bluuebunny/crossref_metadata_2025_split huggingface dataset:
Driver mutations in USP8 wild-type Cushing’s disease
Authors: Sbiera Silviu , Perez-Rivas Luis Gustavo , Taranets Lyudmyla , Weigand Isabel , Flitsch Jörg , Graf Elisabeth , Monoranu Camelia-Maria , Saeger Wolfgang , Hagel Christian , Honegger Jürgen , Assie Guillaume , Hermus Ad R , Stalla Günter K , Herterich Sabine , Ronchi Cristina L , Deutschbein Timo , Reincke Martin , Strom Tim M , Popov Nikita , Theodoropoulou Marily , Fassnacht Martin 
Published: June 2019

Abstract

Background
Medical treatment in Cushing’s disease (CD) is limited due to poor understanding of its pathogenesis. Pathogenic variants of ubiquitin specific peptidase 8 (USP8) have been confirmed as causative in around half of corticotroph tumors. We aimed to further characterize the molecular landscape of those CD tumors lacking USP8 mutations in a large cohort of patients.

Methods
Exome sequencing was performed on 18 paired tumor–blood samples with wild-type USP8 status. Candidate gene variants were screened by Sanger sequencing in 175 additional samples. The most frequent variant was characterized by further functional in vitro assays.

Results
Recurrent somatic hotspot mutations in another deubiquitinase, USP48, were found in 10.3% of analyzed samples. Several possibly damaging variants were found in TP53 in 6 of 18 samples. USP48 variants were associated with smaller tumors and trended toward higher frequency in female patients. They also changed the structural conformation of USP48 and increased its catalytic activity toward its physiological substrates histone 2A and zinc finger protein Gli1, as well as enhanced the stimulatory effect of corticotropin releasing hormone (CRH) on pro-opiomelanocortin production and adrenocorticotropic hormone secretion.

Conclusions
USP48 pathogenic variants are relatively frequent in USP8 wild-type tumors and enhance CRH-induced hormone production in a manner coherent with sonic hedgehog activation. In addition, TP53 pathogenic variants may be more frequent in larger CD tumors than previously reported.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Pediatric Myelomeningocele: Executive Summary
Authors: Mazzola Catherine A , Assassi Nadege , Baird Lissa C , Bauer David F , Beier Alexandra D , Blount Jeffrey P , Durham Susan R , Flannery Ann Marie , Klimo Paul , McClung-Smith Catherine , Nikas Dimitrios C , Rehring Patricia , Tamber Mandeep S , Tyagi Rachana 
Published: June 2019

Abstract

BACKGROUND
The incidence of spina bifida (SB) in the developing world is higher than in the United States because of malnutrition and folic acid deficiency during pregnancy. Advances in technology have made prenatal repair of myelomeningocele (MM) possible.

OBJECTIVE
The objective of the guidelines are, (1) To create clinical recommendations for best practices, based on a systematic review and analysis of available literature, (2) to obtain multi-disciplinary endorsement of these guidelines from relevant organizations, and (3) to disseminate the educational content to physicians to improve the care of infants with MM.

METHODS
The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review.

RESULTS
Guidelines authors aimed to systematically review the literature and make evidence based recommendations about the timing of closure after birth, hydrocephalus, the impact of prenatal closure, and the effect of prenatal closure on ambulation ability and tethered spinal cord. Evidence concerning persistent ventriculomegaly and cognitive impairment was also evaluated. Hundreds of abstracts were identified and reviewed for each of the 5 topics. A total of 14 studies met stringent inclusion criteria.

CONCLUSION
Based on a comprehensive systematic review, a total of 5 clinical practice recommendations were developed, with 1 Level I, 2 Level II and 2 Level III recommendations.
The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-1.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Incidence of Tethered Cord Syndrome in Infants With Myelomeningocele With Prenatal Versus Postnatal Repair
Authors: Mazzola Catherine A , Tyagi Rachana , Assassi Nadege , Bauer David F , Beier Alexandra D , Blount Jeffrey P , Durham Susan R , Flannery Ann Marie , Klimo Jr Paul , McClung-Smith Catherine , Nikas Dimitrios C , Rehring Patricia , Tamber Mandeep S 
Published: June 2019

Abstract

BACKGROUND
The incidence of spina bifida (SB) is higher in the developing world as compared to the United States because of folic acid deficiency during pregnancy. Advances in technology have made prenatal repair of myelomeningocele (MM) possible.

