bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dihydroartemisinin Sensitizes Lung Cancer Cells to Cisplatin Treatment by Upregulating ZIP14 Expression and Inducing Ferroptosis
Authors: Yang Zhuoying , Zhou Zehao , Meng Qingyu , Chen Zhijie , Yun Liang , Jiang Jianjun , He Yujing , Dian Meijuan , Zhang Ruihao , Ge Haotian , Yan Tianbao , Men Biying , Li Zichao , Wu Xu , He Junming , Rao Shuan 
Published: October 2024

ABSTRACTBackgroundDespite significant advances in lung cancer treatment, cisplatin (DDP)‐based chemotherapy remains a cornerstone for managing the disease. However, the prevalence of chemoresistance presents a major challenge, limiting its effectiveness and contributing to poor outcomes. This underscores the urgent need for novel therapeutic strategies to overcome chemoresistance and improve chemotherapy efficacy in lung cancer patients. Exploring approaches to sensitize tumors to cisplatin could enhance treatment responses and overall survival rates.Methods and ResultsOur study utilized a variety of lung cancer models, including cell lines, mouse models, and patient‐derived organoids, to validate the synergistic cytotoxic effects of dihydroartemisinin (DHA) and cisplatin (DDP). When combined with DDP, we demonstrate that DHA is a promising therapeutic agent that effectively triggers ferroptosis in lung cancer cells, offering a potential strategy for overcoming chemoresistance. Mechanistically, the combination of DHA and DDP synergistically enhances ZIP14 expression, modulating iron homeostasis and upregulating oxidative stress, leading to both in vitro and in vivo ferroptosis. Notably, our findings revealed that the sequential administration of DDP followed by DHA significantly increases ZIP14 expression and induces superior therapeutic outcomes compared to the simultaneous administration or DHA followed by DDP. This observation underscores the importance of the drug administration order in optimizing treatment efficacy, providing new insights into enhancing chemotherapy response in lung cancer.ConclusionOur findings suggest that combining dihydroartemisinin (DHA) with cisplatin (DDP) presents a promising strategy to overcome chemoresistance in lung cancer patients. Importantly, administering DHA during chemotherapy intervals could further optimize treatment outcomes, enhancing the overall efficacy of lung cancer chemotherapy.
Upfront Management of Blastoid Variant Mantle Cell Lymphoma: Making the Case for 2nd/3rd‐Generation Bruton Tyrosine Kinase Inhibitor‐Based Therapies
Authors: Lee Benjamin J. , Liu Jenny , Griffin Shawn P. , Doh Jean , Ciurea Stefan O. , Kongtim Piyanuch , Brem Elizabeth A. 
Published: October 2024

ABSTRACTIntroductionBlastoid variant‐mantle cell lymphoma (BV‐MCL) represents an aggressive subset of patients with no established standard of care treatment approach.MethodsWe performed a retrospective analysis of the clinical characteristics and outcomes of 17 de novo BV‐MCL patients treated at our institution between May 2009 and September 2023. In addition, we reviewed the literature supporting 2nd/3rd generation Bruton's Tyrosine‐kinase (BTKi)‐based therapies for upfront management.ResultsThe complete response rate to frontline and salvage therapy was 66.7% and 25%, respectively. Two‐year overall survival (OS) was low at 62.5% (95% CI, 34.7%–81.1%). Variables associated with higher OS included receipt of consolidative HSCT (p = 0.017), TP53‐wild type (p = 0.031), intermediate‐ versus high‐risk Mantle Cell Lymphoma Prognostic Index score (p = 0.026), and achieving complete response with induction therapy (p = 0.027).DiscussionTreatment outcomes with chemo‐immunotherapy in BV‐MCL patients are poor, especially among TP53‐mutated patients. Recent findings describing positive outcomes with novel BTKi‐based therapies are encouraging and should be considered in this high‐risk population.
Resistance and resilience to tau pathology in Alzheimer's disease: Effects of age, sex, and APOE alleles
Authors: Loika Yury , Webster Stephanie , Loiko Elena , Kulminski Alexander M. 
Published: October 2024

