bluuebunny/crossref_metadata_2025_split huggingface dataset:
The HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma
Authors: Yan Fangfang , Jiang Vivian , Jordan Alexa , Che Yuxuan , Liu Yang , Cai Qingsong , Xue Yu , Li Yijing , McIntosh Joseph , Chen Zhihong , Vargas Jovanny , Nie Lei , Yao Yixin , Lee Heng-Huan , Wang Wei , Bigcal JohnNelson R. , Badillo Maria , Meena Jitendra , Flowers Christopher , Zhou Jia , Zhao Zhongming , Simon Lukas M. , Wang Michael 
Published: February 2024

AbstractBrexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton’s tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance.HSP90AB1(Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance.CDK9(Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. BothHSP90AB1andCDK9expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.
“It’s beautiful and it’s messy and it’s tragic”: exploring the role of compassion in the eating disorder recovery processes of 2S/LGBTQ + Canadians
Authors: White Megan , Thomas Andrew , Aston Megan , Joy Phillip 
Published: February 2024

AbstractThis research explores experiences of compassion among 2S/LGBTQ + Canadians living with eating disorders in the context of eating disorder treatment and community support. There is a growing body of scholarship showing disparities in eating disorder care for those within 2S/LGBTQ + communities. Among the reported concerns is a potential lack of compassion in eating disorder treatment and recovery settings, something which may serve to exacerbate feelings of isolation and perpetuate misunderstandings of 2S/LGBTQ + people’s experiences. In an effort to understand these dynamics more deeply, we conducted semi-structured interviews with 2S/LGBTQ + Canadians who have experienced eating disorder care. The data collected were then subjected to Foucauldian discourse analysis, which produced three interconnected discursive considerations: feeling lack of structural compassion, 2S/LGBTQ + communities as places of respite, and 2S/LGBTQ + caregiving. One of the common threads among these discursive considerations was cis-heteronormativity ingrained in eating disorder treatment settings and health care systems more broadly. Our findings underscore the critical need for more enhanced compassion for 2S/LGBTQ + patients in eating disorder care settings. We conclude that compassion, when implemented on the levels of individual clinicians, policy and procedure, and institutions, may represent an avenue toward disrupting ingrained cis-heteronormativity and the associated discursive power structures contained in health care systems.
Brain-based CALL in flipped higher education GE courses held through LMS: Boosting vocabulary learning and reading comprehension
Authors: Abdolmaleki Nasrin , Saeedi Zari 
Published: February 2024

AbstractThe thriving technology penetration in all aspects of today’s life and deficiency of traditional pedagogies necessitate wise adoption of modern approaches in the educational context. As a few studies concerned the simultaneous application of classical educational theories with modern technological pedagogy, the present researchers launched General English (GE) courses enjoying the consolidation of Brain-Based Computer-Assisted-Language-Learning (BBCALL) and Flipped-Model (FM) with the aid of the Learning Management System (LMS) for fourteen 150-min sessions to explore their impact on vocabulary learning and reading comprehension (RC). In this pre/post-test experimental study, conducted in coeducational GE courses of a state university, 61 homogenous non-English major bachelors, selected via the convenience-sampling technique and screened by standard RC and GE-VOC tests, participated. Articulate Storyline software was used to develop intentional instructional content according to 12 BBL principles. BBCALL was the common aspect and in-class content attainment of non-flipped versus in-class content engagement and formative quizzes of flipped courses were the distinguishing features of the applied treatments. The statistical analyses of this action research demonstrated significantly meaningful outperformance of flipped BBCALL participants in vocabulary learning ($$sig=0.001)$$

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. To enhance results interpretation precision, gender was considered in groups’ differences. Although females in flipped course meaningfully outperformed on RC, male partakers of flipped course experienced the most meaningful improvement in VOC learning. Additionally, low-proficient learners benefited the most from such a self-paced and learner-centered education. The findings suggest that flexible instructional materials and effective tech integration could facilitate the improvement of higher-order thinking, creative problem-solving, and scaffolding.
Empowering PET: harnessing deep learning for improved clinical insight
Authors: Artesani Alessia , Bruno Alessandro , Gelardi Fabrizia , Chiti Arturo 
Published: February 2024

