Πέμπτη, 13 Σεπτεμβρίου 2018

Role of Relative Malnutrition in Exercise-Hypogonadal Male Condition

Objective Exercise Hypogonadal Male Condition (EHMC) is a well-recognized condition in women but much less understood in men. The aim of this case report is to highlight exercise induced hypogonadotropic hypogonadism in a male who recovered with lifestyle modifications. Methods We report a case of an adolescent male who developed hypogonadotropic hypogonadism secondary to excessive exercise and malnutrition that was followed up for a year without exogenous testosterone supplementation. Informed consent was obtained from the patient for his information to be used in a manuscript submitted to a journal. Results 18-year-old adolescent male presented to the clinic with symptoms of fatigue and low endurance, low libido and lack of morning erections. At the time of his presentation, he was running about 60 miles per week for school cross-country team in addition to cross training with kick-boxing. Physical examination was remarkable for low BMI (Body mass index) of 19 but was otherwise normal. Biochemical work up confirmed hypogonadotropic hypogonadism and a mild pancytopenia. Other pituitary laboratory values and MRI of the brain were unremarkable. Bone marrow biopsy performed for anemia showed features consistent with malnutrition. With a working diagnosis of EHMC, he was advised to reduce the frequency and intensity of his exercise and increase calorie intake. Cell counts and testosterone levels normalized and his symptoms resolved without any further interventions. Conclusion Significant reversible hypogonadism can develop after intensive and prolonged exercise. One of the mechanisms of hypogonadism in endurance athletes performing intensive exercise could be relative malnutrition. Further studies to evaluate the role of nutrition and BMI in male endurance athletes presenting with hypogonadism are needed to identify the underlying mechanism of this condition. No funding received for this work. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. Conflict of Interest: The authors declare that there are no conflicts of interest. © 2018 American College of Sports Medicine

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Mental health in EMS and signs to look for in partners

Our co-hosts wrap up National Suicide Prevention Week with a discussion on signs to look for in ourselves and partners

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Diverse Plasmids Harboring blaCTX-M-15 in Klebsiella pneumoniae ST11 Isolates from Several Asian Countries

Microbial Drug Resistance, Ahead of Print.


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Divergent Roles for cAMP--PKA Signaling in the Regulation of Filamentous Growth in Saccharomyces cerevisiae and Saccharomyces bayanus

The cyclic AMP - Protein Kinase A (cAMP-PKA) pathway is an evolutionarily conserved eukaryotic signaling network that is essential for growth and development. In the fungi, cAMP-PKA signaling plays a critical role in regulating cellular physiology and morphological switches in response to nutrient availability. We undertook a comparative investigation of the role that cAMP-PKA signaling plays in the regulation of filamentous growth in two closely related budding yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus. Using chemical and genetic perturbations of this pathway and its downstream targets we discovered divergent roles for cAMP-PKA signaling in the regulation of filamentous growth. While cAMP-PKA signaling is required for the filamentous growth response in both species, increasing or decreasing the activity of this pathway leads to drastically different phenotypic outcomes. In S. cerevisiae, cAMP-PKA inhibition ameliorates the filamentous growth response while hyper-activation of the pathway leads to increased filamentous growth; the same perturbations in S. bayanus result in the obverse. Divergence in the regulation of filamentous growth between S. cerevisiae and S. bayanus extends to downstream targets of PKA, including several kinases, transcription factors, and effector proteins. Our findings highlight the potential for significant evolutionary divergence in gene network function, even when the constituent parts of such networks are well conserved.



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Empirical Comparisons of Different Statistical Models To Identify and Validate Kernel Row Number-Associated Variants from Structured Multi-parent Mapping Populations of Maize

Advances in next generation sequencing technologies and statistical approaches enable genome-wide dissection of phenotypic traits via genome-wide association studies (GWAS). Although multiple statistical approaches for conducting GWAS are available, the power and cross-validation rates of many approaches have been mostly tested using simulated data. Empirical comparisons of single variant (SV) and multi-variant (MV) GWAS approaches have not been conducted to test if a single approach or a combination of SV and MV is effective, through identification and cross-validation of trait associated loci. In this study, kernel row number (KRN) data were collected from a set of 6,230 entries derived from the Nested Association Mapping (NAM) population and related populations. Three different types of GWAS analyses were performed: 1) single-variant (SV), 2) stepwise regression (STR) and 3) a Bayesian-based multi-variant (MV) model. Using SV, STR, and BMV models, 257, 300, and 442 KRN-associated variants (KAVs) were identified in the initial GWAS analyses. Of these, 231 KAVs were subjected to genetic validation using three unrelated populations that were not included in the initial GWAS. Genetic validation results suggest that the three GWAS approaches are complementary. Interestingly, KAVs in low recombination regions were more likely to exhibit associations in independent populations than KAVs in recombinationally active regions, probably as a consequence of linkage disequilibrium. The KAVs identified in this study have the potential to enhance our understanding of the genetic basis of ear development.