OBJECTIVE
The objective of this guideline was to determine if there is a difference in the rate of development of tethered cord syndrome (TCS) in infants who had prenatal closure compared to infants who had MM repair after birth.

METHODS
The Guidelines Task Force developed search terms and strategies to search PubMed and Embase for the relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used. Full text articles were reviewed and, when appropriate, included as evidence.

RESULTS
A total of 261 abstracts were reviewed. Fifty-four full-text articles were selected for further analysis. Three studies met inclusion criteria.

CONCLUSION
There was Class II evidence from 1 study and Class III evidence from another 2 studies demonstrating that TCS develops in infants with prenatal MM closure at an equal or higher rate than with postnatal closure. There was an increased risk of development of inclusion cysts in infants who underwent in utero closure. Continued surveillance for TCS and/or the development of inclusion cysts in children with prenatal and postnatal closure of MM is indicated (Level II). Differences between prenatal and postnatal repair with respect to the development of TCS and/or inclusion cysts should be considered alongside other relevant maternal and fetal outcomes when deciding upon a preferred method for MM closure.
The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-6.
Quantile regression for survival data in modern cancer research: expanding statistical tools for precision medicine
Authors: Hong Hyokyoung G , Christiani David C , Li Yi 
Published: June 2019

AbstractQuantile regression links the whole distribution of an outcome to the covariates of interest and has become an important alternative to commonly used regression models. However, the presence of censored data such as survival time, often the main endpoint in cancer studies, has hampered the use of quantile regression techniques because of the incompleteness of data. With the advent of the precision medicine era and availability of high throughput data, quantile regression with high-dimensional predictors has attracted much attention and provided added insight compared to traditional regression approaches. This paper provides a practical guide for using quantile regression for right censored outcome data with covariates of low- or high-dimensionality. We frame our discussion using a dataset from the Boston Lung Cancer Survivor Cohort, a hospital-based prospective cohort study, with the goals of broadening the scope of cancer research, maximizing the utility of collected data, and offering useful statistical alternatives. We use quantile regression to identify clinical and molecular predictors, for example CpG methylation sites, associated with high-risk lung cancer patients, for example those with short survival.
Gut microbiota metabolite regulation of host defenses at mucosal surfaces: implication in precision medicine
Authors: Bilotta Anthony J , Cong Yingzi 
Published: June 2019

AbstractThe gut microbiota has a well-established role in the regulation of host homeostasis. Multiple factors control the composition and function of the microbiota. The westernization of diet, a shift away from nutrient-dense foods toward diets high in saturated fats, has been implicated in the rise of chronic inflammatory diseases such as inflammatory bowel disease (IBD). Diet is critical in the development and maintenance of a healthy microbiome, where dietary fiber (found in the highest amounts in fruits, vegetables, and legumes) is metabolized by the microbiome. In turn, the bacterial metabolites of dietary fiber, short chain fatty acids (SCFAs), regulate gut homeostasis. SCFAs engage G-protein coupled receptors (GPRs) and act as histone deacetylase inhibitors (HDACi) to module epithelial and immune cell functions in the intestines, where they generally promote an anti-inflammatory state. This review highlights the functions of SCFAs and their roles in the pathogenesis of IBD to provide insights into their potential therapeutic application for the treatment of IBD for the purposes of precision medicine.
Linking Persistent Pain and Frailty in Older Adults
Authors: Guerriero Fabio , Reid M C 
Published: June 2019

Abstract

Objective
In older adults, the impact of persistent pain goes beyond simple discomfort, often contributing to worsening functional outcomes and ultimately frailty. Frailty is a geriatric syndrome that, like persistent pain, increases in prevalence with age and is characterized by a decreased ability to adapt to common stressors such as acute illness, thereby increasing risk for multiple adverse health outcomes. Evidence supports a relationship between persistent pain and both the incidence and progression of frailty, independent of health, social, and lifestyle confounders.

