Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucagon-Like Peptide 1 Receptor Agonists and the Risk of Incident Diabetic Retinopathy

OBJECTIVE Previous studies suggested that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may initially worsen and possibly increase the risk of diabetic retinopathy. However, data on this possible association remain limited. Thus, this population-based study aimed to determine whether use of GLP-1 RAs is associated with an increased risk of incident diabetic retinopathy. RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink (CPRD), we conducted a cohort study among 77,115 patients with type 2 diabetes initiating antidiabetic drugs between January 2007 and September 2015. Adjusted hazard ratios (HRs) and 95% CIs of incident diabetic retinopathy were estimated using time-dependent Cox proportional hazards models, comparing use of GLP-1 RAs with current use of two or more oral antidiabetic drugs. In an ancillary analysis, new users of GLP-1 RAs were compared with new users of insulin. RESULTS During 245,825 person-years of follow-up, 10,763 patients were newly diagnosed with diabetic retinopathy. Compared with current use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy overall (HR 1.00, 95% CI 0.85–1.17). Compared with insulin, GLP-1 RAs were associated with a decreased risk of diabetic retinopathy (HR 0.67, 95% CI 0.51–0.90). CONCLUSIONS The associations with diabetic retinopathy varied according to the type of comparator. When compared with use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy. The apparent lower risk of diabetic retinopathy associated with GLP-1 RAs compared with insulin may be due to residual confounding.
Maternal infection during pregnancy and type 1 diabetes mellitus in offspring: a systematic review and meta-analysis

Abstract Previous studies have demonstrated that type 1 diabetes mellitus (T1DM) could be triggered by an early childhood infection. Whether maternal infection during pregnancy is associated with T1DM in offspring is unknown. Therefore, we aimed to study the association using a systematic review and meta-analysis. Eighteen studies including 4304 cases and 25 846 participants were enrolled in this meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were synthesised using random-effects models. Subgroup analyses and sensitivity analyses were conducted to assess the robustness of associations. Overall, the pooled analysis yielded a statistically significant association between maternal infection during pregnancy and childhood T1DM (OR 1.31, 95% CI 1.07–1.62). Furthermore, six studies that tested maternal enterovirus infection showed a pooled OR of 1.54 (95% CI 1.05–2.27). Heterogeneity from different studies was evident (I2 = 70.1%, P < 0.001) and was mainly attributable to the different study designs, ascertaining methods and sample size among different studies. This study provides evidence for an association between maternal infection during pregnancy and childhood T1DM.
The Ability of Quantitative, Specific, and Sensitive Point-of-Care/Chair-Side Oral Fluid Immunotests for aMMP-8 to Detect Periodontal and Peri-Implant Diseases

The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth rinse, gingival crevicular fluid (GCF), and peri-implantitis fluid (PISF)) is demanding. Several hosts and microbial factors may influence their expression, release, and levels. The type of saliva/oral fluids utilized for the diagnostics affects the analysis. High sensitivity and specificities together with sophisticated methods and techniques are essential for valuable outcome. We describe here recently developed practical, convenient, inexpensive, noninvasive, and quantitative mouth rinse and PISF/GCF/chair-side/point-of-care (PoC) lateral-flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyser) to detect, predict, and monitor successfully the course, treatment, and prevention of periodontitis and peri-implantitis, respectively. The tests have been independently and successfully validated to differentiate periodontal and peri-implant health and disease in Finland, Germany, Netherland, Sweden, Turkey, Nigeria, Malawi, and USA. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires additional studies utilizing these noninvasive screening, diagnostic, and preventive aMMP-8 PoC/chair-side technologies.
High-Intensity Interval Training Is Equivalent to Moderate-Intensity Continuous Training for Short- and Medium-Term Outcomes of Glucose Control, Cardiometabolic Risk, and Microvascular Complication Markers in Men With Type 2 Diabetes

