bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of neoadjuvant chemotherapy‐resistant muscle‐invasive bladder cancer that markedly responded to pembrolizumab before conversion radical cystectomy
Authors: Yonese Ichiro , Numao Noboru , Inamura Kentaro , Yoneoka Yusuke , Fujiwara Ryo , Yasuda Yosuke , Oguchi Tomohiko , Yamamoto Shinya , Yuasa Takeshi , Yonese Junji 
Published: November 2023

IntroductionRecently, perioperative use of immune checkpoint inhibitors has improved the prognosis of muscle‐invasive bladder cancer. It is unclear whether radical cystectomy or systemic pembrolizumab is the optimal next treatment in patients with muscle‐invasive bladder cancer and progressive disease in the pelvic lymph node following neoadjuvant chemotherapy (NAC).Case presentationA 62‐year‐old woman with cT3N0M0 bladder cancer and high programmed death‐ligand 1 expression developed solitary obturator lymph node metastasis following 5 cycles of neoadjuvant chemotherapy. Six subsequent cycles of pembrolizumab shrank the lymph node significantly, and conversion radical cystectomy was planned. Pathologically, only carcinoma in situ around the scar of transurethral resection of bladder tumor remained in the primary tumor, and the accumulation of foamy macrophages and fibrosis without viable tumor cells was observed in the dissected lymph node. Eighteen months passed without a recurrence following radical cystectomy.ConclusionPembrolizumab administration before radical cystectomy achieved a good response in a patient with obturator lymph node metastasis following neoadjuvant chemotherapy.
Thriving in foreign learning environments: The case of hands‐on activities in early years of dental education
Authors: Maragha Tala , Shuler Charles , Walker Judith , von Bergmann HsingChi 
Published: November 2023

AbstractObjectivesHands‐on learning environments can challenge learners’ wellbeing in dental education, given their unfamiliarity with students. As today's learners are more aware about their wellbeing needs, it is important to explore the depth and complexity of the challenges they experience and provide them with the necessary support strategies. This study aims to identify the challenges and sources of cognitive overload of early years’ dental students across two time‐points: 2012 and 2022. We also aim to describe the students’ recommendations for future program revision considerations to support students’ wellbeing.MethodsThis study employs both qualitative and quantitative methods. Qualitatively, we utilized an Interpretive Description approach and conducted focus groups with first‐year dental students in 2023. Quantitively, we utilized first‐year dental students’ responses to the Study Habits survey administered in 2012/2013.ResultsFive main concerns and sources of cognitive load emerged from the focus groups and survey data: steepness of the learning curve, inconsistent feedback, stigma around asking for support, structural and organizational challenges, and lack of resources. Students also identified several suggestions to support their wellbeing, including time, instructor support, non‐graded exercises, additional resources, and re‐organizing the curriculum.ConclusionThis study adopts a wellbeing lens to examine students’ transition into hands‐on learning activities. These findings were utilized to propose the TIPSS Support Framework (Time, Instructor Capacity Building, Peer Learning and Other Resources, Safe Learning Spaces, and Spiraling Curriculum). The proposed model can serve as a prototype for future studies to explore its applicability and effectiveness in other dental programs.
Identification of mitogen‐activated protein kinase 7 inhibitors from natural products: Combined virtual screening and dynamic simulation studies
Authors: Alharbi Bandar , Alnajjar Lina I. , Alhassan Hassan H. , Khan Shama , Jawaid Talha , Abdullaev Bekhzod S. , Alshammari Nawaf , Yadav Dharmendra Kumar , Adnan Mohd , Shamsi Anas 
Published: November 2023

