Miracle-dz/UniFAR-FTUs huggingface dataset:
ECL cells: biology and pathobiology.

During recent years, the so-called ECL cells of the acid-producing part of the stomach have attracted much attention, mainly due to the fact that mice and rats were found to develop gastric carcinoids (ECL cell tumors) following life-long treatment with blockers of acid secretion. These observations touched off concern about the safety of the long-term clinical use of such drugs. The ECL cells are the predominant endocrine cell population in the oxyntic mucosa. They produce histamine, chromogranin A/pancreastatin and an as yet unidentified peptide hormone. They respond to gastrin by the release of secretory products; more long-term responses include adaptation to the gastrin stimulus, hypertrophy and hyperplasia. Intravenous infusion of maximally effective doses of gastrin promptly reduced the number of cytoplasmic vesicles in the ECL cells and their content of histamine and pancreastatin. Despite the ongoing infusion of gastrin, the number of vesicles and the content of histamine and pancreastatin were back to normal 4-6 h after the start of the infusion. The histidine decarboxylase (HDC) activity and HDC mRNA level increased progressively until plateaus were reached after 6-8 h of gastrin infusion. The size of the ECL cells started to increase about 4 days after the start of a subcutaneous gastrin infusion (resulting in half-maximally effective serum gastrin concentrations). The ECL cell size reached maximum after about 2 weeks and then remained at this level.The number of cytoplasmic vesicles was increased; this effect seemed to reach a maximum after 1-2 weeks. (ABSTRACT TRUNCATED AT 250 WORDS)
Outcomes After Weekend Admission for Deceased Donor Kidney Transplantation: A Population Cohort Study

Background Outcomes for weekend hospital admissions or emergency procedures have become a topical and controversial issue for the UK National Health Service. Deceased-donor kidney transplantation is frequently performed at weekends and evidence for its relative safety are lacking. Methods We undertook a population-based cohort analysis, obtaining data from every deceased-donor kidney-alone transplant procedure performed in England between January 2003 and December 2014. Data were extracted from Hospital Episode Statistics, with linkage to the Office for National Statistics to create a comprehensive dataset for mortality, rehospitalization and kidney allograft failure/rejection for weekend (defined as Friday to Sunday) versus weekday transplantation. Results Data were extracted for 12 902 deceased-donor kidney alone transplants performed in all 19 English transplant centres between 2003 and 2014. Based on initial &khgr;2 tests, no significant difference was observed when comparing weekend versus weekday transplantation in 30-day (0.9% vs 1.2%; P = 0.126) or 1-year mortality (3.7% vs 3.8%; P = 0.788), 1-year kidney allograft failure/rejection (16.7% vs 16.8%; P = 0.897), delayed graft function (29.97% vs 29.36%; P = 0.457) or 1-year risk for readmission (63.5% vs 63.3%; P = 0.774). In a Cox regression model, transplantation at the weekend was not associated with any increased risk for 1-year mortality, rehospitalization, or allograft failure/rejection. Conclusions Deceased-donor kidney transplants performed at the weekend do not have inferior short-term outcomes on the basis of 1-year risk for rehospitalization, mortality, or allograft failure/rejection. Our data are reassuring for patients and professionals alike, but may also provide speculative insight into models of care that attenuate the weekend effect.
Ubiquitylation‐dependent oligomerization regulates activity of Nedd4 ligases