We sought to determine the efficacy of 12 weeks high-intensity interval training (HIIT), compared to moderate-intensity continuous training (MICT) on glucose control, cardiometabolic risk and microvascular complication markers in men living with type 2 diabetes (T2D). Both modalities were combined with resistance training (RT). Additionally, the study aimed to determine the medium-term durability of effects. After a 12-week, thrice weekly, training intervention incorporating either MICT+RT (n = 11) or HIIT+RT (n = 12), the study concluded with a 6-month follow-up analysis. The middle-aged study participants were obese, had moderate duration T2D and were taking multiple medications including insulin, statins and beta-blockers. Participants, randomized via the method of minimization, performed MICT (progressing to 26-min at 55% maximum estimated workload [eWLmax]) or HIIT (progressing to two variations in which twelve 1-min bouts at 95% eWLmax interspersed with 1-min recovery bouts, alternated with eight 30-s bouts at 120% eWLmax interspersed with 2:15 min recovery bouts) under supervision at an exercise physiology facility. To account for fixed and random effects within the study sample, mixed-effect models were used to determine the significance of change following the intervention and follow-up phases and to evaluate group*time interactions. Beyond improvements in aerobic capacity (P < 0.001) for both groups, both training modalities elicited similar group*time interactions (P > 0.05) while experiencing benefits for glycated hemoglobin (HbA1c; P = 0.01), subcutaneous adiposity (P < 0.001), and heart rate variability (P = 0.02) during the 12-week intervention. Adiposity (P < 0.001) and aerobic capacity (P < 0.001) were significantly maintained in both groups at the 6-month follow-up. In addition, during the intervention, participants in both MICT+RT and HIIT+RT experienced favorable reductions in their medication usage. The study reported the inter-individual variability of change within both groups, the exaggerated acute physiological responses (using exercise termination indicators) that occurred during the interventions as well as the incidence of precautionary respite afforded in such a study sample. To reduce hyperglycaemia, and prevent further deterioration of cardiometabolic risk and microvascular complication markers (in both the short- and medium-term), future strategies that integrate the adoption and maintenance of physical activity as a cornerstone in the treatment of T2M for men should (cognisant of appropriate supervision) include either structured MICT+RT, or HIIT+RT. Clinical Trials Registration Number: ACTRN12617000582358 http://www.anzctr. org.au/default.aspx
Biological responses to environmental contamination. How can metal pollution impact signal honesty in avian species?

Abstract Environmental pollution, for example with metals, can significantly affect the ecosystem balance leading to severe changes. Biologically active pigments are relevant for the appearance and condition of birds. Melanin and carotenoid particles are the most frequently deposited pigments in avian integument. They are responsible for the majority of colors of bird plumage. The phenotypic expression can be affected by metal contamination. It can be manifested as color bleaching or differences in the size of plumage badges. In this study, we performed a comprehensive review of related studies in order to estimate the underlying population effect of this potential dependency. The study is based on the review of the literature regarding several avian species. It was designed to identify an area where the effect of the exposure is still poorly known. The analysis was specifically conducted to investigate the correlation between trace element concentration and eumelanin deposition. Moreover, we searched for factors that could affect spectral properties of feathers with carotenoid‐based pigmentation. As a result, we found carotenoid‐based pigmentation to be of a good use in terms of visual condition assessment. Changes in melanin‐based pattern should be analyzed separately for eu‐ and pheomelanin as well as for a range of essential and toxic elements. Comprehensive studies on the subject are still scarce. Therefore, the issue requires further investigation.
Flower preferences and pollen transport networks for cavity‐nesting solitary bees: Implications for the design of agri‐environment schemes

Abstract Floral foraging resources are valuable for pollinator conservation on farmland, and their provision is encouraged by agri‐environment schemes in many countries. Across Europe, wildflower seed mixtures are widely sown on farmland to encourage pollinators, but the extent to which key pollinator groups such as solitary bees exploit and benefit from these resources is unclear. We used high‐throughput sequencing of 164 pollen samples extracted from the brood cells of six common cavity‐nesting solitary bee species (Osmia bicornis, Osmia caerulescens, Megachile versicolor, Megachile ligniseca, Megachile centuncularis and Hylaeus confusus) which are widely distributed across the UK and Europe. We documented their pollen use across 19 farms in southern England, UK, revealing their forage plants and examining the structure of their pollen transport networks. Of the 32 plant species included currently in sown wildflower mixes, 15 were recorded as present within close foraging range of the bees on the study farms, but only Ranunculus acris L. was identified within the pollen samples. Rosa canina L. was the most commonly found of the 23 plant species identified in the pollen samples, suggesting that, in addition to providing a nesting resource for Megachile leafcutter bees, it may be an important forage plant for these species. Higher levels of connectance and nestedness were characteristic of pollen transport networks on farms with abundant floral resources, which may increase resilience to species loss. Our data suggest that plant species promoted currently by agri‐environment schemes are not optimal for solitary bee foraging. If a diverse community of pollinators is to be supported on UK and European farmland, additional species such as R. canina should be encouraged to meet the foraging requirements of solitary bees.
Factors related to hypertensive phase after glaucoma drainage device implantation

