bluuebunny/crossref_metadata_2025 huggingface dataset:
Classifying Hypoxia in Breast Cancer Xenografts Using a Single‐Cell Mass Spectrometry Imaging Model
Authors: Claes Britt S. R. , Biemans Rianne , Lieuwes Natasja , Theunissen Lynn , Glunde Kristine , Dubois Ludwig , Heeren Ron M. A. , Cuypers Eva
Published: December 2024

Hypoxia is a common feature in solid tumors that arises when there is insufficient oxygen available. This lack of oxygen causes molecular adaptations required for the tumor cells to survive. Additionally, oxygen‐deprived cancer cells tend to become less responsive to conventional cancer therapies. Hence, hypoxia plays an important role in contributing to tumor aggressiveness and therapy resistance. Hypoxia‐related markers are gaining interest as prognostic and predictive markers for tumor response and treatment strategies. However, the detection of hypoxia in the tumor microenvironment without employing any labeling strategies poses significant challenges. Here, we present a classification model based on lipidomic single‐cell mass spectrometry imaging data to classify hypoxia in breast cancer xenografts. Our approach is based on a classification model built from the lipid profiles of single breast cancer cells cultured under various oxygen conditions. Lipidomic alterations caused by differences in available oxygen concentrations were subsequently used to classify and spatially determine hypoxic regions in breast cancer xenografts without the need for any labeling. This approach, using cells as hypoxia markers, contributes to a better understanding of tumor biology and provides a foundation for improving diagnostic and therapeutic strategies for cancer treatments.
Preparation and Property Study of Polyvinyl Alcohol–Based Hydrogels Loaded With Traditional Chinese Medicine for Textile Applications
Authors: Feng Mengyuan , Jiang Yaming , Li Zheng
Published: December 2024

This study addresses the limitations of drug‐carrying gels regarding mechanical properties, process complexity, and slow‐release control by developing a green, nonpolluting, high‐toughness hydrogel for traditional Chinese medicine that exhibits excellent slow‐release properties. PVA (polyvinyl alcohol) hydrogels, along with various ratios of PVA/HACC (hydroxypropyltrimethyl ammonium chloride chitosan) hydrogels and PVA/HACC/CNW (cellulose nanowhisker) hydrogels, were prepared using a cyclic freeze–thaw method. The results indicated that the maximum tensile strength of the composite hydrogel reached 0.845 MPa, and its toughness was measured at 113.38 MJ/m3, demonstrating superior mechanical properties. Berberine hydrochloride (BBR), selected for its low toxicity and excellent antibacterial and antioxidant properties, served as the model drug. The drug‐loaded composite hydrogels exhibited a highly porous structure, where the increased HACC content led to larger pore sizes and enhanced drug release rates. Overall, the findings suggest that these drug‐carrying gels possess favorable mechanical properties and exceptional drug release capabilities, indicating their significant potential for drug delivery applications.
C(sp3)−H Bond Functionalization of 8‐Methylquinolines
Authors: Parmar Diksha , Kumar Rohit , Sharma Upendra
Published: December 2024

Quinolines have emerged as essential components in various medicinal agents, playing a key role in treating various ailments. Numerous drugs with a quinoline core have been recognized for their antimalarial, antibacterial, and anticancer activities and have been successfully commercialized, including chloroquine, ciprofloxacin, topotecan, etc. Over the past two decades, a tremendous expansion in the C−H bond functionalization of quinoline scaffolds to widen this chemical space for drug discovery have been witnessed. This review article summarizes the efforts toward C(sp3)−H functionalization of 8‐methylquinolines for C(sp3)−C/X bond formation under metal and metal‐free strategies. Each section briefly overviews the C(sp3)−H functionalization of 8‐methylquinoline, highlighting the metal and metal‐free approaches.
The Impact of Firm‐Level Political Risk on Eco‐Innovation: The Moderating Effect of CEO Power
Authors: Owolabi Ayotola , Mousavi Mohammad Mahdi , Gozgor Giray , Li Jing
Published: December 2024

This study examines the impact of firm‐level political risk on eco‐innovation at the firm level, particularly emphasizing the moderating role of CEO power in this relationship. Using a dataset from 33 countries from 2006 to 2022, we employ two‐step dynamic panel data estimations to address endogeneity concerns. The findings highlight a positive impact of political risk on eco‐innovation, which is further strengthened in the presence of a powerful CEO. This evidence implies that effective leadership from CEOs can assist firms in navigating political risks and advancing sustainable initiatives. The results remain robust across various specifications, including alternative measurements for firm‐level political risk. The study highlights the crucial role of CEOs in managing political risks and facilitating eco‐innovative practices within firms.
The Multi‐Kinase Inhibitor GZD824 (Olverembatinib) Shows Pre‐Clinical Efficacy in Endometrial Cancer
Authors: Liu Dongli , Glubb Dylan , O'Mara Tracy , Ford Caroline E.
Published: December 2024

Objective

Endometrial cancer is one of the few cancers for which mortality is still increasing. A lack of treatment options remains a major challenge, particularly for some subtypes of the disease. GZD824, also known as olverembatinib, is a multi‐kinase inhibitor previously investigated in clinical trials for chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia as a BCR‐ABL inhibitor. This study aimed to investigate the pre‐clinical efficacy of GZD824 for the treatment of EC.

Methods

Here, we undertook pre‐clinical evaluation of GZD824 in seven endometrial cancer cell lines (HEC‐1‐A, HEC‐1‐B, MFE296, RL95‐2, Ishikawa, KLE and ARK‐1), one normal immortalised endometrium derived cell line (E6E7hTERT) and primary mesothelial and fibroblast cells isolated from normal omentum samples.

