bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incident Heart Failure in Patients With Rheumatoid Arthritis: A Nationwide Cohort Study
Authors: Khalid Usman , Egeberg Alexander , Ahlehoff Ole , Lane Deirdre , Gislason Gunnar H. , Lip Gregory Y.H. , Hansen Peter R. 
Published: January 2018

Background

Rheumatoid arthritis (
RA
) is a chronic inflammatory disease associated with a wide range of comorbidities, including cardiovascular disease, but its association with heart failure (
HF
) is not fully clear. We investigated the risk of incident
HF
in a nationwide cohort of patients with
RA
.

Methods and Results

The study comprised the entire Danish population aged ≥18 years followed from January 1, 2008 until first hospitalization for
HF
, emigration, December 31, 2012, or death. Information on comorbidity, medication, and socioeconomic status was identified by individual‐level linkage of administrative registers. Patients with a rheumatologist diagnosis of
RA
between 1978 and 2008 were included. The primary study outcome was incident
HF
defined as first hospital admission for
HF
. Incidence rates of
HF
per 1000 person‐years were calculated and incidence rate ratios adjusted for age, sex, calendar year, comorbidity, medications, socioeconomic status, smoking, and alcohol consumption were estimated. A total of 4 305 225 subjects with no history of
HF
were eligible for analysis at the study start. Of these subjects, 24 343 developed
RA
and 50 623 were hospitalized for
HF
. Overall incidence rates of incident
HF
were 2.43 and 6.64 for the reference population (n=49 879) and patients with
RA
(n=744), respectively. Correspondingly, the fully adjusted incidence rate ratio for incident
HF
was increased in patients with
RA
with incidence rate ratio 1.30 (95% confidence interval, 1.17–1.45).

Conclusions

In this cohort study,
RA
was associated with an increased hospitalization for
HF
. These findings add significantly to the existing evidence of
RA
as a clinically relevant risk factor for
HF
.
Effect of Dysphagia Screening Strategies on Clinical Outcomes After Stroke: A Systematic Review for the 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke
Authors: Smith Eric E. , Kent David M. , Bulsara Ketan R. , Leung Lester Y. , Lichtman Judith H. , Reeves Mathew J. , Towfighi Amytis , Whiteley William N. , Zahuranec Darin B. 
Published: January 2018

Introduction—
Dysphagia screening protocols have been recommended to identify patients at risk for aspiration. The American Heart Association convened an evidence review committee to systematically review evidence for the effectiveness of dysphagia screening protocols to reduce the risk of pneumonia, death, or dependency after stroke.

Methods—
The Medline, Embase, and Cochrane databases were searched on November 1, 2016, to identify randomized controlled trials (RCTs) comparing dysphagia screening protocols or quality interventions with increased dysphagia screening rates and reporting outcomes of pneumonia, death, or dependency.

Results—
Three RCTs were identified. One RCT found that a combined nursing quality improvement intervention targeting fever and glucose management and dysphagia screening reduced death and dependency but without reducing the pneumonia rate. Another RCT failed to find evidence that pneumonia rates were reduced by adding the cough reflex to routine dysphagia screening. A smaller RCT randomly assigned 2 hospital wards to a stroke care pathway including dysphagia screening or regular care and found that patients on the stroke care pathway were less likely to require intubation and mechanical ventilation; however, the study was small and at risk for bias.

