bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model validation and selection in metabolic flux analysis and flux balance analysis
Authors: Kaste Joshua A. M. , Shachar‐Hill Yair 
Published: November 2023

Abstract13C‐Metabolic Flux Analysis (13C‐MFA) and Flux Balance Analysis (FBA) are widely used to investigate the operation of biochemical networks in both biological and biotechnological research. Both methods use metabolic reaction network models of metabolism operating at steady state so that reaction rates (fluxes) and the levels of metabolic intermediates are constrained to be invariant. They provide estimated (MFA) or predicted (FBA) values of the fluxes through the network in vivo, which cannot be measured directly. These fluxes can shed light on basic biology and have been successfully used to inform metabolic engineering strategies. Several approaches have been taken to test the reliability of estimates and predictions from constraint‐based methods and to compare alternative model architectures. Despite advances in other areas of the statistical evaluation of metabolic models, such as the quantification of flux estimate uncertainty, validation and model selection methods have been underappreciated and underexplored. We review the history and state‐of‐the‐art in constraint‐based metabolic model validation and model selection. Applications and limitations of the χ2‐test of goodness‐of‐fit, the most widely used quantitative validation and selection approach in 13C‐MFA, are discussed, and complementary and alternative forms of validation and selection are proposed. A combined model validation and selection framework for 13C‐MFA incorporating metabolite pool size information that leverages new developments in the field is presented and advocated for. Finally, we discuss how adopting robust validation and selection procedures can enhance confidence in constraint‐based modeling as a whole and ultimately facilitate more widespread use of FBA in biotechnology.
Chemotherapy in pediatric brain tumor and the challenge of the blood–brain barrier
Authors: Malik Johid Reza , Podany Anthony T. , Khan Parvez , Shaffer Christopher L. , Siddiqui Jawed A. , Baranowska‐Kortylewicz Janina , Le Jennifer , Fletcher Courtney V. , Ether Sadia Afruz , Avedissian Sean N. 
Published: November 2023

AbstractBackgroundPediatric brain tumors (PBT) stand as the leading cause of cancer‐related deaths in children. Chemoradiation protocols have improved survival rates, even for non‐resectable tumors. Nonetheless, radiation therapy carries the risk of numerous adverse effects that can have long‐lasting, detrimental effects on the quality of life for survivors. The pursuit of chemotherapeutics that could obviate the need for radiotherapy remains ongoing. Several anti‐tumor agents, including sunitinib, valproic acid, carboplatin, and panobinostat, have shown effectiveness in various malignancies but have not proven effective in treating PBT. The presence of the blood–brain barrier (BBB) plays a pivotal role in maintaining suboptimal concentrations of anti‐cancer drugs in the central nervous system (CNS). Ongoing research aims to modulate the integrity of the BBB to attain clinically effective drug concentrations in the CNS. However, current findings on the interaction of exogenous chemical agents with the BBB remain limited and do not provide a comprehensive explanation for the ineffectiveness of established anti‐cancer drugs in PBT.MethodsWe conducted our search for chemotherapeutic agents associated with the blood–brain barrier (BBB) using the following keywords: Chemotherapy in Cancer, Chemotherapy in Brain Cancer, Chemotherapy in PBT, BBB Inhibition of Drugs into CNS, Suboptimal Concentration of CNS Drugs, PBT Drugs and BBB, and Potential PBT Drugs. We reviewed each relevant article before compiling the information in our manuscript. For the generation of figures, we utilized BioRender software.FocusWe focused our article search on chemical agents for PBT and subsequently investigated the role of the BBB in this context. Our search criteria included clinical trials, both randomized and non‐randomized studies, preclinical research, review articles, and research papers.FindingOur research suggests that, despite the availability of potent chemotherapeutic agents for several types of cancer, the effectiveness of these chemical agents in treating PBT has not been comprehensively explored. Additionally, there is a scarcity of studies examining the role of the BBB in the suboptimal outcomes of PBT treatment, despite the effectiveness of these drugs for other types of tumors.
Primary breast diffuse large B‐cell lymphoma in the rituximab era: A retrospective study of the Chinese Southwest Oncology Group
Authors: Weng Huawei , Shrestha Prem Raj , Hong Huangming , Chen Zegeng , Yu Le , Yao Yuyi , Zhang Zhihui , Zou Liqun , Zhu Bo , Zhou Hui , Liu Xianling , Liu Yao , Guo Hongqiang , Huang He , Lin Tongyu 
Published: November 2023

