bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms
Authors: Morken Siren , Langer Seppo W. , Sundlöv Anna , Vestermark Lene Weber , Ladekarl Morten , Hjortland Geir Olav , Svensson Johanna B. , Tabaksblat Elizaveta Mitkina , Haslerud Torjan Magne , Assmus Jörg , Detlefsen Sönke , Couvelard Anne , Perren Aurel , Sorbye Halfdan 
Published: October 2023

Abstract
Background
The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy and safety of everolimus and temozolomide as first-line treatment for these patients.

Methods
Patients received everolimus 10 mg daily continuously and temozolomide 150 mg/m2 for 7 days every 2 weeks. Endpoints included response, survival, safety and quality of life (QoL). Histopathological re-evaluation according to the 2019 WHO classification was performed.

Results
For 37 eligible patients, the primary endpoint with 65% disease control rate (DCR) at 6 months (m) was reached. The response rate was 30%, the median progression-free survival (PFS) 10.2 months and the median overall survival (OS) 26.4 months. Considering 26 NET G3 patients, 6 months DCR was 77% vs. 22% among nine NEC patients (p = 0.006). PFS was superior for NET G3 vs. NEC (12.6 months vs. 3.4 months, Log-rank-test: p = 0.133, Breslow-test: p < 0.001). OS was significantly better for NET G3 (31.4 months vs. 7.8 months, p = 0.003). Grade 3 and 4 toxicities were reported in 43% and 38%. QoL remained stable during treatment.

Conclusion
Everolimus and temozolomide may be a treatment option for selected GEP-NET G3 patients including careful monitoring. Toxicity did not compromise QoL.

Clinical trial registration
ClinicalTrials.gov (NTC02248012).
Potent Rifampicin derivatives can clear MRSA infections at single low doses when concomitantly dosed with Vancomycin
Authors: Nittoli Thomas , Zumsteg Anna Brotcke , Bandyopadhyay Abira , Federici Stephanie , Coppi Alida , Jorgenson Susan , Choi Seung-Yong , Saha Mrinmoy , Wertz Benjamin , Trivedi Priyanka , Korgaonkar Chandrashekhar , Chin Harvey , Luong Onson , Kyratsous Christos , Olson William 
Published: October 2023

AbstractFor a number of years, antimicrobial resistance (AMR) has been a critical issue for humanity. Drug discovery efforts have been very limited and the spread of bacterial pathogens has over-run our traditional arsenal of antibiotics. Bacteria can involve to evade compounds that can halt their rapid growth. The authors have discovered a potent macrocycle derivative that when dosed concomitantly with the standard of care (SOC) antibiotic vancomycin, can clear methicillin resistant Staphylococcus aureus (MRSA) infections. In addition, we have probed the lead compounds in Salmonella typhimurium bacterial strains. In vitro, in vivo, and ADME data have been included to stress the virtues of this new antibiotic.
Blood pressure in atrial fibrillation and in sinus rhythm during ambulatory blood pressure monitoring: data from the TEMPLAR project
Authors: Lundwall Kristina , Kahan Thomas , Omboni Stefano 
Published: October 2023

AbstractThe coexistence of hypertension and atrial fibrillation (AF) is common and accounts for a worse prognosis. Uncertainties exist regarding blood pressure (BP) measurements in AF patients by automated oscillometric devices. The Microlife WatchBP 03 AFIB ambulatory BP monitoring (ABPM) device including an AF algorithm with each measurement was used in 430 subjects aged >65 years referred for ABPM and with assumed paroxysmal AF to perform intra-individual comparisons of BP during both AF-indicated and sinus rhythm. Only subjects with >30% of measurements indicating AF and episodes >30 min for assumed AF and for sinus rhythm were included. Mean age was 78 ± 7 years, 43% were male, 77% hypertensive, and 72% were treated. Compared to sinus rhythm, 24-h mean arterial pressure was similar (87.2 ± 9.5 vs 87.5 ± 10.6 mm Hg, p = 0.47), whereas 24-h systolic BP tended to be lower (123.6 ± 13.9 vs 124.7 ± 16.1 mm Hg, p = 0.05) and night-time diastolic BP higher (64.6 ± 10.9 vs 63.3 ± 10.4 mm Hg, p = 0.01) in assumed AF. Diastolic (not systolic) BP variability was higher in AF (p < 0.001). Results were similar with heart rates <90 and ≥90 bpm. In conclusion, this is the first study to use intra-individual comparisons of averaged BP during an ABPM in assumed paroxysmal AF and sinus rhythm. Our results imply that ABPM is feasible and informative also in patients with AF. We also suggest that an AF detection algorithm offers a new approach to evaluate the reliability of averaged BP values in AF compared to SR during an ABPM.
Parametric simulation of electron backscatter diffraction patterns through generative models
Authors: Ding Zihao , De Graef Marc 
Published: October 2023