Conclusions—
There were insufficient RCT data to determine the effect of dysphagia screening protocols on reducing the rates of pneumonia, death, or dependency after stroke. Additional trials are needed to compare the validity, feasibility, and clinical effectiveness of different screening methods for dysphagia.
A Two-Stage Deep Neural Network Framework for Precipitation Estimation from Bispectral Satellite Information
Authors: Tao Yumeng , Hsu Kuolin , Ihler Alexander , Gao Xiaogang , Sorooshian Soroosh 
Published: January 2018

AbstractCompared to ground precipitation measurements, satellite-based precipitation estimation products have the advantage of global coverage and high spatiotemporal resolutions. However, the accuracy of satellite-based precipitation products is still insufficient to serve many weather, climate, and hydrologic applications at high resolutions. In this paper, the authors develop a state-of-the-art deep learning framework for precipitation estimation using bispectral satellite information, infrared (IR), and water vapor (WV) channels. Specifically, a two-stage framework for precipitation estimation from bispectral information is designed, consisting of an initial rain/no-rain (R/NR) binary classification, followed by a second stage estimating the nonzero precipitation amount. In the first stage, the model aims to eliminate the large fraction of NR pixels and to delineate precipitation regions precisely. In the second stage, the model aims to estimate the pointwise precipitation amount accurately while preserving its heavily skewed distribution. Stacked denoising autoencoders (SDAEs), a commonly used deep learning method, are applied in both stages. Performance is evaluated along a number of common performance measures, including both R/NR and real-valued precipitation accuracy, and compared with an operational product, Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks–Cloud Classification System (PERSIANN-CCS). For R/NR binary classification, the proposed two-stage model outperforms PERSIANN-CCS by 32.56% in the critical success index (CSI). For real-valued precipitation estimation, the two-stage model is 23.40% lower in average bias, is 44.52% lower in average mean squared error, and has a 27.21% higher correlation coefficient. Hence, the two-stage deep learning framework has the potential to serve as a more accurate and more reliable satellite-based precipitation estimation product. The authors also provide some future directions for development of satellite-based precipitation estimation products in both incorporating auxiliary information and improving retrieval algorithms.
Daylight-Mediated Photodynamic Therapy With Methyl Aminolevulinate in Actinic Keratosis Treatment
Authors: Demay Shantel D. J. , Sharma Kunal , Sapra Sheetal , Sapra Rahul , Sapra Priya 
Published: January 2018

Background: Research has shown daylight-mediated photodynamic therapy (PDT) for the treatment of actinic keratosis (AK) to be effective, tolerable, and convenient, with excellent patient satisfaction and cosmesis. Although success has been demonstrated in areas with similar latitudes to Switzerland and Scandinavia, this treatment has not been studied in a Canadian population. Objectives: The purpose of this study is to investigate the effectiveness, safety, and patient satisfaction of daylight-mediated methyl 5-aminolevulinate (MAL)–PDT to make recommendations for its use in Canadian practice. Methods: A retrospective chart review of patients who received treatment of daylight-mediated MAL-PDT for the indication of AK at the Institute of Cosmetic and Laser Surgery in Oakville, Ontario, between 2009 and 2016. Results: A total of 112 patients were included, consisting of 94 males and 18 females with a mean age of 63.79 years. A total of 177 sites were treated among all patients, mostly consisting of the face (n = 92) and scalp (n = 55). A total of 13.4% of patients experienced side effects, the most common being redness (n = 4) and scabbing (n = 4). Of the 42 patients who expressed their level of satisfaction, 83.3% reported being happy with the treatment, χ2(1) = 18.67, P ≤ .05; 6.3% of patients were noted to be completely clear, 86.6% had a good response, 0.9% had a mild response, and 0% had no response, χ2(1) = 101.04, P ≤ .05. Conclusions: Daylight-mediated MAL-PDT is a suitable treatment option for AK lesions in a Canadian population due to the demonstrated efficacy, patient satisfaction, tolerability, and convenience.
ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis
Authors: Montalban Xavier , Gold Ralf , Thompson Alan J , Otero-Romero Susana , Amato Maria Pia , Chandraratna Dhia , Clanet Michel , Comi Giancarlo , Derfuss Tobias , Fazekas Franz , Hartung Hans Peter , Havrdova Eva , Hemmer Bernhard , Kappos Ludwig , Liblau Roland , Lubetzki Catherine , Marcus Elena , Miller David H , Olsson Tomas , Pilling Steve , Selmaj Krysztof , Siva Aksel , Sorensen Per Soelberg , Sormani Maria Pia , Thalheim Christoph , Wiendl Heinz , Zipp Frauke 
Published: January 2018

