bluuebunny/crossref_metadata_2025_split huggingface dataset:
Charge-based interactions through peptide position 4 drive diversity of antigen presentation by human leukocyte antigen class I molecules
Authors: Jackson Kyle R , Antunes Dinler A , Talukder Amjad H , Maleki Ariana R , Amagai Kano , Salmon Avery , Katailiha Arjun S , Chiu Yulun , Fasoulis Romanos , Rigo Maurício Menegatti , Abella Jayvee R , Melendez Brenda D , Li Fenge , Sun Yimo , Sonnemann Heather M , Belousov Vladislav , Frenkel Felix , Justesen Sune , Makaju Aman , Liu Yang , Horn David , Lopez-Ferrer Daniel , Huhmer Andreas F , Hwu Patrick , Roszik Jason , Hawke David , Kavraki Lydia E , Lizée Gregory 
Published: July 2022

Abstract
Human leukocyte antigen class I (HLA-I) molecules bind and present peptides at the cell surface to facilitate the induction of appropriate CD8+ T cell-mediated immune responses to pathogen- and self-derived proteins. The HLA-I peptide-binding cleft contains dominant anchor sites in the B and F pockets that interact primarily with amino acids at peptide position 2 and the C-terminus, respectively. Nonpocket peptide–HLA interactions also contribute to peptide binding and stability, but these secondary interactions are thought to be unique to individual HLA allotypes or to specific peptide antigens. Here, we show that two positively charged residues located near the top of peptide-binding cleft facilitate interactions with negatively charged residues at position 4 of presented peptides, which occur at elevated frequencies across most HLA-I allotypes. Loss of these interactions was shown to impair HLA-I/peptide binding and complex stability, as demonstrated by both in vitro and in silico experiments. Furthermore, mutation of these Arginine-65 (R65) and/or Lysine-66 (K66) residues in HLA-A*02:01 and A*24:02 significantly reduced HLA-I cell surface expression while also reducing the diversity of the presented peptide repertoire by up to 5-fold. The impact of the R65 mutation demonstrates that nonpocket HLA-I/peptide interactions can constitute anchor motifs that exert an unexpectedly broad influence on HLA-I-mediated antigen presentation. These findings provide fundamental insights into peptide antigen binding that could broadly inform epitope discovery in the context of viral vaccine development and cancer immunotherapy.
Women in rheumatology: major contributions and key discoveries of the twentieth century
Authors: Ishchenko Alla , Scriffignano Silvia , Coates Laura 
Published: July 2022

AbstractIn the twentieth century, rheumatology saw an exponential growth. Discoveries in the pathophysiology of rheumatic diseases, progress in research methodology and novel treatments cardinally changed the natural course of rheumatic diseases and revolutionized patient management. Although underrepresented in this field, women have made considerable input in advancing our specialty towards the new era. In this article we acknowledge key scientific discoveries and major contributions made by 18 brilliant women scientists that shaped the field of rheumatology in the twentieth century. We hope that the achievements of these remarkable women will inspire young rheumatologists and researchers.
ESTIMATION OF PEDIATRIC DOSE DESCRIPTORS ADAPTED TO INDIVIDUAL SPECIFIC SIZE FROM CT EXAMINATIONS
Authors: Abdulkadir Muhammad Kabir , Shuaib Ibrahim Lutfi , Achuthan Anusha , Nasirudin Radin A , Samsudin Ahmad Hadif Zaidin , Osman Noor Diyana 
Published: July 2022

AbstractClinical challenges in pediatrics dose estimation by the displayed computed tomography (CT) dose indices may lead to inaccuracy, and thus size-specific dose estimate (SSDE) is introduced for better-personalized dose estimation. This study aims to estimate pediatric dose adapted to specific size. This retrospective study involved pediatric population aged 0–12 y. SSDE was derived from scanner reported volume CT dose index (CTDIvol), based on individual effective diameter (Deff) with corresponding size correction factors. The correlations of Deff with other associated factors such as age, exposure setting, CTDIvol and SSDE were also studied. The average Deff of Malaysian pediatric was smaller than reference phantom size (confidence interval, CI = 0.28, mean = 14.79) and (CI = 0.51, mean = 16.33) for head and abdomen, respectively. These have led to underestimation of pediatric dose as SSDE was higher than displayed CTDIvol. The percentage differences were statistically significant (p &lt; .001) ranged from 0 to 17% and 37 to 60% for head and abdominal CT, respectively. In conclusion, the clinical implementation of SSDE in pediatric CT imaging is highly relevant to reduce radiation risk.
The multiple ‘epidemic’: debating responsibility in US medicine, media and the law
Authors: Lambe Jennifer 
Published: July 2022