Results

GZD824 inhibited the proliferation of all endometrial cancer cell lines, which were significantly more sensitive to GZD824 compared to normal cells (p = 0.030). GZD824 significantly inhibited migration in Ishikawa (endometrioid) and ARK1 (serous) endometrial cancer cell lines and significantly inhibited invasion in the ARK1 cells. Whole transcriptome regulation following two doses (0.1 and 1 μM) of GZD824 in Ishikawa and ARK1 cells was investigated via RNA‐seq, and key components of enriched pathways were investigated at the translational level. Key pathways altered included ROR1/Wnt, GCN2‐ATF4, epithelial to mesenchymal transition (EMT) and PI3K‐AKT.

Conclusion

Together, these studies support further investigation of GZD824 as a potential therapeutic agent in endometrial cancer, potentially in combination with immune checkpoint inhibitors.
Guiding Sole Intraoperative Radiotherapy in Breast Cancer According to ASTRO Guidelines: Mitigating Adverse Outcomes in a Taiwan Single‐Center
Authors: Yang Hsin‐Yi , Tsang Yuk‐Wah , Tu Chi‐Wen , Hsu Yu‐Chen
Published: December 2024

Background

Intraoperative radiotherapy (IORT) is considered a de‐escalating adjuvant treatment for breast cancer low‐risk patients. However, the broader criteria applied by the Taiwan IORT Study Cooperative Group led to an increased rate of locoregional recurrence (LRR) among patients receiving only IORT. Consequently, we revised the criteria for sole IORT treatment to include patients who meet the American Society for Radiation Oncology (ASTRO) eligibility standards. This study aims to investigate how aligning treatment strategies with ASTRO guidelines impacts oncological outcomes in patients receiving IORT.

Methods

From September 2014 to March 2022, a retrospective review of 632 patients with invasive breast cancer undergoing breast‐conserving surgery assessed outcomes following External Beam Radiation Therapy (EBRT), sole IORT, or IORT combined with supplemental EBRT (IORT+boost), with a mean follow‐up period of 4.71 ± 2.10 years. Strategic modifications following the ASTRO guidelines were implemented in April 2021 for sole IORT recipients.

Results

ASTRO‐suitable patients had significantly lower rates of LRR (0.00% vs. 10.64%), distant metastasis (0.00% vs. 4.00%), and any recurrence (0.00% vs. 7.79%) than non‐suitable patients (p < 0.05). After adjusting for confounders, the overall and non‐suitable patients in the IORT group both exhibited significantly higher hazard ratios for LRR than those in the EBRT group, with values of 5.79 (95% confidence intervals (CI) = 1.75–19.18) and 5.48 (95% CI = 1.66–18.02), respectively.

Conclusions

Aligning treatment criteria with ASTRO guidelines for sole IORT significantly reduces locoregional recurrence rates in patients with invasive breast cancer, highlighting the efficacy of these strategic modifications in improving oncological outcomes.
The 340B Drug Pricing Program and Management of Advanced Prostate Cancer
Authors: Faraj Kassem S. , Kaufman Samuel R. , Oerline Mary , Dall Christopher , Srivastava Arnav , Caram Megan E. V. , Shahinian Vahakn B. , Hollenbeck Brent K.
Published: December 2024

Introduction

Oral targeted therapies are a standard of care for men with advanced prostate cancer. However, these therapies are expensive, which may be a barrier to some, particularly the most economically disadvantaged. Through investment in programs to assist this population, savings generated from the 340B program have the potential to mitigate barriers to initiating treatment with targeted therapies in these men.

Methods

We performed a retrospective study using a 20% national sample of fee‐for‐service Medicare beneficiaries diagnosed with advanced prostate cancer between 2012 and 2019. The outcome was the patient‐level use of a targeted therapy for the first time. This study had two exposures. The first was 340B penetration, representing the percentage of all outpatient hospital revenue in a hospital referral region generated by a 340B hospital. The second was the degree of socioeconomic disadvantage, as measured by the social vulnerability index (SVI). Two separate Cox models were fit to measure relationships between each exposure and use of a targeted therapy. A third model was fitted to assess whether differences in utilization by SVI were mitigated by increasing 340B penetration.

Results

The use of a targeted therapy did not vary with 340B penetration (adjusted HR 1.1, 95% CI 0.96–1.2) for high versus low penetration. Conversely, socioeconomically disadvantaged men were less likely to initiate treatment. Those residing in the third SVI tertile (i.e., most vulnerable) were less likely to start on a targeted therapy compared to men in the first tertile (adjusted HR 0.85, 95% CI 0.78–0.92). However, increasing 340B penetration did not attenuate these differences (Wald test for the interaction term p = 0.10).

Conclusions

There was no association between a region's 340B penetration and use of a targeted therapy. Furthermore, although the use of a targeted therapy decreased with increased SVI, the 340B penetration of a region did not reduce this gap.
The Advancement of Peptides Derived From Kitasatospora
Authors: Haedar Jabal Rahmat , Khan Abujunaid Habib , Zīle Anitra , Phan Chin‐Soon
Published: December 2024

Kitasatospora continue to be a rich source of chemically diverse and bioactive peptide natural products. This review highlights two strategies in peptide natural products research of Kitasatospora: (1) a natural products–first approach guided by a major compound, biological activity, or genomic analysis, and (2) an enzyme‐first approach guided by bioinformatic tools to construct a sequence similarity network for the discovery of biosynthetic enzymes. The structures of peptides, biosynthetic origins of unique building blocks, recent reports of post‐translational modifying enzymes for constructing these peptides, and knowledge gaps in biosynthesis will also be presented. Actinobacteria belonging to the genus Kitasatospora are a source of biosynthetic enzymes to expand the biocatalytic toolbox for synthetic biology.
Melatonin promotes the proliferation and differentiation of antler chondrocytes via RUNX2 dependent on the interaction between NOTCH1 and SHH signaling pathways
Authors: Zhang Qiaoling , Zhang Yan , Li Baiyu , Wang Chenhao , Yang Zhanqing , Guo Bin , Yue Zhanpeng
Published: December 2024

