bluuebunny/crossref_metadata_2025_split huggingface dataset:
Siblings reduce multiple sclerosis risk by preventing delayed primary Epstein–Barr virus infection
Authors: Rostgaard Klaus , Nielsen Nete Munk , Melbye Mads , Frisch Morten , Hjalgrim Henrik 
Published: November 2022

Abstract
Epstein–Barr virus infection, and perhaps almost exclusively delayed Epstein–Barr virus infection, seems to be a prerequisite for the development of multiple sclerosis. Siblings provide protection against infectious mononucleosis by occasionally preventing delayed primary Epstein–Barr virus infection, with its associated high risk of infectious mononucleosis. Each additional sibling provides further protection according to the age difference between the index child and the sibling. The closer the siblings are in age, the higher the protection, with younger siblings being more protective against infectious mononucleosis than older siblings. If the hypothesis that delayed Epstein–Barr virus infection is necessary for the development of multiple sclerosis is true, then the relative risk of multiple sclerosis as a function of sibship constellation should mirror the relative risk of infectious mononucleosis as a function of sibship constellation. Such an indirect hypothesis test is necessitated by the fact that age at primary Epstein–Barr virus infection is unknown for practically all people who have not experienced infectious mononucleosis.
In this retrospective cohort study using nationwide registers, we followed all Danes born during the period 1971–2018 (n = 2 576 011) from 1977 to 2018 for hospital contacts with an infectious mononucleosis diagnosis (n = 23 905) or a multiple sclerosis diagnosis (n = 4442), defining two different end points. Relative risks (hazard ratios) of each end point as a function of sibship constellation were obtained from stratified Cox regression analyses.
The hazard ratios of interest for infectious mononucleosis and multiple sclerosis could be assumed to be identical (test for homogeneity P = 0.19), implying that having siblings, especially of younger age, may protect a person against multiple sclerosis through early exposure to the Epstein–Barr virus. Maximum protection per sibling was obtained by having a 0–2 years younger sibling, corresponding to a hazard ratio of 0.80, with a 95% confidence interval of 0.76–0.85. The corresponding hazard ratio from having an (0–2 years) older sibling was 0.91 (0.86–0.96).
Our results suggest that it may be possible essentially to eradicate multiple sclerosis using an Epstein–Barr virus vaccine administered before the teenage years. Getting there would require both successful replication of our study findings and, if so, elucidation of why early Epstein–Barr virus infection does not usually trigger the immune mechanisms responsible for the association between delayed Epstein–Barr virus infection and multiple sclerosis risk.
Quantitation of Venetoclax in Human Plasma by High-Performance Liquid Chromatography with Ultraviolet Detection
Authors: Fukuda Natsuki , Kobayashi Takahiro , Sato Honami , Akamine Yumiko , Takahashi Naoto , Miura Masatomo 
Published: November 2022

AbstractA simple, highly sensitive and specific method based on high-performance liquid chromatography (HPLC) with ultraviolet detection was developed for the measurement of venetoclax concentrations in plasma samples. The chromatographic method employed a mobile phase of acetonitrile: 0.5% KH2PO4 (pH 3.5) (80/20, v/v) on a CAPCELL PAK C18 UG120 column at a flow rate of 0.5 mL/min. The quantitative method was validated based on standards described in “Bioanalytical Method Validation: Guidance for Industry” published by the US Food and Drug Administration. The separation of venetoclax and the internal standard R051012 was satisfactory, and the chromatograms were free of interfering peaks from the biological matrix. The intra- and inter-day coefficients of variation for venetoclax assays were &lt;12.9%, whereas intra- and inter-day accuracies were within 13.6%. Only 100 μL of human plasma was required to detect a lower limit of quantification of 10 ng/mL for venetoclax. The recoveries of venetoclax extracted with an Oasis HLB cartridge were between 81 and 85%. The developed HPLC method was successfully applied to the determination of venetoclax concentrations in plasma of acute myeloid leukemia patients taking venetoclax. The degree of drug interactions between venetoclax and CYP3A4 inhibitors can be determined by this HPLC assay.
Histological Features Associated With Human Mpox Virus Infection in 2022 Outbreak in a Nonendemic Country
Authors: Chalali Faris , Merlant Marie , Truong Audrey , Ghosn Jade , Phung Bao-Chau , Mollo Bastien , Perrineau Ségolène , Rahi Mayda , Fidouh-Houhou Nadhira , Ferré Valentine Marie , Brunet-Possenti Florence , Descamps Vincent , Bouscarat Fabrice , Yazdanpanah Yazdan , Deschamps Lydia , Bertin Chloé 
Published: November 2022

