bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of ramucirumab combination chemotherapy as second‐line treatment in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction after exposure to checkpoint inhibitors and chemotherapy as first‐line therapy
Authors: Masetti Michael , Al‐Batran Salah‐Eddin , Goetze Thorsten O. , Thuss‐Patience Peter , Knorrenschild Jorge Riera , Goekkurt Eray , Folprecht Gunnar , Ettrich Thomas Jens , Lindig Udo , Luley Kim Barbara , Pink Daniel , Dechow Tobias , Sookthai Disorn , Junge Sabine , Loose Maria , Pauligk Claudia , Lorenzen Sylvie 
Published: March 2024

AbstractFOLFOX plus nivolumab represents a standard of care for first‐line therapy of advanced gastroesophageal cancer (aGEC) with positive PD‐L1 expression. The efficacy of second‐line VEGFR‐2 inhibition with ramucirumab (RAM) plus chemotherapy after progression to immunochemotherapy remains unclear. Medical records of patients with aGEC enrolled in the randomized phase II AIO‐STO‐0417 trial after treatment failure to first‐line FOLFOX plus nivolumab and ipilimumab were retrospectively analyzed. Patients were divided into two groups based on second‐line therapy: RAM plus chemotherapy (RAM group) or treatment without RAM (control group). Eighty three patients were included. In the overall population, progression‐free survival (PFS) in the RAM group was superior to the control (4.5 vs 2.9 months). Responders (CR/PR) to first‐line immunochemotherapy receiving RAM containing second‐line therapy had prolonged OS from start of first‐line therapy (28.9 vs 16.5 months), as well as second‐line OS (9.6 vs 7.5 months), PFS (5.6 vs 2.9 months) and DCR (53% vs 29%) compared to the control. PD‐L1 CPS ≥1 was 42% and 44% for the RAM and the control, respectively. Patients with CPS ≥1 in the RAM group showed better tumor control (ORR 25% vs 10%) and improved survival (total OS 11.5 vs 8.0 months; second‐line OS 6.5 vs 3.9 months; PFS 4.5 vs 1.6 months) compared to the control. Prior exposure to first‐line FOLFOX plus dual checkpoint inhibition followed by RAM plus chemotherapy shows favorable response and survival rates especially in patients with initial response and positive PD‐L1 expression and has the potential to advance the treatment paradigm in aGEC.
Gene–environment transactions between peer cigarette use, parental supervision, and Chinese adolescent cigarette smoking initiation
Authors: Meyer Zachary , Unger Jennifer B. , Zheng Yao 
Published: March 2024

AbstractIntroductionThe initiation and continued use of tobacco products constitute an ongoing source of preventable disease that continues to pose a significant risk to global adolescent health. Scarce research has sought to explore the influences of two well‐known environmental risk factors, parental supervision and peer cigarette use, on genetic and environmental contributions to adolescent cigarette use, especially in non‐Western populations.MethodsFollowing 602 Chinese twin pairs (52% female, N = 1204) from early to middle adolescence at two‐time points (Mage = 12 and 15) from 2006 to 2009 and using multivariate biometric modeling, this study examined gene–environment interplay (i.e., gene‐environment correlation and interaction) between perceived parental supervision, peer cigarette use, and adolescent cigarette smoking initiation.ResultsFrom early to middle adolescence, genetic influences on cigarette smoking initiation became more pronounced, whereas shared environmental influences that promote similarity between family members diminished. Genetic factors primarily explained the links between parental supervision and cigarette smoking initiation in mid‐adolescence. Peer cigarette use displayed stronger associations with and moderating potential in adolescent cigarette smoking initiation than parental supervision. High levels of peer cigarette use amplified genetic risk for cigarette smoking initiation in mid‐adolescence.ConclusionsChinese adolescent cigarette smoking initiation involves dynamic gene–environment transactions primarily with peer processes over development. Mid‐adolescence constitutes a developmental period wherein underlying genetic risk for cigarette smoking initiation is particularly sensitive to peer influences. Targeted interventions aimed at reducing Chinese adolescent cigarette smoking initiation should focus on peer processes during this developmental period.
Integrated analysis of ceRNA‐miRNA changes in paraquat‐induced pulmonary epithelial‐mesenchymal transition via high‐throughput sequencing
Authors: Ma Zhiyu , Wang Nana , Meng Tingting , Zhang Ruoying , Huang Yang , Li Tiegang 
Published: March 2024