Melatonin (MT), an endogenous hormone secreted by pineal gland, has the sedative, anti‐inflammatory and antioxidant functions. However, there are few studies on whether MT affects the proliferation and differentiation of antler chondrocytes. The present study investigated the influences of MT on the proliferation and differentiation of antler chondrocytes, explored its regulation on runt‐related transcription factor 2 (RUNX2), NOTCH1 and sonic hedgehog (SHH) signaling, and elucidated their interplays. The results showed that MT promoted the proliferation of antler chondrocytes and induced the differentiation of chondrocytes into hypertrophic chondrocytes as evidenced by the significant increase of collagen type X (COL X), alkaline phosphatase (ALP) and matrix metalloproteinase 13 (MMP13) expression and ALP activity, the well‐established markers for hypertrophic chondrocytes, but this effectiveness was neutralized by the addition of MT receptor antagonist. Further analysis indicated that MT activated the NOTCH1 and SHH signaling whose blockage abrogated the inducement of MT on the proliferation and differentiation of antler chondrocytes. SHH was identified as a downstream target of recombination signal binding protein for immunoglobulin kappa J region (RBPJ), a transcription factor of NOTCH1 signaling. Meanwhile, MT stimulated the expression of RUNX2 through activating the SHH signaling whose downstream transcription factor glioma‐associated oncogene 1 (GLI1) directly controlled the transcription of RUNX2 through binding to its promoter region. Moreover, repression of GLI1 counteracted the proliferative effect of MT on antler chondrocytes and attenuated the advancement of MT on chondrocyte differentiation, while supplementation of recombinant RUNX2 protein recued above effects. Collectively, MT induced the proliferation and differentiation of antler chondrocytes via RUNX2 dependent on the interaction between NOTCH1 and SHH signaling pathways.
Growth and yield components of bread wheat as affected by seed and nitrogen‐phosphorous fertilizer rates in Burie District, Northwestern Ethiopia
Authors: Nakachew Kelemu , Yigermal Habtamu , Assefa Fenta , Ali Solomon , Simachew Mulugeta , Gebeyehu Tewabe
Published: December 2024

Achieving high bread wheat (Triticum aestivum L.) productivity in a specific region is challenging without clear guidelines on optimal seeding rates and nitrogen‐phosphorus (NP) fertilizer levels. The study aimed to determine the optimal seeding rate and NP fertilizer levels for maximizing bread wheat productivity in Burie District, Northwestern Ethiopia, during the 2021 and 2022 main cropping seasons. Factorial combinations of four seed rates (100, 120, 150, and 200 kg ha−1) and four NP fertilizer rates (64–46, 87–46, 96–69, and 119–69 kg ha−1 of N‐P2O5) were examined in a randomized complete block design with three replications. Data on various growth and yield parameters were collected and analyzed using SAS 9.4, with mean separation for significant treatments determined by the least significant difference. The combined analysis revealed significant interactions between seed and NP fertilizer rates, affecting parameters such as days to 90% physiological maturity, plant height, number of effective tillers, spike length, number of kernels per spike, 1000‐kernel weight, aboveground dry biomass yield, and grain yield. Days to 50% heading, straw yield, and harvest index were significantly influenced by the main effects of seed and NP fertilizer rates. The highest values for days to 90% maturity, number of effective tillers, and 1000‐kernel weight were observed with the lowest seeding rate (100 kg ha−1) combined with the highest NP fertilizer level (119–69 kg ha−1). The highest grain yield (3.70 t ha−1) was achieved with a seeding rate of 150 kg ha−1 and NP fertilizer level of 96–69 kg ha−1, which also yielded the highest net benefit ($1355.60 ha−1) with an acceptable marginal rate of return (8.98%). This treatment combination is recommended for bread wheat production in the Burie district and similar agroecology.
Twisted Cucurbit[14]uril‐Based Supramolecular Self‐Assembly Induces Fluorescence Emission of Dye Molecules for Multi‐Channel Cell Imaging
Authors: Yuan Xing‐Yue , Xiao Han , Wu Li , Zhao Jie , Wu Jia‐Rui , Ni Yu , Xiao Xin , Yang Hai‐Ping
Published: December 2024