Ubiquitylation controls protein function and degradation. Therefore, ubiquitin ligases need to be tightly controlled. We discovered an evolutionarily conserved allosteric restraint mechanism for Nedd4 ligases and demonstrated its function with diverse substrates: the yeast soluble proteins Rpn10 and Rvs167, and the human receptor tyrosine kinase FGFR1 and cardiac IKS potassium channel. We found that a potential trimerization interface is structurally blocked by the HECT domain α1‐helix, which further undergoes ubiquitylation on a conserved lysine residue. Genetic, bioinformatics, biochemical and biophysical data show that attraction between this α1‐conjugated ubiquitin and the HECT ubiquitin‐binding patch pulls the α1‐helix out of the interface, thereby promoting trimerization. Strikingly, trimerization renders the ligase inactive. Arginine substitution of the ubiquitylated lysine impairs this inactivation mechanism and results in unrestrained FGFR1 ubiquitylation in cells. Similarly, electrophysiological data and TIRF microscopy show that NEDD4 unrestrained mutant constitutively downregulates the IKS channel, thus confirming the functional importance of E3‐ligase autoinhibition.
The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis

Rationale In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain. Objectives To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years. Methods Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records. Measurements and main results Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2–78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years. Conclusions In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age.
Bereaved Siblings’ Advice to Health Care Professionals Working With Children With Cancer and Their Families

Introduction: Siblings of children with cancer experience psychosocial distress during the illness and after bereavement, but often stand outside the spotlight of attention and care. This study explored bereaved siblings’ advice to health care professionals (HCPs) working with children with cancer and their families. Materials and Methods: In a nationwide Swedish survey of bereaved siblings, 174/240 (73%) participated. Of these, 108 answered an open-ended question about what advice they would give to HCPs working with children with cancer and their families. In this study, responses to this single question were analyzed using content analysis. Results: The most common advice, suggested by 56% of siblings, related to their own support. One third suggested giving better medical information to siblings. Some siblings wanted to be more practically involved in their brother’s/sister’s care and suggested that HCPs should give parents guidance on how to involve siblings. Other common advice related to psychosocial aspects, such as the siblings’ wish for HCPs to mediate hope, yet also realism, and the importance of asking the ill child about what care they wanted. Conclusion: Information, communication, and involvement should be emphasized by HCPs to support siblings’ psychosocial needs in both the health care setting and within the family.
Aspectos da geometria complexa das variedades bandeira

Novas familias de metricas invariantes (1,2)-simpleticas sobre F(n), diferentes das de Kahler e das parabolicas, sao estudadas. Mais precisamente, para cada n maior ou igual a 5 sao caracterizadas n - 3 familias n-dimensionais distintas de metricas ir-variantes (1,2)-simpleticas. Cada uma destas familias corresponde a uma classe de estructuras quase-complexas invariantes distintas sobre F( n). Os casos das variedades F(5), F(6) e F(7) sao estudados completamente. Obtem-se as seguintes familias de metricas (1,2)-simpleticas distintas das de Kahler e das parabolicas: Em F(5), 2 familias 5-parametricasj em F(6), 4 familias 6-parametricas, das quais duas generalizam as mencionadas para F(5) e em F(7), 8 familias 7-parametricas, das quais 4 generalizam as 4 familias mencionadas para F( 6). Estas metricas sao usadas para produzir novos exemplos de aplicacoes harmonicas φ M2- F(n), aplicandoum conhecidoTeorema de Lichnerowicz. Finalmente, usando resultados de Negreiros estudamos a estabilidade destas aplicacoes harmonicas. Abstract
Recent advances in understanding clonal haematopoiesis in aplastic anaemia

Acquired aplastic anaemia (AA) is an immune‐mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic mutations and/or structural chromosomal abnormalities detected as early as at diagnosis. In contrast to other conditions linked to clonal haematopoiesis, the clonal signature of AA reflects its immune pathophysiology. The most common alterations are clonal expansions of cells lacking glycophosphotidylinositol‐anchored proteins, loss of human leucocyte antigen alleles, and mutations in BCOR/BCORL1, ASXL1 and DNMT3A. Here, we present the current knowledge of clonal haematopoiesis in AA as it relates to aging, inherited bone marrow failure, and the grey‐zone overlap of AA and myelodysplastic syndrome (MDS). We conclude by discussing the significance of clonal haematopoiesis both for improved diagnosis of AA, as well as for a more precise, personalized approach to prognostication of outcomes and therapy choices.
Executive Function in Patients with Remitted Bipolar Disorder and Schizophrenia and Its Relationship with Functional Outcome

