Miracle-dz/UniFAR-FTUs huggingface dataset:
Ataxia‐telangiectasia: A review of clinical features and molecular pathology

Ataxia‐telangiectasia (A‐T) is an autosomal recessive primary immunodeficiency (PID) disease that is caused by mutations in ataxia‐telangiectasia mutated (ATM) gene encoding a serine/threonine protein kinase. A‐T patients represent a broad range of clinical manifestations including progressive cerebellar ataxia, oculocutaneous telangiectasia, variable immunodeficiency, radiosensitivity, susceptibility to malignancies, and increased metabolic diseases. This congenital disorder has phenotypic heterogeneity, and the severity of symptoms varies in different patients based on severity of mutations and disease progression. The principal role of nuclear ATM is the coordination of cellular signaling pathways in response to DNA double‐strand breaks, oxidative stress, and cell cycle checkpoint. The pathogenesis of A‐T is not limited to the role of ATM in the DNA damage response (DDR) pathway, and it has other functions mainly in the hematopoietic cells and neurons. ATM adjusts the functions of organelles such as mitochondria and peroxisomes and also regulates angiogenesis and glucose metabolisms. However, ATM has other functions in the cells (especially cell viability) that need further investigations. In this review, we described functions of ATM in the nucleus and cytoplasm, and also its association with some disorder formation such as neurologic, immunologic, vascular, pulmonary, metabolic, and dermatologic complications.
Pattern of FDG and MET Distribution in High- and Low-Grade Gliomas on PET Images

Purpose of the Report This study aimed to determine the most effective metabolic index of FDG-PET and MET-PET to differentiate high- and low-grade gliomas, and then to characterize tumor metabolism according to the 2016 WHO classification. We also developed a new calculation method of potential infiltrative tumor volume to overcome the current limitations of tumor evaluation according to metabolic index, which focuses solely on tumor core area. Materials and Methods Patients who underwent both FDG-PET and MET-PET, as well as surgical treatment, were retrospectively identified. All tumors were diagnosed histologically and included 44 high-grade and 19 low-grade gliomas. Metabolic indices of tumor-to-normal (T/N) ratio and maximum value within the tumor itself were compared between high- and low-grade tumors. A calculation method for potential infiltrative tumor volume was developed and compared between these 2 grades. Results T/N, calculated as tumor value divided by normal cortex value, was the most effective (area under the curve, 0.800 for FDG-PET; area under the curve, 0.773 for MET-PET) for differentiating high- and low-grade gliomas. Potential infiltrative volume effectively distinguished between high- and low-grade glioma (43.8 ± 30.2 mL vs 14.0 ± 12.6 mL; P = 0.005 [t test]). A combination of T/N, with a cutoff value of 0.9 or higher on FDG-PET and/or 3.0 or higher on MET-PET, and potential infiltrative volume, with a cutoff value of 20.0 mL or higher, provided a diagnostic accuracy of 89% in distinguishing high- from low-grade gliomas. Conclusions Evaluation of potential infiltrative volume surrounding the tumor core area, in addition to the T/N ratio of the tumor core, may help distinguish between high- and low-grade gliomas.
Complement inhibition as a therapeutic strategy in retinal disorders

ABSTRACT Introduction: Dry age-related macular degeneration (AMD) and Stargardt Macular Dystrophy (STGD1) result in vision loss due to progressive atrophy of the macula and lack of effective treatments. Numerous studies have implicated complement-associated inflammation as a contributor to both diseases. Areas covered: The complement factor D inhibitor, lampalizumab, failed to halt geographic atrophy (GA) progression in phase 3 studies. The complement factor 3 (C3) inhibitor, APL-2, has shown potential to reduce GA growth in a phase 2 trial, supporting advancement to phase 3 trials. The intravenous complement factor 5 (C5) inhibitor, eculizumab, failed to halt GA progression in a phase 2 study. Another C5 inhibitor, avacincaptad pegol, is delivered by intravitreal injection, and will be studied for safety and preliminary signs of efficacy for AMD and STGD1 patients in phase 2 trials. LFG316 (C5 inhibitor) and CLG561 (properdin inhibitor) failed to halt GA progression in phase 2 studies. A phase 1 trial is evaluating the effects of combining LFG316 and CL561. Complement inhibition by gene therapy will be explored in the phase 1 trial of HMR59 in AMD patients. Expert opinion: While complement inhibition has not yet demonstrated the ability to halt GA progression in a phase 3 trial, further study is warranted.
Ectomycorrhizal fungi and soil enzymes exhibit contrasting patterns along elevation gradients in southern Patagonia.