AbstractMitogen‐activated protein kinase 7 (MAPK7) is a serine/threonine protein kinase that belongs to the MAPK family and plays a vital role in various cellular processes such as cell proliferation, differentiation, gene transcription, apoptosis, metabolism, and cell survival. The elevated expression of MAPK7 has been associated with the onset and progression of multiple aggressive tumors in humans, underscoring the potential of targeting MAPK7 pathways in therapeutic research. This pursuit holds promise for the advancement of anticancer drug development by developing potential MAPK7 inhibitors. To look for potential MAPK7 inhibitors, we exploited structure‐based virtual screening of natural products from the ZINC database. First, the Lipinski rule of five criteria was used to filter a large library of ~90,000 natural compounds, followed by ADMET and pan‐assay interference compounds (PAINS) filters. Then, top hits were chosen based on their strong binding affinity as determined by molecular docking. Further, interaction analysis was performed to find effective and specific compounds that can precisely bind to the binding pocket of MAPK7. Consequently, two compounds, ZINC12296700 and ZINC02123081, exhibited significant binding affinity and demonstrated excellent drug‐like properties. All‐atom molecular dynamics simulations for 200 ns confirmed the stability of MAPK7‐ZINC12296700 and MAPK7‐ZINC02123081 docked complexes. According to the molecular mechanics Poisson–Boltzmann surface area investigation, the binding affinities of both complexes were considerable. Overall, the result suggests that ZINC12296700 and ZINC02123081 might be used as promising leads to develop novel MAPK7 inhibitors. Since these compounds would interfere with the kinase activity of MAPK7, therefore, may be implemented to control cell growth and proliferation in cancer after required validations.
Linalool, 1,8‐Cineole, and Eugenol Transfer from a Curry Dish into Human Urine
Authors: Debong Marcel W. , N'Diaye Katharina , Schöberl Daniela , Yin Yue , Lang Roman , Buettner Andrea , Hofmann Thomas , Loos Helene M. 
Published: November 2023

ScopeFor most substances, there are several routes of excretion from the human body. This study focuses on urinary excretion of dietary odorants and compares the results with previously obtained results on excretion into milk.Methods and resultsLactating mothers (n = 18) are given a standardized curry dish and donate urine samples before and after the intervention. The odorants 1,8‐cineole, linalool, cuminaldehyde, cinnamaldehyde, 4‐hydroxy‐2,5‐dimethyl‐3(2H)‐furanone, sotolone, eugenol, vanillin, and γ‐nonalactone are quantitatively analyzed. A significant transition of up to 6 µg g−1 creatinine into urine is observed for linalool, 1,8‐cineole, and eugenol. Maximum concentrations are reached 1.5 h after the intervention for 1,8‐cineole and eugenol as well as 2.5 h after the intervention for linalool. Comparison with previous results reveals that the excretion pattern of odorants into urine is divergent from the one into milk. In a second intervention study (n = 6), excretion of phase II metabolites into urine is studied using β‐glucuronidase treatment. Linalool and eugenol concentrations are 23 and 77 times higher after treatment than before treatment with β‐glucuronidase, respectively.ConclusionThe study demonstrates transition of linalool, 1,8‐cineole, and eugenol from the diet into urine and excretion of glucuronides in the case of linalool, eugenol, and vanillin.
Intrauterine enzyme replacement therapies for lysosomal storage disorders: Current developments and promising future prospects
Authors: Herzeg Akos , Borges Beltran , Lianoglou Billie R. , Gonzalez‐Velez Juan , Canepa Emma , Munar Dane , Young Sarah P. , Bali Deeksha , Gelb Michel H. , Chakraborty Pranesh , Kishnani Priya S. , Harmatz Paul , Cohen Jennifer L. , MacKenzie Tippi C. 
Published: November 2023

AbstractLysosomal storage disorders (LSDs) are a group of monogenic condition, with many characterized by an enzyme deficiency leading to the accumulation of an undegraded substrate within the lysosomes. For those LSDs, postnatal enzyme replacement therapy (ERT) represents the standard of care, but this treatment has limitations when administered only postnatally because, at that point, prenatal disease sequelae may be irreversible. Furthermore, most forms of ERT, specifically those administered systemically, are currently unable to access certain tissues, such as the central nervous system (CNS), and furthermore, may initiate an immune response. In utero enzyme replacement therapy (IUERT) is a novel approach to address these challenges evaluated in a first‐in‐human clinical trial for IUERT in LSDs (NCT04532047). IUERT has numerous advantages: in‐utero intervention may prevent early pathology; the CNS can be accessed before the blood‐brain barrier forms; and the unique fetal immune system enables exposure to new proteins with the potential to prevent an immune response and may induce sustained tolerance. However, there are challenges and limitations for any fetal procedure that involves two patients. This article reviews the current state of IUERT for LSDs, including its advantages, limitations, and potential future directions for definitive therapies.
Genome‐wide identification and expression analysis of Na+/H+antiporter (NHX) genes in tomato under salt stress
Authors: Cavusoglu Erman , Sari Ugur , Tiryaki Iskender 
Published: November 2023