AbstractBackgroundPrimary breast diffuse large B‐cell lymphoma (PB‐DLBCL) is a rare subtype of extranodal DLBCL, and the standard treatment remains controversial. In this study, we aimed to define the optimal treatment management in the rituximab era.MethodsA total of 5089 newly diagnosed DLBCL patients treated with rituximab‐containing immunochemotherapy between 2008 and 2019 from the Chinese Southwest Oncology Group‐affiliated institutes were identified, of whom 135 diagnosed with PB‐DLBCL were eligible for this analysis.ResultsPB‐DLBCL accounted for 2.7% of all DLBCLs. With a median follow‐up of 4.2 years, the 5‐year overall survival and progression‐free survival rates were 84.8% and 71.6%, respectively. Breast and central nervous system (CNS) relapses were the main cause of treatment failure. We observed that consolidative breast radiotherapy (RT) significantly decreased breast relapse risk (5‐year risk, 2.9% vs. 20.1%, p = 0.007). The CNS relapse risk was lower for patients who received high‐dose methotrexate (HD‐MTX) than for patients who did not (5‐year risk, 0% vs. 15.2%, p = 0.015). We further screened the genetic mutation profile of 20 patients from two institutes, and found that MYD88 (25%) and CD79B mutations (25%) frequently occur in PB‐DLBCL. In addition, four patients with MYD88 and/or CD79B mutations experienced CNS relapse, while three patients with MYD88 and/or CD79B mutations who received HD‐MTX did not experience CNS relapse.ConclusionCollectively, our results indicate combined modality therapy including rituximab‐containing immunochemotherapy and consolidative breast RT is a promising approach for PB‐DLBCL, while HD‐MTX is useful for preventing CNS relapse.
Botanical‐based simulation of color change in fruit ripening: Taking tomato as an example
Authors: Xu Yixin , Liu Shiguang 
Published: November 2023

AbstractThe color change of plant fruit in ripening is a typical time‐varying phenomenon involving various factors. Due to its complexity and biodiversity, it is challenging to model this phenomenon. To address this issue, we take the tomato as an example and propose a botanical‐based framework considering variety, environment, phytohormone, and genes to simulate fruit color change during the ripening process. Specifically, we propose a first‐order kinetic model that integrates varietal, environmental, and phytohormonal factors to represent the variation of pigment concentrations in the pericarp. Moreover, we introduce a logistic model to describe the change in pigment concentration in the epidermis. Based on the gene expression pathway of tomato color in botany, we propose a genotype‐to‐phenotype simulation method to represent its biodiversity. An improved method is proposed to convert pigment concentrations into color accurately. Furthermore, we propose a gradient descent‐based method to assist the user in quickly setting pigment concentration parameters. Experiments verified that the proposed framework can simulate a wide range of tomato colors. Both qualitative and quantitative experiments validated the proposed method. Furthermore, our framework can be applied to more fruits.
Catheter‐based therapy for intermediate or high‐risk pulmonary embolism is associated with lower in‐hospital mortality in patients with cancer: Insights from the National Inpatient Sample
Authors: Leiva Orly , Yuriditsky Eugene , Postelnicu Radu , Yang Eric H. , Mukherjee Vikramjit , Greco Allison , Horowitz James , Alviar Carlos , Bangalore Sripal 
Published: November 2023