AbstractINTRODUCTIONNeurofibrillary tangles (NFTs), a hallmark of tau pathology in Alzheimer's disease (AD), accumulate in the aging brain. However, some individuals remain cognitively intact despite high Braak (III–VI) stages, which characterize NFTs’ accumulation.METHODSWe studied resistance and resilience to tau pathology by assessing Braak stages based on apolipoprotein E (APOE) alleles, sex, and age in a sample of 1932 cognitively intact individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP).RESULTSResistance, characterized by low (0–II) Braak stages, was observed in men and women younger than 85 years of age. Resilience, indicated by high (III–VI) Braak stages, increased significantly with age in both men and women for each APOE allele. It became more pronounced, with the proportion of high Braak stages exceeding 50% at 85 years and older in women, irrespective of the APOE allele.DISCUSSIONThe identification of factors underlying resistance and resilience against AD‐related pathologies is essential for promoting cognitively healthy aging.Highlights
We investigated cognitive resistance and resilience to tau pathology in Alzheimer's disease (AD).
This study included individuals who were not diagnosed with AD.
Braak stages 0–II and III–VI were considered as a measure of resistance and resilience, respectively.
Resistance was stronger at ages younger than 85 years in non‐carriers of the apolipoprotein E (APOE) ε4 allele.
Resilience increased with age for each APOE allele independently of sex.
At age 85 years and older, high resilience (>50%) was observed in women regardless of the APOE allele.
Value of image enhancement of endoscopic ultrasound for diagnosis of gastrointestinal subepithelial lesions
Authors: Yamazaki Hirofumi , Yamashita Yasunobu , Tamura Takaaki , Kawaji Yuki , Tamura Takashi , Itonaga Masahiro , Ashida Reiko , Shimokawa Toshio , Kojima Fumiyoshi , Hayata Keiji , Maekita Takao , Iguchi Mikitaka , Kitano Masayuki 
Published: October 2024

AbstractObjectivesAmong subepithelial lesions (SELs), gastrointestinal stromal tumors (GISTs) should be identified and surgically treated at an early stage. However, it is difficult to diagnose SELs smaller than 20 mm. In recent years, endoscopic ultrasound (EUS) elastography (EUS‐EG) and contrast‐enhanced harmonic EUS (CH‐EUS) have been reported to be useful for the diagnosis of SELs, although the diagnostic accuracy of a combination of EUS techniques with image enhancement is unknown.MethodsPatients with SELs who underwent EUS‐guided tissue acquisition, EUS shear‐wave elastography (EUS‐SWE), EUS strain elastography (EUS‐SE), and CH‐EUS from January 2019 to June 2023 were enrolled. To assess the diagnostic accuracy for differentiating GISTs from other SELs, shear‐wave velocity on EUS‐SWE, the strain ratio on EUS‐SE, and vascularity on CH‐EUS were determined and their diagnostic accuracies were compared.ResultsForty‐three patients were enrolled. When the cut‐off value was set at 3.27 m/s, the sensitivity, specificity, and diagnostic accuracy of shear‐wave velocity were 28.6%, 86.2%, and 34.9%, respectively. When the cut‐off value was set at 3.79, the sensitivity, specificity, and diagnostic accuracy of the strain ratio were 93.1%, 64.3%, and 83.7%, respectively. The sensitivity, specificity, and diagnostic accuracy of CH‐EUS were 79.3%, 92.3%, and 83.7%, respectively. When EUS‐SE was combined with CH‐EUS, the sensitivity and diagnostic accuracy were the highest among binary combinations of image enhancement modalities.ConclusionsEUS‐SE and CH‐EUS are useful for differentiating GISTs from other SELs. Furthermore, the use of both modalities may further improve the identification of GISTs.
Demonstration of an End‐To‐End Workflow Using Atmospheric Solids Analysis Probe–Mass Spectrometry (ASAP‐MS) With Real‐Time Sample Recognition Software for the Identification of Falsified and Substandard Pharmaceutical Tablets
Authors: Smillie Fiona , Glinka Weronika , Henry Christopher , McCudden Adam , Thorpe Jennifer , Holman Stephen W. 
Published: October 2024

