Miracle-dz/UniFAR-FTUs huggingface dataset:
Anthelminthic treatment receipt and its predictors in Lake Victoria fishing communities, Uganda: Intervention coverage results from the LaVIISWA cluster randomised trial

Background Mass drug administration (MDA) is a cornerstone of control of parasitic helminths. In schistosomiasis-endemic areas with >50% of school-aged children infected, community-wide MDA with praziquantel is recommended by the World Health Organisation (WHO), with target coverage of >75%. Using data from a cluster-randomised trial of MDA treatment strategies, we aimed to describe the proportion of eligible residents who received MDA and predictors of treatment receipt, and to assess associations with helminth prevalence. Methods In the Koome islands of Lake Victoria, Uganda, where baseline schistosomiasis prevalence (by single stool sample, Kato Katz) was 52% overall (all ages) and 67% among school-aged children, we conducted a cluster-randomised trial of community-wide, intensive MDA (quarterly single-dose praziquantel 40mg/kg; triple-dose albendazole 400mg) versus standard, Uganda government intervention (annual single-dose praziquantel 40mg/kg; 6-monthly single-dose albendazole). Twenty-six fishing villages were randomised, 13 per trial arm, for four years. At each treatment round, praziquantel treatment and the first dose of albendazole treatment were directly observed by the study team, registers of village residents were updated and the proportion receiving treatment among those eligible recorded. Results During the four-year MDA, at each treatment round an average of 13,382 people were registered in the 26 villages (7,153 and 6,229 in standard and intensive intervention villages, respectively). Overall, the proportion of those eligible receiving praziquantel was lower than for albendazole (60% versus 65%), particularly in the standard arm (61% versus 71%) compared to the intensive arm (60% versus 62%). Albendazole receipt was lower when given concurrently with praziquantel. Absence was the commonest reason for non-receipt of treatment (81% albendazole, 77% praziquantel), followed by refusal (14% albendazole, 18% praziquantel). Proportions receiving treatment were lowest among school-aged children, but did not differ by sex. Longitudinal analysis of a subgroup of residents who did not move during the study period found that persistent non-receipt of treatment in this subgroup was rare. Refusal to receive treatment was highest among adults and more common among females. Conclusion In schistosomiasis high-risk communities, a combination of approaches to increasing treatment coverage, such as extended periods of treatment delivery, and the provision of incentives, may be required to achieve WHO targets.
Phylogeny of the Caninae (Carnivora): Combining morphology, behaviour, genes and fossils

Phylogenetic relationships among 36 Recent and 42 extinct species of the Caninae (Canidae) were analysed, based on 360 morphological, developmental, ecological, behavioural and cytogenetic characters and 24 mitochondrial and nuclear markers. Primary phylogenetic analyses were accompanied by experimental analyses based on various combinations of data partitions and taxon samples. Leptocyon was recovered as a paraphyletic stem lineage of the Caninae; monophyly/paraphyly of the fox‐like canids (Vulpini) remains uncertain; Urocyon and Metalopex form a clade, possibly sister to all non‐Leptocyon canids; Otocyon, Nyctereutes and Nurocyon form a clade; dog‐like canids (Canini) are monophyletic (with South American Cerdocyonina and Afro‐Holarctic Canina); all South American hypercarnivores (Canis gezi, Protocyon, Speothos, Theriodictis) form a clade, close to Chrysocyon and Dusicyon; Canis arnensis, C. ferox, C. thooides, C. lepophagus and Eucyon spp. are basal to the Canina; Lycaon is an isolated African hypercarnivore; Cuon and its relatives (Xenocyon, possibly also Canis antonii, C. falconeri and Cynotherium) form a clade close to Canis s. str. ; C. edwardii–C. etruscus–C. mosbachensis–C. palmidens–C. variabilis and hypercarnivorous Canis armbrusteri–C. dirus clades belong to Canis s. str. As the highly homoplastic morphological characters connected to dietary biology are the prominent characters available for the key fossil species, we conclude that macroevolutionary and palaeoecological analyses of the extinct and extant Caninae were to some extent compromised by the phylogenies used.
Analysis of fatal industrial accidents in forensic postmortem investigations in South Osaka.