In this study, a supramolecular fluorescent material was constructed by using double‐cavity twisted cucurbit[14]uril (tQ[14]) and positively charged Astrazon Pink FG (APFG) based on the non‐covalent host‐guest interaction for the first time. The thermodynamic parameters of the APFG@tQ[14] in aqueous solution were determined by isothermal titration calorimetry (ITC), the results indicated that the spontaneous assembly of APFG@tQ[14] is mainly driven by enthalpy. The intramolecular charge transfer (ICT) effect induced the APFG@tQ[14] probe to emit a strong orange‐red fluorescence. Due to its good optical properties and low toxicity, APFG@tQ[14] was successfully applied to multi‐channel imaging of HK2 cells. This demonstrates the great potential of APFG@tQ[14] in labeling and tracking living cells.
Towards a common approach for managing food allergy and serious allergic reactions (anaphylaxis) at school. GA2LEN and EFA consensus statement
Authors: Deschildre Antoine , Alvaro‐Lozano Montserrat , Muraro Antonella , Podesta Marcia , de Silva Debra , Giovannini Mattia , Barni Simona , Dribin Timothy E. , Sandoval‐Ruballos Mónica , Anagnostou Aikaterini , Fiocchi Alessandro , Toniolo Alice , Bird Andrew , Sanz Angel Sánchez , Asarnoj Anna , Nowak‐Wegrzyn Anna , Vlieg‐Boerstra Berber , Vickery Brian P. , Venter Carina , Nilsson Caroline , Parente Cecilia , Demoulin Céline , Fleischer David M. , Bijlhout Diola , Knol Edward F. , Garrow Eleanor , Cook Emma E. , Schultz Fallon , Lazzarotto Francesca , Mori Francesca , Wong Gary , Lack Gideon , Roberts Graham , Marino Gustavo Andres , Elberink H. N. G. Oude , Brough Helen A. , Sampson Hugh A. , Lieberman Jay , Gerdts Jennifer , Zhao Jing , Gradman Josefine , Upton Julia E. M. , Wang Julie , Palosuo Kati , Järvinen Kirsi M. , Beyer Kirsten , Shen Kunling , Polloni Laura , Mandelbaum Lianne , Tanno Luciana Kase , Bilaver Lucy A. , Shaker Marcus S. , Worm Margitta , Said Maria , Kelly Mary , Marchisotto Mary Jane , Makris Michael , Odemyr Mikaela , Fernandez‐Rivas Montserrat , Ebisawa Motohiro , Patel Nandinee , Rodríguez del Río Pablo , Vichyanond Pakit , Turner Paul , Smith Pete , Gaspar Pilar Morón , Chinthrajah R. Sharon , Rachid Rima , Bonaguro Roberta , Gupta Ruchi , Schnadt Sabine , Sato Sakura , Arasi Stefania , Leonard Stephanie , Poblete Sung , Halken Susanne , Le Thuy‐My , Pouessel Guillaume , Dunn Tracey , Cardona Victoria , Zuberbier Torsten
Published: December 2024

GA2LEN and EFA propose minimum specifications for all industrialised countries/regions to work towards to support students with food allergies in educational settings. We reviewed research and legislation and gained feedback from over 100 patient and professional groups. We built shared expectations around: 1. training all school staff about what food allergy is, the symptoms of allergic reactions, what to do in an emergency, and when and how to use and store devices that laypeople can use to administer adrenaline (epinephrine). 2. preventing allergic reactions by using clear labelling on school menus and prepacked and non‐prepacked foods and regular cleaning where students eat. 3. preparing for serious allergic reactions, with written emergency action plans for every student with food allergies, legislation allowing schools to store adrenaline for anyone who needs it in an emergency (not just those prescribed it), and training and legal safeguards for staff administering adrenaline. 4. including affected students by discussing food allergy in the curriculum, raising awareness among all students and caregivers and reviewing school processes regularly. It is time for national and international action at the policy level. Patient groups, education networks and professional societies all play a role in campaigning for shared next steps.
Product Oriented Upcycling of Waste Polyethylene Terephthalate Plastic and Carbon Dioxide via Decoupled Electrolysis
Authors: Kong Wei , Ren Yue , Zou Kang , Han Zishan , Zhang Yixuan , Zhou Hua , Shao Mingfei
Published: December 2024

End‐of‐life plastics and carbon dioxide (CO2) are anthropogenic waste carbon resources; it is imperative to develop efficient technologies to convert them to value‐added products. Here we report the upcycling of polyethylene terephthalate (PET) plastic and CO2 toward valuable potassium diformate, terephthalic acid, and H2 fuel via decoupled electrolysis. This product‐oriented process is realized by two electrolyzers: (1) a solid‐state‐electrolyte based CO2 electrolyzer and (2) a solid‐polymer‐electrolyte‐based PET electrolyzer. Using a bismuth‐based catalyst, the CO2 electrolyzer showed more than 140 h continuous operation at current of 250 mA, resulting in 850 mL pure HCOOH solution with a concentration of 683 mM. Furthermore, we constructed a solid‐polymer‐electrolyte electrolyzer with an electrode area of 50 cm2 for the electrooxidation of ethylene glycol to formate, achieving 30 A of current at ~1.9 V cell voltage and 80 % formate Faradaic efficiency. With this electrolyzer, we demonstrated the efficient transformation of PET hydrolysate to a mixture of terephthalate and formate. Additionally, combining CO2 derived HCOOH and PET electrolyte, we obtained recycled terephthalic acid and potassium diformate. This work provides an integrated strategy for the valorization of waste carbon resources with less using external resources.
Academic Leaders Should Encourage Good Citizenship
Authors: Hodges Dawn Z.
Published: December 2024

One of the main goals of education, particularly higher education, is to help students become engaged and productive citizens. What does it mean to be a “productive” citizen? To me, a productive citizen is gainfully employed, pays taxes, votes on a regular basis, respects and follows the law, participates in community activities, establishes and raises families, is neighborly, and treats others as they want to be treated.
Exploring the Protective Mechanisms of Chayote (Sechium edule) Juice in Mitigating Streptozotocin‐Induced Pancreatic Dysfunction
Authors: Jeon Yoon A. , Natraj Premkumar , Paik Soo‐Heui , Kim Seong Cheol , Lee Young Jae
Published: December 2024