ABSTRACTCounterfeit pharmaceuticals are a subclass of falsified and substandard medicines. They are illicit products, purporting to be genuine medicines, that are made and sold by criminal organisations. They represent a significant risk to patient safety, as well as a financial and reputational threat to the companies who make the genuine medicines. It is essential to have analytical methods to determine if suspect samples seized by law enforcement agencies are counterfeit, with mass spectrometry (MS) being a commonly used technique in forensic cases. Speed‐to‐answer is vital to enable law enforcement agencies to progress investigations, as well as for pharmaceutical companies so that they can notify health authorities of the circulation of counterfeit medicines. In this work, an atmospheric solids analysis probe (ASAP)–MS was assessed as a fast and simple‐to‐use approach to analyse tablets on a commercially available instrument. Complementing the analytics with real‐time sample recognition software demonstrated that the classification of tablets as authentic or counterfeit could be achieved quickly (< 2 min) and without the need for MS interpretation skills. Authentication of five tablets (two authentic pharmaceuticals, one placebo and two counterfeits containing the correct active pharmaceutical ingredient [API] but at lower quantities than in the genuine medicine and with different excipient contents) of unknown origin was achieved with 100% success. This creates the opportunity to deploy the end‐to‐end workflow as a tool for non‐scientists, such as law enforcement officers and border control staff, for use in‐territory to obtain fast answers and make data‐led decisions to control the illegal trading of medicines.
The Complete Mitochondrial Genomes of Five Nivanini Species (Hemiptera: Cicadellidae: Evacanthinae) With Phylogenetic Analysis
Authors: Wang Wei , Jiang Lina , Li Ran , Jiang Sai , Liu Yongcheng , Xing Jichun , Li Yujian 
Published: October 2024

ABSTRACTTo delve deeper into the phylogenetic relationships within Cicadellidae and the taxonomic arrangement of Evacanthinae, our study focuses on the mitochondrial genome sequencing of five Nivanini species: Extensus latus, Concavepiana hamulusa, Sophonia nigrilineata, Sophonia microstaina, and Sophonia fuscomarginata. The results showed that the length of the five mitochondrial genomes ranged from 15,610 to 16,032 bp and included 37 typical genes. The A + T content of Nivanini ranged from 72.5% to 78.7%, which is consistent with that of other sequenced Evacanthinae species. All transfer RNAs (tRNAs) exhibit the typical cloverleaf secondary structure, except for trnS (AGY), which lacks the dihydrouracil (DHU) arm. With regard to protein‐coding genes, all started with ATN codons, except for atp8, and most of them use TAA or TAG as termination codons. Using the Bayesian inference and maximum likelihood methods, a phylogenetic tree based on all 37 genes was constructed, with a total of 57 Cicadellidae species and two outgroups included as research objects. The analyses confirmed the monophyletic nature of each subfamily, highlighting Deltocephalinae as the oldest, distinctively parallel to the others.
Metabolic profile in elite badminton match play and training drills
Authors: Edel Antonia , Vuong Jo‐Lâm , Kaufmann Sebastian , Hoos Olaf , Wiewelhove Thimo , Ferrauti Alexander 
Published: October 2024

AbstractAim of the study was to analyze the metabolic profile of badminton matches and training drills. Therefore, 11 male (23.2 ± 3.8 years, 182 ± 7 cm, 74.4 ± 8.4 kg) and five female (19.3 ± 1.5 years, 170 ± 6 cm, 62.6 ± 9.2 kg) elite badminton players participated in either a training match (TM; n = 7) and/or three protocols of multifeeding drills (T10, T30, T50; n = 13), that varied in interval and rest durations (10 s/10 s, 30 s/30 s, 50 s/50 s). Absolute and relative energetic costs (Wtot and Etot) and contribution to oxidative (WOxid), phosphagen (WPCr), and anaerobic glycolytic (WLa) metabolism were calculated by the three‐component PCr‐La‐O2‐method based on an indirect calorimetric approach from oxygen consumption during exercise, post exercise, and net blood lactate concentration. A novel intermittent approach was used to consider replenishment of phosphocreatine during each resting phase. Results show that during TM, Etot was 676 ± 98J·kg−1 min−1, while metabolic pathways contributed by 56.9 ± 8.6% (WOxid), 42.7 ± 8.7% (WPCr), and 0.4 ± 0.6% (WLa). In the multifeeding drills Etot was comparable between T10 (1020 ± 160J·kg−1 min−1) and T30 (985 ± 173 J·kg−1 min−1) but higher in T50 (1266 ± 194J·kg−1 min−1) (p < 0.001). Relative contribution of WOxid was lower in T10 (47.3 ± 7.7%) but similar in T30 (56.5 ± 6.2%) and T50 (57.3 ± 6.0%) (p < 0.001). WPCr was highest in T10 (51.1 ± 8.3%) followed by T30 (42.2 ± 6.9%) and lowest in T50 (31.2 ± 7.7%) (p < 0.001). WLa was similar between T10 (1.6 ± 1.0%) and T30 (2.1 ± 1.0%) but higher in T50 (11.6 ± 4.8%) (p < 0.001). Concludingly, metabolic costs in badminton are predominantly covered by oxidative and phosphagen energetic pathways. Metabolic profiles of the multifeeding drills differ depending on rally/interval duration, with increasing contribution of anaerobic glycolysis and decreasing phosphagen contribution in case of longer intervals.
Evaluation of segmentation and semi‐supervised learning for spotted spurge recognition in bermudagrass turf
Authors: Joseph Mikerly M. , Gawron Katarzyna A. , Zhao Chang , MacDonald Gregory E. , Schumann Arnold W. , Boyd Nathan S. , Petelewicz Pawel 
Published: October 2024

