bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy
Authors: Liu Fangfang , Zhang Xuemei , Lu Mengyao , Liu Chun , Zhang Xiaodong , Chu Qian , Chen Yuan , Zhang Peng 
Published: February 2024

AbstractBackgroundThe study focuses on PD‐L1 expression as an essential biomarker for gauging the response of EGFR/ALK wild‐type NSCLC patients to FDA‐approved immune checkpoint inhibitors (ICIs). It aims to explore clinical, molecular, and immune microenvironment characteristics associated with PD‐L1 expression in EGFR/ALK wild‐type lung adenocarcinoma patients eligible for ICI therapy.MethodsIn this retrospective study, tumor samples from 359 Chinese EGFR/ALK wild‐type lung adenocarcinoma patients underwent comprehensive evaluations for PD‐L1 expression and NGS‐targeted sequencing. The investigation encompassed the analysis and comparison of clinical traits, gene mutations, pathways, and immune signatures between two groups categorized by PD‐L1 status: negative (TPS < 1%) and positive (TPS ≥ 1%). Additionally, the study explored the link between genomic changes and outcomes following immunotherapy.ResultsHigh tumor mutational burden correlated significantly with PD‐L1 positivity in patients with EGFR/ALK wild‐type lung adenocarcinoma. Gene alterations, including TP53, KRAS, and others, were more pronounced in the PD‐L1 positive group. Pathway analysis highlighted higher frequencies of alterations in pathways like RTK/RAS, p53, and Hippo in PD‐L1‐positive patients. The Hippo pathway's relevance was confirmed in separate immunotherapy cohorts, associated with better outcomes. In terms of immune cell infiltration, Hippo mutants exhibited higher levels of CD68+PD‐L1+ macrophages, CD8+ T cells, and CD8+PD‐1− T cells.ConclusionsThis study offers insights into genomic features of Chinese EGFR/ALK wild‐type lung adenocarcinoma patients based on PD‐L1 expression. Notably, Hippo pathway alterations were linked to improved immunotherapy outcomes. These findings suggest connections between the Hippo pathway and PD‐L1 expression, warranting further clinical and functional investigations. The research advances our understanding of PD‐L1 expression's genomic context and immunotherapy response in EGFR/ALK wild‐type lung adenocarcinoma.
Finding a needle in a haystack: The identification of clinical practice guidelines for psychosocial oncology through an environmental scan of the academic and gray literature
Authors: Bergeron Catherine , Azzi Michelle , Coroiu Adina , Loiselle Carmen G. , Drapeau Martin , Körner Annett 
Published: February 2024

AbstractObjectiveClinical practice guidelines (CPGs) are evidence‐based tools well‐suited to translate the latest research evidence into recommendations for routine clinical care. Given the rapid expansion of psychosocial oncology research, they represent a key opportunity for informing the treatment decisions of overburdened clinicians, standardizing service delivery, and improving patient‐reported outcomes. Yet, there is little consensus on how clinicians can most effectively access these tools and little to no information on the current availability and scope of CPGs for the range of psychosocial symptoms and concerns experienced by patients with cancer.MethodOur environmental scan consisted of an academic and gray literature designed to identify currently available CPGs addressing a range of cancer‐related psychosocial symptoms.ResultsFindings revealed a total of 23 existing psychosocial oncology CPGs that met full eligibility criteria. The gray literature search was found to be more effective at identifying CPGs (n = 22) compared to the academic search (n = 9).ConclusionSeveral concerns arose from the systematic search. The limited publication of CPGs in peer‐reviewed journals may make clinicians and stakeholders more hesitant to implement CPGs due to uncertainties about the methodological rigor of the development process. Further, many existing CPGs are outdated or failed to be updated according to guideline recommendations, meaning that the recommendations may fall short of their purpose to translate up‐to‐date research findings.Future directionsFuture research should seek to systematically assess the quality of existing psychosocial oncology CPGs and shed light on the current state of implementation and adherence in clinical practice in order to better inform guideline developers on the current needs of the psychosocial oncology community.
Guidelines for outpatient administration of naxitamab: Experience from Atrium Health Levine Children's Hospital
Authors: Trovillion Erin Murphy , Michael Meghan , Jordan Cathryn C. , Brown Lauren , Phillips Katlin , Oesterheld Javier , Saulnier‐Sholler Giselle 
Published: February 2024