AbstractPlant Na+/H+ antiporter (NHX) genes enhance salt tolerance by preventing excessive Na+ accumulation in the cytosol through partitioning of Na+ ions into vacuoles or extracellular transport across the plasma membrane. However, there is limited detailed information regarding the salt stress responsive SlNHXs in the most recent tomato genome. We investigated the role of this gene family's expression patterns in the open flower tissues under salt shock in Solanum lycopersicum using a genome‐wide approach. A total of seven putative SlNHX genes located on chromosomes 1, 4, 6, and 10 were identified, but no ortholog of the NHX5 gene was identified in the tomato genome. Phylogenetic analysis revealed that these genes are divided into three different groups. SlNHX proteins with 10–12 transmembrane domains were hypothetically localized in vacuoles or cell membranes. Promoter analysis revealed that SlNHX6 and SlNHX8 are involved with the stress‐related MeJA hormone in response to salt stress signaling. The structural motif analysis of SlNHX1, −2, −3, −4, and −6 proteins showed that they have highly conserved amiloride binding sites. The protein–protein network revealed that SlNHX7 and SlNHX8 interact physically with Salt Overly Sensitive (SOS) pathway proteins. Transcriptome analysis demonstrated that the SlNHX2 and SlNHX6 genes were substantially expressed in the open flower tissues. Moreover, quantitative PCR analysis indicated that all SlNHX genes, particularly SlNHX6 and SlNHX8, are significantly upregulated by salt shock in the open flower tissues. Our results provide an updated framework for future genetic research and development of breeding strategies against salt stress in the tomato.
Bis‐aniline‐1,3,5‐trinitrobenzene complexes: (Short Communication)
Authors: Foster R. , Payne H.A.S. 
Published: November 2023

AbstractRecently, it has been shown1 that the association constants of 1,3,5‐trinitrobenzene with various hydrocarbons containing two equivalent, symmetrically disposed, phenyl rings have twice the values of the complexes of the corresponding “half” molecules (Table I). It is generally considered that these interactions are electron donor‐acceptor (charge‐transfer) complexes, in which the donor site is the aromatic ring2. The values of the association constants may be accounted for if each site in the bis‐phenyl compounds behaves independently of the remaining sites so that such molecules simply provide, on a statistical basis, twice the number of sites per molecule compared with the corresponding “half” molecules. It is recognised that such behaviour is remarkable in the cases of tolan and trans‐stilbene in which there is conjugation between the two phenyl rings. The complexing behaviour of a series of bis‐anilines has now been studied.
Deazapurine Derivatives. VIII: Synthesis of 7‐substituted 3‐β‐D‐ribofuranosylimidazo[4,5‐b]pyridines: 1‐deazaadenosine and related compounds
Authors: de Roos K.B. , Salemink C.A. 
Published: November 2023

AbstractFusion of 7‐chloroimidazo[4,5‐b]pyridine (IV, 6‐chloro‐1‐deazapurine) with tetra‐O‐acetyl‐β‐D‐ribofuranose (V), gave predominantly the tri‐O‐acetyl derivative of 7‐chloro‐3‐β‐D‐ribofuranosylimidazo[4,5‐b]pyridine (β‐VI) and a small amount of the corresponding α‐anomer (α‐VI). After removal of the acetyl groups, the ribofuranosides β‐VII and α‐VII were obtained as crystalline compounds. It has been shown, that the sugar residue in both anomers is attached to position 3. The anomeric configuration has been assigned with the assistance of several independent methods. Starting from the β‐ribofuranoside β‐VII, l‐deazaadenosine (XII) and some related compounds were synthesized.
Electron donor‐acceptor complex formation by compounds of biological interest: IV. Complexes of Local Anaesthetics with Electron Acceptors
Authors: Foster R. , Fyfe C.A. 
Published: November 2023

AbstractThe association constants of benzocaine, procaine, lignocaine and prilocaine with the electron acceptors 1,3,5‐trinitrobenzene and 1,4‐dicyano‐2,3,5,6‐tetrafluorobenzene have been determined from NMR chemical‐shift measurements. The results have been compared with corresponding constants for complexes of aniline, 2,6‐dimethylaniline and 2‐methylaniline. For solutions in carbon tetrachloride, unexpectedly high association constants are obtained for the drug molecules compared with the corresponding simple ring‐methylated anilines. It is suggested that these results may be due to the cooperative binding by the amino group in the side‐chain which increases the overall binding of the drug molecule to the acceptor.
Two‐Step Catalytic Against Polysulfide Shuttling to Enhance Redox Conversion for Advanced Lithium–Sulfur Batteries
Authors: Tian Chengxiang , Li Pengcheng , Hu Xin , Yan Wensheng , Xiang Xia , Lu Li 
Published: November 2023