AbstractSkin histology of papules and pustules from 5 men having sex with men with mpox infection showed viral intracytoplasmic cytopathic changes, interface dermatitis, marked inflammatory dermic infiltrate including superficial neutrophils and perivascular and periadnexal deep lymphocytes. Histologic description of mpox lesions improves our understanding about clinical presentations and may have some therapeutic implications.
Successful Treatment of Prolonged, Severe Coronavirus Disease 2019 Lower Respiratory Tract Disease in a B cell Acute Lymphoblastic Leukemia Patient With an Extended Course of Remdesivir and Nirmatrelvir/Ritonavir
Authors: Ford Emily S , Simmons William , Karmarkar Ellora N , Yoke Leah H , Braimah Ayodale B , Orozco Johnnie J , Ghiuzeli Cristina M , Barnhill Serena , Sack Coralynn L , Benditt Joshua O , Roychoudhury Pavitra , Greninger Alexander L , Shapiro Adrienne E , Hammond Jennifer L , Rusnak James M , Dolsten Mikael , Boeckh Michael , Liu Catherine , Cheng Guang-Shing , Corey Lawrence 
Published: November 2022

Abstract
A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, intravenous (IV) remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to full recovery.
Fertility and Assisted Reproductive Technologies Outcomes of Women with Non-surgically Managed Inflammatory Bowel Diseases: A Systematic Review
Authors: Vieujean Sophie , De Vos Michel , Paridaens Kristine , Daftary Gaurang S , Danese Silvio , Peyrin-Biroulet Laurent 
Published: November 2022

Abstract

Background and Aim
In view of their frequent onset during childbearing years, the impact of inflammatory bowel diseases [IBD] on reproductive health is of important concern to young women and to the IBD physician. This study aims to assess the fertility and assisted reproductive technologies outcomes in non-surgically treated IBD females.

Methods
A systematic review was conducted using MEDLINE, SCOPUS, and EMBASE [until March 2022] to identify studies assessing fertility and assisted reproductive technologies outcomes in women with non-operated IBD, compared with non-IBD patients. Two reviewers independently selected studies, assessed risk of bias, and extracted study data.

Results
A total of 14 studies encompassing 18 012 patients with ulcerative colitis [UC] and 14 353 patients with Crohn’s disease [CD] were included for analysis. The fertility rate in UC patients and in the general population was comparable, but UC patients tended to have fewer children, mainly by choice. On the contrary, the fertility of CD patients appeared to be reduced. Although a deliberate component cannot be not excluded, the disease itself could affect fertility. Disease activity was associated with reduced fertility in both UC and CD patients. In CD, the colonic involvement of the disease and perianal damage could be associated with subfertility, but data are less consistent. According to the only study reporting the assisted reproductive technologies outcomes, pregnancy rates after in vitro fertilization in subfertile non-operated UC patients and non-IBD patients were similar.

Conclusions
There is low-quality evidence from observational studies that patients with CD and relapsing UC may have impaired fertility. After assisted reproductive technologies, pregnancy rates of subfertile non-operated UC patients were similar to those of the general population, although this observation requires further scrutiny in larger studies that should include UC and CD patients.
Association of Neutrophil Extracellular Traps with Fistula Healing in Patients with Complex Perianal Fistulizing Crohn’s Disease
Authors: Cao Dongxing , Qian Keyu , Zhao Ying , Hong Jie , Chen Haoyan , Wang Xiaohui , Yang Nailin , Zhang Cheng , Cao Jingkai , Jia Keyu , Wu Guangyu , Zhu Mingming , Shen Jun , Zhang Ye , Cui Zhe , Wang Zheng 
Published: November 2022

Abstract

Background and Aims
Perianal fistulizing Crohn’s disease [pfCD] is a disabling phenotype of Crohn’s disease [CD] with suboptimal outcomes. We assessed neutrophil extracellular traps [NETs] in perianal fistulas and implicated their roles in pfCD healing.