Background: Multiple sclerosis (MS) is a complex disease with new drugs becoming available in the past years. There is a need for a reference tool compiling current data to aid professionals in treatment decisions. Objectives: To develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS. Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients–Intervention–Comparator–Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion: The present guideline will enable homogeneity of treatment decisions across Europe.
Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair–Deficient/Microsatellite Instability–High Metastatic Colorectal Cancer
Authors: Overman Michael J. , Lonardi Sara , Wong Ka Yeung Mark , Lenz Heinz-Josef , Gelsomino Fabio , Aglietta Massimo , Morse Michael A. , Van Cutsem Eric , McDermott Ray , Hill Andrew , Sawyer Michael B. , Hendlisz Alain , Neyns Bart , Svrcek Magali , Moss Rebecca A. , Ledeine Jean-Marie , Cao Z. Alexander , Kamble Shital , Kopetz Scott , André Thierry 
Published: January 2018

Purpose Nivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported. Patients and Methods Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR. Results Of 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%. Statistically significant and clinically meaningful improvements were observed in patient-reported outcomes, including functioning, symptoms, and quality of life. Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable. Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population. Conclusion Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti–programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC.
The IgCAM CLMP regulates expression of Connexin43 and Connexin45 in intestinal and ureteral smooth muscle contraction in mice
Authors: Langhorst Hanna , Jüttner René , Groneberg Dieter , Mohtashamdolatshahi Azadeh , Pelz Laura , Purfürst Bettina , Schmidt-Ott Kai M. , Friebe Andreas , Rathjen Fritz G. 
Published: January 2018

ABSTRACT
CAR-like membrane protein (CLMP), an immunoglobulin cell adhesion molecule (IgCAM), has been implicated in congenital short-bowel syndrome in humans, a condition with high mortality for which there is currently no cure. We therefore studied the function of CLMP in a Clmp-deficient mouse model. Although we found that the levels of mRNAs encoding Connexin43 or Connexin45 were not or were only marginally affected, respectively, by Clmp deficiency, the absence of CLMP caused a severe reduction of both proteins in smooth muscle cells of the intestine and of Connexin43 in the ureter. Analysis of calcium signaling revealed a disordered cell-cell communication between smooth muscle cells, which in turn induced an impaired and uncoordinated motility of the intestine and the ureter. Consequently, insufficient transport of chyme and urine caused a fatal delay to thrive, a high rate of mortality, and provoked a severe hydronephrosis in CLMP knockouts. Neurotransmission and the capability of smooth muscle cells to contract in ring preparations of the intestine were not altered. Physical obstructions were not detectable and an overall normal histology in the intestine as well as in the ureter was observed, except for a slight hypertrophy of smooth muscle layers. Deletion of Clmp did not lead to a reduced length of the intestine as shown for the human CLMP gene but resulted in gut malrotations. In sum, the absence of CLMP caused functional obstructions in the intestinal tract and ureter by impaired peristaltic contractions most likely due to a lack of gap-junctional communication between smooth muscle cells.
α5β1 integrin trafficking and Rac activation are regulated by APPL1 in a Rab5-dependent manner to inhibit cell migration
Authors: Diggins Nicole L. , Kang Hakmook , Weaver Alissa , Webb Donna J. 
Published: January 2018