Předkládaná studie zkoumala aktuální stav a příčiny smrtelných pracovních úrazů ze zdravotně-sociálního hlediska. Retrospektivně jsme hodnotili případy smrtelných pracovních úrazů mezi lety 2007 a 2016 v Ósace, která je druhým nejlidnatějším městem v Japonsku, z forenzních posmrtných dat 1689 zemřelých. Z těchto případů jsme analyzovali celkem 57 smrtelných průmyslových nehod. Oběťmi byli typicky muži v relativně pokročilém věku pracující generace, téměř polovina případů (přesněji 28) byli muži mezi 50 a 70 lety života. Nejčastějším typem nehody byl pád z výše (24 případů) a nejčastějším místem, kde k nehodám docházelo, bylo staveniště (28 případů). Většina nehod (29 případů) se odehrála na pracovišti s malým pracovním týmem. V 60 % případů oběť na sobě neměla ochranou helmu a ve 34 případech (60 %) byla nehoda připisována vlastní nedbalosti. Nehody se nejčastěji stávaly v úterý. Nejběžnější doba, kdy k nehodám docházelo, byla kolem 10. a 11. hodiny dopolední a kolem 1. a 2. hodiny odpolední. V přibližně 60 % případů žaludeční obsah zahrnoval i zbytky potravy, což naznačuje, že k nehodám typicky docházelo po jídle. V předkládané studii jsme zjistili, že pracovní nehody, z nichž nejčastější byl pád z výše, vykazují tendenci se vyskytovat na pracovišti s malým pracovním týmem. Pouze pár obětí mělo na sobě ochranou helmu. Tato zjištění naznačují, že na pracovištích by měly být důkladně zaváděny systémy monitorování a řízení bezpečnosti a že pracovníci by měli před i po jídle dbát zvýšené opatrnosti.
S-Methylcysteine (SMC) Ameliorates Intestinal, Hepatic, and Splenic Damage Induced by Cryptosporidium parvum Infection Via Targeting Inflammatory Modulators and Oxidative Stress in Swiss Albino Mice

Cryptosporidiosis has been proposed to be one of the major causes of diarrhoeal disease in humans worldwide that possesses zoonotic concern. Thereby, this study investigated the potential effects of s-Methylcysteine (SMC) on the parasite in vivo followed by the measurement of cytokines, oxidative stress parameters, and an investigation of the major histopathological changes. Sixty male Swiss albino mice weighing 20–25 g were allocated equally into five groups and orally administered saline only (control), SMC only (SMC50) (50 mg/kg b.w.), and 104 Cryptosporidium parvum oocysts per mouse via an esophageal tube (C + ve untreated). The fourth and fifth groups (C + SMC25, C + SMC50) administrated 104 C. parvum oocysts combined with SMC25 (low dose) and 50 (high dose) mg/kg b.w. , respectively. At days 7 and 14 post-infection (PI), the feces was collected from each group in order to count C. parvum oocysts. After two weeks of treatment, the animals were euthanized and the serum was collected for biochemical analysis. Next, the intestinal, spleen, and liver sections were dissected for histopathological examination. The results revealed lower oocyst numbers in the C + SMC25 and C + SMC50 groups compared to the infected untreated group. Moreover, higher doses of SMC treatment significantly reduced the enteritis induced by C. parvum in a dose-dependent manner. The hepatic lesions were also mitigated as demonstrated in C + SMC25 and C + SMC50 groups unlike the infected group via lowering the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes and increasing albumin and globulin serum levels. SMC administration also reduced cytokines production (SAP, TNF-α, IL-6, and IFN-γ) mediated by Cryptosporidium infection in contrast to the infected untreated group. There were marked lymphoid depletion and amyloidosis observed in the infected untreated group, while the treated groups showed obvious increase in the lymphoid elements. Moreover, the scoring of intestinal parasites, hepatic, and splenic lesions in the SMC-treated groups exhibited significantly lower pathological lesions in different organs in a dose-dependent manner, compared to the infected untreated group. Our results also revealed a significant change in the malondialdehyde content with an elevation of glutathione and superoxide dismutase in the intestines collected from C + SMC25 and C + SMC50 mice relative to the untreated group. Taken together, our results indicated that SMC could be a promising effective compound for treating and declining C. parvum infestation via restoring structural alterations in different tissues, enhancing antioxidant enzymes, and suppressing the cytokines liberation.
Comparison between two autorefractor performances in large scale vision screening in Chinese school age children.

