Miracle-dz/UniFAR-FTUs huggingface dataset:
Recurrent Gestational Diabetes Mellitus: A Narrative Review and Single-Center Experience

Gestational diabetes mellitus (GDM) is a frequently observed complication of pregnancy and is associated with an elevated risk of adverse maternal and neonatal outcomes. Many women with GDM will go on to have future pregnancies, and these pregnancies may or may not be affected by GDM. We conducted a literature search, and based on data from key studies retrieved during the search, we describe the epidemiology of GDM recurrence. This includes a summary of the observed clinical risk factors of increasing maternal age, weight, ethnicity, and requirement for insulin in the index pregnancy. We then present our data from Mayo Clinic (January 2013–December 2017) which identifies a GDM recurrence rate of 47.6%, and illustrates the relevance of population-based studies to clinical practice. Lastly, we examine the available evidence on strategies to prevent GDM recurrence, and note that more research is needed to evaluate the effect of interventions before, during and after pregnancy.
Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family

ABSTRACT Betaine is a natural compound present in commonly consumed foods and may have a potential role in the regulation of glucose and lipids metabolism. However, the underlying molecular mechanism of its action remains largely unknown. Here, we show that supplementation with betaine contributes to improved high-fat diet (HFD)-induced gut microbiota dysbiosis and increases anti-obesity strains such as Akkermansia muciniphila, Lactobacillus, and Bifidobacterium. In mice lacking gut microbiota, the functional role of betaine in preventing HFD-induced obesity, metabolic syndrome, and inactivation of brown adipose tissues are significantly reduced. Akkermansia muciniphila is an important regulator of betaine in improving microbiome ecology and increasing strains that produce short-chain fatty acids (SCFAs). Increasing two main members of SCFAs including acetate and butyrate can significantly regulate the levels of DNA methylation at host miR-378a promoter, thus preventing the development of obesity and glucose intolerance. However, these beneficial effects are partially abolished by Yin yang (YY1), a common target gene of the miR-378a family. Taken together, our findings demonstrate that betaine can improve obesity and associated MS via the gut microbiota-derived miR-378a/YY1 regulatory axis, and reveal a novel mechanism by which gut microbiota improve host health.
Basophil counting in hematology analyzers: time to discontinue?

Abstract Basophils (basophilic granulocytes) are the least abundant cells in blood. Nowadays, basophils are included in the complete blood count performed by hematology analyzers and therefore reported in practically all patients in whom hematologic investigations are requested. However, hematology analyzers are not reliable enough to report clinically useful results. This is due to a combination of very high analytical imprecision and poor specificity, because the chemical and physical methods used for basophil counting in hematology analyzers are ill-defined and thus basophils are not well recognized by the analyzers. As a result, false basophil counts are quite common. In view of increasing analytical performance demands, hematology laboratories should stop reporting basophil counts produced by hematology analyzers. Suggestions for alternative pathways are presented for those situations where basophils are of clinical relevance.
Helicobacter hepaticus is required for immune targeting of bacterial heat shock protein 60 and fatal colitis in mice

ABSTRACT Gut microbiota and the immune system are in constant exchange shaping both host immunity and microbial communities. Here, improper immune regulation can cause inflammatory bowel disease (IBD) and colitis. Antibody therapies blocking signaling through the CD40–CD40L axis showed promising results as these molecules are deregulated in certain IBD patients. To better understand the mechanism, we used transgenic DC-LMP1/CD40 animals with a constitutive CD40-signal in CD11c+ cells, causing a lack of intestinal CD103+ dendritic cells (DCs) and failure to induce regulatory T (iTreg) cells. These mice rapidly develop spontaneous fatal colitis, accompanied by dysbiosis and increased inflammatory IL-17+IFN-γ+ Th17/Th1 and IFN-γ + Th1 cells. In the present study, we analyzed the impact of the microbiota on disease development and detected elevated IgA- and IgG-levels in sera from DC-LMP1/CD40 animals. Their serum antibodies specifically bound intestinal bacteria, and by proteome analysis, we identified a 60 kDa chaperonin GroEL (Hsp60) from Helicobacter hepaticus (Hh) as the main specific antigen targeted in the absence of iTregs. When re-derived to a different Hh-free specific-pathogen-free (SPF) microbiota, mice showed few signs of disease, normal microbiota, and no fatality. Upon recolonization of mice with Hh, the disease developed rapidly. Thus, the present work identifies GroEL/Hsp60 as a major Hh-antigen and its role in disease onset, progression, and outcome in this colitis model. Our results highlight the importance of CD103+ DC- and iTreg-mediated immune tolerance to specific pathobionts to maintain healthy intestinal balance.
High-Temperature Short-Time and Holder Pasteurization of Donor Milk: Impact on Milk Composition

