bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering Low Volume Resuscitants for the Prehospital Care of Severe Hemorrhagic Shock
Authors: Pichon Trey J. , Wang Xu , Mickelson Ethan E. , Huang Wen‐Chia , Hilburg Shayna L. , Stucky Sarah , Ling Melissa , S. John Alexander E. , Ringgold Kristyn M. , Snyder Jessica M. , Pozzo Lilo D. , Lu Maggie , White Nathan J. , Pun Suzie H. 
Published: May 2024

AbstractGlobally, traumatic injury is a leading cause of suffering and death. The ability to curtail damage and ensure survival after major injury requires a time‐sensitive response balancing organ perfusion, blood loss, and portability, underscoring the need for novel therapies for the prehospital environment. Currently, there are few options available for damage control resuscitation (DCR) of trauma victims. We hypothesize that synthetic polymers, which are tunable, portable, and stable under austere conditions, can be developed as effective injectable therapies for trauma medicine. In this work, we design injectable polymers for use as low volume resuscitants (LVRs). Using RAFT polymerization, we evaluate the effect of polymer size, architecture, and chemical composition upon both blood coagulation and resuscitation in a rat hemorrhagic shock model. Our therapy is evaluated against a clinically used colloid resuscitant, Hextend. We demonstrate that a radiant star poly(glycerol monomethacrylate) polymer did not interfere with coagulation while successfully correcting metabolic deficit and resuscitating animals from hemorrhagic shock to the desired mean arterial pressure range for DCR – correcting a 60 % total blood volume (TBV) loss when given at only 10 % TBV. This highly portable and non‐coagulopathic resuscitant has profound potential for application in trauma medicine.
Electrochemical Generation of Aryl Radicals from Organoboron Reagents Enabled by Pulsed Electrosynthesis
Authors: Boudjelel Maxime , Zhong Jessica , Ballerini Lorenzo , Vanswearingen Ian , Al‐Dhufari Rossul , Malapit Christian A. 
Published: May 2024

AbstractAryl radicals play a pivotal role as reactive intermediates in chemical synthesis, commonly arising from aryl halides and aryl diazo compounds. Expanding the repertoire of sources for aryl radical generation to include abundant and stable organoboron reagents would significantly advance radical chemistry and broaden their reactivity profile. While traditional approaches utilize stoichiometric oxidants or photocatalysis to generate aryl radicals from these reagents, electrochemical conditions have been largely underexplored. Through rigorous mechanistic investigations, we identified fundamental challenges hindering aryl radical generation. In addition to the high oxidation potentials of aromatic organoboron compounds, electrode passivation through radical grafting, homocoupling of aryl radicals, and decomposition issues were identified. We demonstrate that pulsed electrosynthesis enables selective and efficient aryl radical generation by mitigating the fundamental challenges. Our discoveries facilitated the development of the first electrochemical conversion of aryl potassium trifluoroborate salts into aryl C−P bonds. This sustainable and straightforward oxidative electrochemical approach exhibited a broad substrate scope, accommodating various heterocycles and aryl chlorides, typical substrates in transition‐metal catalyzed cross‐coupling reactions. Furthermore, we extended this methodology to form aryl C−Se, C−Te, and C−S bonds, showcasing its versatility and potential in bond formation processes.
Fabrication of porous poly(L‐lactide‐co‐ε‐caprolactone) micropowder for microbubble effect and ultrasound‐mediated drug delivery
Authors: Lim Jin Ik 
Published: May 2024

