bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of neutrophil activation marker in patients with vitiligo
Authors: El-Sadek Hala M. , Elmadbouly Asmaa A. , Risha Basma E. M. 
Published: August 2024

Abstract
Background
Vitiligo is an inflammatory, autoimmune disorder. Its pathogenesis is unclear. A neutrophil activation marker (calprotectin) is a protein complex present in many different types of cells and may be used as an indicator of inflammation.

Aims
This study is to assess calprotectin levels in non-segmental vitiligo patients and compare them to the severity of the illness to identify potential associations.

Methods
The present inquiry was conducted on thirty non-segmental vitiligo patients and thirty healthy volunteers matched in terms of age and gender. The Vitiligo Area Scoring Index was used to assess the vitiligo severity. Calprotectin levels were measured in serum samples obtained from all participants by Enzyme Linked Immunosorbent Assay.

Results
Compared to controls, non-segmental vitiligo patients had considerably elevated serum calprotectin levels. Additionally, calprotectin levels were shown to have a significant positive association with disease severity (r = 0.833, P = 0.000).

Conclusions
Elevated levels of serum calprotectin in non-segmental vitiligo patients relative to healthy individuals with high sensitivity indicated that it may have a role in the vitiligo pathophysiology and can act as a marker for disease monitoring.
Optimal $$L^{2}$$-growth of the generalized Rosenau equation
Authors: Li Xiaoyan , Ikehata Ryo 
Published: August 2024

AbstractWe report that the quantity measured in the $$L^2$$

L
2

norm of the solution itself of the generalized Rosenau equation, which was completely unknown in this equation, grows in the proper order at time infinity. It is also immediately apparent that this growth aspect does not occur in three or more spatial dimensions, so we will apply the results obtained in this study to provide another proof that Hardy-type inequalities do not hold in the case of one or two spatial dimensions.
Gewalt junger Menschen mit Migrationshintergrund im Amateurfußball
Authors: Kaya Fatih , Uslucan Hacɪ-Halil 
Published: August 2024

ZusammenfassungDie mediale Berichterstattung über den deutschen Amateurfußball wird oft von Spielunterbrechungen aufgrund eskalierender Gewalt begleitet, an der häufig junge Menschen mit Migrationshintergrund beteiligt sind. Dabei werden zum Teil ethnische Stigmatisierungen vorgenommen, gleichwohl die Ursachen dafür komplexer und vielschichtiger sind. Um einen Einblick in die Ursachen zu bekommen, werden in dem folgenden Beitrag individuelle und gesellschaftliche Prozesse erörtert und die Frage aufgeworfen, wie diese auf die Betroffenen wirken. In diesem Kontext wird zudem diskutiert, welche möglichen Präventionsmaßnahmen hier eingeführt werden können.
Enterprise Foundations and Faithful Agency as Drivers of Sustainable Long-Termism in Philanthropy
Authors: Ørberg Mark 
Published: August 2024

AbstractThe literature on enterprise foundations – foundations that own companies – is booming. As something new, this article compares the (civil law) public good enterprise foundation with the (common law) perpetual purpose trust. While the article is focused on Danish and US law, the analysis and discussions are designed to be useful for anyone interested in enterprise foundation law. The article offers insights on enterprise foundations as ownerless special-purpose institutions with legal personhood becoming majority owners of an otherwise traditional enterprise. The article bridges existing comparative law scholarship on civil law foundations and common law trusts in the light of recent developments within enterprise foundations and similar hybrids in Europe and the US. The US Patagonia perpetual purpose trust and the Danish Novo Nordisk enterprise foundation are used as examples of the different approaches in common law and civil law. Although trusts and foundations may functionally appear remarkably similar, significant differences exist. The article discusses a broad range of policy arguments regarding public good variants of the Danish enterprise foundation model. It argues that enterprise foundations may function as drivers of sustainable long-termism in US business and philanthropy, and explains how and why. Particularly, the article highlights that the ‘purpose lock’ and ‘asset lock’ combined with strong supervision powers may deliver a non-profit entity which includes public good distributions as well as responsible and active ownership, taking the hard edges off capitalism. Arguably, the public good enterprise foundation is one of the ‘queens’ of non-profit succession planning.
The associated risk factors for type 2 diabetes mellitus among adults: a cross-sectional study using electronic medical records in the Primary Health Care Corporation, Qatar
Authors: Elshaikh Usra , Elashie Sana , Alhussaini Nour Waleed Zuhair , Yaseen Manar , Mohamed Hafiz Ahmed , Syed Mohamed Ahmed , Zainel Abduljaleel Abdullatif 
Published: August 2024