The biological and functional diversity of ectomycorrhizal (ECM) associations remain largely unknown in South America. In Patagonia, the ECM tree Nothofagus pumilio forms monospecific forests along mountain slopes without confounding effects of vegetation on plant-fungi interactions. To determine how fungal diversity and function are linked to elevation, we characterized fungal communities, edaphic variables, and eight extracellular enzyme activities along six elevation transects in Tierra del Fuego (Argentina and Chile). We also tested whether pairing ITS1 rDNA Illumina sequences generated taxonomic biases related to sequence length. Fungal community shifts across elevations were mediated primarily by soil pH with the most species-rich fungal families occurring mostly within a narrow pH range. By contrast, enzyme activities were minimally influenced by elevation but correlated with soil factors, especially total soil carbon. The activity of leucine aminopeptidase was positively correlated with ECM fungal richness and abundance, and acid phosphatase was correlated with nonECM fungal abundance. Several fungal lineages were undetected when using exclusively paired or unpaired forward ITS1 sequences, and these taxonomic biases need reconsideration for future studies. Our results suggest that soil fungi in N. pumilio forests are functionally similar across elevations and that these diverse communities help to maintain nutrient mobilization across the elevation gradient.
Clinicopathologic features of incidental meningiomas: A review of the literature and the University of Rochester autopsy experience.

OBJECTIVE Features of incidental meningiomas, found at autopsy, have not been extensively reported and may offer insight into their biology and management. DESIGN Review of the literature on unsuspected incidental antemortem and postmortem meningiomas and those from autopsies, at the University of Rochester from 2005 to 2016. RESULTS At autopsy, incidental meningiomas were usually found in 2 - 3% of cases. Incidental meningiomas found by neuroimaging were more commonly seen over the convexities, although our findings suggest that parasellar meningiomas are common. They are and are more commonly in males, WHO grade I, and fibrous or meningothelial, but our findings suggest psammomatous meningiomas are over-represented. CONCLUSION Incidental meningiomas are a relatively common unrecognized tumor. They are more likely to be in males, WHO grade I, parasellar, and with calcification.
The detrimental effects of lipopolysaccharide-induced neuroinflammation on adult hippocampal neurogenesis depend on the duration of the pro-inflammatory response

Adult hippocampal neurogenesis is a finely tuned process regulated by extrinsic factors. Neuroinflammation is a hallmark of several pathological conditions underlying dysregulation of neurogenesis. In animal models, lipopolysaccharide (LPS)-induced neuroinflammation leads to a neurogenic decrease mainly associated to the early inflammatory response. However, it is not well understood how the neuroinflammatory response progresses over time and if neurogenesis continues to be diminished during the late neuroinflammatory response. Moreover, it is unknown if repeated intermittent administration of LPS along time induces a greater reduction in neurogenesis. We administered one single intraperitoneal injection of LPS or saline or four repeated injections (one per week) of LPS or saline to young-adult mice. A cohort of new cells was labeled with three 5-bromo-2-deoxyuridine injections (one per day) 4 days after the last LPS injection. We evaluated systemic and neuroinflammation-associated parameters and compared the effects of the late neuroinflammatory response on neurogenesis induced by each protocol. Our results show that 1) a single LPS injection leads to a late pro-inflammatory response characterized by microglial activation, moderate astrocytic reaction and increased interleukin-6 levels. This response correlates in time with decreased neurogenesis and 2) a repeated intermittent injection of LPS does not elicit a late pro-inflammatory response although activated microglia persists. The latter profile is not accompanied by a continued long-term hippocampal neurogenic decrease. Hereby, we provide evidence that the neuroinflammatory response is a dynamic process that progresses in a milieu-dependent manner and does not necessarily lead to a neurogenic decrease, highlighting the complex interaction between the immune system and neurogenesis.
Lignocellulosic biomass for bioethanol: an overview on pretreatment, hydrolysis and fermentation processes