AbstractBiodegradable elastic poly(L‐lactide‐co‐ε‐caprolactone) (PLCL) copolymer (50:50, lactide:caprolactone molar ratio) was synthesized and porous PLCL micropowders was fabricated by a simple method involving rapid cooling of 0.1, 0.5, and 1% (wt/vol) PLCL/dioxane spray into liquid nitrogen. The physicochemical properties of the porous PLCL micropowders were examined by measuring their pore size, pore morphology, and microbead size using a scanning electron microscopy (SEM) and dye and temozolomide (TMZ)‐release testing under ultrasound. Human U‐87MG, glioblastoma (GBM) cell culture tests were performed to evaluate cell cytotoxicity by released drug from PLCL micropowders. In this study, the porous PLCL micropowders prepared from 1 wt%/vol% PLCL solutions showed a highly porous structure, satisfactory mechanical properties, and optimal drug release efficiency compared with those produced from 0.1 or 0.5 wt%/vol% solutions. The results of the accumulated release test with the results of the absorbance of the dye initially applied, it was confirmed that more than 80% of the added dye was trapped inside the micropowder, and clearly GBM cytotoxicity effect could be observed by the released TMZ. The drug release system using micropowders and ultrasound can be applied as a drug supply system for various diseases such as brain tumors with low drug permeability.
Identification of collagen subtypes of gastric cancer for distinguishing patient prognosis and therapeutic response
Authors: Wang Di , Zhang Jing , Wang Jianchao , Cai Zhonglin , Jin Shanfeng , Chen Gang 
Published: May 2024

AbstractBackgroundGastric cancer is a highly heterogeneous disease, presenting a major obstacle to personalized treatment. Effective markers of the immune checkpoint blockade response are needed for precise patient classification. We, therefore, divided patients with gastric cancer according to collagen gene expression to indicate their prognosis and treatment response.MethodsWe collected data for 1250 patients with gastric cancer from four cohorts. For the TCGA‐STAD cohort, we used consensus clustering to stratify patients based on expression levels of 44 collagen genes and compared the prognosis and clinical characteristics between collagen subtypes. We then identified distinct transcriptomic and genetic alteration signatures for the subtypes. We analyzed the associations of collagen subtypes with the responses to chemotherapy, immunotherapy, and targeted therapy. We also established a platform‐independent collagen‐subtype predictor. We verified the findings in three validation cohorts (GSE84433, GSE62254, and GSE15459) and compared the collagen subtyping method with other molecular subtyping methods.ResultsWe identified two subtypes of gastric adenocarcinoma: a high‐expression collagen subtype (CS‐H) and a low‐expression collagen subtype (CS‐L). Collagen subtype was an independent prognostic factor, with better overall survival in the CS‐L subgroup. The inflammatory response, angiogenesis, and phosphoinositide 3‐kinase (PI3K)/Akt pathways were transcriptionally active in the CS‐H subtype, while DNA repair activity was significantly greater in the CS‐L subtype. PIK3CA was frequently amplified in the CS‐H subtype, while PIK3C2A, PIK3C2G, and PIK3R1 were frequently deleted in the CS‐L subtype. CS‐H subtype tumors were more sensitive to fluorouracil, while CS‐L subtype tumors were more sensitive to immune checkpoint blockade. CS‐L subtype was predicted to be more sensitive to HER2‐targeted drugs, and CS‐H subtype was predicted to be more sensitive to vascular endothelial growth factor and PI3K pathway‐targeting drugs. Collagen subtyping also has the potential to be combined with existing molecular subtyping methods for better patient classification.ConclusionsWe classified gastric cancers into two subtypes based on collagen gene expression and validated these subtypes in three validation cohorts. The collagen subgroups differed in terms of prognosis, clinical characteristics, transcriptome, and genetic alterations. The subtypes were closely related to patient responses to chemotherapy, immunotherapy, and targeted therapy.
Treatment and prognosis study of spontaneous rupture hemorrhage in hepatocellular carcinoma: Recommendations for adding the A1 stage to the BCLC staging system
Authors: Ni Qingqiang , Jia Hongtao , Zhang Yazhou , Lu Jun , Chang Hong 
Published: May 2024