ABSTRACT
Cell migration is a tightly coordinated process that requires the spatiotemporal regulation of many molecular components. Because adaptor proteins can serve as integrators of cellular events, they are being increasingly studied as regulators of cell migration. The adaptor protein containing a pleckstrin-homology (PH) domain, phosphotyrosine binding (PTB) domain, and leucine zipper motif 1 (APPL1) is a 709 amino acid endosomal protein that plays a role in cell proliferation and survival as well as endosomal trafficking and signaling. However, its function in regulating cell migration is poorly understood. Here, we show that APPL1 hinders cell migration by modulating both trafficking and signaling events controlled by Rab5 in cancer cells. APPL1 decreases internalization and increases recycling of α5β1 integrin, leading to higher levels of α5β1 integrin at the cell surface that hinder adhesion dynamics. Furthermore, APPL1 decreases the activity of the GTPase Rac and its effector PAK, which in turn regulate cell migration. Thus, we demonstrate a novel role for the interaction between APPL1 and Rab5 in governing crosstalk between signaling and trafficking pathways on endosomes to affect cancer cell migration.
This article has an associated First Person interview with the first author of the paper.
Dileucine-like motifs in the C-terminal tail of connexin32 control its endocytosis and assembly into gap junctions
Authors: Ray Anuttoma , Katoch Parul , Jain Nimansha , Mehta Parmender P. 
Published: January 2018

ABSTRACT
Defects in assembly of gap junction-forming proteins, called connexins (Cxs), are observed in a variety of cancers. Connexin32 (Cx32; also known as GJB1) is expressed by the polarized cells in epithelia. We discovered two dileucine-based motifs, which govern the intracellular sorting and endocytosis of transmembrane proteins, in the C-terminal tail of Cx32 and explored their role in regulating its endocytosis and gap junction-forming abilities in pancreatic and prostate cancer cells. One motif, designated as LI, was located near the juxtamembrane domain, whereas the other, designated as LL, was located distally. We also discovered a non-canonical motif, designated as LR, in the C-terminal tail. Our results showed that rendering these motifs non-functional had no effect on the intracellular sorting of Cx32. However, rendering the LL or LR motif nonfunctional enhanced the formation of gap junctions by inhibiting Cx32 endocytosis by the clathrin-mediated pathway. Rendering the LI motif nonfunctional inhibited gap junction formation by augmenting the endocytosis of Cx32 via the LL and LR motifs. Our studies have defined distinct roles of these motifs in regulating the endocytosis of Cx32 and its gap junction-forming ability.
This article has an associated First Person interview with the first author of the paper.
Epithelial and stromal circadian clocks are inversely regulated by their mechano-matrix environment
Authors: Williams Jack , Yang Nan , Wood Amber , Zindy Egor , Meng Qing-Jun , Streuli Charles H. 
Published: January 2018

ABSTRACT
The circadian clock is an autonomous molecular feedback loop inside almost every cell in the body. We have shown that the mammary epithelial circadian clock is regulated by the cellular microenvironment. Moreover, a stiff extracellular matrix dampens the oscillations of the epithelial molecular clock. Here, we extend this analysis to other tissues and cell types, and identify an inverse relationship between circadian clocks in epithelia and fibroblasts. Epithelial cells from mammary gland, lung and skin have significantly stronger oscillations of clock genes in soft 3D microenvironments, compared to stiff 2D environments. Fibroblasts isolated from the same tissues show the opposite response, exhibiting stronger oscillations and more prolonged rhythmicity in stiff microenvironments. RNA analysis identified that a subset of mammary epithelial clock genes, and their regulators, are upregulated in 3D microenvironments in soft compared to stiff gels. Furthermore, the same genes are inversely regulated in fibroblasts isolated from the same tissues. Thus, our data reveal for the first time an intrinsic difference in the regulation of circadian genes in epithelia and fibroblasts.
Septins are involved at the early stages of macroautophagy in S. cerevisiae
Authors: Barve Gaurav , Sridhar Shreyas , Aher Amol , Sahani Mayurbhai H. , Chinchwadkar Sarika , Singh Sunaina , K. N. Lakshmeesha , McMurray Michael A. , Manjithaya Ravi 
Published: January 2018

