bluuebunny/crossref_metadata_2025_split huggingface dataset:
Untersuchung der Adressierbarkeit des Cysteinoms der Proteinkinasen durch Kovalente Fragmente
Authors: Wang Guiqun , Seidler Nico J. , Röhm Sandra , Pan Yufeng , Liang Xiaojun Julia , Haarer Lisa , Berger Benedict‐Tilman , Sivashanmugam Saran Aswathaman , Wydra Valentin R. , Forster Michael , Laufer Stefan A. , Chaikuad Apirat , Gehringer Matthias , Knapp Stefan 
Published: December 2024

AbstractProteinkinasen sind wichtige Zielstrukturen für Arzneistoffe, jedoch wurden bisher nur für einen Bruchteil der mehr als 500 menschlichen Kinasen spezifische Hemmstoffe entwickelt. Eine große Herausforderung bei der Entwicklung von Inhibitoren für eng verwandte Kinasen ist die Selektivität. Im Gegensatz zu ihren nicht kovalenten Gegenstücken bieten kovalente Inhibitoren hierbei den Vorteil, dass sie selektiv auf strukturell ähnliche Kinasen abzielen können, indem sie spezifische Proteinseitenketten, insbesondere nicht konservierte Cysteine, modifizieren. Bisherige kovalente Fragment‐Screens ergaben potente und selektive Verbindungen für einzelne Kinasen wie ERK1/2, jedoch wurde dieser Ansatz noch nicht auf einen breiteren Teil des Kinoms angewendet. Darüber hinaus wurden viele der potenziell zugänglichen Cysteinpositionen bisher noch nicht adressiert. Mit dieser Arbeit stellen wir einen allgemein anwendbaren Ansatz vor, um die Adressierbarkeit von Cysteinen in der Nähe der ATP‐Bindetasche mit fragmentartigen kovalenten Inhibitoren zu untersuchen. Wir präsentieren die Entwicklung einer auf Kinasen fokussierten Fragmentbibliothek und ihr systematisches Screening gegen eine kuratierte Auswahl von 47 Kinasen mit 60 Cysteinen in der Nähe der ATP‐Bindestellte. Dazu wurden LC/MS‐ und Differential Scanning Fluorimetry (DSF)‐Assays verwendet, gefolgt von einer Hit‐Validierung durch verschiedene ergänzende Techniken. Unsere Ergebnisse erweitern das Repertoire an adressierbaren Cysteinen in der Enzymfamilie der Proteinkinasen, geben Einblick in einzigartige Bindungsmodi, die anhand von Kristallstrukturen identifiziert wurden und liefern isoformspezifische Hit‐Moleküle mit vielversprechenden Profilen als Ausgangspunkte für die Entwicklung hochwirksamer und selektiver kovalenter Hemmstoffe.
Optimizing the Power Performance of Lithium‐Ion Batteries: The Role of Separator Porosity and Electrode Mass Loading
Authors: Choi Seungyeop , Seo Jun Pyo , Lim Jaejin , Dzakpasu Cyril Bubu , Roh Youngjoon , Bak Cheol , Kim Suhwan , Lee Hongkyung , Lee Yong Min 
Published: December 2024

AbstractThis study investigates the concealed effect of separator porosity on the electrochemical performance of lithium‐ion batteries (LIBs) in thin and thick electrode configuration. The effect of the separator is expected to be more pronounced in cells with thin electrodes due to its high volumetric/resistance ratio within the cell. However, the electrochemical analyses show similar power performance regardless of the separator porosity in the thin electrode configuration. In contrast, for cells with thick electrodes, separator porosity significantly impacts the direct current‐internal resistance (DC‐IR) and the capacity retention at a high rate. This behavior is attributed to ion concentration gradients in the upper regions of thick electrodes, while Li+ transfer to lower regions is hampered as the electrode thickness increases. These findings suggest that the intrinsic properties of individual cell components, such as separator porosity, are highly dependent on the overall cell design. Moreover, while high‐porosity separators enhance power performance, particularly in thick electrode configurations, they exhibit lower thermal stability and tensile strength. In conclusion, this study highlights the need for an integrated approach to optimizing separator characteristics, considering both electrochemical performance and safety trade‐offs in LIBs.
Boc‐Protected Phenylalanine and Tryptophan‐Based Dipeptides: A Broad Spectrum Anti‐Bacterial Agent
Authors: Halder Arpita , Pasupuleti Ravikumar , Sivagnanam Subramaniyam , Das Priyadip , Mukherjee Oindrilla 
Published: December 2024