AbstractBackgroundThe Barcelona Clinic Liver Cancer (BCLC) staging system is an internationally recognized clinical staging system for hepatocellular carcinoma (HCC). However, this staging system does not address the staging and surgical treatment strategies for patients with spontaneous rupture hemorrhage in HCC. In this study, we aimed to investigate the prognosis of patients with BCLC stage A undergoing liver resection for HCC with spontaneous rupture hemorrhage and compare it with the prognosis of patients with BCLC stage A undergoing liver resection without rupture.MethodsClinical data of 99 patients with HCC who underwent curative liver resection surgery were rigorously followed up and treated at Shandong Provincial Hospital from January 2013 to January 2023. A retrospective cohort study design was used to determine whether the presence of ruptured HCC (rHCC) is a risk factor for recurrence and survival after curative liver resection for HCC. Prognostic comparisons were made between patients with ruptured and non‐ruptured BCLC stage A HCC (rHCC and nrHCC, respectively) who underwent curative liver resection.ResultsrHCC (hazard ratio [HR] = 2.974, [p] = 0.016) and tumor diameter greater than 5 cm (HR = 2.819, p = 0.022) were identified as independent risk factors for overall survival (OS) after curative resection of BCLC stage A HCC. The postoperative OS of the spontaneous rupture in the HCC group (Group I) was shorter than that in the BCLC stage A group (Group II) (p = 0.008). Tumor invasion without penetration of the capsule was determined to be an independent risk factor for recurrence‐free survival (RFS) after liver resection for HCC (HR = 2.584, p = 0.002).ConclusionHCC with concurrent spontaneous rupture hemorrhage is an independent risk factor for postoperative OS after liver resection. The BCLC stage A1 should be added to complement the current BCLC staging system to provide further guidance for the treatment of patients with spontaneous rupture of HCC.
Exploring the perspective of adolescent childhood cancer survivors on follow‐up care and their concerns regarding the transition process—A qualitative content analysis
Authors: Winzig Jana , Inhestern Laura , Sigmund Désirée , Paul Verena , Hail Lesley‐Ann , Rutkowski Stefan , Escherich Gabriele , Bergelt Corinna 
Published: May 2024

AbstractPurposeIn Germany, children diagnosed with cancer survive their initial disease in more than 80%, and the majority will become long‐term survivors. Around the age of 18, survivors are transferred to adult healthcare. The transition can be a critical period in the process of care at which many childhood cancer survivors discontinue to participate in regular follow‐up care. Hence, the objective of the paper was to explore (a) survivors' attitudes towards pediatric follow‐up care and (b) their concerns regarding the transition process to draw conclusions for optimizing pediatric care and transition processes.MethodsWe conducted semi‐structured interviews with 21 adolescent childhood cancer survivors between the ages of 14 and 20. The survivors were recruited via a pediatric oncology department of a university hospital in Germany. Based on the principles of qualitative content analysis, a deductive‐inductive method according to Kuckartz was applied.ResultsBased on the interview guide and derived from the exploratory research questions, two key categories were generated: (a) Survivors' attitudes towards pediatric follow‐up care, which encompasses all formal and emotional aspects of survivors regarding follow‐up care, and (b) their concerns regarding transition from pediatric to adult healthcare, where hindering and facilitating factors for a successful transition occur. Our results show high satisfaction among survivors with follow‐up care. Nevertheless, they wish to be more integrated into processes and the organization of their follow‐up care. Most adolescent survivors do not feel ready for transition.ConclusionThe integration of survivors into the organization processes and routines, and the promotion of emotional detachment from pediatric health care professionals (HCPs) are important to reduce concerns and uncertainties of adolescent survivors regarding the transition process and to promote subjective readiness for transition. To gain confidence in the adult healthcare, it is crucial to provide tailored education depending on individual requirements and needs and to build trusting relationships between survivors and adult HCPs.
Role of melatonin in carcinogenesis and metastasis: From mechanistic insights to intermeshed networks of noncoding RNAs
Authors: Lin Xiukun , Qureshi Muhammad Zahid , Tahir Fatima , Yilmaz Seher , Romero Mirna Azalea , Attar Rukset , Farooqi Ammad A. 
Published: May 2024

AbstractIn recent years, seminal studies have been devoted to unraveling the puzzling mysteries associated with the cancer preventive/inhibitory role of melatonin. Our current knowledge of the translational mechanisms and the detailed structural insights have highlighted the characteristically exclusive role of melatonin in the inhibition of carcinogenesis and metastatic dissemination. This mini‐review outlines recent discoveries related to mechanistic role of melatonin in prevention of carcinogenesis and metastasis. Moreover, another exciting facet of this mini‐review is related to phenomenal breakthroughs linked with regulation of noncoding RNAs by melatonin in wide variety of cancers.
Sequence‐Guided Redesign of an Omega‐Transaminase from Bacillus megaterium for the Asymmetric Synthesis of Chiral Amines
Authors: Xu Zhexian , Xu Jiaqi , Zhang Tao , Wang Ziyuan , Wu Jianping , Yang Lirong 
Published: May 2024