Holder pasteurization (HoP; 62.5 °C, 30 min) is commonly used to ensure the microbiological safety of donor human milk (DHM) but diminishes its nutritional properties. A high-temperature short-time (HTST) system was designed as an alternative for human milk banks. The objective of this study was to evaluate the effect of this HTST system on different nutrients and the bile salt stimulated lipase (BSSL) activity of DHM. DHM was processed in the HTST system and by standard HoP. Macronutrients were measured with a mid-infrared analyzer. Lactose, glucose, myo-inositol, vitamins and lipids were assayed using chromatographic techniques. BSSL activity was determined using a kit. The duration of HTST treatment had a greater influence on the nutrient composition of DHM than did the tested temperature. The lactose concentration and the percentage of phospholipids and PUFAs were higher in HTST-treated than in raw DHM, while the fat concentration and the percentage of monoacylglycerides and SFAs were lower. Other nutrients did not change after HTST processing. The retained BSSL activity was higher after short HTST treatment than that following HoP. Overall, HTST treatment resulted in better preservation of the nutritional quality of DHM than HoP because relevant thermosensitive components (phospholipids, PUFAs, and BSSL) were less affected.
HIV-1 Infection Transcriptomics: Meta-Analysis of CD4+ T Cells Gene Expression Profiles

HIV-1 infection elicits a complex dynamic of the expression various host genes. High throughput sequencing added an expressive amount of information regarding HIV-1 infections and pathogenesis. RNA sequencing (RNA-Seq) is currently the tool of choice to investigate gene expression in a several range of experimental setting. This study aims at performing a meta-analysis of RNA-Seq expression profiles in samples of HIV-1 infected CD4+ T cells compared to uninfected cells to assess consistently differentially expressed genes in the context of HIV-1 infection. We selected two studies (22 samples: 15 experimentally infected and 7 mock-infected). We found 208 differentially expressed genes in infected cells when compared to uninfected/mock-infected cells. This result had moderate overlap when compared to previous studies of HIV-1 infection transcriptomics, but we identified 64 genes already known to interact with HIV-1 according to the HIV-1 Human Interaction Database. A gene ontology (GO) analysis revealed enrichment of several pathways involved in immune response, cell adhesion, cell migration, inflammation, apoptosis, Wnt, Notch and ERK/MAPK signaling.
A Core Module of Nuclear Genes Regulated by Biogenic Retrograde Signals from Plastids

Chloroplast biogenesis during seedling development of angiosperms is a rapid and highly dynamic process that parallels the light-dependent photomorphogenic programme. Pre-treatments of dark-grown seedlings with lincomyin or norflurazon prevent chloroplast biogenesis upon illumination yielding albino seedlings. A comparable phenotype was found for the Arabidopsis mutant plastid-encoded polymerase associated protein 7 (pap7) being defective in the prokaryotic-type plastid RNA polymerase. In all three cases the defect in plastid function has a severe impact on the expression of nuclear genes representing the influence of retrograde signaling pathway(s) from the plastid. We performed a meta-analysis of recently published genome-wide expression studies that investigated the impact of the aforementioned chemical and genetic blocking of chloroplast biogenesis on nuclear gene expression profiles. We identified a core module of 152 genes being affected in all three conditions. These genes were classified according to their function and analyzed with respect to their implication in retrograde signaling and chloroplast biogenesis. Our study uncovers novel genes regulated by retrograde biogenic signals and suggests the action of a common signaling pathway that is used by signals originating from plastid transcription, translation and oxidative stress.
The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes

