bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term clinical outcomes in sustained responders with chronic hepatitis C after treatment with direct-acting antivirals
Authors: Alem Shereen Abdel , Eletreby Rasha , Abdellatif Zeinab , Ramadan Ahmed , Nagy Ahmed , AbdAllah Mohamed , Elsharkawy Aisha , Fouad Rabab , Esmat Gamal , Tantawi Omnia 
Published: July 2021

Objective:
Little is known about how the achievement of sustained virological response (SVR) after treatment with direct-antiviral agents (DAAs) affects fibrosis and clinical outcomes in the long term. Our study aimed to evaluate the impact of achieving SVR on long-term changes in fibrosis and clinical outcomes in CHC patients treated with different DAAs-based regimens.

Methods:
a prospective, 3-year follow-up study of 113 CHC patients who had achieved SVR after treatment with different DAAs-based regimens between January and June 2015 was conducted. The clinical outcomes of SVR on the biochemical profile, changes in fibrosis, ALBI score and grade and occurrence of liver-related events were analyzed.

Results:
Overall, liver function parameters and serum alpha-fetoprotein level showed improvement from baseline to SVR12 and remained steady thereafter. Moreover, the ALBI score showed nonsignificant change at baseline to SVR12 (P = 0.2) but it was significantly better at 3-years follow-up than at SVR12 (P = 0.001). Regarding liver stiffness (LS) by transient elastography, a significant decrease in TE values was observed between baseline to SVR12 (P ≤ 0.0001) as well as between SVR12 to 3-years follow-up (P = 0.0005). Stratified by fibrosis stage, patients with advanced fibrosis and cirrhosis showed a more pronounced and significant improvement of LS during follow-up after SVR compared to patients with less advanced fibrosis stage. During the follow-up period, 3 (5.2%) cirrhotic patients developed liver-related events, including 2 (3.4%) patients with de novo HCC and one (1.7%) patient experienced ascites for the first time.

Conclusion:
This 3-year follow-up study provides evidence for the durability of SVR, improvement of liver function parameters and ALBI score and grade in patients with an advanced stage of fibrosis, in particular, and reduction of the clinical events after successful treatment with DAAs.
Comparison of transient elastography and Model for End-Stage Liver Disease-sodium to Model for End-Stage Liver Disease-sodium alone to predict mortality and liver transplantation
Authors: Trivedi Hirsh D. , Danford Christopher J. , Iriana Sentia , Ochoa-Allemant Pedro , Rourke Meredith , Yang Kuen-Cheh , Curry Michael P. , Lai Michelle 
Published: July 2021

Objectives
Model for End-Stage Liver Disease (MELD) alone and with sodium (MELD-Na) have decreasing predictive capacity as trends in liver disease evolve. We sought to combine transient elastography (TE) with MELD-Na to improve its predictive ability.

Methods
This is a retrospective cohort study comparing the use of TE, MELD-Na, and composite MELD-Na-TE to predict liver transplantation and all-cause mortality, with hepatic decompensation as a secondary outcome. Cox proportional hazards regression was used to measure predictive ability and control for confounders.

Results
Of the 214 patients, the mean age was 53 years with 35% being female and 76% being Caucasian. Hepatitis C (59%) and nonalcoholic fatty liver disease (22%) were the most frequent liver disease etiologies. On univariable analysis, MELD-Na [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06–1.2, P < 0.001], TE (HR 1.04, 95% CI 1.03–1.06, P < 0.001) and composite MELD-Na-TE (HR 1.13, 95% CI 1.08–1.19, P < 0.001) were associated with death or transplant. On multivariable analysis, MELD-Na was no longer significant (HR 1.08, 95% CI 0.95–1.22, P = 0.27) after adjusting for TE (HR 1.05, 95% CI 1.03–1.07, P < 0.001) while composite MELD-Na-TE remained significant (HR 1.16, 95% CI 1.09–1.24, P < 0.001). Composite MELD-Na-TE predicts mortality or liver transplant with the highest C-statistic of 0.81. Age (HR 1.05, 95% CI 1–1.09, P = 0.04), TE (HR 1.04, 95% CI 1.03–1.06, P < 0.001) and composite MELD-Na-TE (HR 1.11, 95% CI 1.06–1.15, P < 0.001) were significantly associated with hepatic decompensation.

