bluuebunny/crossref_metadata_2025_split huggingface dataset:
P650 A trend to higher adoption of mesalazine suppository use for UC patients in 15 European countries
Authors: Mackenzie-Smith L , Wüthrich H , Laoun R 
Published: May 2021

Abstract

Background
In a previous abstract (ECCO 2014), we showed geographical differences between European countries in the use of 5ASA suppositories. The updated ECCO guidelines published in 2016 reiterated the importance of mesalazine suppositories in patients with ulcerative colitis: A mesalamine 1-g suppository once daily is the preferred initial treatment for mild or moderately active proctitis, mesalamine foam or enemas are an alternative, but suppositories deliver the drug more effectively to the rectum and are better tolerated [Statement 11A]. We wanted to look at the changes in mesalazine suppositories use and compare it to 2012.

Methods
We collected the data of suppositories consumption from April 2019 until March 2020 from IMS, the prevalence of UC in 2019 from the Global Health Data Exchange and the estimation of the population for 15 European countries (Czech Republic, Denmark, Estonia, Finland, France, Greece, Germany, Ireland, Latvia, Lithuania, Norway, Portugal, Spain, Sweden and the United Kingdom) from the Eurostat database. For comparison purposes, we assumed that all the patients could receive a 1000 mg daily dose of mesalazine suppository.

Results
The aggregate sales data from IMS show that 26979 kg of mesalazine suppository were consumed during the full year in 15 European countries. If we exclude Spain from the analysis, 23096 kg were consumed by 14 countries and this is a 1.6-fold increase in comparison to 2012. Assuming a cut-off of 33% of UC patients receiving the maximum daily dose of 1000 mg, 4 countries showed high use of mesalazine suppositories above that cut off: Greece, Ireland, Spain and Portugal. Except for Ireland, those 3 other countries are from Southern Europe.
In addition when we compare the data from 2019 to 2012, we see a clear increase in the use of mesalazine suppository in the 14 countries. All countries showed an increase in suppository use that is above 50% except for Czech Republic, Denmark, France and Sweden. The increase in those countries was less pronounced.
Sweden and Norway had the lowest rate of suppository use compared to the other countries.

Conclusion
Despite all the uncertainty around the UC prevalence and parallel import (due to price difference between the different European countries), there is a clear trend toward a higher use of suppositories in all the European countries. A full analysis of the topical use of mesalazine (suppository, foam and enema) would be interesting to evaluate more accurately the adherence to the ECCO guidelines in clinical practice.
P659 Colonoscopic screening of symptomatic patients suggests an emerging inflammatory bowel disease (IBD) in urban and rural south India
Authors: Banerjee R , Pal P , Tevethia H , Ganesh G , Chandayapeta J , Adigopula B , Mudigonda S , Reddy D N 
Published: May 2021

Abstract

Background
Recent studies suggest that IBD is on the rise in the developing world. This is also the region with limited access to healthcare facilities, poor physician and patient awareness of the disease and diagnostic dilemmas with the infectious bacterial diarrheas preventing adequate diagnosis. There is very limited data on the relative prevalence of IBD compared to the infectious diarrhoeas. We screened symptomatic patients to assess the diagnostic profile in the real world settings with free of cost service to people below poverty line and the un-insured.

Methods
The study is being conducted in a large tertiary care centre in Southern India from March 2020 till date. We present the results of an interim analysis. Symptomatic patients with diarrhea, unintentional weight loss, bleeding per rectum, chronic abdominal pain and unexplained anemia were screened with a blood test (Haemogram, liver function, serum protein), abdominal ultrasound and colonoscopy/ileoscopy to ensure an early diagnosis and initiation of treatment. Data including the demographics of the patients, predominant symptoms, rural/urban residence, investigations, biopsy and final diagnosis were entered into an excel spreadsheet and analysed.