Diabetes is a chronic metabolic disorder characterized by inappropriately elevated glucose levels as a result of impaired pancreatic β cell function and insulin resistance. Extensive studies have been conducted to elucidate the mechanism involved in the development of β cell failure and death under diabetic conditions such as hyperglycemia, hyperlipidemia, and inflammation. Of the plethora of proposed mechanisms, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and oxidative stress have been shown to play a central role in promoting β cell dysfunction. It has become more evident in recent years that these 3 factors are closely interrelated and importantly aggravate each other. Oxidative stress in particular is of great interest to β cell health and survival as it has been shown that β cells exhibit lower antioxidative capacity. Therefore, this review will focus on discussing factors that contribute to the development of oxidative stress in pancreatic β cells and explore the downstream effects of oxidative stress on β cell function and health. Furthermore, antioxidative capacity of β cells to counteract these effects will be discussed along with new approaches focused on preserving β cells under oxidative conditions.
Microvasculature in murine tracheal allografts after combined therapy with clopidogrel and everolimus.

OBJECTIVES Survival after lung transplantation is mainly limited by the development of chronic lung allograft dysfunction. Previous studies have suggested T-cell mediated proliferation and microvascular changes in experimental small airways models as potential therapeutic targets. The aim of this study was to assess microvascular changes in murine orthotopic tracheal allografts after treatment with everolimus alone or in combination with clopidogrel. METHODS C57Bl/6 (H-2b) donor tracheas were orthotopically transplanted into CBA (H-2k) recipients. Mice received daily injections of everolimus (0.05 mg/kg) alone or combined with clopidogrel (1 mg/kg). Twenty-eight days after transplantation, ratio of the thickness of tracheal epithelium and lamina propria was measured as an indicator for chronic rejection. Additionally, graft oxygenation and graft perfusion were detected on postoperative days 4, 10 and 28. Quantitative reverse transcription polymerase chain reaction analysis was used for gene expression analysis. RESULTS While syngeneic grafts showed a stable tissue pO2 and undisturbed microvascular perfusion, rejecting allografts had a drastic decline in both parameters as well as a flattened epithelium and an increased thickness of the lamina propria. Treatment with everolimus reduced allogeneic fibroproliferation, but had no protective effects on the microvasculature; polymerase chain reaction analysis indicated hypoxic stress and inflammation. Combining everolimus with clopidogrel improved microvascular integrity in the tracheal grafts, but had no synergistic effect in preventing obliterative bronchiolitis development. CONCLUSIONS These data demonstrate that the ability of everolimus to reduce the development of post-transplant obliterative bronchiolitis is not caused by microvascular protection and has no synergistic effects with clopidogrel in acute airway rejection.
TPD Study of Mordenite-Type Zeolites for Selective Catalytic Reduction of NO by NH3

The effect of the adsorption of NO and NH3on catalytic activity has been examined by temperature-programmed desorption over a series of cation-exchanged mordenite catalysts for selective catalytic reduction (SCR) of NO by NH3. The catalytic activity observed in a packed-bed flow reactor was well correlated with the cation content of the catalyst and its adsorption properties, making it possible to elucidate the role of metals and acidity in this reaction system. The amount of NH3and NO adsorbed on the catalyst surface proportionally increased with the degree of cation exchange of the catalyst, especially at the Bronsted acid site (H+) and the metal site (Cu2+). SCR activity also gradually increased with the acidity of the catalyst and/or its degree of catalyst cation exchange. Surface acidity of the mordenite catalysts appears to be a dominant factor in the high performance of the SCR reaction system. The common activation energy is observed to be about 12 kcal/mole for NaHM and CuHM catalysts, independent of their cation content on the catalyst surface. The active sties of this catalytic system are both the Bronsted acid site and the metal site. Furthermore, the reaction occurred in a Langmuir–Hinshewood manner with a dual-site catalysis mechanism.
Survival and Causes of Death Among Veterans With Lower Extremity Revascularization With Paclitaxel‐Coated Devices: Insights From the Veterans Health Administration