Background: Recent studies have reported that differences in cognitive performance between schizophrenic and bipolar patients seem to be smaller than expected. Patients with schizophrenia have consistently shown frontal executive dysfunctions, but studies regarding executive abilities in bipolar patients are scarce and discrepant. As executive function has been associated with psychosocial functioning in schizophrenia, we wanted to investigate if such a relationship is also present in bipolar disorder and the differences between the two groups. Methods: Executive function was assessed in 49 euthymic (at least 6 months in remission, Hamilton Depression Rating Scale ≤8 and Young Mania Rating Scale ≤6) bipolar and in 49 schizophrenic, residual-type (with at least 1 year without acute exacerbation and predominant negative symptomatology) patients, by the Wisconsin Card Sorting Test (WCST), FAS Test (COWAT) and Trail Making Test. Baseline clinical and psychosocial variables were controlled and psychopathology evaluated by means of the Positive and Negative Syndrome Scale (PANSS). Results: The two groups showed a similar pattern of cognitive deficits in tests of executive function, except for the number of categories achieved in the WCST, which was significantly lower in the schizophrenic group (F = 7.26; p = 0.009). Functional outcome was predicted by the negative syndrome (PANSSN) and perseverative errors (WCST) in schizophrenic patients, and general psychopathology (PANSSG) was the best predictor of functional outcome in the bipolar group. Conclusion: Executive function was a good predictor of functional outcome in the schizophrenic group, whereas clinical variables were more predictive of the bipolar one. Patterns of cognitive disturbances in tasks of executive function are similar in both groups but quantitatively more marked in schizophrenia.
Development and evaluation of an experimental protocol for 3-D visualization and characterization of the structure of bacterial biofilms in porous media using laboratory X-ray tomography

Abstract The development of a reliable model allowing accurate predictions of biofilm growth in porous media relies on a good knowledge of the temporal evolution of biofilm structure within the porous network. Since little is known about the real 3-D structure of biofilms in porous media, this work was aimed at developing a new experimental protocol to visualize the 3-D microstructure of the inside of a porous medium using laboratory X-ray microtomography. A reliable and reproducible methodology is proposed for (1) growing a biofilm inside a porous medium, and (2) X-ray tomography-based characterization of the temporal development of the biofilm at the inlet of the biofilter. The statistical analysis proposed here also validates the results presented in the literature based on a biofilm structure single measurement.
Evaluation of a CAT Database and Expert Appraisal of CATs Developed by Students.

Five steps have been recommended to provide evidence-based patient care: formulating a clinical question, searching for literature, evaluating the validity and applicability of results, implementing results into practice, and assessing if the new evidence has led to improved health care. Students can be trained in these steps by the development of knowledge summaries such as critically appraised topics (CATs). The aim of the present project was the development, use, and evaluation of a German-language CAT database and an appraisal of the quality of CATs developed by students. A total of 153 fifth-year veterinary medical students (in 21 groups) were enrolled in the project. Each group developed a CAT and most students participated in a survey. To learn more about the quality of the CATs, we asked experts to appraise the texts written by the students. The CATs were indexed with key words and assigned to specific fields corresponding to the European Colleges of Veterinary Specialisation. Currently, 57 CATs have been developed. The majority of students stated that writing CATs is a good exercise and that "it is important to teach the assessment of scientific information. " In total, 13 experts completed the questionnaires, out of which 9 graded the CAT they appraised as good. In addition to English-language CAT databases, German tools should also be available for students and practitioners.
Neuronal control of astrocytic respiration through a variant of the Crabtree effect