AbstractBackgroundPulmonary embolism (PE) is a common complication among patients with cancer and is a significant contributor to morbidity and mortality. Catheter‐based therapies (CBT), including catheter‐directed thrombolysis (CDT) and mechanical thrombectomy, have been developed and are used in patients with intermediate or high‐risk PE. However, there is a paucity of data on outcomes in patients with cancer as most clinical studies exclude this group of patients.AimsTo characterize outcomes of patients with cancer admitted with intermediate or high‐risk PE treated with CBT compared with no CBT.MethodsPatients with an admission diagnosis of intermediate or high‐risk PE and a history of cancer from October 2015 to December 2018 were identified using the National Inpatient Sample. Outcomes of interest were in‐hospital death or cardiac arrest (CA) and major bleeding. Inverse probability treatment weighting (IPTW) was utilized to compare outcomes between patients treated with and without CBT. Variables that remained unbalanced after IPTW were adjusted using multivariable logistic regression.ResultsA total of 2084 unweighted admissions (10,420 weighted) for intermediate or high‐risk PE and cancer were included, of which 136 (6.5%) were treated with CBT. After IPTW, CBT was associated with lower death or CA (aOR 0.54, 95% CI 0.46–0.64) but higher major bleeding (aOR 1.41, 95% CI 1.21–1.65). After stratifying by PE risk type, patients treated with CBT had lower risk of death or CA in both intermediate (aOR 0.52, 95% CI 0.36–0.75) and high‐risk PE (aOR 0.48, 95% CI 0.33–0.53). However, patients with CBT were associated with increased risk of major bleeding in intermediate‐risk PE (aOR 2.12, 95% CI 1.67–2.69) but not in those with high‐risk PE (aOR 0.84, 95% CI 0.66–1.07).ConclusionsAmong patients with cancer hospitalized with intermediate or high‐risk PE, treatment with CBT was associated with lower risk of in‐hospital death or CA but higher risk of bleeding. Prospective studies and inclusion of patients with cancer in randomized trials are warranted to confirm our findings.
Combination therapy for management of pemphigus patients with unexpected therapeutic response to rituximab: A report of five cases
Authors: Aryanian Zeinab , Riyaz Insha Zainab , Balighi Kamran , Ahmadzade Ali , Mahmoudi Hamid Reza , Azizpour Arghavan , Hatami Parvaneh 
Published: November 2023

Key Clinical MessageThe immunosuppressant agents should be considered earlier in the course of treatment with rituximab, possibly after the unfavorable response at first cycle of treatment, especially in male patients and those with high BMI.AbstractRituximab (RTX) has recently been proposed as an alternative first‐line therapy for pemphigus patients. However, there are some rare reports of worsening of pemphigus following RTX therapy in the literature. This study aimed to evaluate the efficacy and safety of using a combination treatment of mycophenolate mofetil or dapsone and methotrexate in case of nonresponse, exacerbation or development of allergic reactions following rituximab therapy in pemphigus patients. In this case series, archive files of pemphigus patient in a tertiary care hospital from 2016 to 2021 who were treated with rituximab were reviewed and those with failure in treatment process including nonresponsiveness, exacerbation or development of allergic reactions to rituximab were identified and assessed. The study includes five patients out of 1245 RTX‐treated patients, who did not respond to RTX (one patient) or experienced an exacerbation of disease (two patients) or development of allergic reactions (two patients). Male patients with high BMI (BMI > 25) whose response to rituximab was not good at first cycle and happened to receive rituximab later in the course of disease, had highest number of relapses and benefited the most from this combination immunosuppressive treatment as an alternative for repeating rituximab cycles. The lower risk of relapse and a better chance of remission might indicate the efficacy of adjuvant immunosuppressant therapy in patients with no‐response, exacerbation, or allergic reaction to rituximab. These therapeutic effects were better observed in patients who received lower doses of rituximab which could suggest that the immunosuppressant agents should be considered earlier in the course of the disease, possibly after the first failed trial of rituximab therapy.
Eosinophilic granulomatosis with polyangiitis following flu guard influenza vaccination: A case report
Authors: Jafarpour Mehdi , Daneshvar Sara , Eftekharsadat Amir Taher , Khabbazi Alireza , Pourbagherian Omid 
Published: November 2023

Key Clinical MessageThis case highlights a potential association between influenza vaccination and the development of eosinophilic granulomatosis with polyangiitis (EGPA), prompting the need for increased vigilance regarding vaccine‐related autoimmune reactions. While causality remains unclear, clinicians should consider this possibility in patients presenting with EGPA‐like symptoms shortly after vaccination.AbstractEosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by tissue infiltration by eosinophils and hyper eosinophilia. We present a case of EGPA in a middle‐aged man following influenza vaccination. The patient developed respiratory symptoms, skin lesions, joint pain, and neurological deficits. Diagnostic tests revealed eosinophilia, positive anti‐neutrophil cytoplasmic antibodies, and elevated acute phase reactants. This report highlights a potential association between influenza vaccination and EGPA.
Biliary atresia and posterior fossa bleed: Chance or causality. A case report and review of the literature
Authors: Karki Susmin , Chand Vikash , Parajuli Asmita , Shilpakar Sushil Kumar , Regmi Prakash , Bhusal Kabi Raj 
Published: November 2023

