bluuebunny/crossref_metadata_2025_split huggingface dataset:
Base-to-apex Gradient Pattern Assessed by Cardiovascular Magnetic Resonance in Takotsubo Cardiomyopathy
Authors: Cau Riccardo , Muscogiuri Giuseppe , Palmisano Vitanio , Porcu Michele , Pintus Alessandra , Montisci Roberta , Mannelli Lorenzo , Suri Jasjit S. , Francone Marco , Saba Luca 
Published: October 2023

Objectives:
The purpose of this study was to investigate the base-to-apex gradient strain pattern as a noncontrast cardiovascular magnetic resonance (CMR) parameter in patients with Takotsubo cardiomyopathy (TTC) and determine whether this pattern may help discriminate TTC from patients with anterior myocardial infarction (AMI).

Materials and Methods:
A total of 80 patients were included in the analysis: 30 patients with apical ballooning TTC and 50 patients with AMI. Global and regional ventricular function, including longitudinal (LS), circumferential (CS), and radial strain (RS), were assessed using CMR. The base-to-apex LS, RS, and CS gradients, defined as the peak gradient difference between averaged basal and apical strain, were calculated.

Results:
The base-to-apex RS gradient was impaired in TTC patients compared with the AMI group (14.04 ± 15.50 vs. -0.43 ± 11.59, P=0.001). Conversely, there were no significant differences in the base-to-apex LS and CS gradients between the AMI group and TTC patients (0.14 ± 2.71 vs. -1.5 ± 3.69, P=0.054: -0.99 ± 6.49 vs. ±1.4 ± 5.43, P=0.47, respectively). Beyond the presence and extension of LGE, base-to-apex RS gradient was the only independent discriminator between TTC and AMI (OR 1.28; 95% CI 1.08, 1.52, P=0.006) in multivariate logistic regression analysis.

Conclusion:
The findings of this study suggest that the pattern of regional myocardial strain impairment could serve as an additional noncontrast CMR tool to refine the diagnosis of TTC. A pronounced base-to-apex RS gradient may be a specific left ventricle strain pattern of TTC.
Acute Vigorous Exercise Decreases Subsequent Non-Exercise Physical Activity and Body Temperature Linked to Weight Gain
Authors: Funabashi Daisuke , Dobashi Shohei , Sameshima Kazuki , Sagayama Hiroyuki , Nishijima Takeshi , Matsui Takashi 
Published: October 2023

AbstractPurposeExercise benefits the body and mind, but its weight loss effect is less than generally expected. Although this phenomenon is likely primarily due to a decrease in non-exercise physical activity (NEPA) resulting in a decrease in non-exercise activity thermogenesis, the underlying mechanisms and effects of exercise intensity remain unknown. Here we show that acute vigorous exercise decreases subsequent NEPA and body temperature (BT) in association with body weight gain.MethodsAdult male C57BL/6J mice were categorized into three groups: sedentary, moderate exercise, and vigorous exercise, with exercise groups undergoing a 30 min treadmill session. Using an intraperitoneally implanted activity monitor, NEPA and BT were monitored for two days before and three days after exercise. The daily synchrony between NEPA and BT was evaluated using a cross-correlation function. Plasma corticosterone was also detected 6 and 24 h after exercise.ResultsNotably, Only the vigorous exercise group exhibited a decline in both NEPA and BT, resulting in body weight gain the following day, despite no observed changes in food intake. Furthermore, vigorous exercise induces a distinct delay in the daily dynamics of NEPA compared to BT. A positive correlation was observed between plasma corticosterone levels and changes in NEPA levels before and after exercise across all exercise groups.ConclusionsOur findings provide evidence for vigorous exercise-specific reduction in subsequent NEPA, BT, and their synchrony linked to weight gain, likely due to the disturbed circadian rhythm of corticosterone. This ultimately redefines the significance of exercise intensity in beneficial effects beyond the energy expenditure of the exercise itself.
PerSEveML: A Web-Based Tool to Identify Persistent Biomarker Structure for Rare Events Using Integrative Machine Learning Approach
Authors: Dutta Sreejata , Mudaranthakam Dinesh Pal , Li Yanming , Sardiu Mihaela E. 
Published: October 2023