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A Drosophila CRISPR/Cas9 Toolkit for Conditionally Manipulating Gene Expression in the Prothoracic Gland as a Test Case for Polytene Tissues

Targeting gene function with spatial or temporal specificity is a key goal in molecular genetics. CRISPR-Cas9 has greatly facilitated this strategy, but some standard approaches are problematic. For instance, simple tissue-specific or global overexpression of Cas9 can cause significant lethality or developmental delays even in the absence of gRNAs. In particular, we found that Gal4-mediated expression of UAS-Cas9 in the Drosophila prothoracic gland (PG) was not a suitable strategy to disrupt gene expression, since Cas9 alone caused widespread lethality. The PG is widely used for studying endocrine gland function during animal development, but tools validating PG-specific RNAi phenotypes are lacking. Here, we present a collection of modular gateway-compatible CRISPR-Cas9 tools that allow precise modulation of target gene activity with temporal and spatial specificity. We also demonstrate that Cas9 fused to the progesterone ligand-binding domain can be used to activate gene expression via RU486. Using these approaches, we were able to avoid the lethality associated with simple GAL4-mediated overexpression of Cas9 in the PG. Given that the PG is a polytene tissue, we conclude that these tools work effectively in endoreplicating cells where Cas9 has to target multiple copies of the same locus. Our toolkit can be easily adapted for other tissues and can be used both for gain- and loss-of-function studies.



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The specificity of SPECT-CT for the diagnosis of discogenic pain: implications for the future of the lumbar fusion outcome score (LUFOS)

We read with great interest the article of Van de Kelft et al. [1] on single-photon emission computerized tomography with computerized tomography (SPECT-CT) for the evaluation of patients with chronic axial low back pain (CLBP).

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Editorial Board



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Table of Contents



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Meetings Calendar



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It is time to remove the stigma from glial scars: re: Lentivirus-mediated silencing of the CTGF gene suppresses the formation of glial scar tissue in a rat model of spinal cord injury

For over two decades, glial scars were stigmatized for creating a non-permissive environment for axonal regrowth and hampering functional recovery after spinal cord injury (SCI). Since the identification of myelin-derived inhibitors [1,2], much effort has been dedicated to the development of therapies designed to inhibit glial scar formation or change the molecular environment within the scar (chondroitin sulfate proteoglycan barrier) [3,4].

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Intraoperative and postoperative analgesia technique following posterior iliac crest bone graft harvesting in spine surgery: a closer look

I read with interest the article of Sheha et al. in a recent issue of The Spine Journal [1] in which the authors performed a randomized study on 40 patients and demonstrated that pain on the surgical side (iliac crest bone graft harvesting) was slightly higher but was not clinically different from that on the nonsurgical side in patients undergoing spine surgery. The authors should be congratulated for performing a well-designed study on an important topic (eg, acute pain) on patients undergoing spine surgery [2,3].

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Phenotype‐genotype relations in facioscapulohumeral muscular dystrophy type 1

Clinical Genetics, Volume 0, Issue ja, -Not available-.


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Metaboreceptor polymorphisms: Do genes determine your blood pressure response to exercise?

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Ventilatory and integrated physiological responses to chronic hypercapnia in goats

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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What is Short Term Potentiation and Why it May be Relevant to Obstructive Sleep Apnea?

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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When gain is greater than loss: Effects of physical activity on insulin sensitivity after short‐term inactivity in older subjects

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Metabolic dysfunction in a rat model of early‐life scarcity‐adversity: Modulatory role of cafeteria diet

Experimental Physiology, Volume 0, Issue ja, -Not available-.


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Mechanical Performance of Traditional Distraction-Based Dual Growing Rod Constructs

Growing rod constructs are an important contribution in the treatment of children with early onset scoliosis even though these devices experience high rates of rod fracture. The mechanical performance of traditional, distraction-based dual growing rod constructs is not well understood, and mechanical models for predicting device performance are limited.

