bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of The Peripherally Acting µ-Opioid Receptor Antagonist Methylnaltrexone On Acute Pancreatitis Severity: Study Protocol for a Multicentre Double-Blind Randomised Placebo-Controlled Interventional Trial, The PAMORA-AP Trial
Authors: Knoph Cecilie Siggaard , Cook Mathias Ellgaard , Fjelsted Camilla Ann , Novovic Srdan , Mortensen Michael Bau , Nielsen Liv Bjerre Juul , Berner-Hansen Mark , Frøkjær Jens Brøndum , Olesen Søren Schou , Drewes Asbjørn Mohr 
Published: October 2021

Abstract
Background: Moderate to severe acute pancreatitis (AP) is associated with a high rate of complications and increased mortality, yet no targeted pharmacologic treatment currently exists. As pain is a dominant symptom in AP, patients are exposed to excess levels of both endo- and exogenous opioids, which may have harmful effects on the course of AP. This trial investigates the effects of the peripherally acting µ-opioid receptor antagonist (PAMORA) methylnaltrexone on disease severity and clinical outcomes in patients with moderate to severe AP. Methods: PAMORA-AP is a multicentre, investigator-initiated, double-blind, randomised, placebo-controlled, interventional trial, which will be conducted at four referral centres for acute pancreatitis in Denmark. Ninety patients with early-onset AP (pain onset within 48 hours) as well as predicted moderate to severe disease (two or more systemic inflammatory response syndrome criteria upon admission) will be prospectively included. Subsequently, participants will be randomised (1:1) to intravenous treatment with either methylnaltrexone or matching placebo (Ringer’s lactate) during 5 days of admission. The primary endpoint will be the group difference in disease severity as defined and measured by the Pancreatitis Activity Scoring System (PASS) score 48 hours after randomisation. Secondary endpoints include daily PASS scores; disease severity according to the Atlanta classification; quantification of need for analgesics, nutritional support, intravenous fluid resuscitation and antibiotics; duration of hospital admissions, readmission rates and mortality. Pain intensity and gut function will be self-reported using validated questionnaires. Exploratory endpoints include circulating levels of pro-and anti-inflammatory markers, polyethylene glycol recovery from the urine, circulating levels of blood markers of intestinal permeability, the prevalence of pancreatic complications on computed tomography (CT) scans, and colon transit time assessed using a CT-based radiopaque marker method. Discussion: This trial aims to evaluate the PAMORA methylnaltrexone as a novel targeted pharmacotherapy in patients with moderate to severe AP with the potential benefit of improved patient outcomes.Trial registration: ClinicalTrials.gov, Identifier: NCT04743570. Registered 28 January 2021, https://clinicaltrials.gov/ct2/show/NCT04743570. EudraCT, Identifier: 2020-002313-18.
The influence of hla genotype on the development of metal hypersensitivity following joint replacement
Authors: Langton David , Bhalekar Rohan , Joyce Thomas , Wainwright Benjamin , Nargol Matthew , Shyam Nish , Lie Benedicte , Pabbruwe Moreica , Stewart Alan , Waller Susan , Natu Shonali , Ren Renee , Hornick Rachelle , Darlay Rebecca , Su Edwin , Nargol Antoni 
Published: October 2021