Abstract Bioethanol is currently the only alternative to gasoline that can be used immediately without having to make any significant changes in the way fuel is distributed. In addition, the carbon dioxide (CO2) released during the combustion of bioethanol is the same as that used by the plant in the atmosphere for its growth, so it does not participate in the increase of the greenhouse effect. Bioethanol can be obtained by fermentation of plants containing sucrose (beet, sugar cane…) or starch (wheat, corn…). However, large-scale use of bioethanol implies the use of very large agricultural surfaces for maize or sugarcane production. Lignocellulosic biomass (LCB) such as agricultural residues for the production of bioethanol seems to be a solution to this problem due to its high availability and low cost even if its growth still faces technological difficulties. In this review, we present an overview of lignocellulosic biomass, the different methods of pre-treatment of LCB and the various fermentation processes that can be used to produce bioethanol from LCB.
Study on Tooth Movement After the Alveolar Bone Grafting in Patients With Unilateral Cleft Lip and Palate.

OBJECTIVES The aim of the study was to explore the effectiveness of the cleft-adjacent teeth moved into the grafted alveolar bone in unilateral cleft lip and palate (UCLP) patients, and to evaluate the alveolar bone support of the teeth. METHODS Twenty unilateral cleft lip and palate patients were recruited in this study. The average age was 12 years and 8 months. Periapical radiographs were taken for the cleft-adjacent teeth 3 months after bone grafting (T1) and after teeth moving into the grafted bone (T2), and for the contralateral teeth (T3) when teeth aligned. Alveolar bone support of the moved teeth and the contralateral teeth were measured using the ratio of bone support height to root length. Paired t test was performed for statistical analysis with SPSS17.0 software package. RESULTS All the cleft-adjacent teeth were bodily moved into the grafted area. Average alveolar bone support ratio for the moved teeth was 86.48% (T1), 87.11% (T2), and 90.81% (T3) for the contralateral teeth. There was no statistically significant difference between T1 and T2 (P > 0.05). Although the contralateral teeth had the highest alveolar bone support ratio, significant differences were found between T3 and T2 (P < 0.05). CONCLUSIONS Cleft-adjacent teeth could be bodily moved into the grafted bone from the iliac crest in UCLP patients. A successful level of alveolar bone support for the moved teeth was achieved. Moved-in teeth could be functionally loaded and may be benefit to the reduction of the resorption of grafted bone.
Association of Antibiotic Treatment With Outcomes in Patients Hospitalized for an Asthma Exacerbation Treated With Systemic Corticosteroids