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Incidence and Considerations of 90 day Readmissions following Posterior Lumbar Fusion

Posterior lumbar fusion (PLF) is a commonly performed procedure. The evolution of bundled payment plans is beginning to require physicians to more closely consider patient outcomes up to 90 days after an operation. Current quality metrics and other databases often consider only 30 postoperative days. The relatively new Healthcare Cost and Utilization Project National Readmissions Database (HCUP-NRD) tracks patient-linked hospital admissions data for up to one calendar year.

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Page, Wolfberg & Wirth names new partners

MECHANICSBURG, Pa. — Page, Wolfberg & Wirth ("PWW"), the Nation's leading EMS industry law firm has named Daniel J. Pedersen and Ryan S. Stark as partners in the practice. Mr. Stark and Mr. Pedersen became partners on September 1, 2018 and have assumed additional management and planning responsibilities within the firm. PWW Founding Partner, Doug Wolfberg says,...

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Stroke destination: An opportunity for innovation in system design

Solutions to the transportation decision challenges raised by research like the DAWN trial and DEFUSE-3 trial

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Interaction of positive coactivator 4 with histone 3.3 protein is essential for transcriptional activation of the luteinizing hormone receptor gene

Publication date: Available online 13 September 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Peng Zhao, Raghuveer Kavarthapu, Rajakumar Anbazhagan, Mingjuan Liao, Maria L. Dufau

Abstract

The luteinizing hormone receptor (LHR) is essential for sexual development and reproduction in mammals. We have established that Sp1 has a central role in derepression of LHR gene transcription induced by Trichostatin A (TSA) in MCF7 cells. Moreover, the co-activator PC4 which associates directly with Sp1 at the LHR promoter is essential for TSA-mediated LHR transcription. This study explores interactions of PC4 with histone proteins, which presumably triggers chromatin modifications during LHR transcriptional activation. TSA treatment of MCF7 cells expressing PC4-Flag protein induces acetylation of histone 3 (H3) and immunoprecipitation (IP) studies revealed its interaction with PC4-Flag protein. MS/MS analysis of the protein complex obtained after IP from TSA treated samples detected H3.3 acetylated at K9, K14, K18, K23 and K27 as a PC4 interacting protein. The association of PC4 with H3.3 was corroborated by IP and re-ChIP using H3.3 antibody. Similarly, IP and reChIP showed association of PC4 with H3 acetylated protein. Knockdown of PC4 in MCF7 cells reduced H3.3 enrichment, H3 acetylation at the Lys sites and LHR promoter activity in TSA treated cells despite an increase in H3 and H3.3 protein induced by TSA, linking PC4 to H3 acetylation and LHR transcription. Depletion of H3.3 A/B in MCF7 cells impair chromatin accessibility and enrichment of Pol II and TFIIB at the LHR promoter and its activation, resulting in marked reduction of LHR gene expression. Together, these findings point to the critical role of PC4 and its association with acetylated H3.3 in TSA-induced LHR gene transcription.



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The motor unit number index (MUNIX) profile of patients with adult Spinal Muscular Atrophy

Publication date: Available online 13 September 2018

Source: Clinical Neurophysiology

Author(s): Giorgia Querin, Timothée Lenglet, Rabab Debs, Tanya Stojkovic, Anthony Behin, François Salachas, Nadine Le Forestier, Maria del Mar Amador, Lucette Lacomblez, Vincent Meininger, Gaelle Bruneteau, Pascal Laforêt, Sophie Blancho, Véronique Marchand-Pauvert, Peter Bede, Jean-Yves Hogrel, Pierre-François Pradat

Abstract
Objective

Objective of this study is the comprehensive characterisation of motor unit (MU) loss in type III and IV Spinal Muscular Atrophy (SMA) using motor unit number index (MUNIX), and evaluation of compensatory mechanisms based on MU size indices (MUSIX).

Methods

Nineteen type III and IV SMA patients and 16 gender- and age-matched healthy controls were recruited. Neuromuscular performance was evaluated by muscle strength testing and functional scales. Compound motor action potential (CMAP), MUNIX and MUSIX were studied in the abductor pollicis brevis (APB), abductor digiti minimi (ADM), deltoid, tibialis anterior and trapezius muscles. A composite MUNIX score was also calculated.

Results

SMA patients exhibited significantly reduced MUNIX values (p < 0.05) in all muscles, while MUSIX was increased, suggesting active re-innervation. Significant correlations were identified between MUNIX/MUSIX and muscle strength. Similarly, composite MUNIX scores correlated with disability scores. Interestingly, in SMA patients MUNIX was much lower in the ADM than in the ABP, a pattern which is distinctly different from that observed in Amyotrophic Lateral Sclerosis.