Summary
This article examines the medical, legal and social discourses attached to the so-called multiple ‘epidemic’ in the mid- to late- twentieth-century USA. Such discussions were transformed by the development of the first hormonal remedies for infertility in the early 1960s and the debut of IVF in 1978. These debates, I propose, were shaped by racialised discourses of motherhood on one hand and the market imperatives of US medicine and fertility medicine on the other. These influences coincided to produce a unique emphasis on cost, responsibility and blame in discussions of the multiple ‘epidemic’. In the absence of government regulation, a common response in many European countries, doctors and parents assumed unique ethical burdens in managing multiple pregnancies. Following the debut of multifetal pregnancy reduction in the 1980s, these came to include the difficult decision as to whether they should be brought to term at all.
Comparative associations of oximetry patterns in Obstructive Sleep Apnea with incident cardiovascular disease
Authors: Sutherland Kate , Sadr Nadi , Bin Yu Sun , Cook Kristina , Dissanayake Hasthi U , Cistulli Peter A , de Chazal Philip 
Published: July 2022

AbstractStudy ObjectivesIntermittent hypoxia is a key mechanism linking Obstructive Sleep Apnea (OSA) to cardiovascular disease (CVD). Oximetry analysis could enhance understanding of which OSA phenotypes are associated with CVD risk. The aim of this study was to compare associations of different oximetry patterns with incident CVD in men and women with OSA.MethodsSleep Heart Health Study data were used for analysis. n = 2878 Participants (51.8% female; mean age 63.5 ± 10.5 years) with OSA (Apnea Hypopnea Index [AHI] ≥ 5 events/h) and no pre-existing CVD at baseline or within the first 2 years of follow-up were included. Four oximetry analysis approaches were applied: desaturation characteristics, time series analysis, power spectral density, and non-linear analysis. Thirty-one resulting oximetry patterns were compared to incident CVD using proportional hazards regression models adjusted for age, race, smoking, BMI, and sex.ResultsThere were no associations between OSA oximetry patterns and incident CVD in the total sample or in men. In women, there were some associations between incident CVD and time series analysis (e.g. SpO2 distribution standard deviation, HR 0.81, 95% CI 0.68–0.96, p = 0.014) and power spectral density oximetry patterns (e.g. Full frequency band mean HR 0.75; 95% CI 0.59–0.95; p = 0.015).ConclusionsComprehensive comparison of baseline oximetry patterns in OSA found none were related to development of CVD. There were no standout individual oximetry patterns that appear to be candidates for CVD risk phenotyping in OSA, but some showed marginal relationships with CVD risk in women. Further work is required to understand whether OSA phenotypes can be used to predict susceptibility to cardiovascular disease.
Impact of camphor on the in vitro mixed ruminal microorganism fermentation from goats selected for consumption of low and high levels of Juniperus spp. 1
Authors: Seidel Darren S , Walker John W , Musser Jeffrey M , Whitney Travis R , Callaway Todd R 
Published: July 2022

Abstract
Encroaching plant species in West Texas continues to significantly reduce livestock production capacity and cause an imbalance between plant and livestock ecology. Juniperus ashei and Juniperus pinchotii are encroaching species rarely used by browsing animals, mainly due to phytochemical defenses. Juniperus spp. contain large concentrations of monoterpenes in their essential oil profiles to deter herbivory. Since 2003, two divergent bloodlines of meat goats have been selected to consume low or high (LJC or HJC) amounts of juniper foliage, through screening fecal samples with near-infrared reflectance spectroscopy. However, it remains unclear whether HJC goats expressed a physiological ability to consume a greater amount of juniper or if they were colonized by a ruminal microbial population that could detoxify juniper phytochemicals. Therefore, this study aimed to investigate the impact of 0.00 and 1.97 mM of camphor on the mixed ruminal microorganism fermentation after 0, 1, 2, 4, 12, and 24 h of incubation. Five LJC and five HJC goats were fed a juniper-free diet (n = 10) and five LJC and five HJC goats (n = 10), were fed a diet containing 30% fresh J. ashei leaves for 21 days prior to ruminal fluid collection. In vitro fermentations used LJC and HJC, ruminal fluid inoculum was added (33% v/v) to anoxic media in sealed Balch tubes. Total short-chain fatty acid (SCFA) production and acetate to propionate ratio were increased (P &lt; 0.05), but there was no effect on pH (6.56 ± 0.09). Goats that received the juniper-free diet had higher (P &lt; 0.05) SCFA production than juniper-containing diets. There was no consistent difference in LJC and HJC microbial fermentation end products caused by the addition of 1.97 mM of camphor, and goats receiving a juniper-free diet consistently generated more SCFAs in the presence of 1.97 mM of camphor. Furthermore, bloodline differences in juniper consumption were likely related to physiological adaption capacities within the animal and not a ruminal microbial detoxification advantage.
Impact of concentrations of camphor on the in vitro mixed ruminal microorganism fermentation from goats selected for consumption of low and high levels of Juniperus spp.-2
Authors: Seidel Darren S , Walker John W , Musser Jeffrey M , Lourenco Jeferson M , Welch Christina B , Whitney Travis R , Callaway Todd R 
Published: July 2022