AbstractRecent studies have shown that epithelial‐mesenchymal transition (EMT) plays an important role in paraquat (PQ)‐induced tissue fibrosis, which is the main cause of death in patients with PQ poisoning. However, no effective treatment for pulmonary interstitial fibrosis caused by PQ poisoning exists. It is of great significance for us to find new therapeutic targets through bioinformatics in PQ‐induced EMT. We conducted transcriptome sequencing to determine the expression profiles of 1210 messenger RNAs (mRNAs), 558 long noncoding RNAs, 28 microRNAs (miRNAs), including 18 known‐miRNAs, 10 novel‐miRNAs and 154 circular RNAs in the PQ‐exposed EMT group mice. Using gene ontology and Kyoto Encyclopaedia of Genes and Genomes analyses, we identified the pathways associated with signal transduction, cancers, endocrine systems and immune systems were involved in PQ‐induced EMT. Furthermore, we constructed long noncoding RNA‐miRNA‐mRNA interrelated networks and found that upregulated genes included Il22ra2, Mdm4, Slc35e2 and Angptl4, and downregulated genes included RGS2, Gabpb2, Acvr1, Prkd3, Sp100, Tlr12, Syt15 and Camk2d. Thirteen new potential competitive endogenous RNA targets were also identified for further treatment of PQ‐induced pulmonary tissue fibrosis. Through further study of the pathway and networks, we may identify new molecular targets in PQ‐induced pulmonary EMT.
Recent developments in synthetic strategies and pharmacological outcomes of synthetic xanthine oxidase inhibitors: A comprehensive review
Authors: Kaur Gurinder , Sharma Rajiv , Ashu  , Arora Geetakshi , Singh Atamjit , Bedi Preet Mohinder Singh , Bora Kundan Singh 
Published: March 2024

AbstractXanthine oxidase is an important enzyme in purine metabolism that converts hypoxanthine to xanthine and subsequently xanthine to uric acid. Its elevated levels result in an abnormal accumulation of uric acid that results in gout and other pathological conditions, which makes it a prime target for the management of gout. Considering this, numerous reports have been published by the various research groups across the globe focusing on the development of effective xanthine oxidase inhibitors. On that ground, numerous review articles are also available describing the pharmacological outputs of these reports, but a composition highlighting the synthetic strategies used in these research works is still missing. This review will focus on various synthetic strategies adopted by different research groups in developing xanthine oxidase inhibitors with their pharmacological outcomes, along with structure activity relationships. This review will help researchers and pharmaceutical chemists in the design and development of new xanthine oxidase inhibitor leads that are highly efficient and have fewer side effects than existing ones.
A general, most basic rule for ion dissociation: Protonated molecules
Authors: Reis Adriano , Augusti Rodinei , Eberlin Marcos N. 
Published: March 2024

AbstractContrary to the common but potentially misleading belief that when a protonated molecule is excited, it is its most stable protomer that will mandatorily dissociate, we demonstrate herein that, when rationalizing or predicting the chemistry of such ions, we should always search for the most labile protomer. This “most labile protomer” rule, based on the mobile proton model, states therefore that when a protonated molecule is heated, during ionization or by collisions for instance, the loosely bonded proton (H+) can acquire enough energy to detach itself from the most basic site of the molecule and then freely “walk through” the molecular framework to eventually find, if available, another protonation site, forming other less stable but more labile protomers, that is, protomers that may display lower dissociation thresholds. To demonstrate the validity of the “most labile protomer” rule as well as the misleading nature of the “most stable protomer” rule, we have selected several illustrative molecules and have collected their ESI(+)‐MS/MS. To compare energies of precursors and products, we have also performed PM7 calculations and elaborated potential energy surface diagrams for their possible protomers and dissociation thresholds. We have also applied the “most labile protomer” rule to reinterpret—exclusively via classical charge‐induced dissociation cleavages—several dissociation processes proposed for protonated molecules. In an accompanying letter, we have also applied a similar “most labile electromer” rule to ionized molecules.
Dynamic bidirectional regulation of NLRC3 and gammaherpesviruses during viral latency in B lymphocytes
Authors: Kang Hye‐Ri , Han Ji Ho , Ng Yee Ching , Ryu Seungbo , Park Ji‐Yeon , Chung Woo‐Chang , Song Yoon‐Jae , Chen Szu‐Ting , Brickey W. June , Ting Jenny P.‐Y. , Song Moon Jung 
Published: March 2024