Background The aim of the study was to evaluate factors related to hypertensive phase (HP) after glaucoma drainage device (GDD) implantation. Patients and methods Retrospective charts review of glaucoma patients who underwent GDD implantation and completed 12 months of follow-up at King Chulalongkorn Memorial Hospital since 2004 was performed. Patients were divided into two groups according to the presence or absence of HP. The data were analyzed for factors associated with HP. The surgical outcomes including surgical failure, post-operative visual acuity (VA), post-operative number of medications, post-operative intraocular pressure (IOP), and post-operative complication were compared between the two groups. Results Seventy-two patients were included. Most were diagnosed with secondary glaucoma (N=51, 70.8%), and Baerveldt was the most implanted GDD (N=49, 68.1%). Mean ± SD of IOP was significantly lower: 27.1±9.6 mmHg at pre-operation and 13.7±59 mmHg at 12-month follow-up (p<0.001). HP was identified in 38/72 patients (52.8%, 95% CI 40.7–64.7). Risk factor of HP was pre-operative VA equal or better than 20/70 (p=0.021, OR 7.5; 95% CI 1.4–41.4). Presence of underlying heart disease (patients in this group had taken anti-platelets) was found as a protective factor for HP (p=0.027, OR 0.06; 95% CI 0.00–0.72). It was speculated that the anti-inflammatory effect of the anti-platelets, particularly aspirin, may be responsible for controlling inflammation and retarding fibrosis formation around drainage implants. Failure rate at 12 months was 24/72 (33%). There was no difference in all surgical outcomes between the two groups. Survival analysis also showed no significant difference between HP and non-HP group. Conclusion HP commonly occurred after GDD implantation. Pre-operative VA was a risk factor for the development of HP, whereas presence of underlying heart disease was a protective factor. No association between HP and surgical outcomes was identified.
Hodgkin Lymphoma in Adults.

BACKGROUND Hodgkin lymphoma is the most common neoplasm in young adults, with an incidence of 2 to 3 cases per 100 000 persons per year. Risk-adapted chemotherapy and radiotherapy usually lead to cure. Finding ways to lessen the treatment- associated morbidity and mortality is a major goal of current research. METHODS For the creation of an updated guideline (DKH grant number 111778), a systematic literature search was carried out in medical databases (MEDLINE, CENTRAL) and guideline databases (GIN) (search dates: January 2012 to June 2017). RESULTS Results from 10 meta-analyses, 89 randomized and controlled trials, and 81 prospective or retrospective trials were evaluated. The use of positron emission tomography (PET) is strongly recommended in the initial diagnostic evaluation, as well as for the guidance of treatment in advanced stages. In early stages, two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and involved-site radiotherapy (IS-RT) at a dose of 20 Gy are recommended. For the treatment of intermedi- ate stages, two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) + two cycles of ABVD and 30 Gy IS-RT are recommended. In advanced stages, two cycles of escalated BEACOPP are administered, and then PET is performed for the guidance of further treatment: two further cycles of escalated BEACOPP are recommended if the PET is negative and four further cycles if it is positive, followed by radiotherapy of PET- positive residual tumor tissue. The five-year survival of patients with Hodgkin lymphoma is 95%. In case of disease recurrence, high-dose chemotherapy followed by autologous stem-cell transplantation is performed, and targeted drugs including brentuxi- mab vedotin, nivolumab, and pembrolizuab are used. CONCLUSION The highly favorable long-term prognosis of HL necessitates careful consideration of the intensity of treatment as well as thorough follow-up to enable the detection of late sequelae, such as second tumors or organ damage.
In vivo animal studies help achieve international consensus on standards and guidelines for health risk estimates for chronic exposure to low levels of tritium in drinking water

Existing and future nuclear fusion technologies involve the production and use of large quantities of tritium, a highly volatile, but low toxicity beta‐emitting isotope of hydrogen. Tritium has received international attention because of public and scientific concerns over its release to the environment and the potential health impact of its internalization. This article provides a brief summary of the current state of knowledge of both the biological and regulatory aspects of tritium exposure; it also explores the gaps in this knowledge and provides recommendations on the best ways forward for improving our understanding of the health effects of low‐level exposure to it. Linking health effects specifically to tritium exposure is challenging in epidemiological studies due to high uncertainty in tritium dosimetry and often suboptimal cohort sizes. We therefore argued that limits for tritium in drinking water should be based on evidence derived from controlled in vivo animal tritium toxicity studies that use realistically low levels of tritium. This article presents one such mouse study, undertaken within an international collaboration, and discusses the implications of its main findings, such as the similarity of the biokinetics of tritiated water (HTO) and organically bound tritium (OBT) and the higher biological effectiveness of OBT. This discussion is consistent with the position expressed in this article that in vivo animal tritium toxicity studies carried out within large, multi‐partner collaborations allow evaluation of a great variety of health‐related endpoints and essential to the development of international consensus on the regulation of tritium levels in the environment. Environ. Mol. Mutagen. 59:586–594, 2018. © 2018 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society
Cryptococcal Meningitis: A Retrospective Cohort of a Brazilian Reference Hospital in the Post-HAART Era of Universal Access

