis. MF29 is a 3-haloacetamidobenzoate that was shown in vitro to inhibit tubulin assembly in Leishmania. Here, we tested a topical cream formulated with MF29. BALB/c mice were infected in the ear dermis with L. major metacyclic promastigotes and once the lesion appeared, mice were treated with different concentrations of MF29 and compared to the control group treated with the cream used as the vehicle. We observed that topical application of MF29 reduced the progression of the infection while control groups developed an unhealing lesion that became necrotic. The treatment decreased the type 2 immune response. Comparison with SinaAmphoLeish, another topical treatment, revealed that MF29 treatment once a day was sufficient to control lesion development, while application SinaAmphoLeish needed applications twice daily. Collectively, our data suggest that MF-29 topical application could be a promising topical treatment for cutaneous leishmaniasis.
The effect of cysteine and glutamine on human sperm functional parameters during vitrification

Assuming the adverse effects of reactive oxygen species (ROS) on sperm function, this study was conducted to assess the effects of cysteine and glutamine as effective antioxidants on human sperm parameters under vitrification. Twenty normozoospermic samples were used. The samples were subjected to a vitrification process and cysteine (5 and 10 mM) and glutamine (10 and 15 mM). The sperm motility parameters, mitochondrial membrane potential (MMP), plasma membrane integrity (PMI), DNA damage and intracellular ROS damage were assessed for each sample. Statistical analyses showed that motility, mitochondrial membrane potential and DNA damage decreased in the vitrified groups with cysteine 5, 10 mM and glutamine 10, 15 mM separately. Also intracellular ROS increased significantly compared to the fresh group (p < .05). No significant differences were observed for PMI compared with the fresh group (p > .05). Supplementation of cysteine and glutamine in both concentrations separately decreased intracellular ROS and DNA damage of spermatozoa with significant increase in PMI, MMP and progressive motility compared to vitrified control group (p < .05). The results showed no significant effect of a specific concentration in cysteine and glutamine on sperm parameters compared to other concentrations. Both amino acids have the potential to improve the harmful effects of freezing on sperm parameters.
Phloretin, An Apple Polyphenol, Inhibits Pathogen-Induced Mucin Overproduction.

SCOPE Bacterial infection induces mucus overproduction, contributing to acute exacerbations and lung function decline in chronic respiratory diseases. A diet enriched in apples may provide protection from pulmonary disease development and progression. We examined whether phloretin, an apple polyphenol, inhibits mucus synthesis and secretion induced by the predominant bacteria associated with chronic respiratory diseases. METHODS AND RESULTS We analyzed expression of the mucus constituent mucin 5AC (MUC5AC) in FVB/NJ mice and NCI-H292 epithelial cells. Nontypeable Haemophilus influenzae (NTHi)-infected mice developed increased MUC5AC mRNA, which a diet containing phloretin inhibited. In NCI-H292 cells, NTHi, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa increased MUC5AC mRNA, which phloretin inhibited. Phloretin also diminished NTHi-induced MUC5AC protein secretion. NTHi-induced increased MUC5AC required toll-like receptor 4 (TLR4) and NADH oxidase 4 (NOX4) signaling and subsequent activation of the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) pathway. Phloretin inhibited NTHi-induced TLR4/NOX4 and EGFR/MAPK signaling, thereby preventing increased MUC5AC mRNA. EGFR activation can also result from increased EGFR ligand synthesis and subsequent ligand activation by matrix metalloproteinases (MMPs). In NCI-H292 cells, NTHi increased EGFR ligand and MMP1 and MMP13 mRNA, which phloretin inhibited. CONCLUSIONS In summary, phloretin is a promising therapeutic candidate for preventing bacterial-induced mucus overproduction. This article is protected by copyright. All rights reserved.
Characteristics of punctate inner choroidopathy complicated by choroidal neovascularisation on Multispectral Imaging in comparison with other imaging modalities

ABSTRACT Purpose To describe the characteristics seen on multispectral imaging (MSI) in patients with punctate inner choroidopathy (PIC) and choroidal neovascularisation (CNV) and compare the findings with current standard multimodal imaging techniques. Methods This is a retrospective observational case series of 10 patients with PIC complicated by CNV that underwent multimodal retinal imaging examinations. Results Twelve eyes of 10 patients were included. CNV was identified in 11 of the 12 eyes (91.7%) by MSI with nodular or trunk-like hyperreflectance on retinal oxy/deoxyhemoglobin map. MSI revealed choroidal vasculature around CNV in 91.7% eyes and pathological changes including retinal pigment epithelial atrophy and melanin disruption of punctate lesions in all eyes. Conclusion MSI helps in noninvasively detecting CNV in PIC patients and observing associated changes in choroidal vasculature. This imaging technique is also a promising tool for better tracking pathological changes of PIC lesions complementary to current standard multimodal imaging modalities.
SARS‐CoV‐2 persistence and non‐protective immunity in infected haematological patients

We read with great interest the study by Fox et al., reporting the outcomes of patients with SARS-CoV-2 receiving anti-cancer therapy. Data on COVID-19 in haematological patients remains limited indeed. Clinicians should carefully weigh up the timing of elective therapies – leading to profound immunosuppression – with rapid proliferation of the patients’ disease; curative options could improve prognosis. The European Hematology Association has recommended against prophylactic interruption of ongoing therapies; however, the exact intervals between a SARS-CoV-2 infection and therapy administration or allowed regimens remain unclear. On the other hand, it is currently unclear whether longlasting sterilising immunity following SARS-CoV-2 infection is possible. Antibodies against the S1 domain of spike protein (S1), the respective receptor-binding domain (RBD) and the nucleocapsid protein (NP) have been detected in previously infected patients. Cases of clear re-infection, as established by culture-based techniques, have not been documented at the moment; nonetheless, the role of detected antibodies which are present remains ambiguous. In their study, Fox et al. have focused on the binary outcome of recovery/death in these patients. As the authors clearly state, most patients present favourable outcomes despite their profound immunosuppression. However, the need for long-term follow-up could unveil a third outcome measure in this population, that of persistence. We hereby present the first case of a seroconverted SARS-CoV-2 patient with acute lymphoblastic leukaemia (ALL), presenting with a second episode of severe pneumonia shortly following chemotherapy, in a low prevalence setting.
Application of New Efficient Hoveyda–Grubbs Catalysts Comprising an N→Ru Coordinate Bond in a Six-Membered Ring for the Synthesis of Natural Product-Like Cyclopenta[b]furo[2,3-c]pyrroles

The ring rearrangement metathesis (RRM) of a trans-cis diastereomer mixture of methyl 3-allyl-3a,6-epoxyisoindole-7-carboxylates derived from cheap, accessible and renewable furan-based precursors in the presence of a new class of Hoveyda–Grubbs-type catalysts, comprising an N→Ru coordinate bond in a six-membered ring, results in the difficult-to-obtain natural product-like cyclopenta[b]furo[2,3-c]pyrroles. In this process, only one diastereomer with a trans-arrangement of the 3-allyl fragment relative to the 3a,6-epoxy bridge enters into the rearrangement, while the cis-isomers polymerize almost completely under the same conditions. The tested catalysts are active in the temperature range from 60 to 120 °C at a concentration of 0.5 mol % and provide better yields of the target tricycles compared to the most popular commercially available second-generation Hoveyda–Grubbs catalyst. The diastereoselectivity of the intramolecular Diels–Alder reaction furan (IMDAF) reaction between starting 1-(furan-2-yl)but-3-en-1-amines and maleic anhydride, leading to 3a,6-epoxyisoindole-7-carboxylates, was studied as well.