Key Clinical MessageA newborn with a rare form of biliary atresia had posterior fossa bleed and subarachnoid hemorrhage despite vitamin K prophylaxis, indicating biliary atresia is a causality rather than chance.AbstractBiliary atresia frequently causes surgical jaundice, resulting in delayed vitamin K deficiency. We report a 28‐day‐old newborn diagnosed with a rare form of biliary atresia presented with an unusual association of posterior fossa bleed and subarachnoid hemorrhage despite vitamin K prophylaxis. Thus, biliary atresia remains causality rather than chance.
Synovial sarcoma of the maxilla: A challenging diagnostic case report and literature review
Authors: Saghravanian Nasrollah , Rahpeyma Amin , Ghorbani Mahsa , Saeedi Pooya 
Published: November 2023

AbstractSynovial sarcoma, a malignant mesenchymal tumor, is primarily associated with the extremities. Nevertheless, its appearance within the head and neck region, particularly in the maxillary area, is remarkably rare. This rarity underscores the significance of each case in unraveling the complexities of its behavior and management strategies. The core focus of this research is a detailed case report involving a 6‐year‐old female patient who presented with a conspicuous swelling in the left posterior maxilla. Subsequent incisional biopsy led to microscopic identification of malignant spindle cell proliferation, marked by dysplastic changes, and abundant mitoses. Immunohistochemical (IHC) analysis demonstrated negative reactivity for neural and muscular markers, while positive expression of Vimentin, Bcl‐2, and TLE1. These morphological and IHC findings coalesced to definitively diagnose synovial sarcoma, substantiated by a notable 40% Ki67 proliferative index. The chosen treatment strategy encompassed surgery and radiotherapy, which yielded successful outcomes, with no recurrence observed during the one‐year follow‐up period. Beyond the specific case, this article undertakes a review of existing literature, meticulously analyzing nine similar cases reported in scholarly sources.
Optic neuritis after mRNA COVID‐19 vaccination: a case report
Authors: Tarcha Raghad , Ghazal Afraa , Al‐Darwish Lama , Abdoh Hoda , Kudsi Maysoun 
Published: November 2023

Key Clinical MessageOur case reported a 22‐year‐old male presented with headache, and sudden vision loss, 10 days after receiving the first dose of COVID‐19 vaccination. Counting fingers in both eyes was his visual acuity on examination and bilateral optic disc edema on fundoscopy was found. Brain MRI was normal. After methylprednisolone pulse therapy, plasmapheresis, and IV cyclophosphamide courses, the optic disc edema disappeared, and his visual function did not improve. Reported cases of optic neuritis develop after mRNA COVID‐19 vaccination are limited.
A novel telomere biology disease‐associated gastritis identified through a whole exome sequencing‐driven approach
Authors: Setia Namrata , del Gaudio Daniela , Kandikatla Priscilla , Arndt Kelly , Tjota Melissa , Wang Peng , Segal Jeremy , Alikhan Mir , Hart John 
Published: November 2023

AbstractA whole exome sequencing (WES)‐driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastritis with persistent dense inflammation, loss of both parietal and neuroendocrine cells in the oxyntic mucosa, and sparing of the antral mucosa. The patients were found to harbor pathogenic variants in telomeropathic genes (POT1 and DCLRE1B). Clonality testing for one of the patients showed evidence of evolving clonality of TCR‐gene rearrangement. Both patients showed significantly decreased numbers of stem/progenitor cells by immunohistochemistry, which appears to be responsible for the development of mucosal atrophy. No such cases of unusual chronic atrophic gastritis in the setting of telomeropathy have been previously reported. The loss of stem/progenitor cells suggests that stem/progenitor cell exhaustion in the setting of telomere dysfunction is the likely mechanism for development of this unusual chronic atrophic gastritis. The results underscore the need for close monitoring of these gastric lesions, with special regard to their neoplastic potential. This combined WES‐driven approach has promise to identify the cause and mechanism of other uncharacterized gastrointestinal inflammatory disorders.
Life's essential 8 and risk of all‐cause mortality in individuals with cardiovascular diseases: A prospective community‐based study
Authors: Huang Lili , Wang Aitian , Wu Zhijun , Chen Shuohua , Zheng Yan , Wu Shouling , Gao Xiang 
Published: November 2023