Objective Cryptococcus neoformans is a common opportunistic infection in adults with acquired immunodeficiency syndrome worldwide. However, limited data exist for HIV-infected patients in the post-HAART (highly active antiretroviral therapy) era in Brazil. The aim of this study was to describe the clinical characteristics and outcomes of cryptococcosis in a cohort of patients attending a teaching tertiary care hospital in southern Brazil after the introduction of HAART in Brazil. Patients and Methods A retrospective study was conducted in tertiary care hospital in southern Brazil. Detailed data on risk factors, clinical manifestations, diagnosis methods, treatment, and prognosis of patients with meningeal cryptococcosis were evaluated from January 2009 to December 2016. Results Seventy-nine cases of cryptococcal meningitis were identified. Most of the patients presented positive CSF (cerebrospinal fluid) cultures for Cryptococcus neoformans (96%). The prevalence of males and females with meningeal cryptococcosis was similar. The age of the patients ranged from 5 to 67 years. The median time of hospitalization was 28 days. The most common underlying disease was HIV (82%), followed by solid transplant (10%). Fever, nausea, vomiting, headache, and altered mental status were the most common clinical manifestations. Initial opening intracranial pressures varied from 30 to 130 cm H2O. CNS imaging abnormalities include hydrocephalus and hypodensities. Widened Virchow–Robin spaces were described in only 2 patients (2.5%). Induction treatment of the majority of the patients consisted of amphotericin B and flucytosine (67%) followed by amphotericin B and fluconazole (19%). Multivariate analysis of Cox regression identified headache at presentation, mechanical ventilation, CSF glucose <20 mg/dL, and CSF cryptococcal antigen ≥1 : 1000 for independent risk factors for death. All-cause 30-day and 60-day mortalities were 19% and 24%, respectively. Conclusions Meningeal cryptococcosis mostly caused by C. neoformans continues to occur predominantly in HIV-infected adults despite HAART being widely distributed in Brazil. Cryptococcosis remains a significant opportunistic infection in solid organ transplant recipients. Despite adequate antifungal treatment and management of intracranial hypertension in a reference tertiary care hospital, mortality was high. Identification of risk factors and additional treatment modalities, especially for intracranial hypertension, are necessary to improve care for patients with cryptococcal meningitis.
Genome-Wide Bioinformatics Analysis of MAPK Gene Family in Kiwifruit (Actinidia Chinensis)

Mitogen activated protein kinase (MAPK) cascades are universal signal transduction modules that play crucial roles in various biotic and abiotic stresses, hormones, cell division, and developmental processes in plants. Mitogen activated protein kinase (MAPK/MPK), being a part of this cascade, performs an important function for further appropriate cellular responses. Although MAPKs have been investigated in several model plants, no systematic analysis has been conducted in kiwifruit (Actinidia chinensis). In the present study, we identified 18 putative MAPKs in the kiwifruit genome. This gene family was analyzed bioinformatically in terms of their chromosome locations, sequence alignment, gene structures, and phylogenetic and conserved motifs. All members possess fully canonical motif structures of MAPK. Phylogenetic analysis indicated that AcMAPKs could be classified into five subfamilies, and these gene motifs in the same group showed high similarity. Gene structure analysis demonstrated that the number of exons in AcMAPK genes ranged from 2 to 29, suggesting large variation among kiwifruit MAPK genes. The expression profiles of these AcMAPK genes were further investigated using quantitative real-time polymerase chain reaction (qRT-PCR), which demonstrated that AcMAPKs were induced or repressed by various biotic and abiotic stresses and hormone treatments, suggesting their potential roles in the biotic and abiotic stress response and various hormone signal transduction pathways in kiwifruit. The results of this study provide valuable insight into the putative physiological and biochemical functions of MAPK genes in kiwifruit.
The temporal landscape of recursive splicing during Pol II transcription elongation in human cells

Recursive splicing (RS) is an evolutionarily conserved process of removing long introns via multiple steps of splicing. It was first discovered in Drosophila and recently proven to occur also in humans. The detailed mechanism of recursive splicing is not well understood, in particular, whether it is kinetically coupled with transcription. To investigate the dynamic process that underlies recursive splicing, we systematically characterized 342 RS sites in three human cell types using published time-series data that monitored synchronized Pol II elongation and nascent RNA production with 4-thiouridine labeling. We found that half of the RS events occurred post-transcriptionally with long delays. For at least 18–47% RS introns, we detected RS junction reads only after detecting canonical splicing junction reads, supporting the notion that these introns were removed by both recursive splicing and canonical splicing. Furthermore, the choice of which splicing mechanism was used showed cell type specificity. Our results suggest that recursive splicing supplements, rather than replaces, canonical splicing for removing long introns.