Chayote (Sechium edule) has been traditionally used in Mexico to manage diabetes, owing to its hypoglycemic, anti‐oxidant, and anti‐inflammatory properties. However, the specific effects and mechanisms of chayote juice (SEJ) in preventing pancreatic dysfunction remain underexplored. This study investigated the pancreatic protective effects and underlying mechanisms of SEJ in multiple low‐dose streptozotocin (MLD‐STZ)‐induced diabetic mouse model and H2O2‐treated mouse insulinoma cell line (MIN‐6). C57BL/6 mice were administered MLD‐STZ to induce pancreatic dysfunction and treated with SEJ. Diabetic parameters, pancreatic islet morphology, and protein expressions were evaluated. H2O2‐treated MIN‐6 cells were used to assess SEJ's protective mechanisms at the cellular level. Molecular docking studies were performed to elucidate interactions between SEJ phenolic compounds and key proteins involved in oxidative stress. SEJ significantly preserved pancreatic islet structure and insulin levels, reducing blood glucose levels. Mechanistically, SEJ suppressed the expression of apoptosis markers (caspase‐3, PARP, BAX) and inflammatory markers (NF‐κB, iNOS, NLRP3) in the pancreas and MIN6 cells, indicating protection of the pancreas and β‐cells. Furthermore, SEJ upregulates endogenous anti‐oxidant proteins (Nrf‐2, HO‐1), which are essential for mitigating oxidative stress‐induced cell stress in diabetes circumstances. Molecular docking indicated that vicenin‐2 in SEJ exhibit strong binding affinities to KEAP‐1, Nrf‐2, and HO‐1 proteins. SEJ demonstrates substantial pancreatic protective effects through its anti‐oxidant, anti‐apoptotic, and anti‐inflammatory actions. These findings suggest that chayote juice could be developed as a functional food for diabetes management.
Glycosyl Esters as Stable Donors in Chemical Glycosylation
Authors: Pareek Sumit , Mandadi Pavan , Rao Sanapala Someswara
Published: December 2024

Efficient glycosylation methods are continuously being developed to obtain homogeneously pure carbohydrates to study their biological roles. The development of effective and stereoselective glycosylations using novel anomeric leaving groups constitutes an active area of research in synthetic carbohydrate chemistry. Although various glycosyl donors have been developed over the decades, anomeric esters as donors in glycosylation have received significant attention in recent times due to their convenience of preparation, shelf stability, catalytic activation, mild conditions, and high glycosylation efficiency. We focus in this review on several synthetic strategies for the assembly of the glycosyl ester‐containing donors utilized in chemical glycosylation methods, including simple esters, alkenyl, alkynyl‐containing esters, carbonate esters, chelation‐assisted glycosyl esters, allenyl and ynenoate glycosyl esters in glycoside synthesis are summarized.
Clinical characteristics, etiology, and treatment of young adult‐onset epilepsy: A 24‐year retrospective study
Authors: Zhang Xu , Xiang Feng , Wang Ziyu , Li Yang , Shao Chenjing , Lan Xiaoyang , Lang Senyang , Wang Xiangqing
Published: December 2024

Objective

To analyze the clinical characteristics, etiology, drug treatment, and related factors of patients with young adult‐onset epilepsy.

Methods

The study included patients with epilepsy aged between 18 and 44 years and aimed to analyze the clinical characteristics of epilepsy in young people and their response to antiseizure medication (ASM) over a 24‐year period (February 1999 and March 2023).

Results

A total of 4227 patients experienced epilepsy onset between 18 and 44 years of age. The median age of onset was 26 years (interquartile range [IQR]: 21–33), and the median duration from the first seizure to starting treatment was 3 months (IQR: 1.0–6.0). Structural etiology was the most common cause of epilepsy, accounting for 43.2% (1827/4227) of cases, of which head trauma and a history of craniotomy accounted for 64.9% (1186/1827). However, these two causes did not necessarily result in prompt medication or poor epilepsy control. Co‐morbid cognitive decline was more prevalent than headache and anxiety/depression. Multifactorial regression analysis showed that the factors associated with poor seizure control included longer seizure duration (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.58‐2.16; p < 0.001), electroencephalography (EEG) epileptic discharge (OR 1.37; 95% CI 1.17–1.67; p < 0.001), focal seizure (OR 1.69; 95% CI 1.38–2.07; p < 0.001), and seizure clusters (OR 3.35; 95% CI 2.70–4.15; p < 0.001). Initiating treatment after two seizures (OR, 1.18; 95% CI 0.98–1.15; p = .08) or 6 months after the first seizure (OR 0.84; 95% CI 0.67–1.03; p = .09) did not worsen effectiveness.

Significance

Young adult‐onset epilepsy was frequently caused by head trauma or craniotomies. Co‐morbid cognitive decline was more prevalent than headache and anxiety/depression. The median time from the first seizure to follow‐up treatment was 3 months (IQR: 1.0–6.0). Initiating treatment after two seizures did not necessarily indicate poor drug effectiveness.

Plain Language Summary

In this article, we observed that young adult‐onset epilepsy was mainly caused by head trauma and craniotomy; co‐morbid cognitive decline was more common. The median duration from first seizure to initiation of treatment for young‐onset epilepsy was 3 months, and more than one‐third of patients experienced more than two seizures prior to treatment, but this factor had no effect on the drug effectiveness.
The Trend of Utilization of Dental and Oral Health Services Among Children in Iran During 2019–2021: A Cross‐Sectional Study
Authors: Tusi Somayeh Khoramian , Pouragha Behrooz , Hasanpoor Edris , Nazari Morteza
Published: December 2024

Background and Aims

Oral health issues present substantial obstacles for children and teenagers globally, affecting their holistic health. With Iranian children experiencing a high prevalence of dental cavities, understanding their utilization of dental services and the influencing factors is essential. Therefore, this study examined the utilization of dental and oral health services by children aged 6 to 14 at healthcare centers in Karaj, Iran, in 2019–2021.

Methods

This descriptive cross‐sectional study included 361 children between 6 and 14 years old who visited healthcare centers in Karaj for dental services. The researchers developed a questionnaire to collect data. Data analysis was conducted using SPSS‐21 software, Smirnov–Kolmogorov, and Spearman's correlation test.

