bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHENOTYPIC CHARACTERISTICS OF ROD–CONE DYSTROPHY ASSOCIATED WITH MYO7A MUTATIONS IN A LARGE FRENCH COHORT
Authors: Khateb Samer , Mohand-Saïd Saddek , Nassisi Marco , Bonnet Crystel , Roux Anne-Françoise , Andrieu Camille , Antonio Aline , Condroyer Christel , Zeitz Christina , Devisme Céline , Loundon Natalie , Marlin Sandrine , Petit Christine , Bodaghi Bahram , Sahel José-Alain , Audo Isabelle 
Published: September 2019

Purpose:
To document the rod–cone dystrophy phenotype of patients with Usher syndrome type 1 (USH1) harboring MYO7A mutations.

Methods:
Retrospective cohort study of 53 patients (42 families) with biallelic MYO7A mutations who underwent comprehensive examination, including functional visual tests and multimodal retinal imaging. Genetic analysis was performed either using a multiplex amplicon panel or through direct sequencing. Data were analyzed with IBM SPSS Statistics software v. 21.0.

Results:
Fifty different genetic variations including 4 novel were identified. Most patients showed a typical rod–cone dystrophy phenotype, with best-corrected visual acuity and central visual field deteriorating linearly with age. At age 29, binocular visual field demonstrated an average preservation of 50 central degrees, constricting by 50% within 5 years. Structural changes based on spectral domain optical coherence tomography, short wavelength autofluorescence, and near-infrared autofluorescence measurements did not however correlate with age. Our study revealed a higher percentage of epiretinal membranes and cystoid macular edema in patients with MYO7A mutations compared with rod–cone dystrophy patients with other mutations. Subgroup analyses did not reveal substantial genotype–phenotype correlations.

Conclusion:
To the best of our knowledge, this is the largest French cohort of patients with MYO7A mutations reported to date. Functional visual characteristics of this subset of patients followed a linear decline as in other typical rod–cone dystrophy, but structural changes were variable indicating the need for a case-by-case evaluation for prognostic prediction and choice of potential therapies.
CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH LONG-CHAIN 3-HYDROXYACYL-CoA DEHYDROGENASE DEFICIENCY
Authors: Sacconi Riccardo , Bandello Francesco , Querques Giuseppe 
Published: September 2019

Purpose:
To report the first case describing choroidal neovascularization in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.

Methods:
Case report including multimodal imaging discussion.

Results:
A 21-year-old woman affected by LCHAD deficiency (confirmed by 1528 G>C homozygous mutation) was referred to our department for progressive visual decline in both eyes. Best-corrected visual acuities were 20/40 and 20/1,000 in the right and left eye, respectively. Ultra-widefield imaging, fluorescein angiography, structural optical coherence tomography, and optical coherence tomography angiography revealed the presence of macular and midperipheral chorioretinal atrophy complicated by a choroidal neovascularization in the left eye.

Conclusion:
Ocular changes in LCHAD deficiency are long-term complications and severely affect the quality of life of patients. We report for the first time the evidence that choroidal neovascularization could complicate ocular changes accelerating the progressive vision impairment.
Machine-learning–based knowledge discovery in rheumatoid arthritis–related registry data to identify predictors of persistent pain
Authors: Lötsch Jörn , Alfredsson Lars , Lampa Jon 
Published: September 2019

Abstract
Early detection of patients with chronic diseases at risk of developing persistent pain is clinically desirable for timely initiation of multimodal therapies. Quality follow-up registries may provide the necessary clinical data; however, their design is not focused on a specific research aim, which poses challenges on the data analysis strategy. Here, machine-learning was used to identify early parameters that provide information about a future development of persistent pain in rheumatoid arthritis (RA). Data of 288 patients were queried from a registry based on the Swedish Epidemiological Investigation of RA. Unsupervised data analyses identified the following 3 distinct patient subgroups: low-, median-, and high-persistent pain intensity. Next, supervised machine-learning, implemented as random forests followed by computed ABC analysis–based item categorization, was used to select predictive parameters among 21 different demographic, patient-rated, and objective clinical factors. The selected parameters were used to train machine-learned algorithms to assign patients pain-related subgroups (1000 random resamplings, 2/3 training, and 1/3 test data). Algorithms trained with 3-month data of the patient global assessment and health assessment questionnaire provided pain group assignment at a balanced accuracy of 70%. When restricting the predictors to objective clinical parameters of disease severity, swollen joint count and tender joint count acquired at 3 months provided a balanced accuracy of RA of 59%. Results indicate that machine-learning is suited to extract knowledge from data queried from pain- and disease-related registries. Early functional parameters of RA are informative for the development and degree of persistent pain.
Characterization of Student Drinking Behaviors at the Beginning of the First Academic Year at One University in Southern Italy
Authors: De Salvia Maria Antonietta , D'Uggento Angela Maria , Aquilino Giovanni , Tattoli Maria , Finelli Carmine , Imbrici Paola , Desaphy Jean Francois , Giustino Arcangela 
Published: September 2019