AbstractWhile most NOD‐like receptors (NLRs) are predominately expressed by innate immune cells, NLRC3, an inhibitory NLR of immune signaling, exhibits the highest expression in lymphocytes. The role of NLRC3 or any NLRs in B lymphocytes is completely unknown. Gammaherpesviruses, including human Epstein–Barr virus (EBV) and murine gammaherpesvirus 68 (MHV‐68), establish latent infection in B lymphocytes, which requires elevated NF‐κB. This study shows that during latent EBV infection of human B cells, viral‐encoded latent membrane protein 1 (LMP1) decreases NLRC3 transcript. LMP1‐induced‐NF‐κB activation suppresses the promoter activity of NLRC3 via p65 binding to the promoter. Conversely, NLRC3 inhibits NF‐κB activation by promoting the degradation of LMP1 in a proteasome‐dependent manner. In vivo, MHV‐68 infection reduces Nlrc3 transcripts in splenocytes, and Nlrc3‐deficient mice show greater viral latency than controls. These results reveal a bidirectional regulatory circuit in B lymphocytes, where viral latent protein LMP1 reduces NLRC3 expression, while NLRC3 disrupts gammaherpesvirus latency, which is an important step for tumorigenesis.
Empowering SARS‐CoV‐2 variant neutralization with a bifunctional antibody engineered with tandem heptad repeat 2 peptides
Authors: Kim Ji Woong , Lee Ji Hyun , Kim Hyun Jung , Heo Kyun , Lee Yoonwoo , Jang Hui Jeong , Lee Ho‐Young , Park Jun Won , Cho Yea Bin , Shin Ha Gyeong , Yang Ha Rim , Lee Hee Eon , Song Jin Young , Lee Sukmook 
Published: March 2024

AbstractWith the global pandemic and the continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the need for effective and broadly neutralizing treatments has become increasingly urgent. This study introduces a novel strategy that targets two aspects simultaneously, using bifunctional antibodies to inhibit both the attachment of SARS‐CoV‐2 to host cell membranes and viral fusion. We developed pioneering IgG4‐(HR2)4 bifunctional antibodies by creating immunoglobulin G4‐based and phage display‐derived human monoclonal antibodies (mAbs) that specifically bind to the SARS‐CoV‐2 receptor‐binding domain, engineered with four heptad repeat 2 (HR2) peptides. Our in vitro experiments demonstrate the superior neutralization efficacy of these engineered antibodies against various SARS‐CoV‐2 variants, ranging from original SARS‐CoV‐2 strain to the recently emerged Omicron variants, as well as SARS‐CoV, outperforming the parental mAb. Notably, intravenous monotherapy with the bifunctional antibody neutralizes a SARS‐CoV‐2 variant in a murine model without causing significant toxicity. In summary, this study unveils the significant potential of HR2 peptide‐driven bifunctional antibodies as a potent and versatile strategy for mitigating SARS‐CoV‐2 infections. This approach offers a promising avenue for rapid development and management in the face of the continuously evolving SARS‐CoV‐2 variants, holding substantial promise for pandemic control.
Persimmon tannin promotes the growth of Saccharomyces cerevisiae under ethanol stress
Authors: Ilhamzah  , Tsukuda Yuka , Yamaguchi Yoshihiro , Ogita Akira , Fujita Ken‐ichi 
Published: March 2024

AbstractBACKGROUNDSaccharomyces cerevisiae plays a pivotal role in various industrial processes, including bioethanol production and alcoholic beverage fermentation. However, during these fermentations, yeasts are subjected to various environmental stresses, such as ethanol stress, which hinder cell growth and ethanol production. Genetic manipulations and the addition of natural ingredients rich in antioxidants to the culture have been shown to overcome this. Here, we investigated the potential of persimmon tannins, known for their antioxidative properties, to enhance the ethanol stress tolerance of yeast.RESULTSAssessment of the effects of 6.25 mg mL−1 persimmon tannins after 48 h incubation revealed cell viability to be increased by 8.9‐ and 6.5‐fold compared to the control treatment with and without 12.5% ethanol, respectively. Furthermore, persimmon tannins reduced ethanol‐induced oxidative stress, including the production of cellular reactive oxygen species and acceleration of lipid peroxidation. However, persimmon tannins could hardly overcome ethanol‐induced cell membrane damage.CONCLUSIONThe findings herein indicate the potential of persimmon tannin as a protective agent for increasing yeast tolerance to ethanol stress by restricting oxidative damage but not membrane damage. Overall, this study unveils the implications of persimmon tannins for industries relying on yeast. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Widening of tibial resection boundaries increases the rate of femoral component valgus and internal rotation in functionally aligned TKA
Authors: Ollivier Britt , Wakelin Edgar , Plaskos Christopher , Vandenneucker Hilde , Luyckx Thomas 
Published: March 2024