Importance Although professional society guidelines discourage use of empirical antibiotics in the treatment of asthma exacerbation, high antibiotic prescribing rates have been recorded in the United States and elsewhere. Objective To determine the association of antibiotic treatment with outcomes among patients hospitalized for asthma and treated with corticosteroids. Design, Setting, and Participants Retrospective cohort study of data of 19 811 adults hospitalized for asthma exacerbation and treated with systemic corticosteroids in 542 US acute care hospitals from January 1, 2015, through December 31, 2016. Exposures Early antibiotic treatment, defined as an treatment with an antibiotic initiated during the first 2 days of hospitalization and prescribed for a minimum of 2 days. Main Outcomes and Measures The primary outcome measure was hospital length of stay. Other measures were treatment failure (initiation of mechanical ventilation, transfer to the intensive care unit after hospital day 2, in-hospital mortality, or readmission for asthma) within 30 days of discharge, hospital costs, and antibiotic-related diarrhea. Multivariable adjustment, propensity score matching, propensity weighting, and instrumental variable analysis were used to assess the association of antibiotic treatment with outcomes. Results Of the 19 811 patients, the median (interquartile range [IQR]) age was 46 (34-59) years, 14 389 (72.6%) were women, 8771 (44.3%) were white, and Medicare was the primary form of health insurance for 5120 (25.8%). Antibiotics were prescribed for 8788 patients (44.4%). Compared with patients not treated with antibiotics, treated patients were older (median [IQR] age, 48 [36-61] vs 45 [32-57] years), more likely to be white (48.6% vs 40.9%) and smokers (6.6% vs 5.3%), and had a higher number of comorbidities (eg, congestive heart failure, 6.2% vs 5.8%). Those treated with antibiotics had a significantly longer hospital stay (median [IQR], 4 [3-5] vs 3 [2-4] days) and a similar rate of treatment failure (5.4% vs 5.8%). In propensity score–matched analysis, receipt of antibiotics was associated with a 29% longer hospital stay (length of stay ratio, 1.29; 95% CI, 1.27-1.31) and higher cost of hospitalization (median [IQR] cost, $4776 [$3219-$7373] vs $3641 [$2346-$5942]) but with no difference in the risk of treatment failure (propensity score–matched OR, 0.95; 95% CI, 0.82-1.11). Multivariable adjustment, propensity score weighting, and instrumental variable analysis as well as several sensitivity analyses yielded similar results. Conclusions and Relevance Antibiotic therapy may be associated with a longer hospital length of stay, higher hospital cost, and similar risk of treatment failure. These results highlight the need to reduce inappropriate antibiotic prescribing among patients hospitalized for asthma.
Pattern of nitrergic cells and fibers organization in the central nervous system of the Australian lungfish, Neoceratodus forsteri (Sarcopterygii: Dipnoi)

The Australian lungfish Neoceratodus forsteri is the only extant species of the order Ceratodontiformes, which retained most of the primitive features of ancient lobe finned‐fishes. Lungfishes are the closest living relatives of land vertebrates and their study is important for deducing the neural traits that were conserved, modified, or lost with the transition from fishes to land vertebrates. We have investigated the nitrergic system with neural nitric oxide synthase (NOS) immunohistochemistry and NADPH‐diaphorase (NADPH‐d) histochemistry, which yielded almost identical results except for the primary olfactory projections and the terminal and preoptic nerve fibers labeled only for NADPH‐d. Combined immunohistochemistry was used for simultaneous detection of NOS with catecholaminergic, cholinergic, and serotonergic structures, aiming to establish accurately the localization of the nitrergic elements and to assess possible interactions between these neurotransmitter systems. The results demonstrated abundant nitrergic cells in the basal ganglia, amygdaloid complex, preoptic area, basal hypothalamus, mesencephalic tectum and tegmentum, laterodorsal tegmental nucleus, reticular formation, spinal cord, and retina. In addition, low numbers of nitrergic cells were observed in the olfactory bulb, all pallial divisions, lateral septum, suprachiasmatic nucleus, prethalamic and thalamic areas, posterior tubercle, pretectum, torus semicircularis, cerebellar nucleus, interpeduncular nucleus, the medial octavolateral nucleus, nucleus of the solitary tract, and the dorsal column nucleus. Colocalization of NOS and tyrosine hydroxylase was observed in numerous cells of the ventral tegmental area/substantia nigra complex. Comparison with other vertebrates, using a neuromeric analysis, reveals that the nitrergic system of Neoceratodus shares many neuroanatomical features with tetrapods and particularly with amphibians.
Obstructive sleep apnoea and cardiovascular comorbidity-growing evidence of independent association but recent doubts about benefits from therapy.

Obstructive sleep apnoea (OSA) is highly prevalent, affecting up to 50% of the adult male general population (1) and is strongly associated with co-morbidity, especially cardiovascular (2). While the evidence that many co-morbidities such as cardiovascular, metabolic, hepatic, and malignancy are more prevalent in OSA, the evidence of independent association is less clear (3).
Synthesis, Anticancer Evaluation and Synergistic Effects with cisplatin of Novel Palladium Complexes: DNA, BSA Interactions and Molecular Docking Study.