Abstract
It is well recognized that both college and noncollege students are at-risk age groups for alcohol consumption. We investigated the alcohol consumption habits of undergraduate students with an emphasis on binge drinking. Participants (N = 809, 61.2% female) were freshmen attending courses at one of the main universities of southern Italy. They were asked to fill out a paper-and-pencil questionnaire that was administered between October 2017 and January 2018. Nearly 90% of the questioned students reported drinking alcohol during the 12 months before the survey. Among them, 31.4% of female students and 41.5% of male students engaged in binge drinking, mainly once a month; binge drinkers preferred highly alcoholic beverages during parties, underestimated the alcoholic content of their drinks, started drinking alcohol at a younger age than nonbinge drinkers, and drank weekly and between meals. Binge drinkers started smoking earlier than their peers, and a great number of them consumed illicit drugs. Moreover, 30.3% of female and 34.8% of male nonbinge drinkers declared that they consumed 6 or more units of alcohol in one occasion, making them unaware binge drinkers. Furthermore, approximately 50% of students recognized that alcohol consumption has effects similar to those induced by illicit drugs but only considered their peers' drinking behavior to be risky.
This study highlights that most students involved in this survey expose themselves to a risky lifestyle by heavy drinking and, most alarmingly, that some of them are not even aware of that.
State of the Art in European Addictions Nursing
Authors: Clancy Carmel , Kelly Peter , Loth Christien 
Published: September 2019

Abstract
In this article, we discuss the state of the art of addiction nursing in Europe. This state is viewed throughout the United Kingdom, Ireland, and the Netherlands and has a direct link to the future. Despite differences, the three countries share nursing values. The start of International Nurses Society in Addictions Nursing Ireland and the Netherlands is only the beginning of a new connection and cooperation Europe-wide.
Individuals With Opioid Dependence Using Polysubstances
Authors: Jaiteh Christine , Steinauer Regine , Frei Irena Anna 
Published: September 2019

Abstract

Background:
Opioid dependence accompanied by polysubstance use is a chronic illness with severe somatic, psychological and social consequences for those affected. International studies have shown that healthcare provision is inadequate for this population because of stigmatization and lack of expertise among medical professionals. It must be assumed that this is also the case in acute care settings of hospitals in German-speaking areas of Switzerland. To date, there are few studies addressing these patients’ experiences that could provide data for targeted interventions.

Aims:
This qualitative study explored this patient population’s perspective in terms of their experiences and needs regarding care provision in acute hospitals. The results should offer potential adaptations to care provision for this vulnerable group of individuals.

Methods:
Twelve individuals with opioid dependence using polysubstances were interviewed in two urban substitution centers. The data analysis of the material obtained was undertaken using qualitative content analysis according to Mayring.

Results:
As a whole, individuals with opioid dependence using polysubstances are not dissatisfied with care provided in acute hospitals as long as their relationship with health professionals is positive. Substitution medication is critically important to their treatment, but this group’s experiences with its management during hospitalization continue to show widespread stigmatization along with inadequate knowledge and interprofessional collaboration and a failure to integrate these patients and their expertise into treatment and care.

