Miracle-dz/UniFAR-FTUs huggingface dataset:
Abnormal DNA methylation patterns in patients with infection-caused leukocytopenia based on methylation microarrays

The present study aimed to investigate the association between gene methylation and leukocytopenia from the perspective of gene regulation. A total of 30 patients confirmed as having post-infection leukocytopenia at People's Hospital of Xinjiang Uygur Autonomous Region between January 2016 and June 2017 were successively recruited as the leukocytopenia group; 30 patients with post-infection leukocytosis were enrolled as the leukocytosis group. In addition, 30 healthy volunteers who received a health examination at the hospital during the same period were included as the normal control group. In each group, four individuals were randomly selected for whole genome methylation screening. After selection of key methylation sites, the remaining samples in each group were used for verification using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The levels of serum complement factors C3 and C5 in the leukocytopenia group were significantly lower than those in the other two groups (P<0.05). According to whole-genome DNA methylation detection, 66 and 27 methylation loci may be associated with leukocytopenia and leukocytosis, respectively. Most of these abnormal loci are located on chromosomes 2, 6, 7, 1, 17 and 11. The rates of WW domain containing E3 ubiquitin protein ligase 2 gene methylation at cytosine-phosphate-guanine (CpG)_1, CpG_5/6 and CpG_7 in the leukocytopenia group were higher than in the other two groups (P<0.05); the rate of AKT2 CpG_1 methylation was higher in the leukocytopenia group than in the other two groups (P<0.05); the rate of calcium-binding atopy-related autoantigen 1 gene CpG_2 methylation was higher in the leukocytosis group than in the normal control group (P<0.05); and the rate of NADPH oxidase 5 gene CpG_3 methylation was higher in the leukocytosis group than in the normal control group (P<0.05). Chemotactic factor secretion and cell migration abnormalities, ubiquitination modification disorders and reduced oxidative burst may participate in infection-complicated leukocytopenia. The results of this study shed new light on the molecular biological mechanisms of infection-complicated leukocytopenia and provide novel avenues for diagnosis and treatment.
RETRACTED ARTICLE: Serum levels of PTEN mRNA in colorectal cancer: a case-control study

Abstract We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article: Yang Yan, Xiaohui Du, Shaoyou Xia, Songyan Li, Da Teng, Shidong Hu, Yufeng Wang & Rong Li (2020) Serum levels of PTEN mRNA in colorectal cancer: a case-control study. Artificial Cells, Nanomedicine, and Biotechnology, 48:1, 789–793, DOI: 10.1080/21691401.2019. 1576708 It has come to our attention that the full authorship list and affiliations for this manuscript were changed after the article was accepted. We have contacted the corresponding author for an explanation, but we have not received a satisfactory explanation. As determining authorship is core to the integrity of published work, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
Continuous exposure to ambient air pollution and chronic diseases: prevalence, burden, and economic costs

Abstract Studies that assess the connection between the prevalence of chronic diseases and continuous exposure to air pollution are scarce in developing countries, mainly due to data limitations. Largely overcoming data limitations, this study aimed to investigate the association between the likelihood of reporting a set of chronic diseases (diabetes, cancer, stroke and myocardial infarction, asthma, and hypertension) and continuous exposure to carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and coarse particulate matter (PM10). Using the estimated associations, the disease burden and economic costs of continuous exposure to air pollutants were also approximated. A 2011 Health Equity Assessment and Response Tool survey from Tehran, Iran, was used in the main analyses. A sample of 67,049 individuals who had not changed their place of residence for at least 2 years before the survey and reported all relevant socioeconomic information was selected. The individuals were assigned with the average monthly air pollutant levels of the nearest of 16 air quality monitors during the 2 years leading to the survey. Both single- and multi-pollutant analyses were conducted. The country’s annual household surveys from 2002 to 2011 were used to calculate the associated economic losses. The single-pollutant analysis showed that a one-unit increase in monthly CO (ppm), NO2 (ppb), O3 (ppb), and PM10 (μg/m3) during the 2 years was associated with 751 [confidence interval (CI): 512–990], 18 (CI: 12–24), 46 (CI: −27–120), and 24 (CI: 13–35) more reported chronic diseases in 100,000, respectively. The disease-specific analyses showed that a unit change in average monthly CO was associated with 329, 321, 232, and 129 more reported cases of diabetes, hypertension, stroke and myocardial infarction, and asthma in 100,000, respectively. The measured associations were greater in samples with older individuals. Also, a unit change in average monthly O3 was associated with 21 (in 100,000) more reported cases of asthma. The multi-pollutant analyses confirmed the results from single-pollutant analyses. The supplementary analyses showed that a one-unit decrease in monthly CO level could have been associated with about 208 (CI: 147–275) years of life gained or 15.195 (CI: 10.296–20.094) thousand US dollars (USD) in life-time labor market income gained per 100,000 30-plus-year-old Tehranis.
Histiocytic sarcoma in miniature schnauzers: 30 cases.