ABSTRACTDipeptides were constructed using hydrophobic amino acid residues following AMP prediction. After that Boc‐modification was performed on the screened peptides and finally Boc‐Phe‐Trp‐OMe and Boc‐Trp‐Trp‐OMe were synthesized. Even though no inhibition zones were observed in agar well diffusion assays, minimum inhibitory concentration (MIC) analysis revealed anti‐bacterial activity against both Gram‐positive and Gram‐negative bacteria, with MIC90 ranging from 230 to 400 μg/mL. The crystal violet assay confirmed the dipeptides' biofilm eradication and disruption capabilities. Furthermore, membrane permeabilization assays indicated outer and inner membrane permeabilization, while SEM analysis revealed the formation of fibril and spherical nanostructures, likely contributing to this effect. The peptides also exhibited resistance to protein adsorption, non‐cytotoxicity, and non‐hemolytic properties, making them promising broad‐spectrum anti‐bacterial agents with biofilm eradication and disruption potential. This study concludes that Boc‐protected phenylalanine‐ and tryptophan‐based dipeptides can self‐assemble and can be used as broad‐spectrum anti‐bacterial agents. The self‐assembly of these peptides offers a versatile platform for designing biomaterials with tailored properties and functionalities. Research exploring the anti‐bacterial potential of Boc‐protected dipeptides has been limited, prompting our investigation to shed light on this overlooked area. Our analysis of synthesized Boc‐protected dipeptides revealed notable anti‐bacterial activity, marking a significant advancement. This finding suggests that these dipeptides could emerge as potent, broad‐spectrum anti‐bacterial agents, addressing the urgent need for effective treatments against bacterial resistance and opening new avenues in therapy. This study not only enhances our understanding of these dipeptides but also highlights their potential as innovative and efficacious anti‐bacterial agents, making a substantial impact in the clinical field.
Comparison of machine learning models for classifying edible oils using Fourier‐transform infrared spectroscopy
Authors: Lim Hyeona , Lee Seon Yeong , Kim Jin Young , Shin Yeon Ju , Jang Yerin , Kim Hyeonjin , Kim Byung Hee , Ahn Sangdoo 
Published: December 2024

AbstractAccurate classification and authentication of edible oils are essential for maintaining product quality, ensuring consumer safety, and preserving market integrity. Therefore, this study aims to propose Fourier‐transform infrared (FT‐IR) spectroscopy, combined with advanced machine learning models, as a rapid and non‐destructive technique for classifying edible oils. The FT‐IR spectra of seven edible oil types were analyzed across three spectral regions: the full range, the C‐H stretching range, and the fingerprint region. Both absorbance and second derivative spectra were used to evaluate the influence of spectral preprocessing on classification accuracy. Six machine learning models—principal component analysis followed by linear discriminant analysis (PCA‐LDA), k‐nearest neighbors, decision tree, random forest, eXtreme Gradient Boosting, and support vector machines (SVM)—were employed to classify the oils, achieving training accuracies of 96.4%–100% and testing accuracies of 88.1%–100%. The second derivative spectra enhanced model performance by improving the resolution of overlapping peaks, particularly in the CH and CO stretching regions. Additionally, the SHapley Additive exPlanations analysis further revealed the most critical spectral features influencing model predictions, offering valuable insights into the decision‐making processes. This study demonstrates the effectiveness of combining FT‐IR spectroscopy, second derivative preprocessing, and machine learning techniques for classifying edible oils. The findings highlight the benefits of second derivative spectra in enhancing spectral resolution and the superior classification performance of PCA‐LDA and SVM models. These results offer a robust framework for advancing edible oil analysis and emphasize the potential of artificial intelligence in food authentication and quality control.
The Reputation Effect of Repeated Green‐Bond Issuance and Its Impact on the Cost of Capital
Authors: Petreski Aleksandar , Schäfer Dorothea , Stephan Andreas 
Published: December 2024

ABSTRACTThis study explores the effect of frequent green‐bond issuance on a firm's financing costs. Using a sample of listed Swedish real estate companies issuing a total of 1074 bonds over the period from 2011 to 2021, difference‐in‐differences analyses and instrumental variable estimations are applied to identify the causal impact of frequent green‐bond vis‐à‐vis frequent non‐green‐bond issuance on a firm's cost of capital and credit rating. The paper argues that repetitive issuance lowers a firm's cost of capital, while the effects of first or one‐time green‐bond issuance are the opposite. In line with the reputation capital hypothesis, issuing green bonds even lowers the firm's cost of equity capital, while issuing non‐green bonds does not affect the cost of equity.
Improving CO2 Fixation with Epoxides by Replacing Zirconium by Hafnium in UiO66 MOFs
Authors: Nataj Seyedeh Molood Masoom , Ouellet Kaylee , Kaliaguine Serge , Fontaine Frédéric‐Georges 
Published: December 2024