Abstract
Background
Type 2 diabetes mellitus (T2DM) has a high prevalence in Qatar, necessitating a thorough understanding of its risk factors. This study explored the associations between specific risk factors and T2DM among adults attending Primary Health Care Corporation (PHCC) centers in Qatar.

Methods
Employing a cross-sectional study design, data were extracted from the electronic medical records of individuals aged 18 years and older who visited the PHCC health centers during the year 2017. Data analysis was performed using univariate and multiple regression models.

Results
The study included 127,941 participants, 33% of whom were diagnosed with T2DM. Age was the most significant risk factor, with individuals aged 60 years and older having an adjusted odds ratio (aOR) of 7.53, and those aged 40–59 years having an aOR of 3.55. Sex was also found to influence T2DM risk, as males had an aOR of 1.47. Nationality also played a role, as individuals of southern Asian descent exhibited an increased risk of T2DM, with an aOR of 2.40, while Qataris had an aOR of 1.55. Having high blood pressure was associated with more than doubling the risk of developing T2DM.

Conclusion
This study provides essential epidemiological insights that can inform decision-making related to T2DM in Qatar. Our findings highlight that males over the age of 40, particularly those of South Asian descent with high blood pressure are at increased risk of T2DM. Identifying the major risk factors is essential for the prevention and management of T2DM.
Controls on Upper Ocean Salinity Variability in the Eastern Subpolar North Atlantic During 1992–2017
Authors: Siddiqui Ali H. , Haine Thomas W. N. , Nguyen An T. , Buckley Martha W. 
Published: August 2024

AbstractThe upper ocean salinity in the eastern subpolar North Atlantic undergoes decadal fluctuations. A large fresh anomaly event occurred during 2012–2016. Using the ECCOv4r4 state estimate, we diagnose and compare mechanisms of this low salinity event with those of the 1990s fresh anomaly event. To avoid issues related to the choice of reference salinity values in the freshwater budget, we perform a salt mass content budget analysis of the eastern subpolar North Atlantic. It shows that the recent low salt content anomaly occurs due to the circulation of anomalous salinity by mean currents entering the eastern subpolar basin from its western boundary via the North Atlantic Current. This is in contrast to the early 1990s, when the dominant mechanism governing the low salt content anomaly was the transport of the mean salinity field by anomalous currents.
Fracture Characterization Via AI‐Assisted Analysis of Temperature Logs
Authors: Yang Xiaoyu , Horne Roland N. , Tartakovsky Daniel M. 
Published: August 2024