ABSTRACT
Autophagy is a conserved cellular degradation pathway wherein double-membrane vesicles called autophagosomes capture long-lived proteins, and damaged or superfluous organelles, and deliver them to the lysosome for degradation. Septins are conserved GTP-binding proteins involved in many cellular processes, including phagocytosis and the autophagy of intracellular bacteria, but no role in general autophagy was known. In budding yeast, septins polymerize into ring-shaped arrays of filaments required for cytokinesis. In an unbiased genetic screen and in subsequent targeted analysis, we found autophagy defects in septin mutants. Upon autophagy induction, pre-assembled septin complexes relocalized to the pre-autophagosomal structure (PAS) where they formed non-canonical septin rings at PAS. Septins also colocalized with autophagosomes, where they physically interacted with the autophagy proteins Atg8 and Atg9. When autophagosome degradation was blocked in septin-mutant cells, fewer autophagic structures accumulated, and an autophagy mutant defective in early stages of autophagosome biogenesis (atg1Δ), displayed decreased septin localization to the PAS. Our findings support a role for septins in the early stages of budding yeast autophagy, during autophagosome formation.
This article has an associated First Person interview with the first author of the paper.
Unconventional myosin VIIA promotes melanoma progression
Authors: Liu Yuqing , Wei Xiaofan , Guan Lizhao , Xu Sidi , Yuan Yang , Lv Danyu , He Xiaokun , Zhan Jun , Kong Yan , Guo Jun , Zhang Hongquan 
Published: January 2018

ABSTRACT
Unconventional myosin VIIA (Myo7a) is an actin-based motor molecule that normally functions in the cochlear hair cells of the inner ear. Mutations of MYO7A/Myo7a have been implicated in inherited deafness in both humans and mice. However, there is limited information about the functions of Myo7a outside of the specialized cells of the ears. Herein, we report a previously unidentified function of Myo7a by demonstrating that it plays an important role in melanoma progression. We found that silencing Myo7a by means of RNAi inhibited melanoma cell growth through upregulation of cell cycle regulator p21 (also known as CDKN1A) and suppressed melanoma cell migration and invasion through downregulation of RhoGDI2 (also known as ARHGDIB) and MMP9. Furthermore, Myo7a depletion suppressed melanoma cell metastases to the lung, kidney and bone in mice. In contrast, overexpression of Myo7a promoted melanoma xenograft growth and lung metastasis. Importantly, Myo7a levels are remarkably elevated in human melanoma patients. Collectively, we demonstrated for the first time that Myo7a is able to function in non-specialized cells, a finding that reveals the complicated disease-related roles of Myo7a, especially in melanomas.
Mechano-sensitization of mammalian neuronal networks through expression of the bacterial large-conductance mechanosensitive ion channel
Authors: Soloperto Alessandro , Boccaccio Anna , Contestabile Andrea , Moroni Monica , Hallinan Grace I. , Palazzolo Gemma , Chad John , Deinhardt Katrin , Carugo Dario , Difato Francesco 
Published: January 2018

ABSTRACT
Development of remote stimulation techniques for neuronal tissues represents a challenging goal. Among the potential methods, mechanical stimuli are the most promising vectors to convey information non-invasively into intact brain tissue. In this context, selective mechano-sensitization of neuronal circuits would pave the way to develop a new cell-type-specific stimulation approach. We report here, for the first time, the development and characterization of mechano-sensitized neuronal networks through the heterologous expression of an engineered bacterial large-conductance mechanosensitive ion channel (MscL). The neuronal functional expression of the MscL was validated through patch-clamp recordings upon application of calibrated suction pressures. Moreover, we verified the effective development of in-vitro neuronal networks expressing the engineered MscL in terms of cell survival, number of synaptic puncta and spontaneous network activity. The pure mechanosensitivity of the engineered MscL, with its wide genetic modification library, may represent a versatile tool to further develop a mechano-genetic approach.
This article has an associated First Person interview with the first author of the paper.