Abstract
The microbial population in the gastrointestinal tract of ruminant animals aids in the utilization of forages with high levels of secondary plant compounds. Two divergent bloodlines of meat goats have been selected by screening fecal samples with near-infrared reflectance spectroscopy to assess the goat’s consumption of high or low levels of Juniperus sp. leaves containing several monoterpenes, including camphor. The mechanism by which these goats can consume greater concentrations of Juniperus spp. leaves than their counterparts is unclear, and therefore, this study was designed to determine if differences existed between the ruminal microbial populations of the low and high juniper-consuming bloodlines (LJC vs. HJC) by analyzing their ruminal microbiota and fermentation end products. In the present study, concentrations (0.00, 0.5, 0.99, 1.97, or 5.91 mM) of camphor were added to mixed ruminal microorganism fermentation. Five LJC and five HJC goats were fed a juniper-free diet (n = 10), and five LJC and five HJC goats (n = 10) were fed a diet that contained 30% fresh Juniperus ashei leaves for 21 d prior to ruminal fluid collection. In vitro fermentations used LJC and HJC, ruminal fluid inoculum added (33% v/v) to anoxic media in sealed Balch tubes. Camphor increased (P &lt; 0.05) total short-chain fatty acid (SCFA) concentrations for all but one experimental group. Between the main dietary and bloodline goat effects, the diet was significant for all SCFA results except butyrate. In contrast, bloodline was only significant for acetate and butyrate molar proportions. Rumen fluid from juniper-free-fed goats exhibited greater concentrations of Ruminococcaceae, whereas juniper-fed goats contained more Coriobacteriaceae. Results demonstrated that mixed ruminal microorganisms fermentations from HJC goats did not produce greater concentrations of SCFAs or have the ability to degrade camphor at a higher rate than did that from LJC goats. Results suggest that camphor tolerance from J. ashei, was related to hepatic catabolic mechanisms instead of ruminal microbial degradation; however, further in vivo work is warranted.
Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients With COVID-19
Authors: Gupta Neha , Settle Lisa , Brown Brent R. , Armaignac Donna L. , Baram Michael , Perkins Nicholas E. , Kaufman Margit , Melamed Roman R. , Christie Amy B. , Danesh Valerie C. , Denson Joshua L. , Cheruku Sreekanth R. , Boman Karen , Bansal Vikas , Kumar Vishakha K. , Walkey Allan J. , Domecq Juan P. , Kashyap Rahul , Aston Christopher E. ,   on behalf of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group
Published: July 2022

OBJECTIVES:
To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19.

DESIGN:
Retrospective observational study.

SETTING:
Multicenter, international COVID-19 registry.

Subjects:
Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19–1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03–1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81–0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20–1.56]; p < 0.0001).

CONCLUSIONS:
Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.
Electrolytes disturbances in cancer patients
Authors: Turcotte Anna , Achi Sai , Mamlouk Omar , Mandayam Sreedhar 
Published: July 2022

Purpose of review
Hypernatremia, hyperphosphatemia, hypocalcaemia, hyperkalaemia and hypermagnesemia are electrolytes disturbances that can arise in cancer patients in relation to unique causes that are related to the cancer itself or its treatment and can lead to delay or interruption of cancer therapy. This article summarizes these main causes, the proposed pathophysiology and the recommended management for these disturbances.

Recent findings
There have been many cancer drugs approved in the field of oncology over the past several years and a subset of these drugs have been associated with electrolytes disturbances. This includes, for example, immune checkpoint inhibitor related hyperkalemia, fibroblast growth factor 23 inhibitor associated hyperphosphatemia and epidermal growth factor receptor inhibitor associated hypomagnesemia and hypocalcaemia.

Summary
This article provides an updated review of certain electrolytes disturbance in cancer patients and allows clinicians to have a greater awareness and knowledge of these electrolyte abnormalities in efforts to early recognition and timely management.
High-Dose Midazolam for Pediatric Refractory Status Epilepticus: A Single-Center Retrospective Study*
Authors: Daniels Zachary S. , Srdanovic Nina , Rychlik Karen , Smith Craig , Goldstein Joshua , George Alfred L. 
Published: July 2022

Objectives:
We sought to describe the prevalence of midazolam treatment failure in children with refractory status epilepticus (RSE) and define a threshold dose associated with diminishing frequency of seizure cessation.