Results
6878 patients, 2188 female (32%), median 44 years (1–82 years) were screened between March 2020 to January 2021. Bloody diarrhoea was noted in 1212(18%), chronic non-bloody diarrhoea in 887 (13%), altered bowel habits in 2381 (35%), pain abdomen in 4030 (59%), un-intentional weight loss in 648 (10%) and anemia in188 (3%). IBD was diagnosed in 397 patients (6%) of which 169 (2.5%) were UC and 228 (3.3%) were CD. Infective etiology including intestinal tuberculosis was seen in 577 (8.3%). Colorectal cancer was diagnosed in 251 (3.6%), polyps in 614 (8.9%). Overall, 4921 (71.5%) were urban and 1957 (28.5%) rural.
The proportion of UC (2.3% rural vs 2.5% urban, p=0.65) and CD (3.6% rural and 3.2% urban, p=0.43) were not different in rural and urban groups. There was significantly higher proportion of infectious colitis in the rural subgroup (p=0.01)(Table 1).

Conclusion
This interim analysis indicates a rising IBD in both urban and rural India vis a vis the infectious diarrheas. However, proportion of infectious colitis was significantly higher in the rural subgroup compared to the urban.
Quantifying drifting Fish Aggregating Device use by the world's largest tuna fishery
Authors: Escalle Lauriane , Hare Steven R , Vidal Tiffany , Brownjohn Maurice , Hamer Paul , Pilling Graham 
Published: May 2021

Abstract
Drifting Fish Aggregating Devices (dFADs) are a major fishing mode for tropical tuna purse seine fisheries worldwide. However, the extent of dFAD use remains poorly understood. We present novel approaches for estimating annual dFAD deployments and number of dFADs monitored by individual vessels, using empirical data and robust estimation procedures. We leveraged observer and logbook data, combined with new dFAD tracking data from the Western and Central Pacific Ocean (WCPO) purse seine fishery, the largest tuna fishery in the world, to evaluate trends in dFAD use across the entire WCPO between 2011 and 2019. Average estimates ranged between 20 000 and 40 000 deployments per year, depending on the methodology, with the total number of deployments appearing relatively stable over the last decade. The median number of active buoys monitored per vessel per day ranged from 45 to 75 depending on the year, well below the current management limit of 350. Our results contrast with other oceans, having fewer buoys monitored per vessel, a unique stable trend, but overall number of deployments two times higher than any other ocean. This study provides a basis for improved monitoring and management of dFAD use in the WCPO, with applicability for other regions.
Three-dimensional ATUM-SEM reconstruction and analysis of hepatic endoplasmic reticulum‒organelle interactions
Authors: Jiang Yi , Li Linlin , Chen Xi , Liu Jiazheng , Yuan Jingbin , Xie Qiwei , Han Hua 
Published: May 2021

Abstract
The endoplasmic reticulum (ER) is a contiguous and complicated membrane network in eukaryotic cells, and membrane contact sites (MCSs) between the ER and other organelles perform vital cellular functions, including lipid homeostasis, metabolite exchange, calcium level regulation, and organelle division. Here, we establish a whole pipeline to reconstruct all ER, mitochondria, lipid droplets, lysosomes, peroxisomes, and nuclei by automated tape-collecting ultramicrotome scanning electron microscopy and deep learning techniques, which generates an unprecedented 3D model for mapping liver samples. Furthermore, the morphology of various organelles and the MCSs between the ER and other organelles are systematically analyzed. We found that the ER presents with predominantly flat cisternae and is knitted tightly all throughout the intracellular space and around other organelles. In addition, the ER has a smaller volume-to-membrane surface area ratio than other organelles, which suggests that the ER could be more suited for functions that require a large membrane surface area. Our data also indicate that ER‒mitochondria contacts are particularly abundant, especially for branched mitochondria. Our study provides 3D reconstructions of various organelles in liver samples together with important fundamental information for biochemical and functional studies in the liver.
MAF Amplification and Adjuvant Clodronate Outcomes in Early-Stage Breast Cancer in NSABP B-34 and Potential Impact on Clinical Practice
Authors: Paterson Alexander H G , Lucas Peter C , Anderson Stewart J , Mamounas Eleftherios P , Brufsky Adam , Baez-Diaz Luis , King Karen M , Lad Thomas , Robidoux André , Finnigan Melanie , Sampayo Miguel , Tercero Juan Carlos , Mairet Joël Jean , Wolff Antonio C , Fehrenbacher Louis , Wolmark Norman , Gomis Roger R 
Published: May 2021