Abstract
Joint replacement surgery provides pain relief and restoration of mobility for millions of patients around the world each year.[1] However, the release of wear debris from implant surfaces can limit the lifespan of a prosthesis through the promotion of inflammatory responses.[2] Implants must therefore be constructed from materials with sufficient durability and biocompatibility. One such material is cobalt chrome alloy, which is used in the majority of joint replacements.[3] Unfortunately, it is recognised that some patients develop lymphocyte mediated delayed type hypersensitivity (DTH) responses to this material,[4] a response which may result in extensive bone and soft tissue destruction.[5] A genetic predisposition to DTH has been proposed[6], though specific genes have yet to be identified, or the effects quantified. Here we show that variation in HLA class II genotype influences an individual’s susceptibility to DTH. HLA-DQ haplotypes encoding peptide binding grooves with greater affinity for the N terminal peptide sequence of albumin (containing two recognised metal binding sites) confer a greater risk of DTH. We describe the development and validation of a machine learning algorithm to investigate the possibility that a patient’s genotype and basic clinical parameters may be used to predict DTH. Incorporating this novel finding, gradient boosted survival analysis machine learning models were trained and validated using results from 606 patients from three international units. These models were assessed using Uno’s c-index, time-dependent AUROCs, and integrated calibration index performance statistics. At present, there are no tests in widespread clinical use which use a patient’s genetic profile to guide implant selection or inform post-operative management. The algorithm described herein may address this issue.
Systemic Treatment in Advanced Phyllodes Tumor of the Breast: A Multi-Institutional European Retrospective Case-Series Analyses
Authors: Palassini Elena , Mir Olivier , Grignani Giovanni , Vincenzi Bruno , Gelderblom Hans , Sebio Ana , Valverde Claudia , Baldi Giacomo Giulio , Brunello Antonella , Cardellino Giovanni Gerardo , Marrari Andrea , Badalamenti Giuseppe , Martin-Broto Javier , Ferraresi Virginia , Libertini Michela , Turano Salvatore , Gataa Ithar , Collini Paola , Tos Angelo Paolo Dei , Gennaro Massimiliano , Bini Federica , Provenzano Salvatore , Vullo Salvatore Lo , Mariani Luigi , Cesne Axel Le , Casali Paolo Giovanni 
Published: October 2021

Abstract
Background: We aimed at investigating outcome of systemic treatments in advanced breast PT. Methods: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centres involved in the study, were retrospectively reviewed. Results: 56 female patients were identified. Median age was 52 (range 25-76) years. Patients re-ceived a median number of 2 systemic treatments (range 1-4). Best responses according to RECIST were: 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were: 5.7 (IQR, 2.5-9.1) months with AI; 3.2 (IQR, 2.2-5.0) months with anthracycline alone; 3.4 (IQR, 1.4-6.7) months with HD-IFX; 2.1 (IQR, 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR, 0.7-6.6) months with trabectedin; 3.4 (IQR, 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR, 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR, 7.6-39.6) months. Conclusion: In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however with a median PFS of 5.7 months. Other systemic treatments were poorly active.
Genetic Variants of Progesterone Receptor in Etiology of Preterm Delivery
Authors: Kolanowska Dorota , Kurzawińska Grażyna , Szpera-Goździewicz Agata , Drews Krzysztof , Malewski Zbyszko , Kozłowska-Wytyk Martyna , Kamiński Adam , Sulikowski Tadeusz , Seremak-Mrozikiewicz Agnieszka 
Published: October 2021

Abstract
Background: Preterm delivery (PTD) accounts for around 11% of pregnancies worldwide. Unfortunately, no diagnostic indicator, specific mechanism or genetic predisposition has yet been identified. One of the hypotheses suggest local or functional progesterone decrease as a potential reason for preterm uterine contractions leading to preterm delivery. It is believed that any change in progesterone receptor DNA may be crucial for higher risk of preterm delivery due to abnormal response to prostaglandins, normally inhibited by properly built progesterone. The aim of this study was to determine whether there is an association between progesterone gene polymorphisms (PROGINS and +331G/A) and preterm birth. Methods and Results: A total of 230 women were enrolled, including 115 cases of preterm deliveries (between 22 and 36 weeks of gestation) and 115 healthy mothers of full-term infants. Genomic DNA was isolated from the blood sample. Polymerase chain reaction (PCR) amplification was carried out in a final volume of 25µl. Genotyping was assayed by PCR. Statistical analysis of the results was conducted with p<0.05 accepted as statistically significant. For both PROGINS (Alu ins/del) and +331G/A (rs10895068) polymorphisms were equally frequent in case and control group. The prevalence of PGR alleles in both groups was also comparable.Conclusion: The results of our study showed no association between progesterone gene polymorphisms (PROGINS and +331G/A) and risk of preterm delivery. Identifying mechanisms to prolong the length of gestation, particularly in women at risk for preterm delivery, will improve both maternal and fetal outcomes.
Ultraviolet Aging Mechanism of Asphalt Molecular Based on Microscopic Simulation
Authors: Xiao Min min , Fan Lín 
Published: October 2021