Abstractω‐Transaminases (ω‐TAs) are attractive biocatalysts asymmetrically catalyzing ketones to chiral amines. However, poor non‐native catalytic activity and substrate promiscuity severely hamper its wide application in industrial production. Protein engineering efforts have generally focused on reshaping the substrate‐binding pockets of ω‐TAs. However, hotspots around the substrate tunnel as well as distant sites outside the pockets may also affect its activity. In this study, the ω‐TA from Bacillus megaterium (BmeTA) was selected for engineering. The tunnel mutation Y164F synergy with distant mutation A245T which was acquired through a multiple sequence alignment showed improved soluble expression, a 3.7‐fold higher specific activity and a 19.9‐fold longer half‐life at 45 °C. Molecule Dynamics simulation explains the mechanism of improved catalytic activity, enhanced thermostability and improved soluble expression of BmeTAY164F/A245T(2 M). Finally, the resting cells of 2 M were used for biocatalytic processes. 450 mM of S‐methoxyisopropylamine (S‐MOIPA) was obtained with an ee value of 97.3 % and a conversion rate of 90 %, laying the foundation for its industrial production. Mutant 2 M was also found to be more advantageous in catalyzing the transamination of various ketones. These results demonstrated that sites that are far away from the active center also play an important role in the redesign of ω‐TAs.
Community‐Science‐ Projekte in der Wissenschaft
Authors: Ließmann Fabian , Landsmann Anja , Rossa Jan , Meiler Jens 
Published: May 2024

ZusammenfassungCommunity Science erlebt eine kleine Revolution mit vielen neuen Projekten, die teilweise moderne Computerwissenschaft mit menschlicher Kreativität und Spielen kombiniert. In FoldIt können Spieler Proteine falten, designen und passende Liganden dazu bilden. In DrugIt können sie kleine Moleküle für Zielstrukturen kreieren und somit direkt Einblicke in Konzepte der Arzneistoffentwicklung erhalten und diese direkt unterstützen. Die besten Ergebnisse aus dem Spiel werden in der Forschung analysiert und können sogar in der Wissenschaft publiziert werden.
Landscape features influencing gene flow and connectivity of an endangered passerine
Authors: Bustillo‐de la Rosa Daniel , Barrero Adrián , Traba Juan , García Jesús T. , Morales Manuel B. , Vázquez‐Domínguez Ella 
Published: May 2024

AbstractDispersal of individuals and gene flow are crucial aspects to maintain genetic diversity and viability of populations, especially in the case of threatened species. Landscape composition and structure may facilitate or limit individual movement within and among populations. We used a landscape genetics approach to assess the connectivity patterns of the threatened Dupont's lark (Chersophilus duponti subsp. duponti), considering their genetic patterns and the landscape features associated with its gene flow in Spain. We analysed the genetic relatedness based on 11 species‐specific polymorphic microsatellites on 416 Dupont's lark individuals sampled across peninsular Spain between 2017 and 2019, covering most of the European distribution of the species. To assess the relationship between the landscape composition and the species gene flow, we estimated genetic distance at the individual level (Dps). Next, we built a set of environmental surfaces from two time periods (years 1990 and 2018), based on factors such as land use and topography, influencing individuals' movement. We then obtained resistance surfaces from an optimization process on landscape variables. Landscape genetics analyses were done for single and composite surface models for each year separately. Our findings from both time points show that scatter or mosaic‐structured vegetation composed by low agricultural and tree cover and high presence of sclerophyllous shrubs favoured Dupont's lark dispersal, while dense and continuous tree cover, as well as areas of intensive agriculture, were limiting factors. Our results suggest the importance of steppe habitat patches for the species' establishment and dispersal. In addition, our results provide key information to develop conservation measures, including conserving and restoring steppe habitats as scattered and/or mosaic‐structured vegetation that could warrant the connectivity and persistence of Dupont's lark populations.
Identifying animal behaviours from accelerometers: Improving predictive accuracy of machine learning by refining the variables selected, data frequency, and sample duration
Authors: Dunford Carolyn E. , Marks Nikki J. , Wilson Rory P. , Scantlebury D. Michael 
Published: May 2024