Design and Setting
In this article, we synthesize recent evidence linking persistent pain and frailty in an effort to clarify the nature of the relationship between these two commonly occurring geriatric syndromes.

Setting
We propose an integration of the frailty phenotype model by considering the impact of persistent pain on vulnerability toward external stressors, which can ultimately contribute to frailty in older adults.

Results and Conclusions
Incorporating persistent pain into the frailty construct can help us better understand frailty and ultimately improve care for patients with, as well as those at increased risk for, pain and frailty.
Simultaneous determination of the cosmic birefringence and miscalibrated polarization angles from CMB experiments
Authors: Minami Yuto , Ochi Hiroki , Ichiki Kiyotomo , Katayama Nobuhiko , Komatsu Eiichiro , Matsumura Tomotake 
Published: June 2019

Abstract
We show that the cosmic birefringence and miscalibrated polarization angles can be determined simultaneously by cosmic microwave background (CMB) experiments using the cross-correlation between $E$- and $B$-mode polarization data. This is possible because the polarization angles of the CMB are rotated by both the cosmic birefringence and miscalibration effects, whereas those of the Galactic foreground emission are rotated only by the latter. Our method does not require prior knowledge of the $E$- and $B$-mode power spectra of the foreground emission, but uses only the knowledge of the CMB polarization spectra. Specifically, we relate the observed $EB$ correlation to the difference between the observed$E$- and $B$-mode spectra in the sky, and use different multipole dependences of the CMB (given by theory) and foreground spectra (given by data) to derive the likelihood for the miscalibration angle $\alpha$ and the birefringence angle $\beta$. We show that a future satellite mission similar to LiteBIRD can determine $\beta$ with a precision of 10 arcmin.
Epigenetically quantified immune cells in salivary glands of Sjögren’s syndrome patients: a novel tool that detects robust correlations of T follicular helper cells with immunopathology
Authors: Blokland Sofie L M , van Vliet-Moret Fréderique M , Hillen Maarten R , Pandit Aridaman , Goldschmeding Roel , Kruize Aike A , Bouma Gerben , van Maurik André , Olek Sven , Hoffmueller Ulrich , van Roon Joel A G , Radstake Timothy R D J 
Published: June 2019

Abstract

Objective
To investigate whether epigenetic cell counting represents a novel method to quantify immune cells in salivary glands of patients with different forms of Sjögren’s and sicca syndrome and to capture immunopathology and potentially aid in diagnosis.

Methods
DNA from frozen salivary gland tissue sections of sicca patients was used for bisulphite conversion of demethylated DNA cytosine residues, followed by cell-specific quantitative PCR to calculate cell percentages in relation to total tissue cell numbers as quantified by housekeeping gene demethylation. The percentages of epigenetically quantified cells were correlated to RNA expression of matched salivary gland tissue and histological and clinical parameters.

Results
The percentages of epigenetically quantified CD3, CD4, CD8, T follicular helper (Tfh) cells, FoxP3+ regulatory T cells and B cells were significantly increased in the salivary glands of patients with SS. Unsupervised clustering using these percentages identified patient subsets with an increased lymphocytic focus score and local B cell hyperactivity and classifies patients different from conventional classification criteria. In particular, Tfh cells were shown to strongly correlate with the expression of CXCL13, lymphocytic focus scores, local B cell hyperactivity and anti-SSA positivity.

Conclusion
Epigenetic cell counting is a promising novel tool to objectively and easily quantify immune cells in the labial salivary gland of sicca patients, with a relatively small amount of tissue needed. In view of the potential of this technique to include a huge number of (cell-specific) biomarkers, this opens up new standardized ways of salivary gland analysis with high relevance for patient classification, understanding of immunopathology and monitoring of drug responses in clinical trials.
THERMOLUMINESCENCE SPECTRA AND DOSE RESPONSES OF SrSO4 PHOSPHORS DOPED WITH RARE EARTHS (Eu, Dy, Tm) AND PHOSPHORUS
Authors: Tang Qiang , Tang Huaming , Luo Daling , Zhang Chunxiang , Guo Jingyuan , Wu Huiping 
Published: June 2019