AbstractThe impact of replacing Zr4+ with Hf⁴⁺ as the metal site on CO₂ adsorption and catalytic activity in CO₂ fixation reaction with epoxide under mild conditions was investigated in UiO66‐NH₂ grafted with carbodiimides N,N′‐dicyclohexylcarbodiimide (DCC) and N,N′‐diisopropylcarbodiimide (DIC) (UiO66(M)‐DCCBr and UiO66(M)‐DICBr; M = Zr and Hf). Leveraging on Hf⁴⁺’s greater oxophilicity and stronger M—O bonds, Hf‐based UiO66‐NH2 materials exhibited increased CO₂ adsorption capacity, influencing the catalytic performance in CO₂ fixation with epoxides. The materials were characterized by multiple techniques such as PXRD, FTIR, TGA, SEM, elemental analysis, as well as N₂ and CO₂ adsorption equilibrium measurements. UiO66(Hf)‐DCCBr and UiO66(Hf)‐DICBr demonstrated superior activity compared to their Zr‐based counterparts with high yield and TOF (14.6 and 11.9 h⁻¹, respectively) under milder conditions (0.1 MPa, 90 °C, 16 h, co‐catalyst‐free and solvent‐free). These findings underscore the pivotal role of unsaturated metal sites in enhancing the catalytic efficacy of guanidinium ionic UiO66‐NH₂ materials. Moreover, these catalysts exhibit excellent thermal stability and can be recycled and reused at least five times without a noticeable reduction in their catalytic efficiency.
Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis
Authors: Wu Shang‐Gin , Ho Chao‐Chi , Yang James Chih‐Hsin , Yu Shu‐Han , Lin Yen‐Feng , Lin Shu‐Chin , Liao Bin‐Chi , Yang Ching‐Yao , Lin Yen‐Ting , Yu Chong‐Jen , Chuang Ya‐Ting , Liao Wei‐Yu , Yap Kah Yi , Kou Weng Si , Shih Jin‐Yuan 
Published: December 2024

AbstractBackgroundAcquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) remains a significant hurdle for patients with EGFR‐mutated non‐small cell lung cancer (NSCLC), particularly those lacking the EGFRT790M. IMpower 150 study demonstrated promising efficacy for a combination of immune‐chemotherapy and bevacizumab in patients with EGFR‐mutated NSCLC.MethodsThis open‐label, single‐arm, phase II trial evaluated the efficacy and immune cell profile of the modified regimen combining atezolizumab, bevacizumab (7.5 mg/kg) and chemotherapy in patients with EGFR‐mutated NSCLC following TKI failure. The primary endpoint was objective response rate (ORR). The re‐biopsy tissue specimens and serial peripheral blood samples were collected to analyse the immune cell profile and tumour microenvironments.Rresults22 EGFR‐mutant NSCLC patients participated in this study. The ORR was 42.9%, with a disease control rate (DCR) of 100%. Median progression‐free survival (PFS) was 6.3 months. Patients with programmed death‐ligand 1 (PD‐L1) expression ≥1% exhibited significantly higher ORR (75 vs. 23.1%; p = .032) and longer PFS (14.0 vs. 6.1 months; p = .022) compared with those with PD‐L1 expression < 1%. Grade ≥ 3 adverse events occurred in 40.9% of patients. Higher peritumour nature killer (NK) cell infiltration and lower peripheral helper T cell counts before treatment were associated with favourable ORR and longer PFS, respectively. After disease progression, the proportion of S100A9+ myelod‐derived suppressor cells (MDSCs) increased, while regulatory T cells decreased.ConclusionThis modified combination regimen may be a promising therapeutic option for EGFR‐mutant NSCLC patients with TKI resistance, especially those with PD‐L1‐positive tumours. Furthermore, immune cell profiling may aid in identifying patients who may benefit from this approach.Key points
The combination regimen yielded promising efficacy in NSCLC patients after EGFR‐TKI resistance, particularly those with PD‐L1‐positive tumours.
Higher peritumour NK cell and lower peripheral helper T cell were associated with favourable ORR and longer PFS, respectively.
After disease progression, the proportion of S100A9+ MDSC increased, but Treg cells decreased.
Upper gastrointestinal triple stenosis in a patient with trisomy 17p syndrome: Case report and literature review
Authors: Ando Hiroko , Mori Hideki , Takabayashi Kaoru , Matsuura Noriko , Masaoka Tatsuhiro , Matsuzaki Juntaro , Saito Yoshimasa , Kato Motohiko , Kosaki Kenjiro , Kanai Takanori 
Published: December 2024