Significance Neuronal activity is immediately followed by aerobic glycolysis, the partial oxidation of glucose to lactate in the presence of oxygen, a phenomenon that seems paradoxical because full oxidation of glucose to CO2 would yield much more ATP. Here we show that short-term aerobic glycolysis involves a mechanism whereby neurons obtain oxygen by manipulating the glucose metabolism and mitochondrial respiration of neighboring astrocytes. Aerobic glycolysis is a phenomenon that in the long term contributes to synaptic formation and growth, is reduced by normal aging, and correlates with amyloid beta deposition. Aerobic glycolysis starts within seconds of neural activity and it is not obvious why energetic efficiency should be compromised precisely when energy demand is highest. Using genetically encoded FRET nanosensors and real-time oxygen measurements in culture and in hippocampal slices, we show here that astrocytes respond to physiological extracellular K+ with an acute rise in cytosolic ATP and a parallel inhibition of oxygen consumption, explained by glycolytic stimulation via the Na+-bicarbonate cotransporter NBCe1. This control of mitochondrial respiration via glycolysis modulation is reminiscent of a phenomenon previously described in proliferating cells, known as the Crabtree effect. Fast brain aerobic glycolysis may be interpreted as a strategy whereby neurons manipulate neighboring astrocytes to obtain oxygen, thus maximizing information processing.
Improved In Vivo Subcutaneous Tumor Generation by Cancer Cell Sheet Transplantation.

BACKGROUND/AIM In vivo subcutaneous tumor models are generally prepared by the injection of a cancer cell suspension to evaluate the pharmaceutical effects on tumor tissues. However, dispersed cells show low biological activities because of enzyme-induced cell harvest treatment, thus limiting the formation of tumor tissues. In this study, a biologically active cancer cell monolayer (cell sheet) was used to improve the efficiency of subcutaneous tumor formation. MATERIALS AND METHODS Mouse lung squamous cancer cells (KLN-205) were transplanted on the subcutis of immunocompetent and immunodeficient mice in the form of a dispersed cell suspension or cell sheet, and the tumor formation abilities were independently investigated with considering immunological effects. RESULTS Mouse lung squamous cancer cells (KLN-205) scarcely formed malignant tumors on the mouse subcutis following injection of the cell suspension. On the other hand, cell transplantation in the cell sheet form successfully achieved effective tumor development due to only weak immunological reactions at the transplanted area. And thus, the cancer cells maintained their proliferative activity to form tumors. CONCLUSION Transplantation of the cell sheet is effective to generate subcutaneous tumor-bearing mice, providing a useful alternative to the low tumor formation activities induced with the conventional injection method.
Preparation of umami octopeptide with recombined Escherichia coli: Feasibility and challenges

ABSTRACT The taste of umami peptide H-Lys-Gly-Asp-Glu-Glu-Ser-Leu-Ala-OH (LGAGGSLA) is controversial. One possible reason for this controversy is the use of chemically synthesized LGAGGSLA to confirm its taste. To explore other ways to further confirm the flavor of LGAGGSLA, we developed a new strategy to prepare a bio-source peptide by adopting a gene engineering method to express LGAGGSLA in recombinant Escherichia coli. In our previous work, we structured the LGAGGSLA recombinant expression system and optimized the culturing conditions for preparing a fusion protein. However, the fusion protein was not cleaved by enterokinase to obtain LGAGGSLA. Because the cleavage conditions of commercial enterokinase were not specific and recombinant engineered bacteria had the potential to be used in industrial processes, in this addendum, we calculated the mass and volume yields of key processing steps in the preparation of LGAGGSLA, and established a model of cleavage conditions with the cleavage ratio of LGAGGSLA. When the LGAGGSLA was confirmed to show umami taste, it is considered as a new umami or umami enhancer. The gene information of LGAGGSLA should have a great potential in the development of new flavor product and food product containing high umami flavor.
Jaundice and xanthochromia of the spinal fluid.