Methods
Patients with complex pfCD who developed preplaced seton drainage were recruited during the verified maintenance of remission in CD. Fistula tracts were sampled during definitive surgery plus seton removal. Patient demographics, CD classification, medication strategy and healing of pfCD were recorded. RNA sequencing was applied for transcriptomic profile analysis. NET components, including myeloperoxidase [MPO], neutrophil elastase [NE] and citrullinated histone H3 [CitH3], were identified using immunofluorescence. Serum infliximab [IFX], anti-IFX antibodies, and tissue levels of IFX, adalimumab [ADA], MPO and CitH3 were determined using enzyme-linked immunosorbent assays. Peptidyl arginine deiminase IV [PAD4], tumour necrosis factor [TNF]-α, and NE were detected using immunohistochemistry. Gene expression levels of PAD family members were assessed with quantitative PCR.

Results
Twenty-one patients were included, 15 of whom adopted IFX as maintenance treatment. RNA-sequencing revealed differences in neutrophil associated pathways between unhealed and healed fistulas. NET components [MPO/NE/CitH3] were detectable in the fistulas and were parallel with the levels of PAD4. Eleven of 21 [52%] patients experienced complete healing of the pfCD 108 weeks post-operatively. Fistula NETs were significantly increased in patients with unhealed pfCD. Increased NETs were associated with abundant TNF-α production and the absence of IFX in fistulas.

Conclusions
NETs exist in pfCD fistulas, which are associated with unhealed post-operative fistulas in pfCD, suggesting their prognostic roles in pfCD.
Acute myocardial infarction in a patient with congenitally corrected transposition of the great arteries and complex coronary anatomy—a case report
Authors: Asaad Fahd , Sörensson Peder , Rück Andreas , Nagy Edit , Jurga Juliane , Ståhlberg Marcus 
Published: November 2022

Abstract

Background
Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital heart anomaly with atrioventricular and ventriculoarterial discordance that is often associated with other cardiac and coronary artery anomalies. Here, we report a case of a patient with ccTGA and non-ST elevation myocardial infarction (NSTEMI) with challenging coronary anatomy that was treated with stress-perfusion cardiac magnetic resonance imaging (spCMR) guided percutaneous coronary intervention (PCI).

Case summary
A 46-year-old male smoker with ccTGA, dyslipidaemia, diabetes Type 2 managed with dietary restrictions and a family history of premature myocardial infarction, presented with typical chest pain, elevated cardiac troponin levels and ECG-changes indicative of ischaemia. The patient was diagnosed with NSTEMI and underwent initial urgent coronary angiography (CA) without apparent significant stenosis, although the right coronary artery (RCA) could not be selectively investigated. The patient had coronary anatomy 1R-2LCX according to the Leiden convention, which is the usual anatomy in patients with ccTGA. Despite this, CA was challenging due to the different anatomy compared with individuals with normally positioned great vessels. The patient remained highly symptomatic with chest pain at moderate exertion. To improve identification of the anatomic location and extent of ischaemia, we performed spCMR with adenosine. This revealed a limited septal infarction (likely embolic) in the right ventricle and reversible ischaemia in two inferior right ventricular segments. A second angiography, selectively investigating RCA demonstrated a significant stenosis in the distal RCA that was successfully treated with a drug-eluting stent. Fractional flow reserve (FFR) measurements of the left coronary arteries demonstrated hemodynamically non-significant stenosis. The patient’s symptoms resolved, and he remained asymptomatic at one month follow-up.

Discussion
This ccTGA patient had multiple risk factors for coronary artery disease and presented with NSTEMI. Diagnosis and treatment were challenging due to complex cardiac anatomy and associated different origins of the coronary arteries. We highlight the importance of careful evaluation of the coronary anatomy and functional testing using for example spCMR and FFR to target the culprit coronary vessel(s) in ccTGA complicated by NSTEMI.
The multidisciplinary management of a mechanical mitral valve thrombosis in pregnancy: a case report and review of the literature
Authors: Wright Jennifer M , Bottega Natalie , Therrien Judith , Hatzakorzian Roupen , Buithieu Jean , Shum-Tim Dominique , Wou Karen , Ghandour Amale , Pelletier Patricia , Li Pi Shan William , Kaufman Ian , Brown Richard , Malhamé Isabelle 
Published: November 2022

Abstract

Background
The management of anticoagulation for mechanical heart valves during pregnancy poses a unique challenge. Mechanical valve thrombosis is a devastating complication for which surgery is often the treatment of choice. However, cardiac surgery for prosthetic valve dysfunction in pregnant patients confers a high risk of maternofetal morbidity and mortality.