AbstractFractures control fluid flow, mass transport, and heat transfer in a geothermal reservoir. This makes accurate characterization of fracture networks a prerequisite for optimal design and control of a reservoir's exploitation. We develop a deep‐learning procedure to identify fracture locations via interpretation of temporally and spatially continuous downhole temperature measurements. A long short‐term memory fully convolutional network (LSTM‐FCN) is used both to capture long‐term dependencies in sequential temperature data and to distill local features around fractures. A wellbore and fractured‐reservoir thermal model is established to generate temperature data for network training. The trained LSTM‐FCN exhibits a unique ability to detect multiple fractures intersecting a borehole. We use the LSTM‐FCN algorithm to evaluate the effectiveness of different‐stage wellbore temperature measurements on fracture detection in a complex fractured system. Our experiments reveal that the use of various‐stage temperature information as an input feature set improves the robustness of fracture detection to noise interference. This study indicates the practical feasibility of obtaining accurate fracture‐network reconstructions from temperature signals, at reasonable computational cost.
A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia
Authors: Koedijk Joost B. , van der Werf Inge , Penter Livius , Vermeulen Marijn A. , Barneh Farnaz , Perzolli Alicia , Meesters-Ensing Joyce I. , Metselaar Dennis S. , Margaritis Thanasis , Fiocco Marta , de Groot-Kruseman Hester A. , Moeniralam Rubina , Bang Christensen Kristina , Porter Billie , Pfaff Kathleen , Garcia Jacqueline S. , Rodig Scott J. , Wu Catherine J. , Hasle Henrik , Nierkens Stefan , Belderbos Mirjam E. , Zwaan C. Michel , Heidenreich Olaf 
Published: August 2024

AbstractBecause of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2- to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8+ T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease.
Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation
Authors: Dembitz Vilma , Lawson Hannah , Burt Richard , Natani Sirisha , Philippe Céline , James Sophie C. , Atkinson Samantha , Durko Jozef , Wang Lydia M. , Campos Joana , Magee Aoife M. S. , Woodley Keith , Austin Michael J. , Rio-Machin Ana , Casado Pedro , Bewicke-Copley Findlay , Rodriguez Blanco Giovanny , Pereira-Martins Diego , Oudejans Lieve , Boet Emeline , von Kriegsheim Alex , Schwaller Juerg , Finch Andrew J. , Patel Bela , Sarry Jean-Emmanuel , Tamburini Jerome , Schuringa Jan Jacob , Hazlehurst Lori , Copland III John A. , Yuneva Mariia , Peck Barrie , Cutillas Pedro , Fitzgibbon Jude , Rouault-Pierre Kevin , Kranc Kamil , Gallipoli Paolo 
Published: August 2024

AbstractIdentification of specific and therapeutically actionable vulnerabilities, ideally present across multiple mutational backgrounds, is needed to improve acute myeloid leukemia (AML) patients’ outcomes. We identify stearoyl-CoA desaturase (SCD), the key enzyme in fatty acid (FA) desaturation, as prognostic of patients' outcomes and, using the clinical-grade inhibitor SSI-4, show that SCD inhibition (SCDi) is a therapeutic vulnerability across multiple AML models in vitro and in vivo. Multiomic analysis demonstrates that SCDi causes lipotoxicity, which induces AML cell death via pleiotropic effects. Sensitivity to SCDi correlates with AML dependency on FA desaturation regardless of mutational profile and is modulated by FA biosynthesis activity. Finally, we show that lipotoxicity increases chemotherapy-induced DNA damage and standard chemotherapy further sensitizes AML cells to SCDi. Our work supports developing FA desaturase inhibitors in AML while stressing the importance of identifying predictive biomarkers of response and biologically validated combination therapies to realize their full therapeutic potential.
Microfluidic QCM enables ultrahigh Q-factor: a new paradigm for in-liquid gravimetric sensing
Authors: Zhao Yicheng , Parlak Zehra , Yu Wenjun , French Daniel , Aquino Wilkins , Zauscher Stefan 
Published: August 2024

AbstractAcoustic gravimetric biosensors attract attention due to their simplicity, robustness, and low cost. However, a prevailing challenge in these sensors is dissipation which manifests in a low quality factor (Q-factor), which limits their sensitivity and accuracy. To mitigate dissipation of acoustic sensors in liquid environments we introduce an innovative approach in which we combine microfluidic channels with gravimetric sensors. To implement this novel paradigm we chose the quartz crystal microbalance (QCM) as our model system, owing to its wide applicability in biosensing and the relevance of its operating principles to other types of acoustic sensors. We postulate that the crucial determinant for enhancing performance lies in the ratio between the width of the microfluidic channels and the wavelength of the pressure wave generated by the oscillating channel side walls driven by the QCM. Our hypothesis is supported by finite element analysis (FEA) and dimensional studies, which revealed two key factors that affect device performance: (1) the ratio of the channel width to the pressure wavelength ($$W/{\lambda }_{{\rm {p}}}$$