AbstractObserving animals in the wild often poses extreme challenges, but animal‐borne accelerometers are increasingly revealing unobservable behaviours. Automated machine learning streamlines behaviour identification from the substantial datasets generated during multi‐animal, long‐term studies; however, the accuracy of such models depends on the qualities of the training data. We examined how data processing influenced the predictive accuracy of random forest (RF) models, leveraging the easily observed domestic cat (Felis catus) as a model organism for terrestrial mammalian behaviours. Nine indoor domestic cats were equipped with collar‐mounted tri‐axial accelerometers, and behaviours were recorded alongside video footage. From this calibrated data, eight datasets were derived with (i) additional descriptive variables, (ii) altered frequencies of acceleration data (40 Hz vs. a mean over 1 s) and (iii) standardised durations of different behaviours. These training datasets were used to generate RF models that were validated against calibrated cat behaviours before identifying the behaviours of five free‐ranging tag‐equipped cats. These predictions were compared to those identified manually to validate the accuracy of the RF models for free‐ranging animal behaviours. RF models accurately predicted the behaviours of indoor domestic cats (F‐measure up to 0.96) with discernible improvements observed with post‐data‐collection processing. Additional variables, standardised durations of behaviours and higher recording frequencies improved model accuracy. However, prediction accuracy varied with different behaviours, where high‐frequency models excelled in identifying fast‐paced behaviours (e.g. locomotion), whereas lower‐frequency models (1 Hz) more accurately identified slower, aperiodic behaviours such as grooming and feeding, particularly when examining free‐ranging cat behaviours. While RF modelling offered a robust means of behaviour identification from accelerometer data, field validations were important to validate model accuracy for free‐ranging individuals. Future studies may benefit from employing similar data processing methods that enhance RF behaviour identification accuracy, with extensive advantages for investigations into ecology, welfare and management of wild animals.
A Perspective on Centrohexaindane Chemistry and a Deep‐Sleeping “Cartesian” Seed
Authors: Kuck Dietmar 
Published: May 2024

AbstractCentrohexaindane (C41H24), a structurally unique polyaromatic hydrocarbon bearing six mutually fused indane wings stretched out along the Cartesian axes of space, may be viewed as a seed for the construction of covalent and supramolecular three‐dimensional frameworks. A kaleidoscope of established and yet‐to‐be‐explored aspects of centrohexaindane chemistry is presented in this article. After addressing some ideas about the naked centrohexacyclic (and topologically nonplanar) C17‐core, which can be considered a “centrohexaquinacyne”, the diversity of known but mostly unknown functionalization patterns at the framework of centrohexaindane is addressed in increasing order of substitution at the twelve equivalent peripheral positions. The variety of centrohexaindanes bearing three identical groups is displayed including a very first access to a centrohexaindane that bears a C3‐symmetrically functionalized tribenzotriquinacene (TBTQ) unit and, thus, a potential for 3D oligocondensation. The diversity of known tetra‐ and hexasubstituted centrohexaindane derivatives is presented and conceivable synthesis strategies are discussed for even more highly functionalized derivatives. Finally, the successful access to centrohexaindanes with exhaustive functionalization and hydrocarbon extension at the twelve peripheral positions completes this overview on what may be a vastly open field, still.
Volatility forecasting incorporating intraday positive and negative jumps based on deep learning model
Authors: Zhang Yilun , Song Yuping , Peng Ying , Wang Hanchao 
Published: May 2024

AbstractMost existing studies on volatility forecasting have focused on interday characteristics and ignored intraday characteristics of high‐frequency data, especially the asymmetric impact of positive and negative jumps on volatility. In this paper, 5‐min high‐frequency data are used to construct realized volatility which is decomposed into continuous components and jump components with positive and negative directions. Then, this information is combined with the long short‐term memory model for the realized volatility prediction. The empirical analysis demonstrates that negative jumps resulting from negative news have a more significant impact on market volatility than positive jumps. Additionally, the long short‐term memory model, which incorporates positive and negative jump volatility, outperforms traditional econometric and machine learning models in predicting out‐of‐sample volatility. Furthermore, applying the prediction results to value at risk yields a better measurement effect than the generalized autoregressive conditional heteroskedasticity model.