BACKGROUND The long‐term safety of paclitaxel‐coated devices (PCDs; drug‐coated balloon or drug‐eluting stent) for peripheral endovascular intervention is uncertain. We used data from the Veterans Health Administration to evaluate the association between PCDs, long‐term mortality, and cause of death. METHODS AND RESULTS Using the Veterans Administration Corporate Data Warehouse in conjunction with International Classification of Diseases, Tenth Revision (ICD‐10) Procedure Coding System, Current Procedural Terminology, and Healthcare Common Procedure Coding System codes, we identified patients with peripheral artery disease treated within the Veterans Administration for femoropopliteal artery revascularization between October 1, 2015, and June 30, 2019. An adjusted Cox regression, using stabilized inverse probability–weighted estimates, was used to evaluate the association between PCDs and long‐term survival. Cause of death data were obtained using the National Death Index. In total, 10 505 patients underwent femoropopliteal peripheral endovascular intervention; 2265 (21.6%) with a PCD and 8240 (78.4%) with a non‐PCD (percutaneous angioplasty balloon and/or bare metal stent). Survival rates at 2 years (77.4% versus 79.7%) and 3 years (70.7% versus 71.8%) were similar between PCD and non‐PCD groups, respectively. The adjusted hazard for all‐cause mortality for patients treated with a PCD versus non‐PCD was 1.06 (95% CI, 0.95–1.18, P=0.3013). Among patients who died between October 1, 2015, and December 31, 2017, the cause of death according to treatment group, PCD versus non‐PCD, was similar. CONCLUSIONS Among patients undergoing femoropopliteal peripheral endovascular intervention within the Veterans Administration Health Administration, there was no increased risk of long‐term, all‐cause mortality associated with PCD use. Cause‐specific mortality rates were similar between treatment groups.
Laboratory safety of dupilumab for up to 3 years in adults with moderate-to-severe atopic dermatitis: results from an open-label extension study

Abstract Background Most systemic agents used for moderate-to-severe atopic dermatitis (AD) may lead to adverse events requiring routine laboratory monitoring, increasing patient burden and possibly decreasing treatment adherence. Objective To evaluate clinical laboratory findings in adults with moderate-to-severe AD treated with dupilumab up to 3 years. Methods LIBERTY AD OLE (NCT01949311) was a phase 3, multicenter, open-label extension study in adults with moderate-to-severe AD receiving dupilumab 300 mg weekly. Results 2,677 patients were treated up to 3 years. No clinically meaningful changes in mean hematology/serum chemistry parameters from baseline were observed. Few laboratory abnormalities were reported as treatment-emergent adverse events. Serious events included one event each of thrombocytopenia, hematuria, and hemolytic anemia, all unrelated to treatment. Abnormalities leading to treatment withdrawal included thrombocytopenia (one patient), increased hepatic enzymes (two patients), and blood creatine phosphokinase increased (one patient). No patients had Grade 3 anemia or Grade 3/4 thrombocytopenia; one patient had Grade 3 neutropenia (Week 100); two patients had Grade 3 eosinophilia (baseline visit); no eosinophil abnormalities were associated with clinically symptomatic events/permanent treatment discontinuation. Conclusion Dupilumab treatment of adults with moderate-to-severe AD up to 3 years showed no clinically meaningful changes in mean laboratory parameters, supporting continuous long-term use without laboratory monitoring. ClinicalTrials.gov identifier NCT01949311 Video Abstract Read the transcript Watch the video on Vimeo
A retrospective evaluation of the treatment of viscerocranial fractures in Romania. A study of 1007 patients.