Results

Analysis of the data indicated that the utilization of dental and oral health services had significant correlations with the place of residence (p < 0.001), the father's education (p < 0.05), the number of children in the family (p < 0.005), and insurance coverage (p < 0.05). However, household income and the mother's education had no significant relationship with the utilization of dental and oral health services for the children in healthcare centers (p > 0.05).

Conclusions

Advocate for policies promoting oral health equity, addressing dental service access disparities, and supporting preventive measures in underserved communities, provision of insurance coverage for dental services can lead to improving the oral health of children.
Assessing the performance of chest x‐ray screening in detecting early‐stage lung cancer in the general population
Authors: Chei Choy‐Lye , Nakamura Sho , Watanabe Kaname , Mizutani Takashi , Narimatsu Hiroto
Published: December 2024

Chest x‐ray (CXR) is widely used for lung cancer screening in Japan. We evaluated the sensitivity and specificity of CXR in detecting early lung cancer and its histological types. We cross‐referenced lung cancer municipality screening data with the regional cancer registry database. The results of individuals screened at least once from 2016 to 2018 were utilized to calculate CXR's sensitivity and specificity for lung cancer diagnosed within 1 year of screening (n = 161,251) by stage and its histological types. We stratified analyses based on sex, age, smoking status, first screening, and screening intervals. CXR's sensitivity and specificity for early‐stage lung cancer were 73.6% (95% confidence interval [CI], 66.8–79.6) and 94.1% (95% CI, 94.0–94.2), respectively. No significant differences were found in sex or smoking status. The sensitivity for early‐stage adenocarcinoma was 76.0% (95% CI, 68.3–82.7), which was higher than that for early‐stage squamous cell carcinoma (70.4% [95% CI, 67.3–86.0]). However, no significant differences were observed (p = .532). No significant differences were found in sex or smoking status for early‐stage adenocarcinoma or early‐stage squamous cell carcinoma. Due to its moderate sensitivity and high specificity, CXR could be a useful tool for mass screening in the general population. However, because CXR failed to detect 26.4% of early‐stage cases, practitioners should inform high‐risk patients of other screening options.
Life expectancy in rare histological prostate cancer subtypes
Authors: Siech Carolin , de Angelis Mario , Jannello Letizia Maria Ippolita , Di Bello Francesco , Rodriguez Peñaranda Natali , Goyal Jordan A. , Tian Zhe , Saad Fred , Shariat Shahrokh F. , Puliatti Stefano , Longo Nicola , de Cobelli Ottavio , Briganti Alberto , Wenzel Mike , Mandel Philipp , Kluth Luis A. , Chun Felix K. H. , Karakiewicz Pierre I.
Published: December 2024

Survival differences in rare histological prostate cancer (PCa) subtypes relative to age‐matched population‐based controls are unknown. Within Surveillance, Epidemiology, and End Results database (2004–2020), newly diagnosed (2004–2015) PCa patients were identified. Relying on the Social Security Administration Life Tables (2004–2020) with 5 years of follow‐up, age‐matched population‐based controls (Monte Carlo simulation) were simulated for each patient. Kaplan–Meier analyses addressed survival rates. Of 582,220 patients, 580,368 (99.68%) harbored acinar, 867 (0.15%) ductal, 534 (0.09%) neuroendocrine, 368 (0.07%) mucinous, and 83 (0.01%) signet ring cell carcinoma. The metastatic stage was most prevalent in neuroendocrine (62%). In the localized stage, the overall survival difference at 5 years of follow‐up was greatest in neuroendocrine (22% vs. 72%), signet ring cell (78% vs. 84%), and ductal carcinoma (71% vs. 77%). In the locally advanced stage, overall survival difference was greatest in neuroendocrine (16% vs. 79%), signet ring cell (75% vs. 91%), ductal (78% vs. 84%), and mucinous carcinoma (84% vs. 90%). In the metastatic stage, the overall survival difference was greatest in neuroendocrine (3% vs. 81%), mucinous (26% vs. 84%), and acinar carcinoma (27% vs. 85%). Regardless of stage, neuroendocrine carcinoma patients exhibit the least favorable life expectancy compared with population‐based controls. Conversely, all other rare histological PCa subtypes do not meaningfully affect life expectancy in localized or locally advanced stages, except for locally advanced signet ring cell adenocarcinoma.
The therapeutic effects of induced pluripotent stem cell‐derived mesenchymal stem cells on Parkinson's disease
Authors: Ren Hao , Wang Yuwei , Chen Yingying , Ma Feilong , Shi Qing , Wang Zichen , Gui Yaoting , Liu Jianbo , Tang Huiru
Published: December 2024

Parkinson's disease (PD), characterized by progressive degeneration of dopaminergic neurons in substantia nigra, has no disease‐modifying therapy. Mesenchymal stem cell (MSC) therapy has shown great promise as a disease‐modifying solution for PD. Induced pluripotent stem cell‐derived MSC (iMSC) not only has stronger neural repair function, but also helps solve the problem of MSC heterogeneity. So we evaluated the therapeutic effects of iMSCs on PD. iMSCs were administered by tail vein in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced PD models of C57BL/6 mice. The results showed iMSCs increased body weights, inhibited the prolongation of latencies to descend in pole tests, the decrease of grip strength in grip strength tests and increase of open arm entries in elevated plus maze test, and showed a trend to alleviate striatal dopamine loss. They indicate iMSCs might improve functions partially by preserving striatal dopamine in PD. We for the first time (1) found that iMSC has therapeutic effects on PD; (2) tested specifically muscle strength in cell therapy for PD and found it increases muscle strength; (3) found cell therapy alleviated the increase of entries into the open arms in PD. It suggests iMSC is a promising candidate for clinical investigations and drug development for PD.
Primary Cilia Regulate the Homeostasis and Regeneration of the Stem Cell Niche in the Tooth
Authors: Zhang Xinming , Cao Yuxin , Wang Mengge , Li Yujia , Yin Hanxiao , Ni Hua , Yang Song , Yu Fan , Yang Jia , Peng Lisu , Hu Meilin , Li Dengwen , Liu Dayong
Published: December 2024