Abstract

Background
The Adjuvant Zoledronic Acid (ZA) study in early breast cancer (AZURE) showed correlation between a nonamplified MAF gene in the primary tumor and benefit from adjuvant ZA. Adverse ZA outcomes occurred in MAF-amplified patients. NSABP B-34 is a validation study.

Methods
A retrospective analysis of MAF gene status in NSABP B-34 was performed. Eligible patients were randomly assigned to standard adjuvant systemic treatment plus 3 years oral clodronate (1600 mg/daily) or placebo. Tumors were tested for MAF gene amplification and analyzed for their relationship to clodronate for disease-free survival (DFS) and overall survival (OS) in MAF nonamplified patients. All statistical tests were 2-sided .

Results
MAF status was assessed in 2533 available primary tumor samples from 3311 patients. Of these, 37 withdrew consent; in 77 samples, no tumor was found; 536 assays did not meet quality standards, leaving 1883 (77.8%) evaluable for MAF assay by fluorescence in situ hybridization (947 from placebo and 936 from clodronate arms). At 5 years, in MAF nonamplified patients receiving clodronate, DFS improved by 30% (hazard ratio = 0.70, 95% confidence interval = 0.51 to 0.94; P = .02). OS improved at 5 years (hazard ratio = 0.59, 95% confidence interval = 0.37 to 0.93; P = .02) remaining statistically significant for clodronate throughout study follow-up. Conversely, adjuvant clodronate in women with MAF-amplified tumors was not associated with benefit but rather possible harm in some subgroups. Association between MAF status and menopausal status was not seen.

Conclusions
Nonamplified MAF showed statistically significant benefits (DFS and OS) with oral clodronate, supporting validation of the AZURE study.
First use of Braxon® acellular dermal matrix for complex revision aesthetic breast surgery—revision augmentation mastopexy
Authors: Bojanic Christine , Samaras Stavros , Chishimba Mwenya M , Malata Charles M 
Published: May 2021

AbstractAcellular dermal matrices (ADMs) have ushered in a paradigm shift in prosthetic breast reconstruction; however, there has hitherto been no reported use of Braxon® ADM in aesthetic breast surgery. Here, we describe the case of a 42-year-old woman who presented for revision of her bilateral aesthetic augmentation-mastopexy following multiple revision surgeries. The predominant concerns were persistent pain, implant malposition and a wide intermammary distance. Her predicament was worsened by inability to tolerate monopolar diathermy owing to a spinal stimulator—the least invasive operation was sought and Braxon® ADM met this criterion. The procedure was a success, and she remains symptom-free, with soft breasts and stable implant positions. Braxon® ADM, with its preformed shape, total implant-wrapping design and easy suture fixation, lends itself to easy use in cosmetic breast surgery. Its role in cosmetic breast surgery has yet to be established, but this case marks the beginning of this endeavor.
Experiences of using positive airway pressure for treatment of obstructive sleep apnea: a systematic review and thematic synthesis
Authors: Brown Amy , Jones Steven , Perez-Algorta Guillermo 
Published: May 2021