AbstractThis review aims to take a journey into the transformative impact of artificial intelligence (AI) on positron emission tomography (PET) imaging. To this scope, a broad overview of AI applications in the field of nuclear medicine and a thorough exploration of deep learning (DL) implementations in cancer diagnosis and therapy through PET imaging will be presented. We firstly describe the behind-the-scenes use of AI for image generation, including acquisition (event positioning, noise reduction though time-of-flight estimation and scatter correction), reconstruction (data-driven and model-driven approaches), restoration (supervised and unsupervised methods), and motion correction. Thereafter, we outline the integration of AI into clinical practice through the applications to segmentation, detection and classification, quantification, treatment planning, dosimetry, and radiomics/radiogenomics combined to tumour biological characteristics. Thus, this review seeks to showcase the overarching transformation of the field, ultimately leading to tangible improvements in patient treatment and response assessment. Finally, limitations and ethical considerations of the AI application to PET imaging and future directions of multimodal data mining in this discipline will be briefly discussed, including pressing challenges to the adoption of AI in molecular imaging such as the access to and interoperability of huge amount of data as well as the “black-box” problem, contributing to the ongoing dialogue on the transformative potential of AI in nuclear medicine.Relevance statementAI is rapidly revolutionising the world of medicine, including the fields of radiology and nuclear medicine. In the near future, AI will be used to support healthcare professionals. These advances will lead to improvements in diagnosis, in the assessment of response to treatment, in clinical decision making and in patient management.Key points• Applying AI has the potential to enhance the entire PET imaging pipeline.• AI may support several clinical tasks in both PET diagnosis and prognosis.• Interpreting the relationships between imaging and multiomics data will heavily rely on AI.
Graphical Abstract
Survey of current maintenance intravenous fluids prescribing practices among Egyptian pediatricians
Authors: Abdelaziz Alyaa Ahdy , Bazaraa Hafez Mahmoud , Omar Sherif Reda , Ashmawy Rasha , El-Maradny Yousra A. , Ghazy Ramy Mohammed 
Published: February 2024

Abstract
Background
Recent research has firmly linked the administration of hypotonic fluids with the incidence of hospital-acquired hyponatremia in pediatric patients.

Objective
This study examined the prevailing practices in prescribing maintenance intravenous fluids (mIVFs) among Egyptian pediatricians, assessed the compliance of current prescribing practices with the American Academy of Pediatrics Clinical Practice Guidelines (AAP-CPG), and emphasized the urgency for revised educational initiatives.

Materials and methods
To recruit pediatricians for this study, a convenience and snowballing sampling methods were used. The questionnaire was created in Google Forms and then distributed in English to Egyptian Facebook groups devoted to pediatric education. The data collection phase started on January 1, and ended on February 28, 2022. Different case scenarios with increased antidiuretic hormone were introduced, and respondents were asked to choose the optimum mIVFs in each case scenario. Finally, respondents were directly asked how often they use isotonic fluids as their primary mIVFs and what caused them to not use isotonic fluids.

Results
For this study, a total of 513 participatants were included. The survey revealed that Egyptian pediatricians did not not fully comply with AAP-CPG regarding the mIVFs in pediatrics. Hypotonic fluids are still preferred, but there is a shift towards 0.45% sodium chloride (NaCl) from the previously favored 0.2% NaCl. Isotonic fluids are more common in older age groups and conditions that involve potential excessive antidiuretic hormone secretion, while 0.2% NaCl remains popular in neonatal care. Balanced solutions are underused, indicating practice variation.

Conclusions
The utilization of isotonic fluids in the treatment of neurologic conditions has experienced a notable increase, propelled by heightened awareness and a growing demand for continuous medical education. To comprehensively address concerns related to fluid management beyond the scope of AAP-CPG, it is imperative to conduct multicenter studies across governmental, private, and educational pediatric healthcare settings to assess and improve pediatracians' clinical practice.
Prevalence and dissemination of mcr-9.1-producing non-typhoidal Salmonella strains from diarrhea patients throughout China during 2010–2020
Authors: Cui Qingpo , Li Weiwei , Yang Tingting , Qin Xiaoxia , Jiang Xiaotong , Zhao Xiangtan , Yang Xiaorong , Sun Yong , Zhang Meng , Ying Luyu , Gong Xiaowei , Wang Changyu , Zhao Guanzheng , Yang Qin , Fu Mengjiao , Guo Yunchang , Shen Zhangqi 
Published: February 2024

AbstractThe emergence of mobilized colistin resistance (mcr) genes has raised significant concerns as they pose a public health issue. The prevalence of mcr genes, particularly the newly discovered mcr-9 gene, in non-typhoidal Salmonella (NTS) isolates remains unclear. We characterized mcr-9.1-producing NTS isolates from China. Among 7,106 NTS isolates from diarrhea cases in 32 provinces during 2010–2020, 11 mcr-9.1-producing isolates were identified and were all not resistant to colistin. Five isolates belonged to Salmonella Thompson and sequence type (ST) 26, two belonged to Salmonella Typhimurium and ST34, two belonged to Salmonella Typhimurium and ST36, and two belonged to Salmonella 1,4,[5],12:i:- and ST34. Plasmids harboring mcr-9.1 tended to possess the IncHI2 backbone and were ~ 300 kb long. All mcr-9.1 genes shared the same flanking sequence, rcnR-rcnA-pcoS-IS903-mcr-9.1-wbuC. According to the NCBI data, we found that NTS serves as the primary host of mcr-9.1, although the prevalence of specific serotypes differed between domestic and international settings. Notably, most data came from developed countries, such as the USA. mcr-9.1 tended to be transferred as a gene cassette or to be mobilized by a conjugational plasmid in multiple bacteria across humans, animals, and the environment. Furthermore, mcr-9.1 frequently co-existed and was co-transferred with various genes encoding resistance to first-line drugs, reducing the effectiveness of available therapeutic options. In summary, although mcr-9 does not mediate colistin resistance, it can silently spread with some genes encoding resistance to first-line drugs, and therefore warrants research attention.
Weak gravitational lensing by multi-horizons black hole
Authors: Mushtaq Farzan , Tiecheng Xia , Yasir Muhammad , Ahsan Aitazaz 
Published: February 2024