AbstractRecently, discriminative machine learning models have been widely used to predict various attributes from Electron Backscatter Diffraction (EBSD) patterns. However, there has never been any generative model developed for EBSD pattern simulation. On one hand, the training of generative models is much harder than that of discriminative ones; On the other hand, numerous variables affecting EBSD pattern formation make the input space high-dimensional and its relationship with the distribution of backscattered electrons complicated. In this study, we propose a framework (EBSD-CVAE/GAN) with great flexibility and scalability to realize parametric simulation of EBSD patterns. Compared with the frequently used forward model, EBSD-CVAE/GAN can take variables more than just orientation and generate corresponding EBSD patterns in a single run. The accuracy and quality of generated patterns are systematically evaluated. The model does not only summarize a distribution of backscattered electrons at a higher level, but also mitigates data scarcity in this field.
Self-healable stretchable printed electronic cryogels for in-vivo plant monitoring
Authors: Bihar Eloïse , Strand Elliot J. , Crichton Catherine A. , Renny Megan N. , Bonter Ignacy , Tran Tai , Atreya Madhur , Gestos Adrian , Haseloff Jim , McLeod Robert R. , Whiting Gregory L. 
Published: October 2023

AbstractA key challenge in bioelectronics is to establish and improve the interface between electronic devices and living tissues, enabling a direct assessment of biological systems. Sensors integrated with plant tissue can provide valuable information about the plant itself as well as the surrounding environment, including air and soil quality. An obstacle in developing interfaces to plant tissue is mitigating the formation of fibrotic tissues, which can hinder continuous and accurate sensor operation over extended timeframes. Electronic systems that utilize suitable biocompatible materials alongside appropriate fabrication techniques to establish plant-electronic interfaces could provide for enhanced environmental understanding and ecosystem management capabilities. To meet these demands, this study introduces an approach for integrating printed electronic materials with biocompatible cryogels, resulting in stable implantable hydrogel-based bioelectronic devices capable of long-term operation within plant tissue. These inkjet-printed cryogels can be customized to provide various electronic functionalities, including electrodes and organic electrochemical transistors (OECTs), that exhibit high electrical conductivity for embedded conducting polymer traces (up to 350 S/cm), transconductance for OECTs in the mS range, a capacitance of up to 4.2 mF g−1 in suitable structures, high stretchability (up to 330% strain), and self-healing properties. The biocompatible functionalized cryogel-based electrodes and transistors were successfully implanted in plant tissue, and ionic activity in tomato plant stems was collected for over two months with minimal scar tissue formation, making these cryogel-based printed electronic devices excellent candidates for continuous, in-situ monitoring of plant and environmental status and health.
CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial
Authors: Mackensen Andreas , Haanen John B.A.G. , Koenecke Christian , Alsdorf Winfried , Wagner-Drouet Eva , Borchmann Peter , Heudobler Daniel , Ferstl Barbara , Klobuch Sebastian , Bokemeyer Carsten , Desuki Alexander , Lüke Florian , Kutsch Nadine , Müller Fabian , Smit Eveline , Hillemanns Peter , Karagiannis Panagiotis , Wiegert Erol , He Ying , Ho Thang , Kang-Fortner Qing , Schlitter Anna Melissa , Schulz-Eying Catrine , Finlayson Andrew , Flemmig Carina , Kühlcke Klaus , Preußner Liane , Rengstl Benjamin , Türeci Özlem , Şahin Uğur 
Published: October 2023