Conclusion
Composite MELD-Na-TE better predicts liver transplantation, death, and hepatic decompensation compared to MELD/MELD-Na or TE alone.
Functional gastrointestinal disorders as predictors of suicidal ideation. An observational study
Authors: Deutsch David , Bouchoucha Michel , Devroede Ghislain , Raynaud Jean-Jacques , Sabate Jean-Marc , Benamouzig Robert 
Published: July 2021

Background/objectives
Suicidal ideation (SI), a symptom of depression, is known to be associated with irritable bowel syndrome (IBS) but is not known to be associated with other functional gastrointestinal disorders (FGIDs). However, the source of this association is discussed. It could be related to a possible abnormal biochemical pathway implicating neurotransmitters common to both disorders like serotonin or pain and an ill-being associated with a chronic disorder of unknown etiology. The present study aims to search for the FGIDs associated with suicidal ideation.

Design
Observational study.

Methods
A total of 1469 patients with FGIDs (71% of women) were included in the present study. They filled the Rome III questionnaire, Beck depression inventory, and state and trait anxiety questionnaires. Data were analyzed using analysis of variance with Bonferroni correction and logistic regression analysis.

Results
Suicidal ideation was reported by 15% of patients, associated with increased scales of depression (P < 0.001), state (P = 0.006), and trait anxiety (P = 0.021). Clinically, these patients reported a higher prevalence of IBS-diarrhea subtype (P = 0.045), fecal incontinence (P = 0.020), soiling (P = 0.016), and difficult defecation (P = 0.005), and higher perceived severity for constipation, diarrhea, bloating, and abdominal pain (P < 0.001 for all scales).

Conclusions
This study shows that only functional bowel and functional anorectal disorders are associated with suicidal ideation. This result must be taken into account in the management of these patients.
Recent lessons learned for ex-vivo platelet production
Authors: Tang Alice , Mendelson Avital 
Published: July 2021

Purpose of review
Platelet transfusion can be life-saving but carries a risk of infection or alloimmunization and is limited by insufficient donor sources and restricted unit shelf life. Generating sufficient platelets in vitro to replace a unit of collected blood remains a challenge. Here, we examine the latest advances in the regulation of megakaryocyte maturation and expansion along with platelet formation and survival. We also discuss alternative therapies investigated to induce platelet production.

Recent findings
Recent studies examined candidate niche cells in the bone marrow microenvironment for promoting platelet formation and developed an explant-based bioreactor to enhance platelet production ex vivo. Chemical inhibitors were examined for their ability to promote megakaryocyte maturation and expansion. Microparticles from megakaryocytes or platelets were found to improve megakaryocyte maturation and platelet formation. Membrane budding was identified as a novel mode of platelet formation. Lastly, a chemical inhibitor to improve cold-stored platelets was identified.

Summary
Recent advances in the regulation of megakaryocyte expansion and platelet production provide exciting promise for the development of improved approaches to generate platelets in vitro. These findings bring the field one step closer to achieving the ultimate goal of creating a unit of platelets without the need for donation.
The place of robotic-assisted laparoscopy for BPO surgical management in 2021
Authors: Grobet-Jeandin Elisabeth , Pinar Ugo , Rouprêt Morgan 
Published: July 2021

Purpose of review
Robot-assisted laparoscopic simple prostatectomy (RASP) is being used increasingly for the surgical treatment of benign prostatic obstruction (BPO). Our purpose is to review the main outcomes of RASP for the management of BPO.

Recent findings
A computerised bibliographic search of Medline was performed for articles that included detailed results of RASP, published over the past 2 years. Although RASP seems to be associated with better perioperative and functional outcomes, this procedure remains expensive when compared to open or endoscopic surgery. However, considering the enhanced safety of RASP compared to open simple prostatectomy and its favourable learning-curve when compared to endoscopic laser enucleation, RASP seems to be a good and effective option in centres with extended robotic expertise. Single-port robotic surgery appeared to be safe and effective in two preliminary studies. Other studies reported interesting and improved results for the preservation of ejaculatory function.

Summary
Many RASP techniques have been developed, with the common goal of improving the quality of life of patients. Although the cost of RASP is higher than open surgery, the perioperative benefits of the robotic approach make RASP a favourable option in centres with extended robotic expertise.
Laser endoscopic procedures on the prostate: it is the small details that count
Authors: Taratkin Mark , Azilgareeva Camilla , Taratkina Daria , Goryacheva Evgenia , Rapoport Leonid , Enikeev Dmitry 
Published: July 2021

Purpose of review
This review aims to highlight the pros and cons of each laser device and to consider additional possible milestones for the development of laser technologies in the surgical treatment of benign prostate hyperplasia.