Abstract
In order to reveal the nature of the Ultraviolet aging(UV-aging) behavior of asphalt molecules, simulation by Materials Studio software. The effect of UV aging on the transformation, aggregation and motion state of asphalt microstructure is analyzed by the changes in energy, density of dispersive phase, glass transition temperature and viscosity of the asphalt molecular system. The results show that UV aging enhances the bonding degree of asphalt molecules by increasing the heavy components in the asphalt molecules and increasing the distribution width between the asphalt molecule components, which improves the high-temperature resistance of asphalt. At the meantime, the UV aging causes the asphalt molecular movement state to solidify at low temperature so that the rheological behavior is difficult to occur by reducing the lightweight component and free volume of the asphalt molecule and increasing the glass transition temperature, which reduces the low-temperature resistance of asphalt. In addition, among the factors affecting the viscosity of asphalt molecular, the degree of influence of the molecular structure and molecular weight is significantly greater than the molecular activity. The addition of short branched chain hydrocarbon molecules to the UV-aged asphalt molecules could effectively reduce the viscosity of the asphalt molecules and improve the flowability of the asphalt molecules. The results of the study contribute to the understanding of the characteristics of changes in the microstructural pattern and dynamic behavior of asphalt molecules during UV aging, and achieve interpretation and prediction of changes in asphalt properties at the microscopic level.
Socioeconomic Patterns for Global Mangrove Cover Changes with Multivariate Analyses
Authors: Lin Ruihan , Yu Shen , Hong Bing 
Published: October 2021

Abstract
Socioeconomic patterns beyond the land conversions of global mangrove cover changes were few discussed. This study integrated databases of global mangrove covers, i.e., a multi-database in 1980-2016 with a combination of FAO country-survey and the global mangrove watch, and a mangrove biome cover database in 2000-2012. Annual mangrove cover change (%) of each mangrove holding country or territory was incorporated with its socioeconomic indicators in the two periods to testify possible socioeconomic patterns beyond the mangrove deforestation. The socioeconomic indicators consisted of GDP per capita and urban population percentile, and aquacultural indicators (production per capita, sales value per capita, contribution to the national GDP, and product price). Results indicated that annual mangrove cover change was interactively driven by multi-factors of national economy measures, urbanization, and aquaculture, instead of aquacultural dominance or GDP per capita alone. The multi-factor driven patterns of annual mangrove changes differed geographically among the continents. Temporal change of aquacultural product price was significantly and positively correlated to annual mangrove cover change (increase), especially in Asia and Oceania for both the periods, suggesting positive feedbacks of mangrove conservation and restoration in the two continents although the price was used to a motivator of mangrove deforestation, such as currently in Africa. These findings preliminarily bridge the knowledge gap between land conversion losses and socioeconomics of global mangrove cover changes.
Identification and Evaluation of Factors Affecting Nectar Volume and Concentrations of Croton Macrostachyus Hochst.ex Delile
Authors: Jilo Kasim Roba , Sime Getachew 
Published: October 2021