AbstractOmics datasets often pose a computational challenge due to their high dimensionality, large size, and non-linear structures. Analyzing these datasets becomes especially daunting in the presence of rare events. Machine learning (ML) methods have gained traction for analyzing rare events, yet there remains a limited exploration of bioinformatics tools that integrate ML techniques to comprehend the underlying biology. Expanding upon our previously developed computational framework of an integrative machine learning approach1, we introduce PerSEveML, an interactive web-based that uses crowd-sourced intelligence to predict rare events and determine feature selection structures. PerSEveML provides a comprehensive overview of the integrative approach through evaluation metrics that help users understand the contribution of individual ML methods to the prediction process. Additionally, PerSEveML calculates entropy and rank scores, which visually organize input features into a persistent structure of selected, unselected, and fluctuating categories that help researchers uncover meaningful hypotheses regarding the underlying biology. We have evaluated PerSEveML on three diverse biologically complex data sets with extremely rare events from small to large scale and have demonstrated its ability to generate valid hypotheses. PerSEveML is available athttps://biostats-shinyr.kumc.edu/PerSEveML/andhttps://github.com/sreejatadutta/PerSEveML.
Histone deacetylase inhibition mitigates cognitive deficits and astrocyte dysfunction induced by Aβ oligomers
Authors: Morgado Juliana , Diniz Luan Pereira , Araujo Ana Paula Bergamo , Antônio Leticia Maria da Silva , Araujo Hanna Paola Mota , Pinheiro Pedro de Sena Murteira , Sagrillo Fernanda Savacini , Cesar Gabriele Vargas , Ferreira Sérgio T. , Figueiredo Cláudia Pinto , Fraga Carlos Alberto Manssour , Gomes Flávia Carvalho Alcantara 
Published: October 2023

ABSTRACTInhibitors of histone deacetylases (iHDACs) are promising drugs for neurodegenerative diseases. We have evaluated the therapeutic potential of the new iHDAC6 LASSBio-1911 in Aβ oligomer (AβO) toxicity models and astrocytes, key players in neuroinflammation and Alzheimer’s disease (AD). Astrocyte phenotype and synapse density were evaluated by flow cytometry, Western blotting, immunofluorescence and qPCR, in vitro and in mice. Cognitive function was evaluated by behavioural assays using a mouse model of intracerebroventricular infusion of AβO. LASSBio-1911 modulates reactivity and synaptogenic potential of cultured astrocytes and improves synaptic markers in cultured neurons and in mice. It prevents AβO-triggered astrocytic reactivity in mice and enhances the neuroprotective potential of astrocytes. LASSBio-1911 improves behavioural performance and rescues synaptic and memory function in AβO-infused mice. These results contribute to unveiling the mechanisms underlying astrocyte role in AD and provide the rationale for using astrocytes as targets to new drugs for AD.
Extracting diamonds: Identifiability of 4-node cycles in level-1 phylogenetic networks under a pseudolikelihood coalescent model
Authors: Tiley George , Solís-Lemus Claudia 
Published: October 2023

AbstractHere, we investigate the (generic) identifiability of the position of the hybrid node in a 4-node hybridization cycle in a semi-directed level-1 phylogenetic network. While generic identifiability is easily attained under non-restrictive assumptions such ast∈ (0, ∞) for all branches andγ∈ (0, 1) for the inheritance probability of the hybrid edges, simulations show that accurate detection of these cycles can be complicated by inadequate sampling, small sample size or gene tree estimation error. We identify practical advice for evolutionary biologists on best sampling strategies to improve the detection of this type of hybridization cycle.
Biophysical cartography of the native and human-engineered antibody landscapes quantifies the plasticity of antibody developability
Authors: Bashour Habib , Smorodina Eva , Pariset Matteo , Zhong Jahn , Akbar Rahmad , Chernigovskaya Maria , Quý Khang Lê , Snapkov Igor , Rawat Puneet , Krawczyk Konrad , Sandve Geir Kjetil , Gutierrez-Marcos Jose , Gutierrez Daniel Nakhaee-Zadeh , Andersen Jan Terje , Greiff Victor 
Published: October 2023