Recent findings
Over the last three decades, lasers’ role in endourology has gone from strength to strength. Specifically, the primary techniques where laser surgery for BPO relief is concerned are vaporization and enucleation. The idea behind vaporization is that lasers are able to vaporize substantial amounts of tissue due to deep ablation depth and increased power. The most efficient devices for vaporization are those affecting hemoglobin as primary chromophore and/or using a continuous firing mode (KTP/LBO:YAG, diode lasers, Tm:YAG). As for enucleation, multiple devices have been suggested for the adequate anatomical enucleation of the prostate (EEP). As it is a skill-dependent technique, the EEP is effective irrespective of which device the surgeon uses. However, some devices have shown significant advances where enucleation is concerned.

Summary
The choice of device should be based primarily on the technique the surgeon prefers. Although the most suitable lasers for vaporization are hemoglobin-targeting and/or continuous wave devices, the EEP may be done with any enough powered laser, yet some provides specific effects which you should be aware before the surgery.
Use of Lacrimal Symptoms Questionnaire After Punctoplasty Surgery: Retrospective Data of Technical Strategy
Authors: Meduri Alessandro , Tumminello Giuseppe , Oliverio Giovanni William , Inferrera Leandro , Delia Gabriele , Aragona Pasquale , Cicciù Marco 
Published: July 2021

Abstract
The goal of this study is to evaluate postpunctoplasty symptoms with lacrimal symptoms questionnaire (Lac-Q). A retrospective study was conducted on 31 patients (14 men and 17 woman) with a diagnosis of canalicular stenosis: 26 patients with unilateral occlusion and 5 patients with bilateral occlusion. The Lac-Q was administered preoperative and at 1, at 3, and at 6 months following the surgery. Moreover, the Lac-Q questionnaire was administered by an independent observer (SI). The mono-lateral and bilateral postoperative Lac-Q score showed a significant improvement of symptoms at 1, 3, and 6 months than the preoperative results. The Lac-Q questionnaire is a way to evaluate the quality of outcomes after punctoplasty surgery. In this study, all patients showed a significant improvement of symptoms after surgery.
What is behavior? No seriously, what is it?
Authors: Calhoun Adam , Hady Ahmed El 
Published: July 2021

AbstractStudying ‘behavior’ lies at the heart of many disciplines. Nevertheless, academics rarely provide an explicit definition of what ‘behavior’ actually is. What range of definitions do people use, and how does that vary across disciplines? To answer these questions we have developed a survey to probe what constitutes ‘behavior’. We find that academics adopt different definitions of behavior according to their academic discipline, animal model that they work with, and level of academic seniority. Using hierarchical clustering, we identify at least six distinct types of ‘behavior’ which are used in seven distinct operational archetypes of ‘behavior’. Individual respondents have clear consistent definitions of behavior, but these definitions are not consistent across the population. Our study is a call for academics to clarify what they mean by ‘behavior’ wherever they study it, with the hope that this will foster interdisciplinary studies that will improve our understanding of behavioral phenomena.
Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis
Authors: Zeraatkar Dena , Cusano Ellen , Martinez Juan Pablo Díaz , Qasim Anila , Mangala Sophia O. , Kum Elena , Bartoszko Jessica J. , Devji Tahira , Agoritsas Thomas , Lamontagne Francois , Rochwerg Bram , Vandvik Per O , Brignardello-Petersen Romina , Siemieniuk Reed 
Published: July 2021