Abstract
Background: Secretion of nectar is highly influenced by many factors and the objective of the study was also to evaluate factors affecting concentrations of nectar of Croton macrostachyus Hochst.ex Delile. Age of plants highly affect nectar concentration and volume. Honey quality and its medicinal values depends on plants species variety and their sucrose concentration quality and quantity which is governed by many biotic and abiotic factors as well micro climate of the area. Wholesale of nectar and concentration of tend to show more differences in time of day for species study undertaken.Results: As results publicized that nectar concentration and volume of youngest age was not more affected by temperature and relative humidity like that of medium and oldest ages. Temperature and age have significant effect on volume (p = 0.0001) and their interactions is also significant (p = 0.01145). Temperature has significant effects on nectar concentration (p = 0.000). Interaction of relative humidity, time, and layers has significant effects on nectar concentration (p = 0.0024012). The oldest plants had the highest concentration of 10.1 w/w mornings and afternoon 36.5 w/w at 4:00 PM for whereas medium plants had nectar concentration of 5.7 w/w morning and afternoon 16.7 w/w and the smaller or younger plants had nectar concentration of 2.7 w/w mornings and afternoon 9.1 w/w and this shows age significantly affect nectar concentration and volume.Conclusions:Concentration and volume were affected by many biotic and abiotic factors. I conclude imminent fever intensification could harm nectar production since for croton also no nectar could be collected at 30 C⁰ and no nectar recreation was observed after this peak temperature this indicates environmental change can increase the temperature which will have negative influences on honey production in the future unless we combat against climate change which will affect honey production and productivity for the country and we will lose honey and its medicinal values also.
Tracking chromatin state changes using µMap photo-proximity labeling
Authors: Muir Tom , Seath Ciaran , MacMillan David , Burton Antony 
Published: October 2021

Abstract
Interactions between biomolecules, particularly proteins, underlie all cellular processes, and ultimately control cell fate. Perturbation of native interactions through mutation, changes in expression levels, or external stimuli leads to altered cellular physiology and can result in either disease or therapeutic effects. Mapping these interactions and determining how they respond to stimulus is the genesis of many drug development efforts, leading to new therapeutic targets and improvements in human health. However, in the complex environment of the nucleus it is challenging to determine protein-protein interactions due to low abundance, transient or multi-valent binding, and a lack of technologies that are able to interrogate these interactions without disrupting the protein binding surface under study. Chromatin remodelers, modifying enzymes, interactors, and transcription factors can all be redirected by subtle changes to the microenvironment, causing global changes in protein expression levels and subsequent physiology. Here, we describe the Chroma-µMap method for the traceless incorporation of Ir-photosensitizers into the nuclear microenvironment using engineered split inteins. These Ir-catalysts can activate diazirine warheads to form reactive carbenes within a ~10 nm radius, cross-linking with proteins within the immediate microenvironment for analysis via quantitative chemoproteomics. We demonstrate this concept on nine different nuclear proteins with varied function and in each case, elucidating their microenvironments. Additionally, we show that this short-range proximity labeling method can reveal the critical changes in interactomes in the presence of cancer-associated mutations, as well as treatment with small-molecule inhibitors. Chroma-µMap improves our fundamental understand-ing of nuclear protein-protein interactions, as well as the effects that small molecule therapeutics have on the local chromatin environment, and in doing so is expected to have a significant impact on the field of epigenetic drug discovery in both academia and industry.
The Mirror Reversal Mechanism on Black Hole Collapse and Singularity Eruption in Cosmic Continuum
Authors: Wang Xijia 
Published: October 2021

Abstract
In the Big Bang Theory and the Black Hole Theory, the existing laws of physics all fail atthe singularity, and the singularity has become a blind spot in the existing scientific theories. In Cosmiccontinuum, the cosmic system collapse into a Schwarzschild black hole under the action of a stronggravitational field, and the Planck spheres at the center of the black hole continues to collapse into darkmass bodies, forming dark celestial body and singularity. The Schwarzschild radius is the upper limit ofa black hole, and the Planck sphere is the lower limit of a black hole. The singularity is the conversionpoint between the old and new cosmic systems. The singularity erupts the Planck spheres under theaction of a strong gravitational field, and the Planck spheres expands outward to form a new cosmicsystem. The Planck sphere is both the end of the old cosmic system and the starting point of the newcosmic system. The black hole collapse and the singularity eruption are mirror images of each other.The Planck sphere is the front of the mirror, and the singularity is the back of the mirror.
Shockable Rhythm at Hospital Arrival as the Predictor of Favourable Neurological Outcome in Patients with Out-of-Hospital Cardiac Arrest (OHCA) Receiving Extracorporeal Cardiopulmonary Resuscitation (ECPR)
Authors: Su Pei-I , Tsai Min-Shan , Chen Wei-Ting , Wang Chih-Hung , Chang Wei-Tien , Huei-Ming Matthew , Chen Wen-Jone , Huang Chien-Hua 
Published: October 2021