Abstract
The thermoluminescence (TL) spectra and dose responses of strontium sulphate doped with rare earth ions show that the SrSO4:Eu2+ phosphor might reasonably be assumed a isoelectronic trap sample which has unique TL characteristics: there is only one obvious glow peak at 385 nm, 489 K in the TL 3D emission spectra and its TL dose response is linear-sublinear. However, there are several elementary glow peaks in the TL 3D emission spectra and their TL dose responses are linear-supralinear for SrSO4:RE3+ (RE = Dy, Tm). These TL peaks occurred from low to high temperature indicate that the traps are distributed in different energy levels. When a suitable amount of other impurities co-doped into these SrSO4:RE3+, such as phosphorus, the relative intensities of these elementary glow peaks are changed significantly, especially the TL peak ~500 K is enhanced while the peaks at lower temperature are suppressed. The enhanced peak of SrSO4:RE3+,P is attributed to the deep traps. Their dose responses remain in nonlinearity when co-doped phosphorus. The above results and the luminescence properties of other sulphate doped rare earths impurities illustrate that the TL characteristics depend on the structure of defect complexes which can be assumed the basic elements in the TL multi-stage processes.
Medical Surveillance and Medical Confidentiality in an Age of Transition: The Debate over Cancer Registration in West Germany
Authors: Frohman Larry 
Published: June 2019

Summary
In the 1970s, cancer registries emerged as an essential tool in West Germany’s efforts to control cancer. However, they assumed this new importance at the very moment when the West German public was becoming increasingly concerned about personal privacy and the potential harms resulting from the collection and use of personal information, and the ensuing debate over information access and privacy became one of the central axes for a broader rethinking of medical confidentiality between the 1970s and the early 1990s. Although this debate explored the complex relationship between patient privacy, patient treatment and the public interest as it spiralled across the 1980s, in the prevailing political climate, it proved impossible to devise an acceptable compromise. The conflict was not resolved until the turn of the 1990s, when technological and administrative innovation made it possible to sidestep the issue of consent with regard to cancer registration.
Bacillus thuringiensis cry1C expression from the plastid genome of poplar leads to high mortality of leaf-eating caterpillars
Authors: Wu Yuyong , Xu Letian , Chang Ling , Ma Meiqi , You Lili , Jiang Chunmei , Li Shengchun , Zhang Jiang 
Published: June 2019

AbstractPlastid transformation technology has several attractive features compared with traditional nuclear transformation technology. However, only a handful of species are able to be successfully transformed. Here, we report an efficient and stable plastid transformation protocol for poplar, an economically important tree species grown worldwide. We transformed the Bacillus thuringiensis cry1C gene into the poplar plastid genome, and homoplasmic transplastomic poplar was obtained after two to three rounds of regeneration under antibiotic selection for 7–12 months. The transplastomic poplar expressing Cry1C insecticidal protein showed the highest accumulation level in young leaves, which reached up to 20.7 μg g-1 fresh weight, and comparatively low levels in mature and old leaves, and hardly detectable levels in non-green tissues, such as phloem, xylem and roots. Transplastomic poplar showed high toxicity to Hyphantria cunea and Lymantria dispar, two notorious forest pests worldwide, without affecting plant growth. These results are the first successful examples of insect-resistant poplar generation by plastid genome engineering and provide a new avenue for future genetic improvement of poplar plants.
Novel hepatitis D-like agents in vertebrates and invertebrates
Authors: Chang Wei-Shan , Pettersson John H-O , Le Lay Callum , Shi Mang , Lo Nathan , Wille Michelle , Eden John-Sebastian , Holmes Edward C 
Published: June 2019