AbstractThe oncofetal antigen Claudin 6 (CLDN6) is highly and specifically expressed in many solid tumors, and could be a promising treatment target. We report dose escalation results from the ongoing phase 1/2 BNT211-01 trial evaluating the safety and feasibility of chimeric antigen receptor (CAR) T cells targeting the CLDN6 with or without a CAR-T cell-amplifying RNA vaccine (CARVac) at two dose levels (DLs) in relapsed/refractory CLDN6-positive solid tumors. The primary endpoints were safety and tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D). Secondary endpoints included objective response rate (ORR) and disease control rate. We observed manageable toxicity, with 10 out of 22 patients (46%) experiencing cytokine release syndrome including one grade 3 event and 1 out of 22 (5%) with grade 1 immune effector cell-associated neurotoxicity syndrome. Dose-limiting toxicities occurred in two patients at the higher DL, resolving without sequelae. CAR-T cell engraftment was robust, and the addition of CARVac was well tolerated. The unconfirmed ORR in 21 evaluable patients was 33% (7 of 21), including one complete response. The disease control rate was 67% (14 of 21), with stable disease in seven patients. Patients with germ cell tumors treated at the higher DL exhibited the highest response rate (ORR 57% (4 of 7)). The maximum tolerated dose and RP2D were not established as the trial has been amended to utilize an automated manufacturing process. A repeat of the dose escalation is ongoing and will identify a RP2D for pivotal trials. ClinicalTrials.gov Identifier: NCT04503278.
Targeted depletion of TRBV9+ T cells as immunotherapy in a patient with ankylosing spondylitis
Authors: Britanova Olga V. , Lupyr Kseniia R. , Staroverov Dmitry B. , Shagina Irina A. , Aleksandrov Alexey A. , Ustyugov Yakov Y. , Somov Dmitry V. , Klimenko Alesia , Shostak Nadejda A. , Zvyagin Ivan V. , Stepanov Alexey V. , Merzlyak Ekaterina M. , Davydov Alexey N. , Izraelson Mark , Egorov Evgeniy S. , Bogdanova Ekaterina A. , Vladimirova Anna K. , Iakovlev Pavel A. , Fedorenko Denis A. , Ivanov Roman A. , Skvortsova Veronika I. , Lukyanov Sergey , Chudakov Dmitry M. 
Published: October 2023

AbstractAutoimmunity is intrinsically driven by memory T and B cell clones inappropriately targeted at self-antigens. Selective depletion or suppression of self-reactive T cells remains a holy grail of autoimmune therapy, but disease-associated T cell receptors (TCRs) and cognate antigenic epitopes remained elusive. A TRBV9-containing CD8+ TCR motif was recently associated with the pathogenesis of ankylosing spondylitis, psoriatic arthritis and acute anterior uveitis, and cognate HLA-B*27-presented epitopes were identified. Following successful testing in nonhuman primate models, here we report human TRBV9+ T cell elimination in ankylosing spondylitis. The patient achieved remission within 3 months and ceased anti-TNF therapy after 5 years of continuous use. Complete remission has now persisted for 4 years, with three doses of anti-TRBV9 administered per year. We also observed a profound improvement in spinal mobility metrics and the Bath Ankylosing Spondylitis Metrology Index (BASMI). This represents a possibly curative therapy of an autoimmune disease via selective depletion of a TRBV-defined group of T cells. The anti-TRBV9 therapy could potentially be applicable to other HLA-B*27-associated spondyloarthropathies. Such targeted elimination of the underlying cause of the disease without systemic immunosuppression could offer a new generation of safe and efficient therapies for autoimmunity.
Study on creep characteristics and component model of saline soil in hexi corridor
Authors: Yu Yun-yan , Luo Chong-liang , Cui Wen-hao , Tao Jing-yan , Zhang Ting-hua 
Published: October 2023