Case summary
A 39-year-old woman in her first pregnancy at 30 weeks gestation presented to hospital with a mechanical mitral valve thrombosis despite therapeutic anticoagulation with low-molecular-weight heparin. She underwent an emergent caesarean section followed immediately by a bioprosthetic mitral valve replacement. This occurred after careful planning and organization on the part of a large multidisciplinary team.

Discussion
A proactive, rather than reactive, approach to the surgical management of a mechanical valve thrombosis in pregnancy will maximize the chances of successful maternal and fetal outcomes.
Advanced HIV disease and associated attrition after re-engagement in HIV care in Myanmar from 2003 to 2019: a retrospective cohort study
Authors: Mesic Anita , Homan Tobias , Lenglet Annick , Thit Phone , Mar Htay Thet , Sabai Saw Myat , Thandar Moe Pyae , Thwe Thin Thin , Kyaw Aung Aung , Decroo Tom , Spina Alexander , Ariti Cono , Ritmeijer Koert , Van Olmen Josefien , Oo Htun Nyunt , Lynen Lutgarde 
Published: November 2022

Abstract

Background
The burden of advanced HIV disease (AHD) and predictors of outcomes among people living with HIV (PLHIV) re-engaging in care are not well known.

Methods
We conducted a retrospective cohort study of PLHIV who re-engaged in care after being lost to follow-up (LFU), from 2003 to 2019, in Myanmar. We calculated the incidence rates of attrition after re-engagement and performed Cox regression to identify risk factors for attrition.

Results
Of 44 131 PLHIV who started antiretroviral treatment, 12 338 (28.0%) were LFU at least once: 7608 (61.6%) re-engaged in care, 4672 (61.4%) with AHD at re-engagement. The death and LFU rates were 2.21-fold (95% CI 1.82 to 2.67) and 1.46-fold (95% CI 1.33 to 1.61) higher among patients who re-engaged with AHD (p&gt;0.001). Death in patients who re-engaged with AHD was associated with male sex (adjusted HR [aHR] 2.63; 95% CI 1.31 to 5.26; p=0.006), TB coinfection (aHR 2.26; 95% CI 1.23 to 4.14; p=0.008) and sex work (aHR 7.49, 95% CI 2.29 to 22.52; p&lt;0.001). History of intravenous drug use was identified as a predictor of being LFU.

Conclusions
Re-engagement in HIV care in Myanmar is frequent and those who re-engage carry a high burden of AHD. As AHD at re-engagement is associated with higher attrition rates, implementation of differentiated interventions that enable earlier linkage to care and prompt identification and management of AHD in this population is necessary.
N-fertilization of tropical pastures improves performance but not methane emission of Nellore growing bulls
Authors: Lima Lais de Oliveira , Ongaratto Fernando , Dallantonia Erick Escobar , Leite Rhaony Gonçalves , Argentini Gabriella Patrício , Fernandes Marcia Helena Machado da Rocha , Reis Ricardo Andrade , Vyas Diwakar , Malheiros Euclides Braga 
Published: November 2022

Abstract
Grazing management and N-fertilizer have been reported to improve tropical forage productivity and quality, however, their effect on methane emission of grazing animals remains uncertain. Therefore, this study aimed to assess the effects of increasing application rates of nitrogen (N) fertilization of Marandu palisadegrass under continuous stocking on intake, digestibility, nitrogen balance, and enteric methane emissions of Nellore growing bulls. We hypothesized that changes in the forage nutritive value caused by N fertilization of pastures combined with adequate grazing management (e.g., greater crude protein [CP] and digestibility) would lead to an increase in animal productivity (e.g., greater average daily gain [ADG] and gain per area), and then, to a decrease in methane emission intensity. Treatments consisted of different annual application rates of nitrogen fertilization: 0, 75, and 150 kg N/ha using ammonium nitrate (32% N) as the nitrogen source. The experimental design was completely randomized, with three treatments and four replications (12 paddocks). Intake, digestibility, N balance, and methane emissions were measured in eight animals per treatment. CP intake, digestibility and N balance increased linearly with the increase in N fertilization (P &lt; 0.05). In addition, stocking rate (SR) and ADG linearly increased from 1.75 animal unit (AU = 450 kg)/ha and 0.62 kg/d (0 kg N/ha) to 3.75 AU/ha and 0.82 kg/d (150 kg N/ha), respectively. Individual methane emissions nor methane emission intensity were affected by treatment with an average of 164.7 g/d and 199.7 g/kg ADG (P &gt; 0.05). Annual N fertilization with ammonium nitrate between 75 and 150 kg N/ha in palisadegrass pastures under continuous stocking enhances animal performance per unit area yet not affecting neither methane production nor intensity.
Treatment of Hypertrophic Scars with Corticoid-Embedded Dissolving Microneedles
Authors: De Decker Ignace , Szabó Anna , Hoeksema Henk , Speeckaert Marijn , Delanghe Joris R , Blondeel Phillip , Van Vlierberghe Sandra , Monstrey Stan , Claes Karel E Y 
Published: November 2022