AbstractThe development of lithium–sulfur batteries is seriously hindered by the shuttle effect of lithium polysulfides (LiPSs) and the low electrical conductivity of sulfur. To solve these problems, efficient catalysts can be used to improve the conversion rate of LiPSs and the conductivity of sulfur cathode. Herein, annealed melamine foam supported MoSe2 (NCF@MoSe2) is used as interlayer and the MoSe2/MoP heterojunction obtained by phosphating MoSe2 is further used as the catalyst material for metal fusion with a sulfur element. The interlayer can not only improve the electrical conductivity and effectively adsorb and catalyze LiPSs, but more importantly, the MoSe2/MoP heterojunction can also effectively adsorb and catalyze LiPSs, so that the batteries have a dual inhibition shuttling effect strategy. Furthermore, the rapid anchor‐diffusion transition of LiPSs, and the suppression of shuttling effects by catalyst materials are elucidated using theoretical calculations and in situ Raman spectroscopy. The two‐step catalytic strategy exhibits a high reversibility of 983 mAh g−1 after 200 cycles at 0.5 C and a high‐rate capacity of 889 mAh g−1 at 5 C. This work provides a feasible solution for the rational design of interlayer and heterojunction materials and is also conducive to the development of more advanced Li–S batteries.
Resveratrol alleviates fumonisin‐induced intestinal cytotoxicity by modulating apoptosis, tight junction, and inflammation in IPEC‐J2 porcine intestinal epithelial cells
Authors: Yu Song , Zou Lianpeng , Zhao Jiawei , Zhu Yiping 
Published: November 2023

AbstractFumonisins are common contaminants in the global food and environment, pose a variety of health risks to humans and animals. However, the method of mitigating fumonisin toxicity is still unclear. Resveratrol is a natural compound with antioxidant and anti‐inflammatory properties. In this study, the protective effect of resveratrol against fumonisin‐induced intestinal toxicity was investigated by the porcine intestinal epithelial cell line (IPEC‐J2). The cells were treated with 0–40 μM fumonisin for 24 or 48 h with or without the 24 h resveratrol (15 μM) pretreatment. The data showed that resveratrol could alleviate the fumonisin B1 (FB1)‐induced decrease in cell viability and amplify in membrane permeability. At the same time, it could reduce the accumulation of intracellular reactive oxygen species and increase the expression ranges of Nrf2 and downstream genes (SOD1 and NQO‐1), thereby counteracting FB1‐induced apoptosis. Furthermore, resveratrol was able to reduce the expression levels of inflammatory factors (TNF‐α, IL‐1β, and IL‐6), increase the expression levels of tight junction proteins (Claudin‐1, Occludin, and ZO‐1), and the integrity of the IPEC‐J2 monolayer. Our data also showed that resveratrol could attenuate the toxicity of the co‐occurrence of three fumonisins. It is implied that resveratrol represents a promising protective approach for fumonisin, even other mycotoxins in the future. This provided a new strategy for further blocking and controlling the toxicity of fumonisin, subsequently avoiding adverse effects on the human and animal health.
Clinical supervisors' and students' perspectives on preparedness for veterinary workplace clinical training: An international study
Authors: Routh Jennifer , Paramasivam Sharmini Julita , Cockcroft Peter , Wood Sarah , Remnant John , Westermann Cornélie , Reid Alison , Pawson Patricia , Warman Sheena , Nadarajah Vishna Devi , Jeevaratnam Kamalan 
Published: November 2023

AbstractBackgroundThe alignment of student and workplace supervisors’ perspectives on student preparedness for veterinary workplace clinical training (WCT) is unknown, yet misalignment could negatively impact workplace learning. The aim of this study was to quantify the relative importance of WCT preparedness characteristics according to students and supervisors and to identify differences.MethodsA survey was completed by 657 veterinary students and 244 clinical supervisors from 25 veterinary schools, from which rankings of the preparedness characteristics were derived. Significant rank differences were assessed using confidence intervals and permutation tests.Results‘Honesty, integrity and dependability’ was the most important characteristic according to both groups. The three characteristics with the largest rank differences were: students’ awareness of their own and others’ mental wellbeing and the importance of self‐care; being willing to try new practical skills with support (students ranked both of these higher); and having a clinical reasoning framework for common problems (supervisors ranked higher).LimitationsUsing pooled data from many schools means that the results are not necessarily representative of the perspectives at any one institution.ConclusionThere are both similarities and differences in the perspectives of students and supervisors regarding which characteristics are more important for WCT. This provides insights that can be used by educators, curriculum developers and admissions tutors to improve student preparedness for workplace learning.
Genome wide association in Spanish bread wheat landraces identifies six key genomic regions that constitute potential targets for improving grain yield related traits
Authors: López-Fernández Matilde , García-Abadillo Julián , Uauy Cristobal , Ruiz Magdalena , Giraldo Patricia , Pascual Laura 
Published: November 2023

Abstract
Key message
Association mapping conducted in 189 Spanish bread wheat landraces revealed six key genomic regions that constitute stable QTLs for yield and include 15 candidate genes.