AbstractDiverse datasets are crucial for training machine learning‐based weed recognition models. However, annotating (i.e., labeling) images can be laborious and time‐consuming. Choice of annotation method and training approach not only affects the overall model effectiveness but also its minimum training data requirements and development pace. Segmentation and semi‐supervised learning (SSL) may offer performance or training enhancements. This study evaluated (1) segmentation against object detection in spotted spurge [Chamaesyce maculata (L.) Small] recognition in Latitude 36 hybrid bermudagrass [Cynodon dactylon (L.) Pers. × C. transvaalensis Burtt‐Davy] maintained as a golf course fairway and (2) the potential of two‐step SSL‐based training procedure using data labeled both manually and automatically with a pre‐trained model to expedite the model development. The architecture used across this research was You Only Look Once version 8 (YOLOv8) employing nano, small, and medium variants. All models were trained with a dataset restricted to 1200 training and 300 validation images. Both annotation methods resulted in adequate spotted spurge identification, as evidenced with >0.60 (>0.50 acceptability threshold) medium average precision at intersection over union threshold of 0.50 (mAP@50). Although the difference was minimal, object detection performed superior to segmentation. The two‐step training effectively accelerated image annotation while preserving or improving (with 8:4 and 6:6 splits between manually and auto‐labeled data) object detection performance. Segmentation tolerated only 10:2 split and exhibited increased sensitivity to declining dataset quality proportionally to the increase in auto‐labeled images in the final training dataset. Findings show a two‐step SSL‐based training procedure expedites annotation, enhancing model development efficiency.
High‐Resolution Terahertz Spectroscopy for Medical Diagnostics
Authors: Vaks Vladimir , Domracheva Elena , Chernyaeva Maria , Anfertev Vladimir , Ayzenshtadt Andrey , Glushkova Kseniya , Cherniaeva Aleksandra 
Published: October 2024

ABSTRACTThe metabolomics‐based approach to diagnostics and therapy monitoring is a fast‐emerging trend in modern medicine. Terahertz nonstationary spectroscopy based on the induction and disintegration of freely decaying polarization in the gas mixture during the interaction of radiation with molecules at resonance frequencies is a high‐sensitivity method for studying multicomponent gas mixtures, which is promising for identifying metabolites in the thermal decomposition products of biological samples. The paper presents the results of the application of high‐resolution terahertz spectroscopy to the study of biological samples taken from patients with certain diseases (pathologically changed tissues of ear‐nose‐throat organs and similar pathologic tissues formed in other life support systems) to search for characteristic sets of metabolites characterizing the pathology. The world's first measurements of the spectra of pathologic samples of cysts, formed in different life support systems, were carried out, which made it possible to identify similar substances in tissues having the same pathology.
A Novel Ultrasound Finding for the Diagnosis of Giant Cell Arteritis: Comparison With Temporal Artery Biopsy Findings
Authors: Kudo Yusuke , Hara Karin , Murayama Michito , Kaga Sanae , Omotehara Satomi , Iwai Takahito , Kato Masaru , Tomaru Utano , Matsuno Yoshihiro , Ishizu Akihiro 
Published: October 2024

ABSTRACTHypoechoic halo is a typical ultrasound finding in giant cell arteritis (GCA), but it may be a false positive due to arteriosclerosis. Therefore, we focused on the segmental distribution of GCA lesions, defined the luminal irregularity in long‐axis images as the string of beads sign, and examined its diagnostic ability. As a result, the C‐statistic of hypoechoic halo and string of beads sign was better than that of hypoechoic halo alone (1.00 vs. 0.89). Based on the above, the diagnostic ability of GCA can be improved by adding the string of beads sign to the conventional hypoechoic halo.
Toward Understanding the Mechanism of Client‐Selective Small Molecule Inhibitors of the Sec61 Translocon
Authors: Sorout Nidhi , Helms Volkhard 
Published: October 2024