AIM To evaluate the effectiveness of Grand Seiko Ref/Keratometer WAM-5500 compared to Topcon KR800 autorefractor in detecting refractive error in large scale vision screening for Chinese school age children with the WHO criteria. METHODS A total of 886 participants were enrolled with mean age of 9.49±1.88y from Tianjin, China. Spherical equivalent (SE) was obtained from un-cycloplegic autorefraction and cycloplegic autorefraction. Topcon KR 800 (Topcon) and Grand Seiko WAM-5500 (WAM) autorefractors were used. Bland-Altman Plot and regression were generated to compare their performance. The overall effectiveness of detecting early stage refractive error was analyzed with receiver operating characteristic (ROC) curves. RESULTS The mean SE was -0.98±1.81 diopter (D) and the prevalence of myopia was 48.9% defined by WHO criteria according to the result of cycloplegic autorefraction. The mean SE of un-cycloplegic autorefraction with Topcon and WAM were -1.21±1.65 and -1.20±1.68 D respectively. There was a strong linear agreement between result obtained from WAM and cycloplegic autorefraction with an R2 of 0.8318. Bland-Altman plot indicated a moderate agreement of cylinder values between the two methods. The sensitivity and specificity for detecting hyperopia were 90.52% and 83.51%; for detecting myopia were 95.60% and 90.24%; for detecting astigmatism were 79.40% and 90.21%; for detecting high myopia were 98.16% and 98.91% respectively. CONCLUSION These findings suggest that both Grand Seiko and Topcon autorefractor can be used in large-scale vision screening for detecting refractive error in Chinese population. Grand Seiko gives relatively better performance in detecting myopia, hyperopia, and high myopia for school age children.
An overview of carbohydrate-based carbonic anhydrase inhibitors

Abstract Carbonic anhydrases (CAs) are metalloenzymes responsible for the reversible hydration of carbon dioxide to bicarbonate, a fundamental reaction involved in various physiological and pathological processes. In the last decades, CAs have been considered as important drug targets for different pathologies such as glaucoma, epilepsy and cancer. The design of potent and selective inhibitors has been an outstanding goal leading to the discovery of new drugs. Among the different strategies developed to date, the design of carbohydrate-based CA inhibitors (CAIs) has emerged as a versatile tool in order to selectively target CAs. The insertion of a glycosyl moiety as a hydrophilic tail in sulfonamide, sulfenamide, sulfamate or coumarin scaffolds allowed the discovery of many different series of sugar-based CAIs, with relevant inhibitory results. This review will focus on carbohydrate-based CAIs developed so far, classifying them in glycosidic and glycoconjugated inhibitors based on the conjugation chemistry adopted.
COVID-19 Wounds: Unusual Lower Extremity Bullae

As the COVID-19 pandemic emerged, skin manifestations have been reported as part of this disease’s multisystem manifestations. While a rash similar to chilblains in acral distribution has been the most commonly reported complication, we noted a pattern of more severe lower extremity skin complications, specifically large bullae, in a series of COVID-19 patients.
Mutual Interaction of Clinical Factors and Specific microRNAs to Predict Mild Cognitive Impairment in Patients Receiving Hemodialysis

Cognitive impairment (CI) is not uncommon in dialysis patients. Various factors have been implicated. This study aims to examine mutual interaction of various clinical factors for CI in patients receiving hemodialysis. A total of 48 hemodialysis patients in outpatient clinic were recruited from 2015 to 2017. Demographics, circulating uremic toxin concentrations, miRNA concentrations, and nerve injury protein concentrations were collected. Clinical dementia rating (CDR) scores were used to stratify the functional scores of the patients. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic test performance for predicting dichotomous results, and cumulative ROC analysis was used to examine the combined contribution of clinical factors. CDR scale 0 included 15 patients (mean age, 59.1 years); CDR > 0.5 included 33 patients (mean age, 64.0 years). On cumulative ROC analysis, the major predictors of mild CI were hemoglobin, age, sex, homocysteine, neuron-specific enolase (NSE), and miR-486. The cumulative area under the curve (AUC) on combining hemoglobin, age, and miR-486 was the highest (0.897, 95% confidence interval 0.806–0.988). Two dichotomized variables reached 81.82% sensitivity and 86.67% specificity, with the likelihood ratio for positive and negative results being 6.14 and 0.21, respectively. In conclusion, hemoglobin, age, and miR-486 display high-degree combined effects on mild CI in patients receiving hemodialysis.
Coronavirus disease-2019: implications for the gastroenterologist