OBJECTIVES To summarise the clinical presentation and outcomes in a series of miniature schnauzers diagnosed with histiocytic sarcoma. MATERIALS AND METHODS Retrospective review of medical records of miniature schnauzers diagnosed with histiocytic sarcoma between 2008 and 2019 at two referral centres in the UK. Signalment, clinical signs at initial presentation, imaging results and clinico- and histopathological findings, treatment type and outcome were recorded. Progression-free survival and overall survival time were calculated. RESULTS Thirty dogs were included. Twenty-four of 29 dogs undergoing imaging of the thorax had lung and/or mediastinal involvement. The median overall survival time for dogs that were not euthanased within 3 days of diagnosis was 117 days (range 10 to 790). Three dogs underwent surgery; 13 received treatment with lomustine as a sole therapy - with partial responses documented on imaging in five of six dogs and 11 of 13 showing clinical improvement. CLINICAL SIGNIFICANCE Histiocytic sarcoma should be considered as a differential diagnosis for miniature schnauzers with pulmonary masses. Although responses to treatment were common, they were usually short-lived because of the aggressive nature of the disease.
LRRK2 inhibitors induce reversible changes in nonhuman primate lungs without measurable pulmonary deficits

Morphological changes in the lungs of macaques induced by several different LRRK2 inhibitors are reversible and do not lead to lung deficits. Parsing the side effects of LRRK2 inhibitors Preclinical studies have raised concerns about the safety of LRRK2 inhibitors—developed for treating Parkinson’s disease—specifically regarding lung function. Baptista et al. now report that several different LRRK2 inhibitors induce on-target histopathological changes in the lungs of nonhuman primates. However, they show that these morphological changes were reversible after drug withdrawal and had no effect on pulmonary function as demonstrated by a battery of lung function tests. These findings suggest that LRRK2 inhibitor–induced effects on lung tissue should not prevent the clinical testing of these compounds. The kinase-activating mutation G2019S in leucine-rich repeat kinase 2 (LRRK2) is one of the most common genetic causes of Parkinson’s disease (PD) and has spurred development of LRRK2 inhibitors. Preclinical studies have raised concerns about the safety of LRRK2 inhibitors due to histopathological changes in the lungs of nonhuman primates treated with two of these compounds. Here, we investigated whether these lung effects represented on-target pharmacology and whether they were reversible after drug withdrawal in macaques. We also examined whether treatment was associated with pulmonary function deficits. We conducted a 2-week repeat-dose toxicology study in macaques comparing three different LRRK2 inhibitors: GNE-7915 (30 mg/kg, twice daily as a positive control), MLi-2 (15 and 50 mg/kg, once daily), and PFE-360 (3 and 6 mg/kg, once daily). Subsets of animals dosed with GNE-7915 or MLi-2 were evaluated 2 weeks after drug withdrawal for lung function. All compounds induced mild cytoplasmic vacuolation of type II lung pneumocytes without signs of lung degeneration, implicating on-target pharmacology. At low doses of PFE-360 or MLi-2, there was ~50 or 100% LRRK2 inhibition in brain tissue, respectively, but histopathological lung changes were either absent or minimal. The lung effect was reversible after dosing ceased. Lung function tests demonstrated that the histological changes in lung tissue induced by MLi-2 and GNE-7915 did not result in pulmonary deficits. Our results suggest that the observed lung effects in nonhuman primates in response to LRRK2 inhibitors should not preclude clinical testing of these compounds for PD.
Hijacking Germ Cells for Cancer: Examining a 'Dead End' in Male Germ Cell Development

Hijacking Germ Cells for Cancer: Examining a ‘Dead End’ in Male Germ Cell Development by Matthew Simon Cook Department of Cell Biology Duke University Date:_______________________ Approved: ___________________________ Blanche Capel, Supervisor ___________________________ Sally Kornbluth ___________________________ Chris Nicchitta ___________________________ Jack Keene An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Cell Biology in the Graduate School of Duke University 2010 Copyright by Matthew Simon Cook 2010
Dyslipidemia prevalence in adolescents in public schools.