Conclusions and Future Directions:
The treatment of individuals with substance-related disorders in acute hospitals requires staff with somatic and psychiatric training. In this regard, the principles of evidence-based models of reducing harm and multiprofessional treatment teams should be seen as particularly well suited and promising.
Glial Fibrillary Acidic Protein (GFAP) Autoimmunity in the Setting of Seropositive Rheumatoid Arthritis Treated With Etanercept
Authors: Smith Kelsey M. , Amin Shreyasee , Jones Lyell K. , Lachance Daniel H. , Flanagan Eoin P. , Jentoft Mark E. , Kantarci Orhun H. 
Published: September 2019

Introduction:
Glial fibrillary acidic protein (GFAP) immunoglobulin G is a recently discovered biomarker of an autoimmune central nervous system disorder characterized by a steroid-responsive meningoencephalomyelitis.

Case Report:
A 63-year-old man with rheumatoid arthritis on etanercept presented with steroid-responsive subacute encephalopathy and foot drop. Brain and sural nerve biopsies demonstrated a T-cell perivascular infiltrate. Cerebrospinal fluid studies 18 months into the course of the illness demonstrated a GFAP antibody on mouse tissue immunofluorescence confirmed by cell-based assay. The patient was treated with steroids and cyclophosphamide leading to resolution of his symptoms.

Conclusion:
This case expands on the previously reported cases of GFAP immunoglobulin G autoimmunity by describing an associated inflammatory large fiber peripheral neuropathy.
Afatinib, an irreversible ErbB family blocker for the treatment of epidermal growth factor receptor mutation-positive non-small cell lung cancer
Authors: Summers Yvonne , Graham Donna M. 
Published: September 2019

Abstract
Targeted inhibition of epidermal growth factor receptor (EGFR) signaling has emerged as the standard of care for EGFR mutation-positive non-small cell lung cancer (EGFRm+ NSCLC). Afatinib, an oral irreversible ErbB-family blocker, has been extensively studied in this context. Recent studies have highlighted the benefit and tolerability of afatinib treatment in patients with EGFRm+ advanced/metastatic NSCLC. The LUX-Lung 3 and 6 phase III studies showed greater efficacy with first-line afatinib compared with platinum-doublet chemotherapy, whereas LUX-Lung 7 highlighted the enhanced benefits of afatinib over the first-generation EGFR tyrosine kinase inhibitor (TKI), gefitinib. The nearly inevitable emergence of resistance to afatinib, coupled with recent data for the third-generation TKI osimertinib, highlight the need to identify an optimal treatment sequencing strategy to achieve long-term benefit and survival. The available data suggest that optimal treatment could involve first-line afatinib, followed by osimertinib upon acquired resistance to afatinib through the T790M mutation. This review discusses the pharmacology of afatinib, efficacy and safety results of key trials in the afatinib clinical study program, management of adverse events, and sequencing strategies following acquired resistance. Afatinib data are discussed in the context of recent studies of other EGFR TKIs, to provide considerations around their use and inform potential sequential treatment approaches.
Experience with Combining Pediatric Procedures into a Single Anesthetic
Authors: Miketic Renata M. , Uffman Joshua , Tumin Dmitry , Tobias Joseph D. , Raman Vidya T. 
Published: September 2019

Introduction:
The combination of multiple procedures within a single anesthetic may provide many challenges for the perioperative team. Coordination of specialties, consideration for parental time burdens, and travel expenses as well as limiting multiple anesthetic exposures to the children are pertinent factors to consider when advocating the combination of surgical procedures.

Methods:
The electronic medical record at Nationwide Children’s Hospital was retrospectively queried to obtain information on patients having a single anesthetic encounter for 2 or more procedures involving 2 or more services over 1 year (July 2015–June 2016).

Results:
One thousand one hundred twenty patients had 2 procedures during a single anesthetic encounter. The average anesthesia time was 127 ± 102 minutes, and average PACU time was 64 ± 37 minutes. The unanticipated admission rate was 85 of 1,120 cases (7.6%). Five (6%) of the unanticipated admission cases were ASA status 1, 33 (39%) were ASA status 2, and 47 (55%) were ASA status ≥3; compared with 87 (9%), 481 (50%), and 391 (41%) in the group not requiring unanticipated admission (P = 0.032) (see Fig. 1).

Conclusions:
These data demonstrate the feasibility of combining several procedures during a single anesthetic encounter and may result in decreased healthcare costs as well as limitation of parental cost and time obligations.
Red Cell Distribution Width and Mean Platelet Volume in Patients With Ankylosing Spondylitis
Authors: Deng Jixiang , Xu Shanshan , Gao Xing , Xu Shengqian , Shuai Zongwen , Pan Faming 
Published: September 2019

Objective
The results of previous studies regarding the relationship between red cell distribution width (RDW) or mean platelet volume (MPV) levels and ankylosing spondylitis (AS) are inconsistent. Therefore, we conducted this meta-analysis to systematically evaluate the associations.