Abstract
Genetically diverse landraces provide an ideal population to conduct association analysis. In this study, association mapping was conducted in a collection of 189 Spanish bread wheat landraces whose genomic diversity had been previously assessed. These genomic data were combined with characterization for yield-related traits, including grain size and shape, and phenological traits screened across five seasons. The association analysis revealed a total of 881 significant marker trait associations, involving 434 markers across the genome, that could be grouped in 366 QTLs based on linkage disequilibrium. After accounting for days to heading, we defined 33 high density QTL genomic regions associated to at least four traits. Considering the importance of detecting stable QTLs, 6 regions associated to several grain traits and thousand kernel weight in at least three environments were selected as the most promising ones to harbour targets for breeding. To dissect the genetic cause of the observed associations, we studied the function and in silico expression of the 413 genes located inside these six regions. This identified 15 candidate genes that provide a starting point for future analysis aimed at the identification and validation of wheat yield related genes.
MR 4D flow–derived left atrial acceleration factor for differentiating advanced left ventricular diastolic dysfunction
Authors: Reiter Clemens , Reiter Ursula , Kräuter Corina , Kolesnik Ewald , Scherr Daniel , Schmidt Albrecht , Fuchsjäger Michael , Reiter Gert 
Published: November 2023

Abstract
Objectives
The magnetic resonance (MR) 4D flow imaging–derived left atrial (LA) acceleration factor α was recently introduced as a means to non-invasively estimate LA pressure. We aimed to investigate the association of α with the severity of left ventricular (LV) diastolic dysfunction using echocardiography as the reference method.

Methods
Echocardiographic assessment of LV diastolic function and 3-T cardiac MR 4D flow imaging were prospectively performed in 94 subjects (44 male/50 female; mean age, 62 ± 12 years). LA early diastolic peak outflow velocity (vE), systolic peak inflow velocity (vS), and early diastolic peak inflow velocity (vD) were evaluated from 4D flow data. α was calculated from α = vE / [(vS + vD) / 2]. Mean parameter values were compared by t-test; diagnostic performance of α in predicting diastolic (dys)function was investigated by receiver operating characteristic curve analysis.

Results
Mean α values were 1.17 ± 0.14, 1.20 ± 0.08, 1.33 ± 0.15, 1.77 ± 0.18, and 2.79 ± 0.69 for grade 0 (n = 51), indeterminate (n = 9), grade I (n = 13), grade II (n = 13), and grade III (n = 8) LV diastolic (dys)function, respectively. α differed between subjects with non-advanced (grade < II) and advanced (grade ≥ II) diastolic dysfunction (1.20 ± 0.15 vs. 2.16 ± 0.66, p < 0.001). The area under the curve (AUC) for detection of advanced diastolic dysfunction was 0.998 (95% CI: 0.958–1.000), yielding sensitivity of 100% (95% CI: 84–100%) and specificity of 99% (95% CI: 93–100%) at cut-off α ≥ 1.58. The AUC for differentiating grade III diastolic dysfunction was also 0.998 (95% CI: 0.976–1.000) at cut-off α ≥ 2.14.

Conclusion
The 4D flow–derived LA acceleration factor α allows grade II and grade III diastolic dysfunction to be distinguished from non-advanced grades as well as from each other.

Clinical relevance statement
As a single continuous parameter, the 4D flow–derived LA acceleration factor α shows potential to simplify the multi-parametric imaging algorithm for diagnosis of advanced LV diastolic dysfunction, thereby identifying patients at increased risk for cardiovascular events.

Key Points
• Detection of advanced diastolic dysfunction is typically performed using a complex, multi-parametric approach.
• The 4D flow–derived left atrial acceleration factor α alone allows accurate detection of advanced left ventricular diastolic dysfunction.
• As a single continuous parameter, the left atrial acceleration factor α could simplify the diagnosis of advanced diastolic dysfunction.