Primary cilia, functioning as crucial hubs for signal sensing and transduction, are integral to the development and maintenance of homeostasis across various organs. However, their roles in tooth homeostasis and repair remain inadequately understood. In this study, we reveal an indispensable role for primary cilia in regulating the homeostasis and regeneration of teeth, primarily through the regulation of cell proliferation. Using cilium‐deficient mice, we demonstrate that disruption of ciliary homeostasis leads to abnormal tooth morphology, stunted growth and notably impaired tooth repair. RNA sequencing reveals a dysregulation in genes associated with various biological processes such as cell proliferation, differentiation, and cycle regulation. Furthermore, we show that cilium‐deficient mice display reduced cell proliferation. Our findings highlight a critical function for primary cilia in the regulation of tooth homeostasis and regeneration and have important implications for the development of tooth regeneration therapies.
Management Outcomes of Variceal Bleeding in Northern Tanzania: Insights From a Single‐Center Retrospective Analysis
Authors: Nziku Eliada B. , Mkwizu Elifuraha W. , Sadiq Abid M. , Said Fuad H. , Eliah Doreen T. , Muhina Ibrahim Ali Ibrahim , Mirai Tumaini E. , Lyamuya Furaha S. , Chamba Nyasatu G. , Shao Elichilia R. , Kilonzo Kajiru G. , Urasa Sarah J.
Published: December 2024

Aims

Due to the expensiveness and unavailability of endoscopy management in Tanzania, the management outcomes of variceal bleeding are unknown. The objective of this study was to assess the management outcomes of patients with variceal bleeding.

Methods

This was a retrospective study conducted between April 2012 and April 2022. The study enrolled all patients diagnosed with variceal bleeding aged 18 years and older. Socio‐demographic and clinic characteristics, treatment modalities, and outcomes were collected. Statistical analysis was done using a chi‐square test. Multivariable logistic regression was used to determine factors associated with rebleeding and mortality. A p‐value of ≤ 0.05 was considered statistically significant.

Results

A total of 534 patients were enrolled based on diagnostic endoscopy findings. Esophageal varices were identified in 88.9% of patients, gastric varices in 0.9%, and 10.1% had both. Conservative treatment was given to 77.5% of patients, and endoscopic treatment was performed in 22.5%: endoscopic variceal ligation (17.6%), endoscopic injection sclerotherapy (4.3%), and both (0.6%). Rebleeding occurred in 40.1%, and factors associated with rebleeding were patients without insurance (p = 0.037), without comorbidities (p = 0.042), with non‐communicable diseases (p = 0.039), and with chronic infections (p = 0.035). In‐hospital mortality was 8.1%, and factors associated with mortality were a shorter length of stay (p = 0.045), patients without comorbidities (p = 0.041), and grade II esophageal varices (p = 0.043).

Conclusion

This study shows a high rate of variceal bleeding among patients treated conservatively. Mortality and rebleeding rates in our setting remain high, which appears to be due to the expensiveness and unavailability of endoscopic treatment. Available endoscopic interventions will be vital in improving the outcomes of patients with variceal bleeding.
Rapid and Sensitive Digital Droplet PCR Assays for Detecting HPV16 DNA in Liquid Biopsies
Authors: Loo Suet Kee , Feng Jian , Reeder Carly , Elias Danny Azmi , Xu Zhongping , Huang Yufei , Contrera Kevin J. , Zevallos Jose P. , Ferris Robert , Gao Shou‐Jiang
Published: December 2024

The combination of cell‐free DNA (cfDNA) and digital droplet PCR (ddPCR) has significantly advanced the noninvasive screening, diagnosis, and monitoring of diseases, enabling highly sensitive and absolute quantification of target nucleic acids even in the presence of high background DNA. However, widespread adoption of ddPCR is hindered by higher costs, extended processing times, and the requirement for cfDNA purification, which adds expense and variability. To address these limitations, we developed two optimized ddPCR‐based assays tailored for enhanced sensitivity, cost‐efficiency, and ease of use. Our highly sensitive ddPCR assay for human papilloma virus (HPV)16 DNA detection in purified cfDNA from liquid biopsies from head and neck cancer patients significantly improved sensitivity by increasing cfDNA concentration by 8.5‐fold, sample volume loading by 22‐fold, and total cfDNA amount tested by 1200‐fold without the need for restriction enzyme digestion. In parallel, we established a rapid ddPCR assay using unpurified cfDNA processed by heat treatment and centrifugation, achieving detection concordance rates of 55.6%, 66.7%, and 95.8% for plasma, serum, and surgical drain fluid (SDF), respectively, compared to purified cfDNA. Together, these complementary workflows, one optimized for unpurified cfDNA and the other for purified cfDNA, make ddPCR detection of specific targets in cfDNA more cost‐effective, time‐efficient, and standardizable across laboratories, paving the way for broader adoption in clinical diagnostics.
Alterations in Cellular Gene Expression Due to Co‐Infection With Kaposi's Sarcoma‐Associated Herpesvirus and SARS‐CoV‐2: Implications for Disease Severity
Authors: Chen Jungang , Fan Jiaojiao , Malaviarachchi Priyangi A. , Post Steven R. , Lin Zhen , Zhang Xuming , Qin Zhiqiang
Published: December 2024