AbstractUpper gastrointestinal stenosis, which can be congenital or acquired, can lead to dysphagia. The association between trisomy 17p syndrome, a rare chromosomal abnormality, and upper gastrointestinal stenosis is unclear. A 20‐year‐old man diagnosed with trisomy 17p syndrome was referred to our department due to recurrent vomiting. Esophagogastroduodenoscopy revealed stenotic areas in the esophagus, stomach, and duodenum. The congenital gastrointestinal stenosis present in both the duodenum and esophagus suggested that the stasis and reflux of digestive fluids exacerbated stenosis in the stomach and esophagus. Gastric acid suppression therapy and endoscopic dilation of the esophagus and duodenum effectively resolved the patient's vomiting symptoms.
Detection of Oral Testosterone Undecanoate Administration in UGT2B17 del/del and del/ins Individuals. Part I: Urinary Steroid Profile and IRMS Markers
Authors: Coll Sergi , Shiomura Sho , Alechaga Élida , Bressan Claudia , Monfort Núria , Ventura Rosa , Okano Masato 
Published: December 2024

ABSTRACTThe detection of endogenous anabolic androgenic steroids misuse in Asian population using the Steroidal Module of the Athlete Biological Passport (ABP) is a challenge due to the high prevalence of UGT2B17 gene deletion polymorphism and low levels of testosterone (T) glucuronide. In this study, the capabilities of different approaches based on urine analysis for detecting oral T undecanoate administration were evaluated in 13 Asian volunteers, including 11 subjects with del/del genotype and 2 subjects with del/ins genotype. In this part of the work, the effect on the urinary steroid profile (SP) and the isotope ratio mass spectrometry (IRMS) markers were studied. Results showed that the 5α‐androstane‐3α,17β‐diol/epitestosterone ratio is the most sensitive marker of the SP to detect oral T administration in Asian volunteers. All urines that led to suspicious urinary SP were concluded IRMS positive. However, for some subjects, the ABP Steroidal Module was unable to identify suspicious samples that were still detectable by IRMS. Positive IRMS samples were detected up to 24 h (n = 9), 36 h (n = 3), or 48 h (n = 1) after oral administration. Overall, the urinary SP together with IRMS allowed the detection of T administration in Asian volunteers. However, the detection windows are short, as reported for oral T administration in Caucasian volunteers. These findings highlight the need of implementing additional markers in the Steroidal Module of ABP that could enlarge detection windows.
Design and rationale of the eLym™ System for Decompensation of Excess Lymphatic Fluid via the Thoracic Duct in Acute Heart Failure (DELTA‐HF)
Authors: Biegus Jan , Lindenfeld JoAnn , Felker G. Michael , Bakris George , Jonas Michael , Lala Anuradha , Kereselidze Zviad , Khabeishvili George , Gogorishvili Irakli , Núñez Julio , Bayés‐Genís Antoni , Ponikowski Piotr , Abraham William T. 
Published: December 2024

AbstractAimsThe interstitial space is the major compartment in which the excess fluid is located, forming peripheral congestion in acute decompensated heart failure (ADHF). The lymphatic system is responsible for the constant drainage of the compartment. In ADHF, the inefficiency of this system causes extravascular fluid accumulation, underscoring the crucial role of lymphatic system failure in ADHF's pathophysiology. The eLym™ System is a transcutaneous device designed to facilitate lymph drainage by creating a low‐pressure zone in the thoracic duct area, theoretically allowing more efficient decompression of the lymphatic system.Methods and ResultsThe safety and feasibility of the eLym™ System for the Decongestion of Excess Lymphatic Fluid via the Thoracic Duct in Acute Decompensated Heart Failure: DELTA‐HF Study is a prospective, multicentre, single‐arm study designed to evaluate the safety and feasibility of the WhiteSwell eLym™ System in the treatment of fluid overload in ADHF. A maximum of 50 subjects may be enrolled and undergo the treatment. Inclusion criteria include the presence of congestion, a home diuretic dose ≥80 mg furosemide (or equivalent) and elevated natriuretic peptides. The key exclusion criteria include anatomical abnormalities and the inability to undergo systemic anticoagulation. The study endpoints include the safety (short‐ and long‐term) and feasibility of the procedure. Several congestion indexes will be prospectively assessed. Descriptive statistics will summarize the study results. The study was registered in clinicaltrial.gov (NCT05747196).ConclusionsThe results of the DELTA‐HF study will provide information about the safety and feasibility of the eLym™ System and will provide first‐in‐human clinical signals of its use in ADHF patients.
Expanding the Agenda for a More Just Genomics
Authors: Dolan Deanne Dunbar , Pacia Danielle M. , Johnston Josephine , Lee Sandra Soo‐Jin , Cho Mildred K. 
Published: December 2024