OBJECTIVE To evaluate the prevalence of dyslipidemia in adolescents enrolled in the state public education system of the city of Montes Claros, state of Minas Gerais, and compare to a Brazilian population-based study. METHOD This is an epidemiological, cross-sectional, and analytical study with a population of 77,833 students from 63 schools, representing four geographic areas of the city. After a sample calculation, information on 635 adolescents from 10 to 16 years of age was assessed and blood collection was conducted for the analysis of biochemical parameters of total cholesterol, triglycerides, LDL-c, and HDL-c. RESULTS Among the adolescents, 26.8% showed high levels of total cholesterol, 15.7% of triglycerides, and 6.5% of LDL-c, and 40.8% had low HDL-c levels. CONCLUSION Except for HDL-c levels, dyslipidemia prevalence and means in adolescents from Montes Claros, Minas Gerais, were above the levels found in the Brazilian population-based study used as parameter.
Effects of landscapes and range expansion on population structure and local adaptation.

Understanding the origin and distribution of genetic diversity across landscapes is critical for predicting the future of organisms in changing climates. This study investigated how adaptive and demographic forces have shaped diversity and population structure in Pinus densata, a keystone species on Qinghai-Tibetan Plateau (QTP). We examined the distribution of genomic diversity across the range of P. densata using exome capture sequencing. We applied spatially explicit tests to dissect the impacts of allele surfing, geographic isolation and environmental gradients on population differentiation and forecasted how this genetic legacy may limit the persistence of P. densata in future climates. We found that allele surfing from range expansion could explain the distribution of 39% of the ~48,000 genotyped SNPs. Uncorrected, these allele frequency clines severely confounded inferences of selection. After controlling for demographic processes, isolation-by-environment explained 9.2-19.5% of the genetic structure, with ~4.0% of loci being affected by selection. Allele surfing and genotype-environment associations resulted in genomic mismatch under projected climate scenarios. We illustrate that significant local adaptation, when coupled with reduced diversity due to demographic history, constrains potential evolutionary response to climate change. The strong signal of genomic vulnerability in P. densata may be representative for other QTP endemics.
Chapter 1 Structure-Function Relationship of Heart Valves in Health and Disease

The heart valves allow unidirectional and unobstructed passage of blood without regurgitation, trauma to blood elements, thromboembolism, and excessive stress concentrations in the leaflet and supporting tissue. In order to achieve this, the heart valves rely of their unique macroscale anatomy, histoarchitecture and ultrastructural features that allow them to accommodate repetitive changes in shape and dimension throughout the cardiac cycle. This chapter is focused on the structure-function relationship of the heart valves, with particular focus on the aortic and mitral valves, discussing how the biochemical, histoarchitectural and anatomical features influence valvular function during the cardiac cycle and how valvular function dictates valvular architecture and ECM constitution. The chapter examines the structure-function relationship of valvular tissue by correlating its microscale histoarchitecture and biochemical constitution to its mesoscale biomechanics and macroscale function during the cardiac cycle. Moreover, the chapter examines the influence of pathological alterations on the histoarchitectural and biochemical characteristics of the valves on their biomechanical behavior.
Sodium salicylate interferes with quorum-sensing-regulated virulence in chronic wound isolates of Pseudomonas aeruginosa in simulated wound fluid