AbstractObjectiveTo compare the effects of interleukin-6 (IL-6) receptor blockers, with or without corticosteroids, on mortality in patients with COVID-19.DesignSystematic review and network meta-analysisData sourcesWHO COVID-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analysesStudy selectionTrials in which people with suspected, probable, or confirmed COVID-19 were randomized to IL-6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care.ResultsWe assessed the risk of bias of included trials using a modification of the Cochrane risk of bias tool. We performed a Bayesian fixed effect network meta-analysis and assessed the certainty of evidence using the GRADE approach.We identified 45 eligible trials (20,650 patients), 36 (19,350 patients) of which could be included in the network meta-analysis. 27 of 36 trials were rated at high risk of bias, primarily due to lack of blinding. Tocilizumab (20 more per 1000, 15 fewer to 59 more; low certainty) and sarilumab (11 more per 1000, 38 fewer to 55 more; low certainty) alone may not reduce the risk of death. Tocilizumab, in combination with corticosteroids, probably reduces the risk of death compared to corticosteroids alone (35 fewer per 1000, 52 fewer to 18 more; moderate certainty) and sarilumab, in combination with corticosteroids, may reduce the risk of death compared to corticosteroids alone (43 fewer, 73 fewer to 12 more; low certainty). Tocilizumab and sarilumab, both in combination with corticosteroids, may have similar effects (8 more per 1000, 20 fewer to 35 more; low certainty).ConclusionIL-6 receptor blockers, when added to standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality. Tocilizumab and sarilumab may have similar effectiveness.Systematic review registrationNAWhat is already known on this topic?IL-6 receptor blockers have immunosuppressive effects that may be important in COVID-19 patients with immune system dysfunction and inflammationCorticosteroids reduce the risk of death in patients with severe or critical COVID-19What this study addsOur systematic review and network meta-analysis provides a comprehensive review of the evidence addressing the effects of IL-6 receptor blockers, alone or in combination with corticosteroids, in COVID-19IL-6 receptor blockers when added to a standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality.Tocilizumab and sarilumab in combination with corticosteroids may have similar effectiveness for reducing mortality.
Impairment of a cyanobacterial glycosyltransferase that modifies a pilin results in biofilm development
Authors: Suban Shiran , Sendersky Eleonora , Golden Susan S , Schwarz Rakefet 
Published: July 2021

SummaryA biofilm inhibiting mechanism operates in the cyanobacteriumSynechococcus elongatus. Here, we demonstrate that the glycosyltransferase homolog, Ogt, participates in the inhibitory process – inactivation ofogtresults in robust biofilm formation. Furthermore, a mutational approach shows requirement of the glycosyltransferase activity for biofilm inhibition. This enzyme is necessary for glycosylation of the pilus subunit and for adequate pilus formation. In contrast to wild-type culture in which most cells exhibit several pili, only 25% of the mutant cells are piliated, half of which possess a single pilus. In spite of this poor piliation, natural DNA competence was similar to that of wild-type, therefore, we propose that the unglycosylated pili facilitate DNA transformation. Additionally, conditioned medium from wild-type culture, which contains a biofilm inhibiting substance(s), only partially blocks biofilm development by theogt-mutant. Thus, we suggest that inactivation ofogtaffects multiple processes including production or secretion of the inhibitor as well as the ability to sense or respond to it.Originality-Significance StatementThe molecular mechanisms that underlie biofilm development in cyanobacteria are just emerging. Using the cyanobacteriumS. elongatusas a model, we demonstrate that glycosylation of the pilus subunit is crucial for the biofilm self-suppression mechanism, however, it is dispensable for DNA competence.
Proteolytic Activation of Human-specific Olduvai Domains by the Furin Protease
Authors: Pacheco Ashley , Issaian Aaron , Davis Jonathan , Anderson Nathan , Nemkov Travis , Vögeli Beat , Hansen Kirk , Sikela James M. 
Published: July 2021

ABSTRACTOlduvai protein domains (formerly DUF1220) show the greatest human-specific increase in copy number of any coding region in the genome and are highly correlated with human brain evolution and cognitive disease. The majority of human copies are found within four NBPF genes organized in a variable number of a tandemly arranged three-domain blocks called Olduvai triplets. Here we show that these human-specific Olduvai domains are posttranslationally processed by the furin protease, with a cleavage site occurring once at each triplet. These findings suggest that all expanded human-specific NBPF genes encode proproteins consisting of many independent Olduvai triplet proteins which are activated by furin processing. The exceptional correlation of Olduvai copy number and brain size taken together with our new furin data, indicates the ultimate target of selection was a rapid increase in dosage of autonomously functioning Olduvai triplet proteins, and that these proteins are the primary active agent underlying Olduvai’s role in human brain expansion.
Ca2+-dependent liquid-liquid phase separation underlies intracellular Ca2+ stores
Authors: Mayfield Joshua E. , Pollak Adam J. , Worby Carolyn A. , Xu Joy C. , Tandon Vasudha , Newton Alexandra C. , Dixon Jack E. 
Published: July 2021