ABSTRACTThe Sec61 translocon mediates the translocation of numerous, newly synthesized precursor proteins into the lumen of the endoplasmic reticulum or their integration into its membrane. Recently, structural biology revealed conformations of idle or substrate‐engaged Sec61, and likewise its interactions with the accessory membrane proteins Sec62, Sec63, and TRAP, respectively. Several natural and synthetic small molecules have been shown to block Sec61‐mediated protein translocation. Since this is a key step in protein biogenesis, broad inhibition is generally cytotoxic, which may be problematic for a putative drug target. Interestingly, several compounds exhibit client‐selective modes of action, such that only translocation of certain precursor proteins was affected. Here, we discuss recent advances of structural biology, molecular modelling, and molecular screening that aim to use Sec61 as feasible drug target.
Perilymphatic enhancement and endolymphatic hydrops: MRI findings and clinical associations
Authors: Kobayashi Masumi , Yoshida Tadao , Fukunaga Yukari , Hara Daisuke , Naganawa Shinji , Sone Michihiko 
Published: October 2024

AbstractObjectiveIn this study, we aimed to summarize magnetic resonance imaging (MRI) findings of perilymphatic enhancement (PE) and endolymphatic hydrops (EH) of the inner ear, which are associated with vestibular and cochlear symptoms.MethodsWe analyzed data on ears with definite Meniere's disease (MD), sensorineural hearing loss (SNHL), vertigo, and listening difficulties (LiD) from 508 ears of 254 patients who underwent contrast‐enhanced 3‐Tesla MRI between April 2021 and March 2023. We evaluated the degree of endolymphatic hydrops (EH), signal intensity ratios (SIRs) between the basal turns of the cochlea and cerebellum, and hearing levels for all ears. Ears with definite MD were also assessed for changes in vestibular and cochlear symptoms within 6 months.ResultsEars with definite MD exhibited significantly higher percentages of EH in both the vestibule and cochlea compared with ears with other diseases. Furthermore, ears with MD or sensorineural hearing loss (SNHL) had significantly higher SIRs of PE compared with ears with other diseases or asymptomatic ears. Among patients with definite MD, those experiencing hearing fluctuations or vertigo attacks within the last 6 months had significantly higher SIRs of PE compared with those who did not experience any symptoms.ConclusionSignificant EH in the vestibule and cochlea was a major finding for the imaging diagnosis of definite MD. A high SIR of PE was a good indicator for assessing MD activity, reflecting vestibular and cochlear symptoms and fluctuations.Level of Evidence: 4.
Size distribution of aggregates across different aquatic systems around Japan shows that stronger aggregates are formed under turbulence
Authors: Takeuchi Marika , Giering Sarah L. C. , Yamazaki Hidekatsu 
Published: October 2024

AbstractMarine aggregates, composed of various particles, play a crucial role in ocean carbon storage. The overall size distribution of the aggregates (number size spectra) is controlled by the balance between aggregation and disaggregation processes. Turbulence has been proposed to facilitate both aggregation and disaggregation by increasing the collision rate of aggregates or sometimes directly tearing them apart. Predominant processes driven by turbulence typically depend on the level of turbulence—relatively weak turbulence is associated with aggregation while stronger turbulence promotes disaggregation. Aggregate strength also plays a key role, as strongly bonded aggregates can withstand turbulence better, leading to lower disaggregation rates. While the relationship between turbulence and aggregate strength has been studied numerically and experimentally, field measurements remain limited. Here, we compare our number size spectra to turbulence intensity from the field measurements across different environmental settings around Japan to determine the effect of turbulence on aggregate strength. We combined measurements from 10 sites with different environmental settings and observed the flatter slopes (higher net aggregation rate) and shifts in the intersection lengths with an increase of turbulence, while strong turbulence is typically linked with disaggregation. Our findings suggested that stronger aggregates are formed under stronger turbulence and the overall population of strong aggregates also increases with an increase of turbulence intensity. We also compared our number size spectra with three other confounding factors (fluorescence, salinity, and aggregate compositions) to confirm the effects of turbulence are dominant in our aggregate dynamics.