AbstractDesigning effective monoclonal antibody (mAb) therapeutics faces a multi-parameter optimization challenge known as “developability”, which reflects an antibody’s ability to progress through development stages based on its physicochemical properties. While natural antibodies may provide valuable guidance for mAb selection, we lack a comprehensive understanding of natural developability parameter (DP) plasticity (redundancy, predictability, sensitivity) and how the DP landscapes of human-engineered and natural antibodies relate to one another. These gaps hinder fundamental developability profile cartography. To chart natural and engineered DP landscapes, we computed 40 sequence- and 46 structure-based DPs of over two million native and human-engineered single-chain antibody sequences. We found lower redundancy among structure-based compared to sequence-based DPs. Sequence DP sensitivity to single amino acid substitutions varied by antibody region and DP, and structure DP values varied across the conformational ensemble of antibody structures. Sequence DPs were more predictable than structure-based ones across different machine-learning tasks and embeddings, indicating a constrained sequence-based design space. Human-engineered antibodies were localized within the developability and sequence landscapes of natural antibodies, suggesting that human-engineered antibodies explore mere subspaces of the natural one. Our work quantifies the plasticity of antibody developability, providing a fundamental resource for multi-parameter therapeutic mAb design.
Fungal infection alters collective nutritional intake of ant colonies
Authors: Csata Enikő , Pérez-Escudero Alfonso , Laury Emmanuel , Leitner Hanna , Latil Gérard , Heinze Jürgen , Simpson Stephen J. , Cremer Sylvia , Dussutour Audrey 
Published: October 2023

SummaryIn many animals, parasitic infections impose significant fitness costs [1–6]. Animals are known to alter their feeding behavior when infected to help combat various parasites [7–12]. For instance, they can adjust nutrient intake to support their immune system [13,14]. However, parasites can also manipulate host foraging behavior to increase their own development, survival and transmission [15–18]. The mechanisms by which nutrition influences host-parasite interactions are still not well understood. Until now, studies that examine the impact of diet on infection have mainly focused on the host, and less on the parasite [12,13, 19–25]. Using Nutritional Geometry [26], we investigated the role of key nutrients: amino acids and carbohydrates, in a host-parasite system: the Argentine ant,Linepithema humile,and the entomopathogenic fungus,Metarhizium brunneum. We first established that the fungus grew and reproduced better on diets comprising four times less amino acids than carbohydrates (1:4 AA:C ratio). Second, when facing food combinations, the fungus exploited the two complementary food resources to reach the same performance as on this optimal diet, revealing the ability of fungal pathogens to solve complex nutritional challenges. Third, when ants were fed on this optimal fungal diet, their lifespan decreased when healthy, yet not whenMetarhizium-infected, compared to their favored carbohydrate-rich diet. Interestingly, when the ants were given a binary choice between different diets, the foragers of uninfected colonies avoided intake of the fungal optimum diet, whilst choosing it when infected. Experimental disentanglement of full pathogenic infection and pure immune response to fungal cell wall material, combined with immune measurements, allowed us to conclude that this change of nutritional choice in infected ants did not result from pathogen manipulation but likely represents a compensation of the host to counterbalance the cost of using amino acids during the immune response. The observed change in foraging behavior in infected colonies towards an otherwise harmful diet (self-medication), suggests a collective compensatory mechanism for the individual cost of immunity. In short, we demonstrated that infected ants converge on a diet that is proven to be costly for survival in the long term but that could help them fight infection in the short term.HighlightsThe insect-pathogenic fungusMetarhizium brunneumperforms best on protein-rich diets and is able to solve complex nutritional challengesWhile harmful to healthy ants, protein-rich diets did not shorten infected ants’ lifespanContrary to healthy ants, when given a choice, infected and immune-stimulated ants choose a protein-rich diet
Impact of a tilted coverslip on two-photon and STED microscopy
Authors: Le Bourdelles Guillaume , Mercier Luc , Roos Johannes , Bancelin Stephane , Nägerl U. Valentin 
Published: October 2023

AbstractThe advent of super-resolution microscopy has opened up new avenues to unveil brain structures with unprecedented spatial resolution in the living state. Yet, its application to live animals remains a genuine challenge. Getting optical access to the brainin vivorequires the use of a ‘cranial window’, whose mounting greatly influences image quality. Indeed, the coverslip used for the cranial window should lie as orthogonal as possible to the optical axis of the objective, or else significant optical aberrations occur. In this work, we assess the effect of the tilt angle of the coverslip on STED and two-photon microscopy, in particular image brightness and spatial resolution. We then propose an approach to measure and reduce the tilt using a simple device added to the microscope, which can ensure orthogonality with a precision of 0.07°.
The effect of problem-based learning on improving problem-solving, self-directed learning, and critical thinking ability for the pharmacy students
Authors: Zhao Yi-Jing , Huang Feng-Qing , Liu Qun , Li Ying , Alolga Raphael N , Zhang Lei , Ma Gaoxiang 
Published: October 2023