Design:
Single center retrospective cohort study.

Setting:
Single-center, quaternary-care PICU.

Patients:
Children younger than 18 years old admitted to the PICU from 2009 to 2018 who had RSE requiring a continuous midazolam infusion.

Interventions:
None.

Measurements and Main Results:
We identified individuals with RSE through a data analytics inquiry. Receiver operating characteristic (ROC) curve analysis and Youden’s index were used to assess the midazolam dose threshold associated with the highest sensitivity and specificity in identifying seizure cessation. A logistic regression model was used to determine if there was an association between maximum midazolam dose and seizure cessation. Of the 45 patients who met inclusion criteria for this study, 27 (60%) had seizure cessation with a midazolam infusion, whereas 18 (40%) required an additional pentobarbital infusion for seizure cessation. There was an association between maximum midazolam dose and seizure cessation, with patients more likely to fail treatment when midazolam was administered at higher doses. The maximum midazolam dose displayed high area under the ROC curve value for seizure cessation, and the Youden’s J index cut-off point was 525 μg/kg/hr. Treatment above this dose was associated with diminishing frequency of seizure cessation. The median time spent titrating midazolam above 500 μg/kg/hr for those patients who required pentobarbital for seizure cessation was 3.83 hours (interquartile range, 2.28–5.58 hr).

Conclusions:
In pediatric patients with RSE requiring high dose midazolam, considerable time is spent titrating doses in a range (above 500 µg/kg/hr) that is associated with diminishing frequency of seizure cessation.
Novel Benchmark Values for Redo Liver Transplantation
Authors: Abbassi Fariba , Gero Daniel , Muller Xavier , Bueno Alba , Figiel Wojciech , Robin Fabien , Laroche Sophie , Picard Benjamin , Shankar Sadhana , Ivanics Tommy , van Reeven Marjolein , van Leeuwen Otto B. , Braun Hillary J. , Monbaliu Diethard , Breton Antoine , Vachharajani Neeta , Bonaccorsi Riani Eliano , Nowak Greg , McMillan Robert R. , Abu-Gazala Samir , Nair Amit , Bruballa Rocio , Paterno Flavio , Weppler Sears Deborah , Pinna Antonio D. , Guarrera James V. , de Santibañes Eduardo , de Santibañes Martin , Hernandez-Alejandro Roberto , Olthoff Kim , Ghobrial R Mark , Ericzon Bo-Göran , Ciccarelli Olga , Chapman William C. , Mabrut Jean-Yves , Pirenne Jacques , Müllhaupt Beat , Ascher Nancy L. , Porte Robert J. , de Meijer Vincent E. , Polak Wojciech G. , Sapisochin Gonzalo , Attia Magdy , Soubrane Olivier , Weiss Emmanuel , Adam René A. , Cherqui Daniel , Boudjema Karim , Zieniewicz Krzysztof , Jassem Wayel , Dutkowski Philipp , Clavien Pierre-Alain 
Published: July 2022

Objective:
To define benchmark cutoffs for redo liver transplantation (redo-LT).

Background:
In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT.

Methods:
We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers.

Results:
Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks.

Conclusion:
This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
A fitting-extrapolation method of B-H curve for magnetic saturation applications
Authors: Wang Lichao , Ding Fuyan , Yang Dongbo , Wang Ke , Jiao Biaoqiang , Chen Qian 
Published: July 2022

Purpose
This paper aims to provide a new method of generating relatively accurate and smooth saturated B-H curves based on reliable measurement data to improve the accuracy and efficiency of electromagnetic simulation.

Design/methodology/approach
The characteristics of different B-H curve extrapolation models are summarized, and an improved method is proposed. The fitting procedure in low fields and extrapolation procedure in high fields are presented in detail. The saturated B-H curves generated by various methods are compared and discussed. Finally, a simulation case study proved the advantages of the new method in terms of simulation accuracy and efficiency.

Findings
The B-H curve created by the new method avoids extrapolation from a single point and simultaneously smoothens the entire B-H curve, thereby improving the simulation accuracy and efficiency. The low magnetic potential requirements for closed measurements and the small deviation with open measurements indicate that this method is well-suited for implementation.

Research limitations/implications
The results are applicable for materials subject to such excitation levels that saturation has to be taken into account.

Originality/value
While some extrapolation models of B-H curves have been investigated in reference papers, there is still room for improvement in accuracy and smoothness. The new method processes low fields and high fields magnetization data and then connects them based on third-order boundary equations for the first time. This method can generate saturated B-H curves with good accuracy and smoothness while retaining outstanding operability.