Purpose of review The COVID-19 pandemic has impacted the practicing gastroenterologist in several ways. Although majority of COVID-19 patients present with respiratory symptoms, gastrointestinal symptoms are also seen. COVID-19 has also disrupted gastrointestinal endoscopy services in numerous ways. There are also concerns regarding the impact of these changes on gastrointestinal cancer screening and management of chronic gastrointestinal diseases. The purpose of this review is to provide an overview of the implications of COVID-19 for the practicing gastroenterologist. Recent findings COVID-19 patients can have gastrointestinal symptoms including diarrhea, nausea and vomiting, abdominal pain and anorexia. Separate from the management of COVID-19 patients, there has been a reduction in endoscopy volume worldwide. This has also resulted in reduction/cessation of in-person clinic visits and an increasing use of telemedicine services. In addition, patients with certain chronic diseases like chronic liver disease or inflammatory bowel disease may have worse outcomes during the COVID-19 pandemic. Summary Gastroenterologists need to rapidly adapt to the challenges being faced and need to make both systems and practice-based changes to the endoscopy unit and outpatient clinic practices. Gastroenterologists should stay up-to-date with the rapidly evolving literature regarding gastrointestinal symptoms in COVID-19 patients as well as its impact on chronic gastrointestinal illnesses.
Interplay between sphingolipid and nutriente signaling in niemann-pick type C1 disease: new clues from a yeast cell model

The sphingolipid storage disorders are a group of rare diseases characterized by accumulation of lipid waste products inside the lysosomes. This can result from defects on lysosomal proteolytic enzymes or membrane transporters. The last group includes the Niemann-Pick type C (NPC) disease, characterized by a progressive neurodegenerative course that affects mainly infantile and juveniles. It is caused by loss-of-function point mutations in NPC1 (95 % of the reported cases) or NPC2. Both proteins seem to be involved in intracellular transport of endocytosed cholesterol through the endolysosomal system, but its function remains poorly characterized. NPC is characterized by an accumulation of LDLderived cholesterol inside lysosomes and a compromised homeostasis of other lipids, such as gangliosides and sphingolipids (e.g. sphingosine). Sphingolipids are important regulators of cellular processes, including vesicle trafficking and endocytosis, stress responses, cell cycle, apoptosis and senescence. However, the role of sphingosine or other bioactive sphingolipids in pathological alterations observed in NPC cells remains unknown. The NPC1 gene is highly conserved among species. The yeast Saccharomyces cerevisiae expresses Ncr1p, a NPC1 homologue present in the membrane of the vacuole. Yeast cells lacking Ncr1p have been used as a promising eukaryotic model system to characterize conserved molecular mechanisms underlying the pathophysiology of NPC1 disease. The present work aimed to study oxidative stress resistance, chronological lifespan and mitochondrial function in the yeast model of NPC1, identify cell signaling pathways deregulated in ncr1Δ mutants as consequence of changes in sphingolipids homeostasis, and characterize the role of those pathways on ncr1Δ phenotypes. Our results show that ncr1Δ mutant cells display a high sensitivity to oxidative stress induced by hydrogen peroxide that is associated with increased levels of oxidative stress markers, such as protein oxidation, lipid peroxidation and intracellular reactive oxygen species (ROS) levels, impairment of antioxidant defenses and mitochondrial dysfunctions. Taken together, these changes contribute to a shortened chronological lifespan in ncr1Δ cells. Notably, ncr1Δ cells exhibit major changes in sphingolipids metabolism, including the accumulation of long chain sphingoid bases (LCB), and sphingolipid signaling through activation of the Pkh1p-Sch9p pathway mediates ncr1Δ phenotypes. Our findings also implicate changes in the levels of ceramide, particularly increases in
Associations between Pregnane X Receptor and Breast Cancer Growth and Progression