AbstractObjectiveThis study aimed to comprehensively evaluate the effect of PBL on problem-solving, self-directed learning, and critical thinking ability of pharmaceutical students through a randomized controlled trial (RCT) and meta-analysis of RCTs.MethodsIn 2021, 57 third-year pharmacy students from China Pharmaceutical University were randomly divided into a PBL group and a lecture-based learning (LBL) group. Mean scores were compared between the two groups for problem-solving, self-directed learning, communication skills, critical thinking, and final exam grades. Students’ feedback on the implementation of PBL was also collected. A meta-analysis was subsequently performed on eight studies involving 1,819 students.ResultsThe PBL group had significantly higher mean scores for problem-solving (8.43±1.56) and self-directed learning (7.39±1.19) than the LBL group (7.02±1.72 and 6.41±1.28, respectively). The PBL group also showed better communication skills (8.86±1.47) than the LBL group (7.68±1.89). The mean level of critical thinking was significantly higher in the PBL group than the LBL group (p=0.02). The PBL group also had better final exam grades (79.86±1.38) compared to the LBL group (68.1±1.76). Student feedback on PBL implementation was positive. The subsequent meta-analysis confirmed these findings.ConclusionThis study found that PBL is an effective teaching method for pharmacy students.
The CUT&RUN Greenlist: genomic regions of consistent noise are effective normalizing factors for quantitative epigenome mapping
Authors: de Mello Fabio N. , Tahira Ana C. , Berzoti-Coelho Maria Gabriela , Verjovski-Almeida Sergio 
Published: October 2023

AbstractCleavage Under Targets and Release Using Nuclease (CUT&RUN) is a recent development for epigenome mapping, but its unique methodology can hamper proper quantitative analyses. As traditional normalization approaches have been shown to be inaccurate, we sought to determine endogenous normalization factors based on regions of constant nonspecific signal. This constancy was determined by applying Shannon’s information entropy, and the set of normalizer regions, which we named the “greenlist,” was extensively validated using publicly available datasets. We demonstrate here that the greenlist normalization outperforms the current top standards, and remains consistent across different experimental set-ups, cell lines, and antibodies; the approach can even be applied to other organisms or to CUT&Tag. Requiring no additional experimental steps and no added cost, this approach can be universally applied to CUT&RUN experiments to greatly minimize the interference of technical variation over the biological epigenome changes of interest.
Investigation of 3D Printed Bioresorbable Vascular Scaffold Crimping Behavior
Authors: Collins Caralyn P. , Leng Junqing , Fu Rao , Ding Yonghui , Ameer Guillermo , Sun Cheng 
Published: October 2023

AbstractThe rise in additive manufacturing (AM) offers myriad opportunities for 3D-printed polymeric vascular scaffolds, such as customization and on-the-spot manufacturing,in vivobiodegradation, incorporation of drugs to prevent restenosis, and visibility under X-ray. To maximize these benefits, informed scaffold design is critical. Polymeric bioresorbable vascular scaffolds (BVS) must undergo significant deformation prior to implantation in a diameter-reduction process known as crimping which enables minimally invasive surgery. Understanding the behavior of vascular scaffolds in this step provides twofold benefits: first, it ensures the BVS is able to accommodate stresses occurring during this process to prevent failure, and further, it provides information on the radial strength of the BVS, a key metric to understanding its post-implant performance in the artery. To capitalize on the fast manufacturing speed AM provides, a low time cost solution for understanding scaffold performance during this step is necessary. Through simulation of the BVS crimping process in ABAQUS using experimentally obtained bulk material properties, we have developed a qualitative analysis tool which is capable of accurately comparing relative performance trends of varying BVS designs during crimping in a fraction of the time of experimental testing, thereby assisting in the integration of informed design into the additive manufacturing process.
Inhalation Delivered RNA Aptamer for Therapeutics against SARS-CoV2
Authors: Song Minsun , Zhou Jiehua , Herrera Alberto , Baines Peter , Rossi John J. 
Published: October 2023