Methods
The Web of Science, PubMed, and Cochrane Library (as of February 14, 2019) were used to retrieve relevant articles. Pooled standard mean difference (SMD) and its 95% confidence interval (CI) were calculated. All statistical analyses were performed using the “meta” and “metafor” packages of the R 3.5.1 software.

Results
Nine studies on RDW, including 775 AS patients and 972 healthy controls, and 8 studies on MPV, including 743 AS patients and 571 healthy controls, were included. The results showed that RDW levels were significantly higher in AS patients (SMD = 0.67; 95% CI, 0.30 to 1.05; p < 0.001) compared with healthy controls, whereas MPV levels (SMD = 0.01; 95% CI, −0.28 to 0.30; p = 0.929) were not significantly different from healthy controls.

Conclusions
Our current study shows that the elevated levels of RDW may be associated with AS, whereas MPV levels may be not associated with AS
Preoperative Ultrasonographic Staging of Papillary Thyroid Carcinoma With the Eighth American Joint Committee on Cancer Tumor-Node-Metastasis Staging System
Authors: Zhang Jingwen , Fei Mengjia , Dong Yijie , Xu Shangyan , Zhan Weiwei 
Published: September 2019

Objective
The purpose of this study was to evaluate the performance of preoperative ultrasonography (US) in the staging of papillary thyroid carcinoma (PTC) according to the eighth AJCC TNM classification system, to determine the effect of the preoperative US staging in the management of PTC.

Patients and Methods
Preoperative US was performed by 2 highly trained sonographers in 665 consecutive patients with PTC, and the T and N categories were determined preoperatively. The accuracy of preoperative US in clinical staging was evaluated based on the histopathological specimens according to the eighth AJCC TNM classification. Further analysis was performed to identify the high-risk factors of N1b stage.

Results
Overall accuracy of preoperative US for T stage was 92.5% (615/665). The accuracy of sonographic evaluation for T was high except for the T4a. Overall accuracy of preoperative US for N stage was 59% (426/655). The accuracies of sonographic evaluation for N0, N1a, and N1b were 81.8% (274/335), 33.3% (70/250), and 87.5% (70/80), respectively. Of 250 N1a patients, 164 (65.6%) were underestimated by US. Univariate and multivariate analyses showed that larger tumor diameter, multifocality, and higher T stage significantly increase the risk of N1b stage (P < 0.01).

Conclusions
Preoperative US was useful for the evaluation in staging of PTC, but some limitations still existed. For higher-risk patients of N1b (larger tumor size, multifocality, and higher T stage), preoperative US examination for lateral neck region should be further emphasized, and prophylactic lateral nodal dissection should be determined based on both preoperative imaging results and intraoperative evaluation.
Transfusion of Anaerobically or Conventionally Stored Blood After Hemorrhagic Shock
Authors: Williams Alexander T. , Jani Vivek P. , Nemkov Travis , Lucas Alfredo , Yoshida Tatsuro , Dunham Andrew , D’Alessandro Angelo , Cabrales Pedro 
Published: September 2019

ABSTRACT

Background:
Resuscitation from hemorrhagic shock (HS) by blood transfusion restores oxygen (O2) delivery and provides hemodynamic stability. Current regulations allow red blood cells (RBCs) to be stored and used for up to 42 days. During storage, RBCs undergo many structural and functional changes. These storage lesions have been associated with adverse events and increased mortality after transfusion, increasing the need for improved RBC storage protocols. This study evaluates the efficacy of anaerobically stored RBCs to resuscitate rats from severe HS compared with conventionally stored RBCs.

Methods and results:
Rat RBCs were stored under anaerobic, anaerobic/hypercapnic, or conventional conditions for a period of 3 weeks. Hemorrhage was induced by controlled bleeding, shock was maintained for 30 min, and RBCs were transfused to restore and maintain blood pressure near the prhemorrhage level. All storage conditions met current regulatory 24-h posttransfusion recovery requirements. Transfusion of anaerobically stored RBCs required significantly less RBC volume to restore and maintain hemodynamics. Anaerobic or anaerobic/hypercapnic RBCs restored hemodynamics better than conventionally stored RBCs. Resuscitation with conventionally stored RBCs impaired indices of left ventricular cardiac function, increased hypoxic tissue staining and inflammatory markers, and affected organ function compared with anaerobically stored RBCs.