AbstractAimIn this publication, we will share our experience of AE management, provide guidance for appropriate staffing, and the discuss the importance of patient education when treating patients with R/R HR neuroblastoma using naxitamab.BackgroundApproved treatments for patients with refractory and/or relapsed (R/R) high‐risk (HR) neuroblastoma are limited, and there is a high unmet need for new treatment combinations. Naxitamab is a disialoganglioside 2 (GD2)‐binding antibody that was approved by the United States Food and Drug Administration in 2020 for use in combination with granulocyte–macrophage colony‐stimulating factor for the treatment of patients with R/R HR neuroblastoma in the bone and/or bone marrow and who have demonstrated a partial response, minor response, or stable disease with prior therapy.MethodsThe pediatric oncology team at Atrium Health Levine Children’s Hospital has successfully treated several patients with naxitamab both alone and in combination with chemotherapy, with no patients requiring unplanned overnight hospitalization and few severe adverse events (AEs). To accomplish this, the team at Levine Children’s Hospital established standard operating procedures for naxitamab, a therapy defined as high acuity due to the potential for acute AEs with rapid onset and that benefits from continuous monitoring by a nursing team and a dedicated provider.ConclusionsThis will provide a practical guide for institutions offering naxitamab to their patients, and ensure successful administration of this high acuity treatment in the outpatient setting.
2,5‐Thienylene‐Strapped [26]Hexaphyrin as Multifunctional Chemosensor for Hg2+, Cu2+, and F− Ions
Authors: Kerayu Bulti Abdisa , Hung Chen‐Hsiung , Vardhaman Anil Kumar , Ayanie Tibebu Alemu , Geneti Busha Jima 
Published: February 2024

AbstractThe sensing behavior of 2,5‐thienylene‐bridged tetrakis(2,6‐dichlorophenyl)‐[26]hexaphyrin (2) towards various metal ions and anions were investigated by UV–vis and fluorescence spectroscopies. Using this strapped hexaphyrin (2), the molecular sensor displayed highly selective and sensitive colorimetric responses to Cu2+ and Hg2+ in MeOH/THF. The spectral changes are distinctive enough in the visible region of the spectrum to enable naked‐eye detection. The detection limits of Cu2+ and Hg2+ using this chemo‐sensor in a mixed MeOH/THF solution were 1.978 and 1.283 μM, respectively, and 1.052 μM for F− in dichloromethane. Chemosensor 2,5‐thienylene strapped [26]hexaphyrin (2) shows absorption responses both a 1 : 1 molecular ratio for 2 interacting with Cu2+ and Hg2+ and a 1 : 2 ratio between 2 and F− ions.
Curcumin – Bioavailability Enhancement by Prodrug Approach and Novel Formulations
Authors: Chelimela Narsaiah , Alavala Rajasekhar Reddy , Satla Shobha Rani 
Published: February 2024

AbstractCurcumin is a diverse natural pharmacological agent involved in various signal transduction mechanisms. Therapeutically, this potent molecule faces different challenges and issues related to low bioavailability due to its poor aqueous solubility, less permeability, faster elimination and clearance. Experts in synthetic chemistry and pharmaceuticals are continuously sparing their efforts to overcome these pharmacokinetic challenges by using different structural modification strategies and developing novel drug delivery systems. In this mini‐review article, we are focusing on development of curcumin derivatives by different possible routes like conjugation with biomolecules, natural polymers, synthetic polymers, natural products, metal conjugates and co‐ administration with natural metabolic inhibitors. In addition to that, it was also focused on the preparation of modified formulations such as micelles, microemulsions, liposomes, complexes with phospholipids, micro and nanoemulsions, solid lipid nanoparticles, nano lipid carriers, biopolymer nanoparticles and microgels to improve the pharmacokinetic properties of the curcumin without altering its pharmacodynamics activity. This review helps to understand the problems associated with curcumin and different strategies to improve its pharmacokinetic profile.
Acetylated oligopeptide and N‐acetylcysteine protect against iron overload‐induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO‐1 and downregulation of MMP‐9/TIMP‐1 and GFAP
Authors: Kamel Amira A. , Nassar Ahmed Y. , Meligy Fatma Y. , Omar Yomna A. , Nassar Gamal A. Y. , Ezzat Ghada M. 
Published: February 2024

AbstractIron accumulation in the brain causes oxidative stress, blood–brain barrier (BBB) breakdown, and neurodegeneration. We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron‐induced hippocampal damage compared to N‐acetyl cysteine (NAC). This 5‐week study used 40 male albino rats. At the start, all rats received 150 mg/kg/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60 mg/kg/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150 mg/kg/day NAC and iron dextran; and Group IV (AOP group) received 150 mg/kg/day AOP and iron dextran. Enzyme‐linked immunosorbent assay, spectrophotometry, and qRT‐PCR were used to measure MMP‐9, tissue inhibitor metalloproteinase‐1 (TIMP‐1), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP‐9, TIMP‐1, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO‐1, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload‐induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.
Bacterial Glycolipid Acting on Protein Transport Across Membranes
Authors: Mori Shoko , Shionyu Masafumi , Shimamoto Keiko , Nomura Kaoru 
Published: February 2024