AbstractThe integration of genomics into public health and medicine is happening at a faster rate than the accrual of the capabilities necessary to ensure the equitable, global distribution of its clinical benefits. Uneven access to genetic testing and follow‐up care, unequal distribution of the resources required to access and participate in research, and underrepresentation of some descent groups in genetic and clinical datasets (and thus uncertain genetic results for some patients) are just some of the reasons to center justice in genomics. A more just genomics is an imperative rooted in the ethical obligations incurred by a publicly funded science that is reliant on human data. These features of genomics indebt the genomics enterprise and compel the expanded scope of responsibility proposed by the authors of this special report. The report begins to define justice in genomics for different stakeholder groups and proposes substantial shifts in power, resource distribution, scientific practice, and governance that could enable genomics to meet its obligations to humanity.
Confronting the “Weaponization” of Genetics by Racists Online and Elsewhere
Authors: Panofsky Aaron , Dasgupta Kushan , Iturriaga Nicole , Koch Bernard 
Published: December 2024

AbstractGenomics research is regularly appropriated in social and political contexts to publicly legitimize unjust and malicious political views, policies, and actions. In recent years, there have been high‐profile cases of mass shooters, public intellectuals, and political insiders using genomics findings to convince audiences that deadly force and coercive policies against racial minorities are warranted. To create a just genomics, geneticists must consider what makes their research so attractive and adaptable for the legitimization of unjust ends and what they can do to counter such appropriations. We offer insights and recommendations drawing from our research into the many ways online white nationalist and far‐right political movements mobilize genetics research to promote their racist, sexist, antisemitic, and homophobic views. First, geneticists should identify and change routine research practices that feed eugenic thinking. Second, geneticists should adopt creative extra‐scholarly communication efforts to counter the use of their field's research that occurs in nonscholarly spaces. Third, we identify permissive epistemological and professional practices within the genetics field that have enabled such unjust appropriations to thrive, and we recommend strategies for institutional reform.
Rectifying or Reinforcing? The (In)Equity Implications of Recontacting Practices in Genomic Medicine
Authors: Mackley Michael P. , Faghfoury Hanna , Chad Lauren 
Published: December 2024

AbstractThe practice of recontact in genomic medicine has the power to help rectify long‐standing inequities in genetic testing. However, if not delivered systematically, recontacting practices also have the potential to reinforce these same inequities. Recontact, which occurs when contact between a clinician and patient is reinitiated after a relationship has ended, is often in search of or in response to updated interpretation or results. Currently, recontact is happening in a patient‐driven and ad hoc manner, undermining its potential to benefit all patients. In this paper, the authors position justice as an additional argument in favor of systematic recontact and an argument against the predominantly patient‐initiated model. They argue that patients from equity‐deserving groups should be early beneficiaries of an emerging responsibility to recontact patients. The authors share illustrative clinical vignettes and propose role‐specific and systems‐level solutions to rightfully position recontact as a tool to promote a more equitable clinical genomics future.
Where the Genetic Code Meets the Zip Code: Advancing Equity in Rare Disease Genomics
Authors: Wojcik Monica H. , Smith Hadley S. , Fraiman Yarden S. 
Published: December 2024

AbstractThe promise of genomic medicine lies in the opportunity to improve health outcomes via a personalized approach to management, grounded in genetic and genomic variation unique to an individual. However, disparities and inequities mar this remarkable landscape of genomic innovation. Prior efforts to understand these inequities have focused on populations for which genetic testing is relatively protocolized or where test utility varies greatly by ancestry groups, where equitable outcomes are more clearly defined. We therefore consider the current landscape of rare disease genomics, in which diagnostic approaches vary widely and utility remains to be fully understood, and suggest a path forward: how ecosocial theory may be used to guide novel equity‐focused initiatives that incorporate illness narratives to improve population health. We present examples of narrative medicine in rare disease and reimagine the role this discipline may play in genomic sequencing studies, toward incorporation of the unique illness narrative into clinical genetics and genomics practice. Approaches that broaden the definitions of disease and of outcomes of interest will force the field to grapple with its racist history and begin to advance health equity and promote justice so that genomic medicine may truly deliver on its promise.