W
/

λ

p

) and (2) the ratio of the channel height to the shear evanescent wavelength ($$H/{\lambda }_{{\rm {s}}}$$

H
/

λ

s

). To validate our hypothesis, we fabricated a microfluidic QCM (µ-QCM) and demonstrated a remarkable 10-fold improvement in its dissipation when compared to conventional QCM. The novel microfluidic approach offers several additional advantages, such as direct data interpretation, reduced volume requirement for sample liquids, and simplified temperature control, augmenting the sensor’s overall performance. By fostering increased sensitivity, accuracy, and ease of operation, our novel paradigm unlocks new possibilities for advancing gravimetric technologies, potentially for biosensing applications.
Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immunotherapy based on multi-modal data
Authors: Chen Zifan , Chen Yang , Sun Yu , Tang Lei , Zhang Li , Hu Yajie , He Meng , Li Zhiwei , Cheng Siyuan , Yuan Jiajia , Wang Zhenghang , Wang Yakun , Zhao Jie , Gong Jifang , Zhao Liying , Cao Baoshan , Li Guoxin , Zhang Xiaotian , Dong Bin , Shen Lin 
Published: August 2024

AbstractThe sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P < 0.05). These findings not only highlight the significance of multi-modal data analysis in enhancing treatment evaluation and personalized medicine for HER2-positive gastric cancer, but also the potential and clinical value of our model.
Tert promotes cardiac regenerative repair after MI through alleviating ROS-induced DNA damage response in cardiomyocyte
Authors: Wei Xiaomin , Zhou Yilin , Shao Enge , Shi Xiaoran , Han Yuan , Zhang Yeshen , Wei Guoquan , Zheng Hao , Huang Senlin , Chen Yanmei , Sun Jie , Liao Yulin , Liao Wangjun , Wang Yanbing , Bin Jianping , Li Xinzhong 
Published: August 2024

AbstractTelomerase reverse transcriptase (Tert) has been found to have a protective effect on telomeric DNA, but whether it could improve the repair of reactive oxygen species (ROS)-induced DNA damage and promote myocardial regenerative repair after myocardial infarction (MI) by protecting telomeric DNA is unclear. The immunofluorescence staining with TEL-CY3 and the TeloTAGGG Telomerase PCR ELISA kit were used to show the telomere length and telomerase activity. The heart-specific Tert-deletion homozygotes were generated by using commercial Cre tool mice and flox heterozygous mice for mating. We measured the telomere length and telomerase activity of mouse cardiomyocytes (CMs) at different days of age, and the results showed that they were negatively correlated with age. Overexpressed Tert could enhance telomerase activity and lengthen telomeres, thereby repairing the DNA damage induced by ROS and promoting CM proliferation in vitro. The in vivo results indicated that enhanced Tert could significantly improve cardiac function and prognosis by alleviating CM DNA damage and promoting angiogenesis post-MI. In terms of mechanism, DNA pulldown assay was used to identify that nuclear ribonucleoprotein A2B1 (hnRNPA2B1) could be an upstream regulator of Tert in CMs. Overexpressed Tert could activate the NF-κB signaling pathway in CMs and bind to the VEGF promoter in the endothelium to increase the VEGF level. Further immunoblotting showed that Tert protected DNA from ROS-induced damage by inhibiting ATM phosphorylation and blocking the Chk1/p53/p21 pathway activation. HnRNPA2B1-activated Tert could repair the ROS-induced telomeric DNA damage to induce the cell cycle re-entry in CMs and enhance the interaction between CMs and endothelium, thus achieving cardiac regenerative repair after MI.
Single-cell transcriptomics reveal transcriptional programs underlying male and female cell fate during Plasmodium falciparum gametocytogenesis
Authors: Mohammed Mubasher , Dziedziech Alexis , Macedo Diego , Huppertz Frederik , Veith Ylva , Postel Zoé , Christ Elena , Scheytt Richard , Slotte Tanja , Henriksson Johan , Ankarklev Johan 
Published: August 2024