Abstract
Introduction: For patients with out-of-hospital cardiac arrest (OHCA) without return of spontaneous circulation under advanced life support, extracorporeal cardiopulmonary resuscitation (ECPR) is the only lifesaving option. This study aimed to analyse the predictors of favourable neurological outcomes (FO, cerebral performance category 1-2) at hospital discharge among patients with OHCA following ECPR.Methods: In this single-centre retrospective study, 126 patients with OHCA who received ECPR between January 2012 and December 2019 were enrolled. The primary outcome was the FO at hospital discharge. The predictors of FO were assessed using multiple logistic regression analysis. Patients with an initial shockable rhythm were further analysed according to the cardiac rhythm at the time of hospital arrival. Results: Among the patients who received ECPR, the FO at hospital discharge was 21%. Certain resuscitation variables were associated with FO including witnessed collapse (P=0.014), bystander CPR (P=0.05), shorter no-flow time (P=0.008), and a shockable rhythm at hospital arrival (P=0.009). Multiple logistic regression showed that a shockable rhythm at hospital arrival was the only independent predictor of FO at discharge (odds ratio, 3.012; 95% confidence interval, 1.06-8.53; P=0.038). Among patients with an initial shockable rhythm, the group with a shockable rhythm at hospital arrival had a FO of 30%, which was significantly higher than the 11% in the non-shockable rhythm group (P=0.043).Conclusions: In patients with OHCA who received ECPR, a shockable rhythm at the time of hospital arrival was associated with favourable neurological outcomes at discharge. The ECPR selection criteria could consider the rhythm at hospital arrival.
The Treatment Pattern and Economic Burden of Homozygous Familial Hypercholesterolemia in China: A Study based on a Patient-Survey
Authors: yang yan , Wang Lvya , Yang Ya , Wen Wenhui , Tang Mi , He Jiangjiang , Hu Shanlian 
Published: October 2021

Abstract
Objective: The study aimed to investigate the treatment pattern and economic burden of homozygous familial hypercholesterolemia (HoFH) in China, and to evaluate the incidence rate of catastrophic health expenditure (CHE) of HoFH patients and their families.Methods: Patients with HoFH diagnosed and treated in Beijing An’Zhen Hospital was included. A questionnaire was developed to investigate and capture the relevant variables of the participants.Results: A total of 120 HoFH patients were investigated, and the number of children (age under 18) was 1.2 times more than adults (age above 18). There were 113 patients with basic medical insurance (including 61 patients with new rural cooperative medical insurance), 4 patients with commercial insurance and 3 patients without any insurance. There were 35 patients with atherosclerotic cardiovascular disease (ASCVD), including 29 adults and 6 children. Only 6 pediatric patients achieved their low-density lipoprotein cholesterol (LDL-C) treatment targets, and all 54 adult patients did not achieve it. The most commonly used treatment method was diet control with lipid-lowering drugs (16.67%), followed by diet control and lipid-lowering drugs using separately (16.67%). The proportion of patients whose annual personal income reached GDP per capita in 2019 was only 2.5%. The total economic burden of disease was 5,529,100 CNY / year, including direct medical costs of 3,427,200 CNY / year, direct non-medical costs of 1,504,500 CNY / year and indirect costs of 611,300 CNY / year; the per capita economic burden of disease was 46,100 CNY / year, including direct medical costs of 28,600 CNY / year, direct non-medical costs of 12,500 CNY / year and indirect costs of 5,100 CNY / year. There were 32 families with CHE due to the disease, accounting for 26.67%.Conclusion: Patients with HoFH in China are generally at young age, and the economic burden of disease for the family is heavy. The existing treatment is not effective, and it is easy to cause premature death due to ASCVD.