Abstract
Hypertrophic scarring (HTS) is frequently observed after deep dermal and full-thickness skin defects. Local drug delivery in HTS has been shown more effective compared to other (minimally) invasive treatments. Disadvantages being operator-dependency and non-uniform drug distribution. Moreover, injections are painful and difficult when confronted with extensive scars or HTS in children. Corticoid-embedded dissolving microneedles (CEDMN) were developed that provide painless skin penetration and direct dermal drug delivery. Hyaluronic acid-based DMN and CEDMN patches were utilized. Structural analysis was performed via nuclear magnetic resonance (NMR) spectroscopy while gel permeation chromatography (GPC) was applied to determine chain length (molar mass) and dispersity of hyaluronic acid. Mechanical properties were evaluated by compression testing. Five burn victims with HTS were included. For each individual, three comparable scars were chosen. One control scar was left untreated. Two scars were treated with either 600 or 800 µm CEDMN patches. Patients were treated monthly for 4 months. Treatment with 800 µm CEDMN was initiated after 8 weeks. Assessor-blinded POSAS was registered. Hydration, evaporation, color and elasticity were recorded. The physico-chemical characterization suggests that the mechanical properties enable skin penetration and adequate drug delivery. Patients experienced the therapy as painless. According to the POSAS, all scars improved over time. However, the scars that were treated with CEDMN patches improved faster and with increased increment. The 800 µm CEDMN ensured the fastest POSAS-decrease. Hyaluronic acid-based CEDMN patches are valuable alternatives to intracicatrical injections, as they offer a painless and effective method for administering corticosteroids in HTS.
Breast Cancer Screening in Women With Dense Breasts: Current Status and Future Directions for Appropriate Risk Stratification and Imaging Utilization
Authors: Miles Randy C , Chou Shinn-Huey , Vijapura Charmi , Patel Amy 
Published: November 2022

Abstract
Breast density continues to be a prevailing topic in the field of breast imaging, with continued complexities contributing to overall confusion and controversy among patients and the medical community. In this article, we explore the current status of breast cancer screening in women with dense breasts including breast density legislation. Risk-based approaches to supplemental screening may be more financially cost-effective. While all advanced imaging modalities detect additional primarily invasive, node-negative cancers, the degree to which this occurs can vary by density category. Future directions include expanding the use of density-inclusive risk models with appropriate risk stratification and imaging utilization. Further research is needed, however, to better understand how to optimize population-based screening programs with knowledge of patients’ individualized risk, including breast density assessment, to improve the benefit-to-harm ratio of breast cancer screening.
High-quality approximation of log-aesthetic curves based on the fourth-order derivative
Authors: Tsuchie Shoichi , Yoshida Norimasa 
Published: November 2022

Abstract
We propose a new method for approximating log-aesthetic curves ${\boldsymbol C}_{\mathrm{LA}}$ using high-degree Bézier curves. By leveraging the property that higher order derivatives are more sensitive to the quality of approximation, the method minimizes an objective function based on the fourth-order derivative; consequently, ${\boldsymbol C}_{\mathrm{LA}}$ is approximated with high accuracy. In addition, the proposed method is composed of two steps to ensure stable optimization so as not to be negatively affected because of a local minimum and to evaluate the fourth-order derivative. Furthermore, we reveal the difficulty in sufficiently approximating ${\boldsymbol C}_{\mathrm{LA}}$ with Bézier curves from two aspects. One aspect entails the uncertainty of how accurately the low-degree Bézier curves can approximate ${\boldsymbol C}_{\mathrm{LA}}$. The other aspect is the existence of a subset of ${\boldsymbol C}_{\mathrm{LA}}$ that is inherently difficult to approximate with such conventional parametric curves. The experimental results and comparisons demonstrated the validity of the proposed method.