Abstract Measurements of serum and spinal fluid bilirubin from twenty jaundiced patients are presented. Detectable amounts were present in the spinal fluid in every case, including those with jaundice of recent onset. The relationship between serum and spinal fluid bilirubin in our cases is discussed, as well as the clinical implications of the data.
Lateralization of Minicolumns in Human Planum temporale Is Absent in Nonhuman Primate Cortex

Gross analyses of large brain areas, as in MRI studies of macroanatomical structures, average subtle alterations in small regions, inadvertently missing significant anomalies. We developed a computerized imaging program to microscopically examine minicolumns and used it to study Nissl-stained slides of normal human, chimpanzee, and rhesus monkey brains in a region of the planum temporale. With this method, we measured the width of cell columns, the peripheral neuropil space, the spacing density of neurons within columns, and the Gray Level index per minicolumn. Only human brain tissue revealed robust asymmetry in two aspects of minicolumn morphology: wider columns and more neuropil space on the left side. This asymmetry was absent in chimpanzee and rhesus monkey brains.
Long‐term risk of diabetes in women at varying durations after gestational diabetes: a systematic review and meta‐analysis with more than 2 million women

This study aims to investigate the impact of gestational diabetes mellitus (GDM) on the long‐term risks of diabetes in women with prior GDM, including the effect at different time periods after GDM. We searched PubMed and other databases to retrieve articles which were published prior to February 28, 2017. Cohort studies which evaluated the risk and time of onset of diabetes postpartum in women with and without GDM were included. Meta‐analysis with random effects models was used to obtain pooled relative risks and 95% confidence intervals for the risk of diabetes. Subgroup analyses were performed to check for different effect sizes as well as consistency across groups. Multivariable logistic regression was used to adjust for confounders. Thirty cohort studies with 2,626,905 pregnant women were included. Women with prior GDM had 7.76‐fold (95% confidence intervals: 5.10–11.81) unadjusted pooled risk of diabetes as compared with women without GDM, whilst the adjusted risk was 17.92‐fold (16.96–18.94). The adjusted ORs of GDM for diabetes among women at <3, ≥3 – <6 and ≥6 – <10 years after GDM were 5.37 (3.51–9.34), 16.55 (16.08–17.04) and 8.20 (4.53–14.86), respectively. Women with prior GDM had substantially increased risk of diabetes, with the risk highest during the 3–6 years after GDM.
The TOP-SCOPE Survey of Planck Galactic Cold Clumps: Survey Overview and Results of an Exemplar Source, PGCC G26.53+0.17

The low dust temperatures (<14 K) of Planck Galactic cold clumps (PGCCs) make them ideal targets to probe the initial conditions and very early phase of star formation. “TOP-SCOPE” is a joint survey program targeting ∼2000 PGCCs in J = 1–0 transitions of CO isotopologues and ∼1000 PGCCs in 850 μm continuum emission. The objective of the “TOP-SCOPE” survey and the joint surveys (SMT 10 m, KVN 21 m, and NRO 45 m) is to statistically study the initial conditions occurring during star formation and the evolution of molecular clouds, across a wide range of environments. The observations, data analysis, and example science cases for these surveys are introduced with an exemplar source, PGCC G26.53+0.17 (G26), which is a filamentary infrared dark cloud (IRDC). The total mass, length, and mean line mass (M/L) of the G26 filament are ∼6200 M☉, ∼12 pc, and ∼500 M☉ pc−1, respectively. Ten massive clumps, including eight starless ones, are found along the filament. The most massive clump as a whole may still be in global collapse, while its denser part seems to be undergoing expansion owing to outflow feedback. The fragmentation in the G26 filament from cloud scale to clump scale is in agreement with gravitational fragmentation of an isothermal, nonmagnetized, and turbulent supported cylinder. A bimodal behavior in dust emissivity spectral index (β) distribution is found in G26, suggesting grain growth along the filament. The G26 filament may be formed owing to large-scale compression flows evidenced by the temperature and velocity gradients across its natal cloud.