AbstractThe process of protein transport across membranes involves a variety of factors and has been extensively investigated. Traditionally, proteinaceous translocons and chaperones have been recognized as crucial factors in this process. However, recent studies have highlighted the significant roles played by lipids and a glycolipid present in biological membranes in membrane protein transport. Membrane lipids can influence transport efficiency by altering the physicochemical properties of membranes. Notably, our studies have revealed that diacylglycerol (DAG) attenuates mobility in the membrane core region, leading to a dramatic suppression of membrane protein integration. Conversely, a glycolipid in Escherichia coli inner membranes, named membrane protein integrase (MPIase), enhances integration not only through the alteration of membrane properties but also via direct interactions with membrane proteins. This review explores the mechanisms of membrane protein integration mediated by membrane lipids, specifically DAG, and MPIase. Our results, along with the employed physicochemical analysis methods such as fluorescence measurements, nuclear magnetic resonance, surface plasmon resonance, and docking simulation, are presented to elucidate these mechanisms.
NR1H4 mutation and rapid progressive intrahepatic cholestasis in infancy: A case report and literature review
Authors: Yang Chiao‐Yu , Tsai Hung‐Wen , Chou Yen‐Yin , Yang Yao‐Jong 
Published: February 2024

AbstractFarnesoid X receptor (FXR) is a nuclear bile acid receptor encoded by the NR1H4 gene, a vital regulator of bile acid homeostasis. Pathogenic mutations of NR1H4 manifest as low gamma‐glutamyl transferase (GGT) cholestasis with rapid progression to liver failure, which is referred to as progressive familial intrahepatic cholestasis 5 (PFIC‐5). Herein, we present a case with rapid progressive cholestasis, liver failure in early infancy with the NR1H4 termination mutation.
Primary Sjogren's syndrome presenting as ptosis and eyelid swelling: A case report
Authors: Khan Alishba Ashraf , Mumtaz Shamaila , Malik Javeria , Manzoor Muhammad Shahzad , Maqbool Faran , Shafique Mudassir , Nazir Maheen , Ibn‐e‐Shad Zohad , Kandel Kamal 
Published: February 2024

Key Clinical MessageThis unique case report of primary Sjogren's syndrome (pSS) shows bilateral ptosis and significant periorbital edema, compromising vision. To avoid misleading diagnosis, antibody tests must be evaluated and interpreted in the context of clinical findings.AbstractPrimary Sjögren's syndrome is an idiopathic, autoimmune disorder involving the lacrimal and salivary glands characterized by both localized and systemic manifestations including xerostomia and keratoconjunctivitis sicca. Myasthenia Gravis (MG) is also an autoimmune disorder characterized by the development of auto‐antibodies against nicotinic acetylcholine receptors that causes decreased muscle response to stimulation. It usually presents with ptosis and generalized body weakness. Ophthalmological involvement is common in both disorders but ptosis is very rarely seen in pSS. We report the case of a 27‐year‐old woman presenting to our clinic with the complaint of ptosis and eyelid swelling. She also had a positive anti‐acetylcholine receptor antibody test and her initial presentation mimicked Myasthenia Gravis. Her autoimmune workup revealed a positive titer of Anti Ro SSA antibodies. Myasthenia Gravis was ruled out on electrodiagnostic studies which showed no decremental response, and pSS was confirmed on lip biopsy. Our case highlights that it is important to interpret the antibody test results in the context of clinical findings as we can have spurious results in autoimmune diseases. Autoimmune conditions can have varying presenting complaints hence, clinical judgment should always overrule diagnostic investigations and should thus guide patient management.
Small Molecule‐Drug Conjugates: Opportunities for the Development of Targeted Anticancer Drugs
Authors: Zhang Jingjing , Hu Fanchun , Aras Omer , Chai Yichao , An Feifei 
Published: February 2024

AbstractConventional chemotherapy is insufficient for precise cancer treatment due to its lack of selectivity and inevitable side effects. Targeted drugs have emerged as a promising solution for precise cancer treatment. A common strategy is to conjugate therapeutic agents with ligands that can specifically bind to tumor cells, providing targeted therapy. Similar to the more successful antibody drug conjugates (ADCs), small molecule drug conjugates (SMDCs) are another promising class of targeted drugs, consisting of three parts: targeting ligand, cleavable linker and payload. Compared to ADCs, SMDCs have the advantages of smaller size, better permeability, simpler preparation process and non‐immunogenicity, making them a promising alternative to ADCs. This review describes the characteristics of the targeting ligand, linker and payload of SMDCs and the criteria for selecting a suitable one. We also discuss recently reported SMDCs and list some successful SMDCs that have entered clinical trials.
Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram
Authors: De Salvo Gian Luca , Del Bianco Paola , Minard‐Colin Veronique , Chisholm Julia , Jenney Meriel , Guillen Gabriela , Devalck Christine , Van Rijn Rick , Shipley Janet , Orbach Daniel , Kelsey Anna , Rogers Timothy , Guerin Florent , Scarzello Giovanni , Ferrari Andrea , Cesen Mazic Maja , Merks Johannes H. M. , Bisogno Gianni ,   for the European Pediatric Soft Tissue Sarcoma Study Group
Published: February 2024