An outbreak of the novel coronavirus SARS‐CoV‐2, the causative agent of COVID‐19 pandemic, has resulted in over 7 million confirmed deaths. In addition to severe respiratory and systematic symptoms, several comorbidities increase the risk of fatal outcomes. Therefore, it is essential to investigate the impact of COVID‐19 on pre‐existing conditions in patients, such as cancer and other infectious diseases. Recent clinical studies have reported the reactivation of human herpesviruses, including Kaposi's sarcoma‐associated herpesvirus (KSHV), in severe COVID‐19 patients or vaccinated individuals. To support these clinical observations, we established a KSHV/SARS‐CoV‐2 co‐infection system in A549‐hACE2 cells. Our findings indicate that co‐infection with live SARS‐CoV‐2 sharply induces KSHV lytic reactivation. Transcriptomic analysis revealed significant changes in global cellular gene expression in KSHV‐infected A549‐hACE2 cells, both with and without SARS‐CoV‐2 co‐infection. These data provide a molecular basis for understanding whether patients with pre‐existing oncogenic herpesvirus infections are at increased risk for more severe COVID‐19 or for developing virus‐associated cancers even after full recovery from COVID‐19.
Detection and Phylogenetic Analysis of Emerging Human‐Associated Gemykibivirus‐2 in Molossus molossus Bat From Brazil
Authors: Silvério Bruna Stefanie , Sanz Duro Rodrigo Lopes , de Sousa Larissa Leão F. , Guilardi Mariana Dias , Cabral‐Miranda Gustavo , Janini Luiz Mário Ramos , Durães‐Carvalho Ricardo
Published: December 2024

We detected an emerging human‐associated gemykibivirus‐2 (HuGkV‐2) in rectal swab sample from Molossus molossus bat from Brazil. Phylogenetic analysis further revealed well‐supported relationships between our sequence and those associated with human infections. This study underscores the necessity of ongoing monitoring of HuGkV‐2 to elucidate potential spillback events, its role in human infections, and its public health implications.
Assessment of Droughts and Floods During the Indian Summer Monsoon Using the Coupled Model Intercomparison Project Phase 6 Historical and Future Simulations
Authors: George Catherine , Varikoden Hamza , Kuttippurath Jayanarayanan , Chaluvadi Roja , Babu Chethalan Anthony
Published: December 2024

Indian summer monsoon (ISM) is the prominent global monsoon system, which occur annually from June to September and impacts the lives of over a quarter of the world's population. Studies show that global warming is one of the key reasons for the extreme events such as droughts and floods, and that also alter regional dynamics of ISM. Consequently, a comprehensive investigation of flood and drought events in India is imperative, because of their important role in the economy of the country. Here, we employ simulations from the Coupled Model Intercomparison Project phase 6 (CMIP6) models to evaluate the intensity and frequency of droughts and floods across historical (1950–2014) and future (2015–2100) periods. We explore the best‐performing model for the ISM rainfall (ISMR) to unravel the characteristics of floods and droughts by analysing rainfall data from 53 models. Although majority of the models successfully replicate the annual cycle of ISMR, there exists a significant difference in rainfall amounts. Following an initial screening to identify the most efficient models, eight are selected for an in‐depth assessment. The chosen models slightly overestimate drought conditions, although they demonstrate a commendable concurrence in simulating the flood occurrences in India. Regarding the future projections, we analyse the Shared Socioeconomic Pathways (SSP1‐2.6, SSP2‐4.5, SSP3‐7.0 and SSP5‐8.5) for near (2015–2035)‐, mid (2047–2067)‐ and far (2079–2099)‐future periods, in addition to the total projection period (2015–2100). Our analysis reveals an increasing trend of droughts in the near‐future, compared to an increase in floods during the far‐future. It is also highlighted that the intensity of droughts is projected to amplify in the far‐future, while the intensity of floods is likely to diminish. Therefore, this study serves as a valuable resource for decision‐making processes, particularly in the flood, drought and agricultural disaster preparedness.
From deglaciation to the Early Holocene in the northern Appalachians: A multiproxy palaeoenvironmental record from Scotstown Bog, Québec, Canada
Authors: Amon Leeli , St‐Jacques Jeannine‐Marie , Ershova Ekaterina , Hargan Kathryn E. , Whyte Charlotte Mary Cotter , Sachse Dirk , Rach Oliver , Peros Matthew C.
Published: December 2024

A multiproxy study of a sediment sequence from a Québec peatbog characterises the rapid and significant environmental responses to changing climatic conditions from the deglaciation of the Laurentide Ice Sheet to the early Holocene period. Scotstown Bog (45°30'45.0“N, 71°11'42.0“W) is an ombrotrophic peatland on the edge of the Appalachian Uplands in southern Québec, Canada. We reconstructed its Late‐glacial and early Holocene palaeoenvironments for 14 000–6 000 cal a bp using palaeobotanical (plant macrofossil, macrocharcoal, pollen analyses), faunal (chironomid analysis), sedimentological (grain‐size analysis, sediment organic content), and geochemical (sedimentary n‐alkanes and hydrogen isotope analyses) methods. We targeted our multiproxy reconstruction on the Late‐glacial period, which provides an example of how biota can respond to profound changes in climatic and environmental conditions. A major transition occurred between 13 000 and 12 900 cal a 
bp, which is recorded in all palaeoecological proxies. Our reconstruction reveals two major environmental changes at this time. First, the Scotstown basin became isolated from a larger proglacial lake, as shown by sedimentological changes, sediment grain size and chironomid assemblage shift. Second, plant macrofossils and pollen influx show contemporaneous major shifts in the vegetation composition from tundra to tree‐line to closed‐canopy forested communities.