Introduction. An important factor for delayed healing of chronic wounds is the presence of bacteria. Quorum sensing (QS), a cell density-dependent signalling system, controls the production of many virulence factors and biofilm formation in Pseudomonas aeruginosa . Aim. Inhibition by sodium salicylate (NaSa) of QS-regulated virulence expression was evaluated in QS-characterized clinical wound isolates of P. aeruginosa, cultured in serum-containing medium. Methodology. Fourteen clinical P. aeruginosa strains from chronic wounds were evaluated for the production of QS signals and virulence factors. Inhibition of QS by NaSa in P. aeruginosa clinical strains, wild-type PAO1 and QS reporter strains was evaluated using in vitro assays for the production of biofilm, pyocyanin, siderophores, alkaline protease, elastase and stapholytic protease. Results. Six clinical strains secreted several QS-associated virulence factors and signal molecules and two were negative for all factors. Sub-inhibitory concentrations of NaSa downregulated the expression of the QS-related genes lasB, rhlA and pqsA and reduced the secretion of several virulence factors in PAO1 and clinical strains cultured in serum. Compared to serum-free media, the presence of serum increased the expression of QS genes and production of siderophores and pyocyanin but decreased biofilm formation. Conclusions. Pseudomonas aeruginosa from chronic wound infections showed different virulence properties. While very few strains showed no QS activity, approximately half were highly virulent and produced QS signals, suggesting that the targeting of QS is a viable and relevant strategy for infection control. NaSa showed activity as a QS-inhibitor by lowering the virulence phenotypes and QS signals at both transcriptional and extracellular levels.
Glycan-specific antibodies as potential cancer biomarkers: a focus on microarray applications

Abstract Glycosylation is one of the most common posttranslational modifications of proteins and lipids. In the case of tumors, cell transformation accompanied by aberrant glycosylation results in the expression of tumor-associated glycans that promote tumor invasion. As part of the innate immunity, anti-glycan antibodies recognize tumor-associated glycans, and these antibodies can be present in the bloodstream in the early stages of cancer. Recently, anti-glycan antibody profiles have been of interest in various cancer studies. Novel advantages in the field of analytical techniques have simplified the analysis of anti-glycan antibodies and made it easier to have more comprehensive knowledge about their functions. One of the robust approaches for studying anti-glycan antibodies engages in microarray technology. The analysis of glycan microarrays can provide more expanded information to simultaneously specify or suggest the role of antibodies to a wide variety of glycans in the progression of different diseases, therefore making it possible to identify new biomarkers for diagnosing cancer and/or the state of the disease. Thus, in this review, we discuss antibodies to various glycans, their application for diagnosing cancer and one of the most promising tools for the investigation of these molecules, microarrays.
KLASIFIKASI PERKEMBANGBIAKAN PLASMODIUM PENYEBAB PENYAKIT MALARIA DALAM SEL DARAH MERAH MANUSIA DENGAN MENGGUNAKAN SUPPORT VECTOR MACHINE (SVM) DI KOTA JAYAPURA-PAPUA

Malaria adalah penyakit yang ditularkan oleh nyamuk dari manusia dan hewan lain yang disebabkan oleh protozoa parasite (sekelompok mikroorganisme bersel tunggal) dalam tipe Plasmodium . Dalam kasus yang parah dapat menyebabkan kulit kuning, kejang, koma, atau kematian. Penelitian ini melakukan klasifikasi perkembangbiakan plasmodium penyebab penyakit malaria untuk membantu proses diagnosa klinis dan analisa secara dini jenis plasmodium falciparum dengan cepat dan akurat yang meliputi interpretasi secara otomatis dari citra warna dermatoskopis. Dengan menerapkan metode Support Vector Machine (SVM) melakukan segmentasi terhadap ciri dan tekstur pada citra darah merah manusia untuk memisahkan sel yang dikategorikan Plasmodium Falciparum untuk diekstraksi cirinya. Penelitian dilakukan di Rumah Sakit-Rumah Sakit yang ada di Kota Jayapura Propinsi Papua. Tujuan dari penelitian ini adalah untuk menganalisa perkembangbiakan plasmodium sehingga diharapkan dapat mendiagnosa sejak dini plasmodium falciparum, secara cepat dan hasil penelitian menunjukkan akurasi terbaik adalah 73,33 % dengan menggunakan 120 citra data latih dan 30 citra data uji.
Direct kinetic measurements and theoretical predictions of an isoprene-derived Criegee intermediate