AbstractStudy ObjectivesSuboptimal use of positive airway pressure (PAP) to treat obstructive sleep apnea (OSA) continues to be a major challenge to effective treatment. Meanwhile, the individual and societal impacts of untreated OSA make effective treatment a priority. Although extensive research has been conducted into factors that impact PAP use, it is estimated that at least half of users do not use it as prescribed. However, the voice of users is notably minimal in the literature. A systematic review and qualitative metasynthesis of PAP user experience was conducted to contribute to understandings of how PAP is experienced and to inform how usage could be improved.MethodsPsycINFO, MEDLINE, CINAHL, and EMBASE databases were systematically searched. Primary research findings of adult experiences using PAP that had been inductively analyzed were included. Papers were critically appraised using the CASP qualitative checklist to generate a “hierarchy of evidence.” Thematic synthesis was then conducted to generate analytical themes. Results were presented in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).ResultsTwenty-five papers reporting on over 398 people’s experiences were analyzed to generate four themes: Journey to PAP, Discomfort from and around PAP, Adapting to and using PAP, and Benefits from PAP. Author reflexivity and vulnerability to bias is acknowledged.ConclusionsThe findings highlight the applicability of a biopsychosocial understanding to PAP use. This metasynthesis gave voice to user experiences, revealing barriers to PAP use at a healthcare service level across the world, and suggests ways services can address these barriers.PROSPERO registration number: CRD42020157767
A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis
Authors: Fu Qiong , Feng Ping , Sun Ling-Yun , Zuo Xiao-Xia , Zhao Dong-Bao , He Dong-Yi , Wu Hua-Xiang , Zhang Wei , Zhang Wei , Du Fang , Bao Chun-De 
Published: May 2021

Abstract

Background:
Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.

Methods:
Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.

Results:
At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.
99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.

Conclusions:
This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted.

Trial Registration:
Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.
Sexual selection for males with beneficial mutations
Authors: Roberts Gilbert , Petrie Marion 
Published: May 2021

AbstractSexual selection is the process by which traits providing a mating advantage are favoured. Theoretical treatments of the evolution of sex by sexual selection propose that it operates by reducing the load of deleterious mutations. Here, we postulate instead that sexual selection primarily acts through females preferentially mating with males carrying beneficial mutations. We used simulation and analytical modelling to investigate the evolutionary dynamics of beneficial mutations in the presence of sexual selection. We found that female choice for males with beneficial mutations had a much greater impact on genetic quality than choice for males with low mutational load. We also relaxed the typical assumption of a fixed mutation rate. For deleterious mutations, mutation rate should always be minimized, but when rare beneficial mutations can occur, female choice for males with those rare beneficial mutations could overcome a decline in average fitness and allow an increase in mutation rate. We propose that sexual selection for beneficial mutations could overcome the ‘two-fold cost of sex’ much more readily than choice for males with low mutational load and may therefore be a more powerful explanation for the prevalence of sexual reproduction than the existing theory. If sexual selection results in higher fitness at higher mutation rates and if the variability produced by mutation itself promotes sexual selection, then a feedback loop between these two factors could have had a decisive role in driving adaptation.
A modular molecular framework for quickly estimating the binding affinity of the spike protein of SARS-CoV-2 variants for ACE2, in presence of mutations at the spike receptor binding domain
Authors: Tragni Vincenzo , Preziusi Francesca , Laera Luna , Onofrio Angelo , Todisco Simona , Volpicella Mariateresa , De Grassi Anna , Pierri Ciro Leonardo 
Published: May 2021