AIM The treatment of viscerocranial fractures is complex and involves orthopedic, surgical methods, or combinations of both. The aim of this study is to evaluate the treatment methods applied and the type of materials used in the case of viscerocranial fractures in our geographical area, as well as to assess postoperative complications depending on each type of treatment, the location and the characteristics of the fracture lines. MATERIAL AND METHODS A 10-year retrospective statistical analysis of 1007 patients treated in a Romanian university hospital was performed, the data being collected from patients' medical records. RESULTS The most frequent maxillofacial fractures were located in the mandible (62.16%). The zygomatic bone was the most fractured bone of the midface (44.91%). In the majority of the fractures, displacement of the fractured fragments occurred (84.40%). Most of the patients had a favorable evolution (97.8%) Orthopedic/closed treatment was the most frequent treatment applied (78.15%). This was followed by the greatest number of postoperative complications, while ORIF surgical treatment registered the smallest number of complications (p=0.209). The most frequent postoperative complication was osteitis (74.19%). The highest incidence of postoperative complications was found in the case of fractures in multiple locations and displacement of the fractured fragments (p=0.000). CONCLUSIONS The most effective treatment method in the case of maxillofacial fractures is ORIF surgery. The rate of postoperative complications is directly proportional to the number of fracture lines and the degree of bone displacement. KEY WORDS Maxillofacial, Trauma, Treatment.
Chronic Intermittent Mild Whole-Body Hypothermia Is Therapeutic in a Mouse Model of ALS

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes motor neuron degeneration. There are no cures or effective treatments for ALS. Therapeutic hypothermia is effectively used clinically to mitigate mortality in patients with acute acquired brain injury and in surgical settings to minimize secondary brain injury. The efficacy of therapeutic hypothermia in chronic neurodegenerative disorders has not been examined. We tested the hypothesis that mild hypothermia/cold acclimation is therapeutic in a transgenic mouse model of ALS caused by expression of mutated human superoxide dismutase-1 gene. At presymptomatic stages of disease, body temperatures (oral and axial) of mutant male mice were persistently hyperthermic (38–38.5 °C) compared to littermate controls, but at end-stage disease mice were generally hypothermic (36–36.5 °C). Presymptomatic mutant mice (awake-freely moving) were acclimated to systemic mild hypothermia using an environmentally controlled chamber (12 h-on/12-off or 24 h-on/24 h-off) to lower body temperature (1–3 °C). Cooled ALS mice showed a significant delay in disease onset (103–112 days) compared to normothermia mice (80–90 days) and exhibited significant attenuation of functional decline in motor performance. Cooled mice examined at 80 days had reduced motor neuron loss, mitochondrial swelling, and spinal cord inflammation compared to non-cooled mice. Cooling attenuated the loss of heat-shock protein 70, mitochondrial uncoupling protein-3, and sumoylated-1 (SUMO1)-conjugated proteins in skeletal muscle and disengaged the mitochondrial permeability transition pore. Cooled ALS mice had a significant extension of lifespan (148 ± 7 days) compared to normothermic mice (135 ± 4 days). Thus, intermittent systemic mild hypothermia is therapeutic in mouse ALS with protective effects manifested within the CNS and skeletal muscle that target mitochondria.
Crops and the Seed Mass–Seed Output Trade-Off in Plants

Premise of research. A trade-off between seed mass and seed output defines a central axis of ecological variation among plant species. While an observed negative seed mass–seed output relationship is hypothesized to reflect universal constraints on resource allocation in all plants, domestication has likely altered this relationship. Methodology. I use a data set of seed mass and seed output (measured on a per-plant basis) for 41 of the world’s most widespread crops and 1190 wild plant species to evaluate whether and how domestication has influenced seed mass–seed output relationships in crops. I do so by evaluating (i) whether crops differ systematically from wild plants in terms of their position along a seed mass–seed output axis (assessed using standardized major axis regression models) and (ii) whether crops influence the phylogenetic signals in seed mass and seed output observed among plants (assessed using phylogenetic analyses of Pagel’s λ coupled with randomization tests). Pivotal results. Compared with patterns among wild plants, virtually all crops express higher seed mass for a given seed output. This trend is especially pronounced and statistically significant in crops that have been selected for seed production, though the pattern is also pronounced and statistically significant across nonseed crops. The strength of the phylogenetic signal in seed mass and seed output—which is strong and statistically significant across all plants in the data set—was reduced when crops were included in the analyses. Conclusions. Evolved relationships between seed mass and seed output in plants are influenced by both conscious and unconscious artificial selection, such that artificial selection relaxes strong constraints on trait trade-offs within crops as compared with wild plants. These differences represent a key aspect of how the functional biology of crops differs fundamentally from that of wild plants along “universal” plant trait spectra.