AbstractThe continual emergence and re-emergence of infectious diseases has led to a pressing need for the development of swift and targeted therapeutic interventions. SARS-CoV-2, the causative agent of COVID-19, is a prime example of such a rapidly spreading virus[1]. The global crisis caused by this virus has propelled researchers to explore and adopt novel techniques in the hopes of effectively combating its spread[2]. One such innovative approach is the use of aptamers—single-stranded RNA molecules that can bind targets with high specificity.
Potential Impact of a Diagnostic Test for Detecting Prepatent Guinea Worm Infections in Dogs
Authors: Smalley Hannah , Keskinocak Pinar , Swann Julie , Hanna Christopher , Weiss Adam 
Published: October 2023

ABSTRACTChad has seen a considerable reduction in cases of Guinea worm disease (or dracunculiasis) in domestic dogs in recent years. Tethering of dogs and application of Abate®larvicide to water sources appear to have contributed to this progress, but with 767 reported dog cases in 2021, accelerating elimination of the disease in Chad may require additional tools. We investigate the potential benefits of a hypothetical diagnostic test which could be capable of detecting pre-patent infections in dogs. We adapt an agent-based simulation model for forecasting the impact of interventions on guinea worm disease in dogs to examine the interaction of multiple test factors including test accuracy, when the test can detect infection, dog selection, and dog-owner compliance with tethering recommendations. We find that a diagnostic test could be successful if used in conjunction with existing interventions, and elimination can be achieved within two years with 80% or higher test sensitivity, 90% or higher specificity, systematic testing of each dog twice per year, and over 90% long-term tethering compliance when a dog tests positive or a worm is emerging. Because of the long incubation period of Guinea worm disease (10-14 months) and the fact that no treatment exists, the benefits of the test rely on the testing rollout and response of dog owners. If the test could estimate the timing of worm emergence, long-term tethering could be eliminated and infected dogs could be tethered only when the worms are expected, minimizing the related resources (human and financial) to support the intervention.
IGF2 Peptide-Based LYTACs for Targeted Degradation of Extracellular and Transmembrane Proteins
Authors: Mikitiuk Michał , Barczyński Jan , Bielski Przemysław , Arciniega Marcelino , Błaszkiewicz Urszula , Hec Aleksandra , Lipińska Andrea D. , Rychłowski Michał , Holak Tad A. , Sitar Tomasz 
Published: October 2023

AbstractLysosome Targeting Chimeras (LYTACs) have recently been developed to facilitate lysosomal degradation of specific extracellular and transmembrane molecular targets. However, the LYTAC particles described to date are based on glycopeptide conjugates, which are difficult to prepare and produce on a large scale. Here we report the development of pure protein LYTACs based on the non-glycosylated IGF2 peptides, which can be readily produced in virtually any facility capable of monoclonal antibody production. These chimeras utilize the IGF2R/CI-M6PR pathway for lysosomal shuttling and, in our illustrative example, target programmed death ligand 1 (PD-L1), eliciting physiological effects analogous to immune checkpoint blockade. Results from in vitro assays significantly exceed the effects of anti-PD-L1 antibodies alone.
The mtDNA-derived lncMtDloop promotes mitochondrial homeostasis maintenance and implications in AD
Authors: Xiong Wandi , Xu Kaiyu , Sun Jacquelyne Ka-Li , Liu Siling , Zhao Baizhen , Shi Jie , Herrup Karl , Chow Hei-Man , Lu Lin , Li Jiali 
Published: October 2023

AbstractMaintaining mitochondrial homeostasis stands as a critical factor for cell survival and the health of organisms, as evidenced by the links between mitochondrial dysfunction and a spectrum of diseases, including Alzheimer’s disease (AD). Here we report thatlncMtDloop, a lncRNA originating from the mtDNA D-loop, upholds mitochondrial homeostasis.LncMtDloopdemonstrates an affinity for mitochondrial transcription factor A (TFAM), thereby facilitating TFAM’s recruitment to mtDNA promoters and enhancing gene transcription. We further observed decreasedlncMtDloopexpression in the brains of human AD patients and 3xTg mice. Through the introduction of allotropiclncMtDloopwith the 3’UTR ofMRPS12, a significant improvement in mitochondrial homeostasis and a concurrent amelioration of AD-like pathology were found, which exerts a positive influence on synaptic plasticity and behavioral deficits observed in AD mice. Our study provides mechanistic insights intolncMtDloopas a regulator of mitochondrial homeostasis, shedding light on a perspective regarding its contribution to Alzheimer’s pathogenesis.