Conclusions

MUNIX is a sensitive measure of MU loss in adult forms of SMA and correlates with disability.

Significance

MUNIX evaluation is a promising candidate biomarker for longitudinal studies and pharmacological trials in adult SMA patients.



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Calibration of forest 137Cs cycling model ”FoRothCs” via approximate Bayesian computation based on 6-year observations from plantation forests in Fukushima

Publication date: October 2018

Source: Journal of Environmental Radioactivity, Volumes 193–194

Author(s): Kazuya Nishina, Shoji Hashimoto, Naohiro Imamura, Shinta Ohashi, Masabumi Komatsu, Shinji Kaneko, Seiji Hayashi

Abstract

Predicting the environmental fate of 137Cs in forest ecosystems along with the concentrations of 137Cs in tree parts are important for the managements of radioactively contaminated forests. In this study, we calibrate the Forest RothC and Cs model (FoRothCs), a forest ecosystem 137Cs dynamics model, using observational data obtained over six years from four forest sites with different levels of 137Cs contamination from Fukushima Prefecture. To this end, we applied an approximate Bayesian computation (ABC) technique based on the observed 137Cs concentrations (Bq kg−1) of five compartments (leaf, branch, stem, litter, and soil) in a Japanese cedar plantation. The environmental decay (increment) constants of the five compartments were used as the summary statistics (i.e., the metric for model performance) to infer the five parameters related to 137Cs transfer processes in FoRothCs. The ABC technique successfully reconciled the model outputs with the observed trends in 137Cs concentrations at all sites during the study period. Furthermore, the estimated parameters are in agreement with the literature values (e.g., the root uptake rates of 137Cs). Our study demonstrates that model calibration with ABC based on the trends in 137Cs concentrations of multi compartments is useful for reducing the prediction uncertainty of 137Cs dynamics in forest ecosystems.



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Molecular genetics of the POMT1-related muscular dystrophy-dystroglycanopathies

Publication date: Available online 12 September 2018

Source: Mutation Research/Reviews in Mutation Research

Author(s): Pengzhi Hu, Lamei Yuan, Hao Deng

ABSTRACT

Protein O-mannosyltransferase 1 (POMT1) is a critical enzyme participating in the first step of protein O-mannosylation. Mutations in the coding gene, POMT1, have been described to be related to a series of autosomal recessive disorders associated with defective alpha-dystroglycan glycosylation, later termed muscular dystrophy-dystroglycanopathies (MDDGs). MDDGs are characterized by a broad phenotypic spectrum of congenital muscular dystrophy or later-onset limb-girdle muscular dystrophy, accompanied by variable degrees of intellectual disability, brain defects, and ocular abnormalities. To date, at least 76 disease-associated mutations in the POMT1 gene, including missense, nonsense, splicing, deletion, insertion/duplication, and insertion-deletion mutations, have been reported in the literature. In this review, we highlight the present knowledge of the identified disease-associated POMT1 gene mutations and genetic animal models related to the POMT1 gene. This review may help further normative classification of phenotypes, assist in definite clinical and genetic diagnoses, and genetic counseling, and may comprehensively improve our understanding of the basis of complex phenotypes and possible pathogenic mechanisms involved.



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CGPS: A machine learning-based approach integrating multiple gene set analysis tools for better prioritization of biologically relevant pathways

Publication date: Available online 13 September 2018

Source: Journal of Genetics and Genomics

Author(s): Chen Ai, Lei Kong

Abstract

Gene set enrichment (GSE) analyses play an important role in the interpretation of large-scale transcriptome datasets. Multiple GSE tools can be integrated into a single method as obtaining optimal results is challenging due to the plethora of GSE tools and their discrepant performances. Several existing ensemble methods lead to different scores in sorting pathways as integrated results; furthermore, it is difficult for users to choose a single ensemble score to obtain optimal final results. Here, we develop an ensemble method using a machine learning approach called CGPS that integrates the results provided by nine prominent GSE tools into a single ensemble score (R score) to sort pathways as integrated results. Moreover, to the best of our knowledge, CGPS is the first GSE ensemble method built based on a priori knowledge of pathways and phenotypes. Compared with 10 widely used individual methods and five types of ensemble scores from two ensemble methods, we demonstrate that sorting pathways based on the R score can better prioritize relevant pathways, as established by an evaluation of 120 simulated datasets and 45 real datasets. Additionally, CGPS is applied to expression data involving the drug panobinostat, which is an anticancer treatment against multiple myeloma. The results identify cell processes associated with cancer, such as the p53 signaling pathway (hsa04115); by contrast, according to two ensemble methods (EnrichmentBrowser and EGSEA), this pathway has a rank higher than 20, which may cause users to miss this pathway in their analyses. We show that this method, which is based on a priori knowledge, can capture valuable biological information from numerous types of gene set collections, such as KEGG pathways, GO terms, Reactome, and BioCarta. CGPS is publicly available as a standalone source code at ftp://ftp.cbi.pku.edu.cn/pub/CGPS_download/cgps-1.0.0.tar.gz.