Pregnane X receptor (PXR, NR1I2) is a member of the ligand-activated nuclear receptor superfamily. This receptor is promiscuous in its activation profile and is responsive to a broad array of both endobiotic and xenobiotic ligands. PXR is involved in pivotal cellular detoxification processes to include the regulation of genes that encode key drug-metabolizing cytochrome-P450 enzymes, oxidative stress response, as well as enzymes that drive steroid and bile acid metabolism. While PXR clearly has important regulatory roles in the liver and gastrointestinal tract, this nuclear receptor also has biological functions in breast tissue. In this review, we highlight current knowledge of PXR’s role in mammary tumor carcinogenesis. The elevated level of PXR expression in cancerous breast tissue suggests a likely interface between aberrant cell division and xeno-protection in cancer cells. Moreover, PXR itself exerts positive effect on the cell cycle, thereby predisposing tumor cells to unchecked proliferation. Activation of PXR also plays a key role in regulating apoptosis, as well as in acquired resistance to chemotherapeutic agents. The repressive role of PXR in regulating inflammatory mediators along with the existence of genetic polymorphisms within the sequence of the PXR gene may predispose individuals to developing breast cancer. Further investigations into the role that PXR plays in driving tumorigenesis are needed.
Changes in Cigarette Consumption With Reduced Nicotine Content Cigarettes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage

Key Points Question Does reducing the nicotine content of cigarettes decrease smoking rates and nicotine dependence severity among adults with psychiatric disorders or socioeconomic disadvantage? Findings These 3 randomized clinical trials including 775 participants with affective disorders, opioid use disorder, or socioeconomic disadvantage found that reducing nicotine content significantly decreased total cigarettes smoked daily and nicotine dependence severity. Meaning These results further demonstrate that reducing nicotine content of cigarettes to low levels has potential to benefit populations at high risk for tobacco use, addiction, and smoking-attributable morbidity and mortality.
Examining cancer metabolism in vivo

Nutrient requirements for cancer cells are different from those of most normal cells. Understanding these differences, and the factors that are responsible for creating different metabolic dependencies, is critical to understanding the basic requirements of rapid proliferation and identifying potential therapeutic vulnerabilities. In particular, oncogene status, tissue-of-origin, cell-of-origin, and microenvironmental factors all can contribute to defining these requirements, but how to characterize which dependencies exist in various physiological setting are unknown. In this thesis, we address key challenges to study cancer metabolism in the living organism. We present novel experimental and analytical methods to study tumor metabolism in mouse models. This includes: (1) an approach to determine the metabolic fate of any radioactive or stable-isotope tracer in tumors and tissues (2) strategies to create stable-isotope macromolecular (protein) tracers (3) a plasmapheresis strategy to deliver labeled protein in vivo (4) qualitative and quantitative methods to define kinetics of extracellular protein catabolism in live tumors in real-time (5) the characterization of a conditional allele to test the requirements for isoform-specific pyruvate kinase expression. We applied these methods to three mouse models of cancer (models of human lung, pancreas, and prostate cancer) to better characterize metabolism and identify potential metabolic vulnerabilities in these tumors. Our results show that tumors in vivo utilize a metabolic program that is distinct from cells in tissue culture derived from those same tumors. Additionally, we identified that the uptake and subsequent catabolism of extracellular protein provides a substantial proportion of free intracellular amino acids for pancreatic cancer cells in tumors. Finally, we have identified prostate cancer as a tumor type that may benefit from pharmacological activation of pyruvate kinase. Overall, our results demonstrate the importance of studying cancer metabolism in the correct physiological setting. Data generated from patients corroborates our findings in these mouse models and suggests that these approaches can be used to define more effective cancer therapeutic strategies. The methods presented here are adaptable to study the metabolic phenotypes in any tumor or tissue of interest. Further use of these methods enable the examination of cell autonomous and non-cell autonomous metabolic consequences of oncogene status, microenvironment, and in organismal metabolism as a function of cancer initiation and progression. Thesis Supervisor: Professor Matthew G. Vander Heiden Title: Associate Professor of Biology