AbstractThe rapid spread of new SARS-CoV-2 variants needs the development of rapid tools for predicting the affinity of the mutated proteins responsible for the infection, i.e., the SARS-CoV-2 spike protein, for the human ACE2 receptor, aiming to understand if a variant can be more efficient in invading host cells. Here we show how our computational pipeline, previously used for studying SARS-CoV-2 spike receptor binding domain (RBD)/ACE2 interactions and pre-/post-fusion conformational changes, can be used for predicting binding affinities of the human ACE2 receptor for the spike protein RBD of the characterized infectious variants of concern/interest B.1.1.7-UK (carrying the mutations N501Y, S494P, E484K at the RBD), P.1-Japan/Brazil (RBD mutations: K417N/T, E484K, N501Y), B.1.351-South Africa (RBD mutations: K417N, E484K, N501Y), B.1.427/B.1.429-California (RBD mutations: L452R), the B.1.141 variant (RBD mutations: N439K), and the recent B.1.617.1-India (RBD mutations: L452R; E484Q) and the B.1.620 (RBD mutations: S477N; E484K). Furthermore, we searched for ACE2 structurally related proteins that might be involved in interactions with the SARS-CoV-2 spike protein, in those tissues showing low ACE2 expression, revealing two new proteins, THOP1 and NLN, deserving to be investigated for their possible inclusion in the group of host-cell entry factors responsible for host-cell SARS-CoV-2 invasion and immunity response.
Bi-phasic effect of gelatin in myogenesis and skeletal muscle regeneration
Authors: Liu Xiaoling , Zu Er , Chang Xinyu , Wang Ziqi , Li Xiangru , Yu Qing , Kamei Ken-ichiro , Hayashi Toshihiko , Mizuno Kazunori , Hattori Shunji , Fujisaki Hitomi , Ikejima Takashi , Wang Dan Ohtan 
Published: May 2021

AbstractSkeletal muscle regeneration requires extracellular matrix (ECM) remodeling including an acute and transient breakdown of collagen that produces gelatin. However, the physiological function of such a remodeling process on muscle tissue repair is unclear. Here we elaborate on a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by hormetic effects of reactive oxygen species (ROS). Low-dose gelatin stimulates ROS production from NADPH oxidase 2 (NOX2) and simultaneously upregulates antioxidant system for cellular defense, reminiscent of the adaptive compensatory process during mild stress. This response triggers the release of myokine IL-6 which stimulates myogenesis and facilitates muscle regeneration. By contrast, high-dose gelatin stimulates ROS overproduction from NOX2 and mitochondrial chain complex, and ROS accumulation by suppressing antioxidant system, triggering release of TNFα, which inhibits myogenesis and regeneration. Our findings reveal gelatin-ROS-IL-6/TNFα signaling cascades underlying a hormetic response of myogenic cells to gelatin.
Single molecule tracking the uncoupling of assembly and membrane insertion in Perfringolysin O
Authors: Senior Michael J T , Monico Carina , Weatherill Eve E , Gilbert Robert J , Heuck Alejandro P , Wallace Mark I 
Published: May 2021

AbstractWe exploit single-molecule tracking and optical single channel recording in droplet interface bilayers to resolve the assembly pathway and pore-formation of the archetypical cholesterol-dependent cytolysin nanopore, Perfringolysin O. We follow the stoichiometry and diffusion of Perfringolysin O complexes during assembly with 60 millisecond temporal resolution and 20 nanometre spatial precision. Our results suggest individual nascent complexes can insert into the lipid membrane where they continue active assembly. Overall, these data support a model of stepwise irreversible assembly dominated by monomer addition, but with infrequent assembly from larger partial complexes.
Rigorous estimation of post-translational proteasomal splicing in the immunopeptidome
Authors: Cygan Kamil J. , Khaledian Ehdieh , Blumenberg Lili , Salzler Robert R. , Shah Darshit , Olson William , Macdonald Lynn E. , Murphy Andrew J. , Dhanik Ankur 
Published: May 2021

ABSTRACTRecently, de novo peptide sequencing has made it possible to gain new insights into the human immunopeptidome without relying on peptide databases, while identifying peptides of unknown origin. Many recent studies have attributed post-translational proteasomal splicing as the origin of those peptides. Here, we describe a peptide source assignment workflow to rigorously assign the source of de novo sequenced peptides and find that the estimated extent of post-translational splicing in the immunopeptidome is much lower than previously reported. Our approach demonstrates that many peptides that were thought to be post-translationally spliced are likely linear peptides, and many peptides that were thought to be trans-spliced could be cis-spliced. We believe our approach furthers the understanding of post-translationally spliced peptides and thus improves the characterization of immunopeptidome which plays a critical role in the immune response to antigens in cancer, autoimmune disease, and infections.