Conclusions:
Resuscitation from HS via transfusion of anaerobically stored RBCs recovered cardiac function, restored hemodynamic stability, and improved outcomes.
Multivalent proteins rapidly and reversibly phase-separate upon osmotic cell volume change
Authors: Jalihal Ameya P. , Pitchiaya Sethuramasundaram , Xiao Lanbo , Bawa Pushpinder , Jiang Xia , Bedi Karan , Parolia Abhijit , Cieslik Marcin , Ljungman Mats , Chinnaiyan Arul M. , Walter Nils G. 
Published: September 2019

SUMMARYProcessing bodies (PBs) and stress granules (SGs) are prominent examples of sub-cellular, membrane-less compartments that are observed under physiological and stress conditions, respectively. We observe that the trimeric PB protein DCP1A rapidly (within ∼10 s) phase-separates in mammalian cells during hyperosmotic stress and dissolves upon isosmotic rescue (over ∼100 s) with minimal impact on cell viability even after multiple cycles of osmotic perturbation. Strikingly, this rapid intracellular hyperosmotic phase separation (HOPS) correlates with the degree of cell volume compression, distinct from SG assembly, and is exhibited broadly by homo-multimeric (valency ≥ 2) proteins across several cell types. Notably, HOPS sequesters pre-mRNA cleavage factor components from actively transcribing genomic loci, providing a mechanism for hyperosmolarity-induced global impairment of transcription termination. Together, our data suggest that the multimeric proteome rapidly responds to changes in hydration and molecular crowding, revealing an unexpected mode of globally programmed phase separation and sequestration that adapts the cell to volume change.GRAPHICAL ABSTRACTIN BRIEFCells constantly experience osmotic variation. These external changes lead to changes in cell volume, and consequently the internal state of molecular crowding. Here, Jalihal and Pitchiaya et al. show that multimeric proteins respond rapidly to such cellular changes by undergoing rapid and reversible phase separation.HIGHLIGHTSDCP1A undergoes rapid and reversible hyperosmotic phase separation (HOPS)HOPS of DCP1A depends on its trimerization domainSelf-interacting multivalent proteins (valency ≥ 2) undergo HOPSHOPS of CPSF6 explains transcription termination defects during osmotic stress
NODAL/TGFβ signalling mediates the self-sustained stemness induced by PIK3CAH1047R homozygosity in pluripotent stem cells
Authors: Madsen Ralitsa R. , Longden James , Knox Rachel G. , Robin Xavier , Völlmy Franziska , Macleod Kenneth G. , Moniz Larissa S. , Carragher Neil O. , Linding Rune , Vanhaesebroeck Bart , Semple Robert K. 
Published: September 2019

AbstractActivating PIK3CA mutations are known “drivers” of human cancer and developmental overgrowth syndromes. We recently demonstrated that the “hotspot” PIK3CAH1047R variant exerts unexpected allele dose-dependent effects on stemness in human pluripotent stem cells (hPSCs). In the present study, we combine high-depth transcriptomics, total proteomics and reverse-phase protein arrays to reveal potentially disease-related alterations in heterozygous cells, and to assess the contribution of activated TGFβ signalling to the stemness phenotype of PIK3CAH1047R homozygous cells. We demonstrate signalling rewiring as a function of oncogenic PI3K signalling dose, and provide experimental evidence that self-sustained stemness is causally related to enhanced autocrine NODAL/TGFβ signalling. A significant transcriptomic signature of TGFβ pathway activation in PIK3CAH1047R heterozygous was observed but was modest and was not associated with the stemness phenotype seen in homozygous mutants. Notably, the stemness gene expression in PIK3CAH1047R homozygous iPSCs was reversed by pharmacological inhibition of TGFβ signalling, but not by pharmacological PI3Kα pathway inhibition. Altogether, this provides the first in-depth analysis of PI3K signalling in human pluripotent stem cells and directly links dose-dependent PI3K activation to developmental NODAL/TGFβ signalling.