AbstractBackgroundThe objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event‐free survival and provide a rationale for risk stratification in future trials.MethodsThe authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005‐000217‐35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second‐order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5‐year event‐free survival (EFS) probabilities.ResultsThe EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%–73.1%) and 81.0% (95% confidence interval, 78.9%–82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5‐year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low‐risk, intermediate‐risk, high‐risk, and very‐high‐risk groups, respectively, and the corresponding 5‐year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively.ConclusionsThe results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.
Physiologically Based Pharmacokinetic Absorption Model for Pexidartinib to Evaluate the Impact of Meal Contents and Intake Timing on Drug Exposure
Authors: Nakayama Shintaro , Lukacova Viera , Tanabe Shuichi , Watanabe Akiko , Mullin Jim , Suarez‐Sharp Sandra , Shimizu Takako 
Published: February 2024

AbstractPexidartinib is a systemic treatment for patients with tenosynovial giant cell tumor not amenable to surgery. Oral absorption of pexidartinib is affected by food; administration with a high‐fat meal (HFM) or low‐fat meal (LFM) increases absorption by approximately 100% and approximately 60%, respectively, compared with the fasted state. Pexidartinib is currently dosed 250 mg orally twice daily with an LFM (approximately 11‐14 g of total fat). We developed a physiologically based pharmacokinetic model to determine the impact on drug exposure of dose timing with respect to meals, meal type, and caloric content. A 15%‐16% increase in plasma exposure was predicted when consuming an HFM 1 hour after dosing with an LFM, but almost no effect on pharmacokinetics was predicted when an HFM was consumed 3 hours or more before or after pexidartinib dosing with an LFM. Exposure was not significantly affected when pexidartinib was taken with a 500‐kcal LFM over the range of fat (approximately 11‐14 g of total fat; 20%‐25% calories from fat) for an LFM. These findings on timing of pexidartinib dose with respect to meals should be considered by patients and physicians to reduce the potential for side effects.
Production and cultivation dynamics of millets in India
Authors: Yadav O. P. , Singh D. V. , Kumari Vandita , Prasad Manoj , Seni Sushmita , Singh Roshan Kumar , Sood S. , Kant Lakshmi , Rao B. Dayakar , Madhusudhana R. , Bhat B. Venkatesh , Gupta S. K. , Yadava D. K. , Mohapatra T. 
Published: February 2024

AbstractMillets gained a great attention at the global level in 2023 which is celebrated as the “International Year of Millets” to create awareness to eventually promote consumption and production. An attempt is made here to understand the cultivation and production dynamics of millets as influenced by their demand and supply. We also assess challenges and emerging opportunities to make millets more productive, competitive, and relevant to future farming. Millets registered a 60% decline in area and a 200% rise in productivity, but production has remained the same during the last seven decades. The demand of millets decreased as food due to greater incentives (purchasing grain at a pre‐determined price) and policies (distribution of grains to the public at a subsidized rate) in favor of wheat and rice. Millets would play a greater role in future agriculture due to challenges posed by climate change, limited water supply, and reduced agro‐biodiversity. This would need a much greater intensity of investment in millet research and adequate support as extended to wheat and rice. Increased emphasis on their genetic improvement and agronomic management is required to develop cultivars, using new tools and technologies, with high production potential and adequate environmental adaptation to make millets competitive with other crops. Mainstreaming the nutritional traits in millet breeding is also critically important to develop high‐yielding cultivars with improved grain quality traits. Promoting millet consumption would remain the key issue for increasing their demand as food, feed, and industrial raw materials through policies and awareness programs. Strengthening of value chain will help in diversifying agri‐food production system and creating an ecosystem for millet promotion.
Deubiquitination of Abelson tyrosine kinase: A novel regulatory mechanism targeting non‐small cell lung cancer glycolysis
Authors: Yu Tong , Jiang Shuxia , Shan Hongli 
Published: February 2024

AbstractIn this commentary, we briefly introduce the importance of metabolic reprogramming in non‐small celllung cancer (NSCLC) and the role of aberrant glycolysis processes intumorigenesis and metastasis. We further summarize the regulation of deubiquitylation modification on glycolysis‐related kinases in this system. Andwe discusse the major discovery the research by He Yuanming et al. published in Clinical and Translational Medicine.Their study demonstrates targeting the USP7‐c‐Abl‐HK2 axis represents a promising therapeutic strategt for NSCLC.