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Trajectories of self-efficacy and depressed mood, and their relationship in the first 12 months following spinal cord injury

Publication date: Available online 13 September 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Ashley Craig, Yvonne Tran, Rebecca Guest, James Middleton

Abstract
Objective

To establish self-efficacy and depressive mood trajectories in adults with spinal cord injury (SCI), determine their interrelationship over time, and determine the influence that appraisals and co-morbid physical conditions have on the development of self-efficacy.

Design

A prospective cohort design.

Setting

Inpatient rehabilitation and community settings.

Participants

Eighty-eight adults admitted consecutively into three SCI units (mean age 42.6 years, 70.4% male, 61% paraplegia).

Interventions

Multidisciplinary inpatient SCI rehabilitation.

Main outcome measures

The Moorong Self-Efficacy Scale and Hospital Anxiety and Depression Scale were used to model self-efficacy and depressive mood trajectories. Appraisals were assessed by The Appraisals of Disability Scale and frequency/type of secondary conditions using the Secondary Conditions Scale.

Analysis

Growth mixture modelling was used to determine trajectories. Dual trajectory probability analysis was used to determine concurrent changes in self-efficacy and depressive mood. Linear mixed modelling incorporating repeated measures determined the contribution of appraisals and physical complications to self-efficacy trajectories.

Results

Modelling identified four trajectories of self-efficacy and depressive mood. The majority (around 60%) of the sample was estimated to have moderate to high self-efficacy and low levels of depressive mood. Dual trajectory analysis revealed that robust self-efficacy was strongly connected to low depressive mood over time while low self-efficacy was strongly linked to clinically elevated depressive mood. Low self-efficacy was related to higher severity of secondary conditions and negative appraisals.

Conclusions

Findings highlight the importance of self-efficacy, not only as a strategic clinical measure for assessing adjustment following SCI, but they also raise implications for improving SCI rehabilitation.



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Ability of Patient Reported Outcomes to Characterize Patient Acceptable Symptom State (PASS) After Attending a Primary Care Physical Therapist/Medical Doctor Collaborative Service: Cross Sectional Study

Publication date: Available online 13 September 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Jeff Houck, Daniel Kang, Tyler Cuddeford, Sarah Rahkola

Abstract
Objectives

To determine if the patient reported outcome information system (PROMIS) physical function (PF), pain interference (PI), self-efficacy (SE) and global rating of normal function (GRNF) scales are able to accurately characterize a patient's acceptable symptom state (PASS).

Design

A cross sectional analysis, using receiver operator curves and chi-square analysis to explore criteria to determine thresholds (80/95% sensitivity/specificity) for PASS that are applicable to PROMIS and GRNF scales.

Setting

Phone survey after primary care

Participants

Ninety-four patients attending primary care for musculoskeletal problems.

Interventions

Not Applicable

Main Outcomes Measures

Accuracy and proportion of patients classified as PASS Yes or No.

Results

Receiver operator curve analysis showed significant area under the curve(AUC) values for each PROMIS scale (AUC >0.72) and the GRNF rating (AUC=0.74). Identified PROMIS thresholds suggested PASS was achieved when scores were at or slightly worse than the US population average. A score of 7 or higher and 4 or lower characterized patients that were PASS Yes/No, respectively, on the GRNF rating. A moderate (80%) specificity/sensitivity criteria yielded 72.3-73.5%% accuracy for a majority of participants (>69.9%).

Conclusion

This analysis suggests the PROMIS and GRNF scales are able to characterize PASS status with moderate accuracy (∼70%) for a large portion of patients (∼70%). New to this study is the association of self-efficacy with PASS status. PROMIS scales at or slightly worse than the US population average characterized PASS status.



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Efficacy and safety of sofosbuvir–velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis: An open-label phase 3 trial

Journal of Gastroenterology

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Postprandial bile acid levels in intestine and plasma reveal altered biliary circulation in chronic pancreatitis patients

Journal of Lipid Research

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New SMARCE1 variant in a patient with features overlapping with oculoauriculofrontonasal syndrome

Clinical Genetics, EarlyView.


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