AbstractEndoplasmic/sarcoplasmic reticulum Ca2+ stores are essential to myriad cellular processes, however, the structure of these stores is largely unknown and existing models neither explain observations made in vivo nor sufficiently account for physiological data. We investigate CASQ1 - the major Ca2+ binding protein of skeletal muscle – and discover Ca2+-dependent liquid-liquid phase separation activity. The intrinsic disorder of CASQ1 underlies this activity and is regulated via phosphorylation by the secretory pathway kinase FAM20C. This novel divalent cation driven condensation demonstrates liquid-liquid phase separation occurs within the endoplasmic/sarcoplasmic reticulum, mechanistically explains efficient Ca2+ buffering and storage, and represents a largely unexplored mechanism of divalent-cation driven protein association.
Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition
Authors: Chen Rou-An , Wu Wei-Kai , Panyod Suraphan , Liu Po-Yu , Chuang Hsiao-Li , Chen Yi-Hsun , Lyu Qiang , Hsu Hsiu-Ching , Lin Tzu-Lung , Shen Ting-Chin David , Yang Yu-Tang , Zou Hsin-Bai , Huang Huai-Syuan , Lin Yu-En , Chen Chieh-Chang , Ho Chi-Tang , Lai Hsin-Chih , Wu Ming-Shiang , Hsu Cheng-Chih , Sheen Lee-Yan 
Published: July 2021

AbstractAntibiotics used as growth promoters in livestock and animal husbandry can be detected in animal-derived food. Epidemiological studies have implicated that exposure to these antibiotic residues in food may be associated to childhood obesity. Herein, the effect of exposure to residual dose of tylosin—an antibiotic growth promoter—on host metabolism and gut microbiota was explored in vivo. Theoretical maximal daily intake (TMDI) doses of tylosin were found to facilitate high-fat diet-induced obesity, induce insulin resistance, and perturb the composition of gut microbiota in mice. The obesity-related phenotypes were transferrable to germ-free recipient mice, indicating that the effects of TMDI dose of tylosin on obesity and insulin resistance occurred mainly via alteration of the gut microbiota. Tylosin TMDI exposure restricted to early life, which is the critical period of gut microbiota development, altered the abundance of specific bacteria related to host metabolic homeostasis later in life. Moreover, early-life exposure to tylosin TMDI was sufficient to modify the ratio of primary to secondary bile acids, thereby inducing lasting metabolic consequences via the downstream FGF15 signaling pathway. Altogether, these findings demonstrate that exposure to very low dose of antibiotic residues, whether continuously or in early life, can exert long-lasting effects on host metabolism by altering gut microbiota and its metabolites.ImportanceEvidence has indicated that chronic exposure to antibiotic residues in food could contribute to obesity. However, few studies have investigated the effect of chronic exposure to very low-dose antibiotic residue in food (~1000-fold lower than the therapeutic dose) on gut microbiota and host metabolism. Our study demonstrates that even with limited exposure in early life, a residual dose of tylosin causes lasting metabolic disturbances through altering gut microbiota and its metabolites. Our findings reveal that the gut microbiota is susceptible to previously ignored environmental factors.
BAM15 treats mouse sepsis and sepsis-AKI, linking circulating mitochondrial DNA and tubule reactive oxygen species
Authors: Tsuji Naoko , Tsuji Takayuki , Yamashita Tetsushi , Hu Xuzhen , Yuen Peter S.T. , Star Robert A. 
Published: July 2021

AbstractThe pathogenesis of sepsis is complex and heterogeneous; hence, a precision medicine strategy may be required. Acute kidney injury (AKI) following sepsis portends higher mortality. Overproduction of mitochondrial reactive oxygen species (mtROS) is a potential mediator of sepsis and sepsis-induced AKI. BAM15 is a chemical uncoupler that dissipates the mitochondrial proton gradient without generating mtROS, and improves experimental renal ischemic injury. We injected BAM15 into mice at 0 or 6 hours after cecal ligation and puncture (CLP) treated with fluids and antibiotics. BAM15 reduced mortality, even when started at 6 hours, when mice were ill, and reduced kidney damage but did not affect other organs. Serial plasma and urinary levels of mitochondrial DNA (mtDNA) were increased following CLP, and decreased after BAM15 (at 0 and at 6 hours).In vitroBAM15 prevented mtROS overproduction and mtDNA release from septic kidney tubule cells; mtROS generation correlated with mtDNA release. BAM15 also promotes mitochondrial biogenesis signaling. We conclude that BAM15 is an effective preventive and therapeutic candidate in experimental sepsis, and that BAM15 and mtDNA are mechanistically linked via mtROS, which may form a drug-companion diagnostic pair to improve precision medicine approaches to diagnosing and treating clinical sepsis.