AbstractPurposeThe purpose of this study was to investigate the influence of increasing the tibial boundaries in functional alignment on femoral component orientation in total knee arthroplasty (TKA).MethodsA retrospective review of a database of robotic‐assisted TKAs using a digital joint tensioning device was performed (BalanceBot®; Corin). A total of 692 TKAs with correctable deformity were included. Functional alignment with a tibia‐first balancing technique was simulated by performing an anatomic tibial resection to recreate the native medial proximal tibial angle within certain boundaries (A, 87–90°; B, 86–90°; C, 84–92°), while accounting for wear. After balancing the knee, the resulting amount of femoral component outliers in the coronal and axial plane was calculated for each group and correlated to the coronal plane alignment of the knee (CPAK) classification.ResultsThe proportion of knees with high femoral component varus (>96°) or valgus (<87°) alignment increased from 24.5% (n = 170) in group A to 26.5% (n = 183) in group B and 34.2% (n = 237) in group C (p < 0.05). Similarly, more knees with high femoral component external rotation (>6°) or internal rotation (>3°) were identified in group C (33.4%, n = 231) than in group B (23.7%, n = 164) and A (18.4%, n = 127) (p < 0.05). There was a statistically significant (p < 0.01) overall increase in knees with both femoral component valgus <87° and internal rotation >3° from group A (4.0%, n = 28) to B (7.7%, n = 53) and C (15.8%, n = 109), with CPAK type I and II showing a 12.9‐ and 2.9‐fold increase, respectively.ConclusionExtending the tibial boundaries when using functional alignment with a tibia‐first balancing technique in TKA leads to a statistically significant higher percentage of knees with a valgus lateral distal femoral angle < 87° and >3° internal rotation of the femoral component, especially in CPAK type I and II.Level of EvidenceLevel IV.
A Preliminary Study of Thermosets from Epoxy Resins Made Using Low‐Toxicity Furan‐Based Diols
Authors: Shafranska Olena , Sutton Catherine , Kalita Deep , Kannaboina Prakash , Tiwari Sandip , Sibi Mukund P. , Webster Dean C. 
Published: March 2024

AbstractGlycidyl ethers are prepared from a series of furan‐based diols and cured with a diamine to form thermosets. The furan diols demonstrate lower toxicity than bisphenol‐A in a prior study. The diglycidyl ethers show improved thermal stability compared to the parent diols. Cured thermosets are prepared at elevated temperature using isophorone diamine (IPDA). Glass transition temperatures are in the range of 30–54 °C and depend on the structure of the furan diol. Coatings are prepared on steel substrates and show very high hardness, good adhesion, and a range of flexibility. Properties compare favorably with a control based on a bisphenol‐A epoxy resin. The study demonstrates that epoxy resins based on furan diols, which have been shown to have lower toxicity than bisphenol‐A, can form thermosets having properties comparable to a standard epoxy resin system; and thus, are viable as replacements for bisphenol‐A epoxy resins.
The impact of artificial intelligence on the green and low‐carbon transformation of Chinese enterprises
Authors: Liu Tingting , Zhou Bing 
Published: March 2024

AbstractArtificial intelligence (AI) plays a crucial role in addressing resource and environmental constraints and achieving sustainable economic and social development. This study examines the impact and mechanisms of AI on the green and low‐carbon transformation of enterprises using a sample of companies listed on the Shanghai and Shenzhen stock exchanges from 2009 to 2021. The research findings indicate that AI has the capability to effectively mitigate corporate carbon emissions (CCE) and enhance the level of green innovation (GI) in enterprises. Mechanism analysis reveals that energy consumption plays a mediating role in the relationship between AI and CCE. Heterogeneity analysis reveals that the inhibitory effect of AI on CCE is more pronounced in private enterprises and non‐heavy polluting industries. However, the impact of AI on GI is greater in state‐owned enterprises and heavy‐polluting industries. This study sheds light on the influence of AI on the green and low‐carbon transformation of enterprises, as well as its transmission mechanisms. It provides theoretical and empirical insights for promoting GI, reducing emissions, and improving energy efficiency in enterprises.
Time‐lagged associations of mindfulness and self‐regulation with affect and cognition: An ecological momentary assessment study
Authors: Aggarwal Abhishek , Chen Shang‐Ti , Lee Jongwon , Tracy Allison , Qiao Shan , Li Xiaoming , Yang Chih‐Hsiang 
Published: March 2024