AbstractThe Plasmodium falciparum life cycle includes obligate transition between a human and mosquito host. Gametocytes are responsible for transmission from the human to the mosquito vector where gamete fusion followed by meiosis occurs. To elucidate how male and female gametocytes differentiate in the absence of sex chromosomes, we perform FACS-based cell enrichment of a P. falciparum gametocyte reporter line followed by single-cell RNA-seq. In our analyses we define the transcriptional programs and predict candidate driver genes underlying male and female development, including genes from the ApiAP2 family of transcription factors. A motif-driven, gene regulatory network analysis indicates that AP2-G5 specifically modulates male development. Additionally, genes linked to the inner membrane complex, involved in morphological changes, are uniquely expressed in the female lineage. The transcriptional programs of male and female development detailed herein allow for further exploration of the evolution of sex in eukaryotes and provide targets for future development of transmission blocking therapies.
Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted/founder sensitivity to broadly neutralizing antibodies
Authors: Parthasarathy Durgadevi , Pothula Karunakar Reddy , Ratnapriya Sneha , Cervera Benet Héctor , Parsons Ruth , Huang Xiao , Sammour Salam , Janowska Katarzyna , Harris Miranda , Sodroski Joseph , Acharya Priyamvada , Herschhorn Alon 
Published: August 2024

AbstractHIV-1 envelope glycoproteins (Envs) of most primary HIV-1 strains exist in closed conformation and infrequently sample open states, limiting access to internal epitopes. Thus, immunogen design aims to mimic the closed Env conformation as preferred target for eliciting broadly neutralizing antibodies (bnAbs). Here we identify incompletely closed Env conformations of 6 out of 13 transmitted/founder (T/F) strains that are sensitive to antibodies that recognize internal epitopes typically exposed on open Envs. A 3.6 Å cryo-electron microscopy structure of unliganded, incompletely closed T/F Envs (1059-SOSIP) reveals protomer motion that increased sampling of states with incompletely closed trimer apex. We reconstruct de novo the post-transmission evolutionary pathway of a second T/F. Evolved viruses exhibit increased Env resistance to cold, soluble CD4 and 19b, all of which correlate with closing of the adapted Env trimer. Lastly, we show that the ultra-broad N6 bnAb efficiently recognizes different Env conformations and exhibits improved antiviral breadth against VRC01-resistant Envs isolated during the first-in-humans antibody-mediated-prevention trial.
Trophic evolution in ornithopod dinosaurs revealed by dental wear
Authors: Ősi Attila , Barrett Paul M. , Nagy András Lajos , Szenti Imre , Vásárhelyi Lívia , Magyar János , Segesdi Martin , Csiki-Sava Zoltán , Botfalvai Gábor , Jó Viviána 
Published: August 2024

AbstractOrnithopod dinosaurs evolved numerous craniodental innovations related to herbivory. Nonetheless, the relationship between occlusion, tooth wear rate, and tooth replacement rate has been neglected. Here, we reconstruct tooth wear rates by measuring tooth replacement rates and tooth wear volumes, and document their dental microwear. We demonstrate that total tooth volume and rates of tooth wear increased steadily during ornithopod evolution, with deeply-nested taxa wearing up to 3360 mm3 of tooth volume/day. Increased wear resulted in asymmetric tooth crown formation with uneven von Ebner line increment width by the Late Jurassic, and in faster tooth replacement rates in multiple lineages by the mid-Cretaceous. Microwear displays a contrasting pattern, with decreasing complexity and pit percentages in deeply-nested and later-occurring taxa. We hypothesize that early ornithopods were browsers and/or frugivores but deeply nested iguanodontians were bulk-feeders, eating tougher, less nutritious plants; these trends correlate with increasing body mass and longer gut passage times.