Significance Ozonolysis is an important sink of alkenes in Earth’s troposphere, leading to the formation of Criegee intermediates (CIs), whose reactions significantly impact tropospheric composition. The reactivity of the four-carbon unsaturated CIs derived from isoprene, the most abundant alkene, has remained unknown until now. Direct measurements of one such CI, methyl vinyl ketone oxide (MVK-oxide), with water vapor, SO2, and formic acid are reported herein, substantiated by high-level theory, revealing the long lifetime of syn-MVK-oxide with respect to unimolecular decay and reaction with water vapor. Through a combination of direct experiment, high-level theory, and global modelling, syn-MVK-oxide is shown to survive high-humidity tropospheric environments and play a role in sulfuric acid formation and formic acid removal. Isoprene has the highest emission into Earth’s atmosphere of any nonmethane hydrocarbon. Atmospheric processing of alkenes, including isoprene, via ozonolysis leads to the formation of zwitterionic reactive intermediates, known as Criegee intermediates (CIs). Direct studies have revealed that reactions involving simple CIs can significantly impact the tropospheric oxidizing capacity, enhance particulate formation, and degrade local air quality. Methyl vinyl ketone oxide (MVK-oxide) is a four-carbon, asymmetric, resonance-stabilized CI, produced with 21 to 23% yield from isoprene ozonolysis, yet its reactivity has not been directly studied. We present direct kinetic measurements of MVK-oxide reactions with key atmospheric species using absorption spectroscopy. Direct UV-Vis absorption spectra from two independent flow cell experiments overlap with the molecular beam UV-Vis-depletion spectra reported recently [M. F. Vansco, B. Marchetti, M. I. Lester, J. Chem. Phys. 149, 44309 (2018)] but suggest different conformer distributions under jet-cooled and thermal conditions. Comparison of the experimental lifetime herein with theory indicates only the syn-conformers are observed; anti-conformers are calculated to be removed much more rapidly via unimolecular decay. We observe experimentally and predict theoretically fast reaction of syn-MVK-oxide with SO2 and formic acid, similar to smaller alkyl-substituted CIs, and by contrast, slow removal in the presence of water. We determine products through complementary multiplexed photoionization mass spectrometry, observing SO3 and identifying organic hydroperoxide formation from reaction with SO2 and formic acid, respectively. The tropospheric implications of these reactions are evaluated using a global chemistry and transport model.
RESPONSE OF MAIZE HYBRIDS TO VARYING POTASSIUM APPLICATION IN PAKISTAN

), N (0.728%), P (0.078%), K (1.79%) concentration in stalk, crude starch (72.97%), protein (8.15%) and oil (4.46%) contents in grains. K application in all treatments significantly increased growth rate, grain yield, N, P, K concentration in stalk, and improved crude starch, protein and oil contents in grains over control. Maximum growth rate, grain yield (6.05 t ha -1 ), N (0.751% ), P (0.082%), K (1.86%) concentration in stalk, were recorded, when 200 kg K ha -1 was applied, and beyond this limit, tended to decline its growth rate, grain yield (6.02 t ha -1 ), N (0.743%), P (0.071%) and K (1.76%) concentration in stalk when 250 kg K ha -1 was applied, but continued to increase crude starch (72.65%), protein (8.31%) and oil (4.53%) contents in grains. Interactive effects of maize hybrids and potash application levels on growth, yield and N, P, K concentration in stalk, crude starch, oil, and protein contents in grains were, however, non significant. It was concluded that Pioneer-30D55 performed best with 200 kg K ha -1
Understanding Physicians’ Perceptions of Overuse of Health Services in Oncology

Overuse rates in oncology are high, but areas of possible improvement exist for reducing it and improving quality of care. This study explores perceptions and experiences of oncologists in Israel regarding overuse of health services within oncology. In-depth, semistructured interviews were conducted focusing on causes of overuse, facilitators for reduction, and suggestions for improvement. Interviews were audio recorded, transcribed, coded, and thematically analyzed. Physicians reported patient-level causes including “well-informed” and “demanding” patients; physician-level causes including desire to satisfy patients, lack of confidence, time, and skills; and system-level causes like ease of access, and lack of alignment and coordination. Physicians can reduce overuse through patient dialogue, building trust and solidifying patient–physician relationships, and further reduce overuse with better teamwork. Improvements can be made through educational initiatives, and bottom-up solutions. Policy makers and decision makers should develop appropriate interventions addressing health service overuse, including improving patient education and instilling confidence and knowledge in physicians.