AbstractMindfulness and self‐regulation practice have shown benefits in reducing emotional disorders and improving cognitive outcomes. This study uses ecological momentary assessment (EMA) to examine time‐lagged associations of momentary mindfulness and self‐regulation on affective and cognitive outcomes within college students' natural environments. College students (n = 186) received six surveys per day for seven consecutive days in 2021, 2022, and 2023 using the Expiwell application. Each survey measured students' momentary affect, perceived cognition, mindfulness, and self‐regulation levels. Due to nested data structure, multilevel models were used for analysis. Findings from 4982 EMA surveys revealed that higher levels of momentary mindfulness and self‐regulation at one‐time point were positively associated with perceived cognition (β = 0.102, p < 0.001; β = 0.054, p < 0.05) and positive affect (β = 0.061, p < 0.01; β = 0.057, p < 0.05), and negatively associated with negative affect (β = −0.023, p < 0.005; β = −0.019, p < 0.05) at the subsequent timepoints within a day, after controlling for between‐person associations and other covariates. Higher states of momentary mindfulness and self‐regulation were associated with enhanced affect and cognition at later timepoints within a day. Given these associations, targeting health interventions to induce more frequent practice of mindfulness and self‐regulation in students' daily routines could be a potential way to improve their momentary affect and cognition.
Varroa destructor parasitism and Deformed wing virus infection in honey bees are linked to peroxisome‐induced pathways
Authors: Erban Tomas , Kadleckova Dominika , Sopko Bruno , Harant Karel , Talacko Pavel , Markovic Martin , Salakova Martina , Kadlikova Klara , Tachezy Ruth , Tachezy Jan 
Published: March 2024

AbstractThe ectoparasitic mite Varroa destructor transmits and triggers viral infections that have deleterious effects on honey bee colonies worldwide. We performed a manipulative experiment in which worker bees collected at emergence were exposed to Varroa for 72 h, and their proteomes were compared with those of untreated control bees. Label‐free quantitative proteomics identified 77 differentially expressed A. mellifera proteins (DEPs). In addition, viral proteins were identified by orthogonal analysis, and most importantly, Deformed wing virus (DWV) was found at high levels/intensity in Varroa‐exposed bees. Pathway enrichment analysis suggested that the main pathways affected included peroxisomal metabolism, cyto‐/exoskeleton reorganization, and cuticular proteins. Detailed examination of individual DEPs revealed that additional changes in DEPs were associated with peroxisomal function. In addition, the proteome data support the importance of TGF‐β signaling in Varroa–DWV interaction and the involvement of the mTORC1 and Hippo pathways. These results suggest that the effect of DWV on bees associated with Varroa feeding results in aberrant autophagy. In particular, autophagy is selectively modulated by peroxisomes, to which the observed proteome changes strongly corresponded. This study complements previous research with different study designs and suggests the importance of the peroxisome, which plays a key role in viral infections.
A quadratic conservation algorithm for non‐hydrostatic models
Authors: Hao Shifeng , Cui Xiaopeng 
Published: March 2024

AbstractWe propose a quadratic conservation algorithm for non‐hydrostatic models, focusing on energy conservation and consistency. To ensure that the discrete potential and continuity equations are equivalent and to achieve conservation of mass and momentum transport, we introduce a potential reference height into the discrete potential equation. The time integration scheme is based on an explicit fourth‐order Runge–Kutta method with varying time steps, which is specially designed to maintain the quadratic conservation property. To suppress numerical noise, we suggest an adaptive diffusion method that does not lose energy. Numerical noise is estimated by higher order terms of polynomial equations, and diffusion coefficients are determined using a least‐squares method. Numerical tests demonstrate that the quadratic conservation algorithm accurately maintains total energy conservation and produces solutions of comparable quality to those reported in existing literature. Furthermore, it can resolve problems with small‐scale features.
Image of a thawed frozen specimen obtained using a cryoprobe floated with oil droplets in normal saline: An endobronchial lipomatous hamartoma image
Authors: Takigawa Yuki , Sato Ken , Inoue Tomoyoshi , Takada Masahiro , Fujiwara Keiichi 
Published: March 2024

Key messageHereby, we present a rare case of a resected endobronchial tumour that floated or showed oil droplets in saline. In this study, we report an interesting image related to endobronchial lipomatous hamartoma cryotherapy.