BACKGROUND In order to discover new agents for chemotherapy with improved properties related to existing and bearing in mind the fact that some Pd complexes possess better antitumor activity and exhibit less kidney toxicity comparing to cisplatin, series of novel square-planar palladium(II) complexes [Pd (L)2] (3a-f) with O,O bidentate ligands [L = ethyl 2-hydroxy-alkyl(aryl)-4-oxo-2-butenoate] were synthesized. METHODS All complexes were characterized by spectral (UV-Vis, IR, NMR, ESI-MS) and X-ray analysis and examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Fluorescence spectroscopic method was used for investigations of the interactions between CT-DNA or bovine serum albumin (BSA) and complex 3c. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and complex 3c. RESULTS Complexes that showed best results, 3c, 3d, and 3e, were placed under further investigations. Selected complexes induced apoptosis and cell cycle arrest in HeLa and MDA-MB 231 cells. Low concentrations of 3c and 3e showed strong to moderate synergism with low concentrations of cisplatin. The interaction of 3d with cisplatin was antagonistic in all used concentrations, but low IC50 value indicates its' usefulness as a single cytotoxic agent. It was also noted that the change of viscosity is more pronounced in DNA solution after addition of complex 3c. CONCLUSION Obtained results indicate that the novel palladium(II) complexes have the potential to become candidates for treatment in anticancer therapy.
Which clinical and sociodemographic determinants are associated with self-perceived manual ability at one year after stroke?

Abstract Purpose: To evaluate the impact of multiple potential sociodemographic and clinical stroke-related determinants on self-perceived manual ability in an unselected sample of individuals 12 months after first-ever stroke. Methods: A cross-sectional sample of 68 participants (mean age 66) with UE impairments were followed up at 12 months post stroke. Stroke severity at onset was moderate for the majority. Manual ability was assessed by the patient-reported outcome measure ABILHAND Questionnaire. Determinants included in the multivariate regression analysis were age, gender, living situation, vocational situation, affected hand, stroke severity at onset and UE disability (motor function, sensory function, joint motion, pain, grip strength, spasticity and activity capacity) at 12 months post stroke. Results: The strongest associated determinants with self-perceived manual ability were UE motor function and UE activity capacity at 12 months post-stroke. UE motor function together with age and grip strength explained 65% of the variance in one final multivariate model. UE activity capacity and grip strength explained 62% of the variance in a second final model. Conclusion: In order to understand self-perceived difficulties in manual ability in daily activities in persons with stroke, assessments of UE motor function and activity capacity are recommended. Implications for rehabilitation The ultimate goal of the upper extremity rehabilitation after stroke is to regain ability to use the UE in daily activities that are important to the individual in his or her own environment. This requires a good understanding of factors that are associated with self-perceived manual ability in order to tailor effective rehabilitation interventions. Upper extremity motor function and activity capacity are the strongest determinants associated with self-perceived manual ability one year after stroke. These factors are recommended to be included in the assessment battery in stroke to fully understand the disability in daily life.
mzTab-M: A Data Standard for Sharing Quantitative Results in Mass Spectrometry Metabolomics

Mass spectrometry (MS) is one of the primary techniques used for large-scale analysis of small molecules in metabolomics studies. To date, there has been little data format standardization in this field, as different software packages export results in different formats represented in XML or plain text, making data sharing, database deposition, and reanalysis highly challenging. Working within the consortia of the Metabolomics Standards Initiative, Proteomics Standards Initiative, and the Metabolomics Society, we have created mzTab-M to act as a common output format from analytical approaches using MS on small molecules. The format has been developed over several years, with input from a wide range of stakeholders. mzTab-M is a simple tab-separated text format, but importantly, the structure is highly standardized through the design of a detailed specification document, tightly coupled to validation software, and a mandatory controlled vocabulary of terms to populate it. The format is able to represent final quantification values from analyses, as well as the evidence trail in terms of features measured directly from MS (e.g., LC-MS, GC-MS, DIMS, etc.) and different types of approaches used to identify molecules. mzTab-M allows for ambiguity in the identification of molecules to be communicated clearly to readers of the files (both people and software). There are several implementations of the format available, and we anticipate widespread adoption in the field.