Abstract
Hepatitis delta virus (HDV) is the smallest known RNA virus, encoding a single protein. Until recently, HDV had only been identified in humans, where it is strongly associated with co-infection with hepatitis B virus (HBV). However, the recent discovery of HDV-like viruses in metagenomic samples from birds and snakes suggests that this virus has a far longer evolutionary history. Herein, using additional meta-transcriptomic data, we show that highly divergent HDV-like viruses are also present in fish, amphibians, and invertebrates, with PCR and Sanger sequencing confirming the presence of the invertebrate HDV-like viruses. Notably, the novel viruses identified here share genomic features characteristic of HDV, such as a circular genome of only approximately 1.7 kb in length, and self-complementary, unbranched rod-like structures. Coiled-coil domains, leucine zippers, conserved residues with essential biological functions, and isoelectronic points similar to those in the human hepatitis delta virus antigens (HDAgs) were also identified in the putative non-human viruses. Importantly, none of these novel HDV-like viruses were associated with hepadnavirus infection, supporting the idea that the HDV–HBV association may be specific to humans. Collectively, these data not only broaden our understanding of the diversity and host range of HDV, but also shed light on its origin and evolutionary history.
Prospective Study of the Utility of Computed Tomography Triage of Pleural Biopsy Strategies in Patients With Pleural Diseases
Authors: Metintas Muzaffer , Ak Güntülü , Metintas Selma , Yildirim Huseyin , Dündar Emine , Rahman Najib 
Published: June 2019

Background:
This study aimed to prospectively evaluate the efficacy and reliability of a diagnostic workup, triaging pleural biopsy method according to baseline computerized tomography (CT) findings in the diagnosis of pleural diseases.

Methods:
Patients with pleural pathology were divided into 3 arms according to findings on CT scan images. Arm A: patients with pleural thickening/lesion in addition to pleural effusion. These patients underwent CT scan–guided Abrams’ needle pleural biopsy. Arm B: patients with pleural effusion alone or suspected benign asbestos pleurisy. This group underwent medical thoracoscopy (MT). Arm C: patients with only pleural thickening. This group underwent ultrasonography-guided cutting needle pleural biopsy. MT was planned in patients who did not have a specific diagnosis in the CT scan–guided Abrams’ needle pleural biopsy group. When patients with a histopathologic diagnosis of fibrinous pleuritis after MT were assessed in terms of the risk factors for malignant pleural diseases, we offered a further invasive procedure.

Results:
A total of 164 patients were enrolled in the study. Diagnostic sensitivity after the initial procedure was 90.2% in Arm A, 93.3% in Arm B, 95.2% in Arm C, and 92.4% in the entire workup. The negative predictive value of the entire workup was 90.4% for malignant pleural mesothelioma, 97.1% for metastatic malignant pleural diseases, and 100% for tuberculous pleurisy. Five cases who had a diagnosis of fibrinous pleuritis after MT were detected to have risk factors, 4 of which (80%) indicated malignant disease. Complication rates were low and acceptable.

Conclusion:
Use of CT scans to triage an appropriate pleural biopsy method is associated with high diagnostic success. We recommend that the proposed diagnostic workup in this study may be used as a diagnostic algorithm for pleural diseases that require a histopathologic analysis. Determination of risk factors predicting malignant disease in patients where fibrinous pleuritis is reported after MT would be useful for clinical practice.
Effect of Patent Ductus Arteriosus on Splanchnic Oxygenation at Enteral Feeding Introduction in Very Preterm Infants
Authors: Martini Silvia , Corvaglia Luigi , Aceti Arianna , Vitali Francesca , Faldella Giacomo , Galletti Silvia 
Published: June 2019

ABSTRACTBecause of its possible effect on mesenteric blood flow, the presence of a hemodynamically significant patent ductus arteriosus (PDA) is often of concern for the introduction of enteral feeds in preterm neonates. Near‐infrared spectroscopy allows a continuous monitoring of splanchnic oxygenation (SrSO2) and may provide useful hemodynamic information. This observational study evaluated SrSO2 patterns in response to first feed administration in 50 preterm infants <32 weeks’ gestation with different ductal status. According to their echocardiographic characteristics, the enrolled infants were divided into the following groups: pulsatile PDA with hemodynamically significant features, restrictive PDA, and no evidence of PDA. The presence of PDA, either with restrictive or hemodynamically significant characteristics, does not significantly affect SrSO2 response to enteral feeding introduction and is not associated with increased rates of gut complications. This finding may provide encouraging evidence in support of early enteral nutrition in very preterm infants with PDA.