AbstractAccurate mastery of the creep characteristics of unsaturated saline soil is extremely important for the long-term stability and safe operation of all types of buildings. In this paper, the research object focused on the saline soil of the Zhangye area, Hexi corridor. The indoor triaxial CU creep test was carried out by means of graded loading to study the creep characteristics of saline soil under different salt content and loading stress. The Merchant and Burgers models were used to predict the creep behavior of the saline soils, and the predicted results were compared with the experimental values. The results showed that the triaxial creep curve of saline soil developed in stage III. Namely, transient creep stage, deceleration creep stage and steady-state creep stage. The creep deformation increases with the increase of salt content and loading stress. The stress–strain isochronous curve has non-linear growth, and the cluster of curves develops from dense to sparse after increasing to long-term strength (100∼150 kPa). The parameters of the Merchant and Burgers model vary with salt content and loading stress, and the creep curve predicted by the Burgers model is closer to the test value.
Effects of vitamins C and E in tris citric acid glucose extender on chilled semen quality of Kail ram during different storage times
Authors: Akhter Shereen , Zubair Muhammad , Mahmood Majid , Andrabi Syed Murtaza Hassan , Hameed Nasir , Ahmad Ejaz , Saleemi Muhammad Kashif 
Published: October 2023

AbstractMammalian sperm cells are highly vulnerable to lipid peroxidation by free radicals. Antioxidants such as vitamin E, and vitamin C neutralize the activity of free radicals and protect the sperm from reactive oxygen species. The present study was conducted to investigate the effects of vitamin C, vitamin E, and their combination in a Tris-based extender on the semen quality of Kail Ram. Semen samples from five mature Kail rams were collected in this study. The semen samples were diluted by Tris-glucose-egg yolk. Diluted semen samples were divided into four parts. The first part was added with 1 mg/ml of vitamin C, the second part was added with 1 mg/ml of vitamin E and the third part was added with both vitamin C and E, in combination with a dose of 1 mg/ml. The fourth part was considered as control without any addition. The diluted semen samples were cooled gradually and preserved at 5˚C for three days. Sperms in chilled diluted semen samples were examined for motility, viability, and plasma membrane integrity every 24 h for three days (72 h). Present study results showed significant (P < 0.05) effects of vitamins C, E, and their combination on some parameters such as motility, straightness of average special path, linearity of the curvilinear trajectory, and beat-cross frequency. However, there was no significant (P < 0.05) effect of storage duration and antioxidants (vitamin C, E, and their combination) on viability, sperm plasma membrane integrity, and some CASA parameters. From the present study, it could be concluded that the supplementation of vitamins C, and E, and their combination do not enhance the life span and quality of semen in Kail ram during liquid storage at 5 °C.
Targeting allosteric binding site in methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to identify natural product inhibitors via structure-based computational approach
Authors: Rana Nisarg , Patel Dhaval , Parmar Meet , Mukherjee Nandini , Jha Prakash C. , Manhas Anu 
Published: October 2023

AbstractCancer has been viewed as one of the deadliest diseases worldwide. Among various types of cancer, breast cancer is the most common type of cancer in women. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a promising druggable target and is overexpressed in cancerous cells, like, breast cancer. We conducted structure-based modeling on the allosteric site of the enzyme. Targeting the allosteric site avoids the problem of drug resistance. Pharmacophore modeling, molecular docking, HYDE assessment, drug-likeness, ADMET predictions, simulations, and free-energy calculations were performed. The RMSD, RMSF, RoG, SASA, and Hydrogen-bonding studies showed that seven candidates displayed stable behaviour. As per the literature, average superimposed simulated structures revealed a similar protein conformational change in the αEʹ-βfʹ loop, causing its displacement away from the allosteric site. The MM-PBSA showed tight binding of six compounds with the allosteric pocket. The effect of inhibitors interacting in the allosteric site causes a decrease in the binding energy of J49 (active-site inhibitor), suggesting the effect of allosteric binding. The PCA and FEL analysis revealed the significance of the docked compounds in the stable behaviour of the complexes. The outcome can contribute to the development of potential natural products with drug-like properties that can inhibit the MTHFD2 enzyme.
Computational prognostic evaluation of Alzheimer’s drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches
Authors: Hassan Mubashir , Shahzadi Saba , Yasir Muhammad , Chun Wanjoo , Kloczkowski Andrzej 
Published: October 2023