AbstractBackgroundAlthough risk factors for mortality in individuals with cardiovascular diseases (CVD) have been reported, little is known regarding the association between the comprehensive cardiovascular health (CVH) index assessed by life's essential 8 (LE8) and the risk of mortality.HypothesisThe aim of this study was to evaluate the CVH assessed by LE8 and risk of mortality in individuals with CVD.MethodsA total of 1391 participants with CVD diagnosed before 2014 from the Kailuan cohort were included in the analysis. The CVH score ranged from 0 to 100 was assessed using the LE8 metrics (diet quality, physical activity, sleep health, cigarette smoking, body mass index, lipids, blood glucose, and blood pressure). Cox regression model was used to estimate the association between the CVH score and risk of all‐cause mortality.ResultsDuring a mean follow‐up of 6.1 ± 1.5 years, 229 deaths occurred. The hazard ratio for all‐cause mortality was 0.57 (95% confidence interval [CI]: 0.38, 0.84) in the highest quartiles compared with the lowest quartiles of CVH scores and 0.85 (95% CI: 0.75, 0.95) for each 10 points increment in CVH scores (ptrend = .009), after adjustment for age, sex, CVD duration, social‐economic status, alcohol consumption, inflammation, medicine use, and kidney function. We did not observe significant interactions between the CVH scores and age, sex, and duration of CVD diagnosis (pinteraction > .05 for all).ConclusionsThe CVH assessed by the LE8 metrics was associated with a lower risk of all‐cause mortality in individuals with CVD.
Analysis and numerical investigation of bile flow dynamics within the strictured biliary duct
Authors: Peng Tao , Zhong Yunlong , Lin Xiaodong , Jiang Bingyan , Wang Ping , Jia Yanwei 
Published: November 2023

AbstractThe mechanics of bile flow in the biliary system plays an important role in studying bile stasis and gallstone formation. Bile duct stricture is an abnormal phenomenon that refers to the bile duct getting smaller or narrower. The main objective of this study is to study the influence of stricture on bile flow dynamics using numerical methods. We employed a numerical Computational Fluid Dynamics model of the bile flow within a strictured hepatic duct. We studied and compared the influence of stricture severity, stricture length, eccentricity, and bile flow property on the bile flow dynamics. The bile flow velocity, pressure distribution, pressure drop, and wall shear stress are provided in detail. The stricture alters the normal bile flow pattern and increases flow resistance. At the location upstream and downstream of the stricture, bile flow slows down. In the area of the stricture throat, bile flow is accelerated, and recirculation forms behind the stricture. The maximum pressure drop of the biliary system increases with the stricture length. The eccentricity makes the flow deflect away from the duct's centerline. The behavior of the deflected flow is significantly altered downstream of the stricture. Such bile flow behavior as deceleration and recirculation may lead to cholestasis. Stricture alters bile flow in the biliary tract, causing changes in biliary hydrodynamic indexes, which could potentially serve as an omen for gallstone formation and other related diseases. The consideration of the bile duct stricture could lead to better patient stratification.
Adaptive kernel density estimation weighted twin support vector machine and its sample screening method
Authors: Lv Li , Zhang Faying , Qiu Shenyu , Fan Tanghuai 
Published: November 2023

SummaryIn twin support vector machines (TSVM), noise blurs the boundary between positive and negative samples, increasing the probability of classification errors. In this article, we propose an adaptive kernel density estimation weighted twin support vector machine(AKWTSVM). AKWTSVM uses KDE based on K‐nearest neighbor estimation to calculate the probability density of samples. It automatically selects the optimal bandwidth based on the local density of the samples to improve the robustness of the algorithm. However, TSVM has high time complexity, to reduce the time costs, a sample screening method is proposed for AKWTSVM, named AKWTSVM‐SSM, which is based on the overall distance and local density, and reduces the time costs of the algorithm by reducing the sample size while ensuring the accuracy of the algorithm. The experiment with differently scaled noise environments of 0%, 5%, 10%, 15%, and 20% on 12 UCI datasets validate the accuracy and running time of AKWTSVM and AKWTSVM‐SSM. Experimental results prove the effectiveness and robustness of AKWTSVM, the robustness of AKWTSVM‐SSM, and its applicability to large‐scale datasets.