AbstractDrug designing is high-priced and time taking process with low success rate. To overcome this obligation, computational drug repositioning technique is being promptly used to predict the possible therapeutic effects of FDA approved drugs against multiple diseases. In this computational study, protein modeling, shape-based screening, molecular docking, pharmacogenomics, and molecular dynamic simulation approaches have been utilized to retrieve the FDA approved drugs against AD. The predicted MADD protein structure was designed by homology modeling and characterized through different computational resources. Donepezil and galantamine were implanted as standard drugs and drugs were screened out based on structural similarities. Furthermore, these drugs were evaluated and based on binding energy (Kcal/mol) profiles against MADD through PyRx tool. Moreover, pharmacogenomics analysis showed good possible associations with AD mediated genes and confirmed through detail literature survey. The best 6 drug (darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar) further docked and analyzed their interaction behavior through hydrogen binding. Finally, MD simulation study were carried out on these drugs and evaluated their stability behavior by generating root mean square deviation and fluctuations (RMSD/F), radius of gyration (Rg) and soluble accessible surface area (SASA) graphs. Taken together, darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar displayed good lead like profile as compared with standard and can be used as possible therapeutic agent in the treatment of AD after in-vitro and in-vivo assessment.
Uncovering the global ranking of greenhouse gases intensity, efficiency and structural transformation
Authors: Saleem Muhammad , Aslam Muhammad , Janjua Azhar Ali 
Published: October 2023

AbstractThis study incorporated the index decomposition analysis to drive the GHGs emissions intensity and separate the impact into true efficiency and structural transformation of economic activities on GHGs emissions. The global perspective is investigated in three aspects; (i) global groups of countries regarding income level, (ii) global countries bifurcated into geo-political regions and, (iii) hundred countries are taken to perform individual country level analysis, by taking 20 years (2000–2019) data. The hundred countries are ranked regarding GHGs intensity, efficiency and economic activities with respect to (i) for the latest year performance, (ii) twenty years average performance and, (iii) annual average reduction of GHGs emissions, comparable with base year 2000. Income-based countries groups explicate the improvement of GHGs intensity for HIC only and the economic transformation contributed to it. Efficiency index for all income groups while economic activities of LMIC, MIC and UMIC deteriorated the GHGs emissions. Global geo-political regions explicate the mixed pattern of GHGs intensity. Efficiency index is best for Azerbaijan and least for Uzbekistan. While ranking average GHGs emission reduction countries; Zimbabwe is the best and Qatar is the last country in the intensity list.
Biomechanical explanation of W-plasty effectiveness using a finite element method approach
Authors: Papadakis Marios , Manios Georgios , Zacharopoulos Georgios , Koumaki Dimitra , Manios Andreas 
Published: October 2023

AbstractThe finite element method has often been used to assist analyzing local flaps in terms of deformation and stress measurements as it takes into account complex skin properties. We, herein, present an isotropic two-dimensional finite element skin model applied to the W-plasty method to demonstrate that the good outcomes of W-plasty should be attributed to the geometry itself, as it generates lower stresses. The skin was modeled as a two-dimensional (2D) planar geometry. The model was created and solved as a plane stress problem. The model was based on simulation of the loading and stitching of W-plasties of various angles. Each central triangular flap was segmented in nine triangular elements. The stitching was modeled with one suture at the top of each triangular flap with the center of the opposite corner. X- and Y-axis stresses and shearing stresses Txy in the elements involved in the broken stitching line, show lower stresses than the elements behind the stitching line. Interestingly, in the triangular flaps, the stresses were clearly lower than those of their neighboring areas. The maximum compressive stresses in the 2D model we used, correspond to the dog ears. We conclude that the effectiveness of W-plasty should be attributed not only to the scar orientation in relation to the relaxed tension skin lines but also to the special design of the triangular flaps used. This finding assists the general understanding of the method and should be taken into account by the clinician during flap designing.