Abstract
We investigate the weak gravitational lensing caused by multi-horizon black hole (MHBH) on light. Using the Gauss-Bonnet theorem, which demonstrates that light bending is a topological and global phenomenon, we are able to deduce the deflection angle of light in the weak field limits. First, we use the Gauss-Bonnet theorem to estimate the Gaussian optical curvature and determine the MHBH deflection angle for spherically balanced spacetime. Further, we evaluate the deflection angle of light within the plasma medium framework. Likewise, the impact of plasma and the non-plasma medium clearly illustrate the dynamics of the deflection angle by multi-horizons black hole.
mTOR Regulates Mineralocorticoid Receptor Transcriptional Activity by ULK1-Dependent and -Independent Mechanisms
Authors: Ali Yusuf , Gomez-Sanchez Celso E , Plonczynski Maria , Naray-Fejes-Toth Aniko , Fejes-Toth Geza , Gomez-Sanchez Elise P 
Published: February 2024

Abstract
The mineralocorticoid receptor (MR) is a transcription factor for genes mediating diverse, cell-specific functions, including trophic effects as well as promoting fluid/electrolyte homeostasis. It was reported that in intercalated cells, phosphorylation of the MR at serine 843 (S843) by Unc-51–like kinase (ULK1) inhibits MR activation and that phosphorylation of ULK1 by mechanistic target of rapamycin (mTOR) inactivates ULK1, and thereby prevents MR inactivation. We extended these findings with studies in M1 mouse cortical collecting duct cells stably expressing the rat MR and a reporter gene. Pharmacological inhibition of ULK1 dose-dependently increased ligand-induced MR transactivation, while ULK1 activation had no effect. Pharmacological inhibition of mTOR and CRISPR/gRNA gene knockdown of rapamycin-sensitive adapter protein of mTOR (Raptor) or rapamycin-insensitive companion of mTOR (Rictor) decreased phosphorylated ULK1 and ligand-induced activation of the MR reporter gene, as well as transcription of endogenous MR-target genes. As predicted, ULK1 inhibition had no effect on aldosterone-mediated transcription in M1 cells with the mutated MR-S843A (alanine cannot be phosphorylated). In contrast, mTOR inhibition dose-dependently decreased transcription in the MR-S843A cells, though not as completely as in cells with the wild-type MR-S843. mTOR, Raptor, and Rictor coprecipitated with the MR and addition of aldosterone increased their phosphorylated, active state. These results suggest that mTOR significantly regulates MR activity in at least 2 ways: by suppressing MR inactivation by ULK1, and by a yet ill-defined mechanism that involves direct association with MR. They also provide new insights into the diverse functions of ULK1 and mTOR, 2 key enzymes that monitor the cell's energy status.
A Prospective Observational Cohort Study of Language Preference and Preoperative Cognitive Screening in Older Adults: Do Language Disparities Exist in Cognitive Screening and Does the Association Between Test Results and Postoperative Delirium Differ Based on Language Preference?
Authors: Canales Cecilia , Ramirez Cecilia M. , Yang Shangyang C. , Feinberg Sharon A. , Grogan Tristan R. , Whittington Robert A. , Sarkisian Catherine , Cannesson Maxime 
Published: February 2024

BACKGROUND:
A greater percentage of surgical procedures are being performed each year on patients 65 years of age or older. Concurrently, a growing proportion of patients in English-speaking countries such as the United States, United Kingdom, Australia, and Canada have a language other than English (LOE) preference. We aimed to measure whether patients with LOE underwent cognitive screening at the same rates as their English-speaking counterparts when routine screening was instituted. We also aimed to measure the association between preoperative Mini-Cog and postoperative delirium (POD) in both English-speaking and LOE patients.

METHODS:
We conducted a single-center, observational cohort study in patients 65 years old or older, scheduled for surgery and evaluated in the preoperative clinic. Cognitive screening of older adults was recommended as an institutional program for all patients 65 and older presenting to the preoperative clinic. We measured program adherence for cognitive screening. We also assessed the association of preoperative impairment on Mini-Cog and POD in both English-speaking and LOE patients, and whether the association differed for the 2 groups. A Mini-Cog score ≤2 was considered impaired. Postoperatively, patients were assessed for POD using the Confusion Assessment Method (CAM) and by systematic chart review.

RESULTS:
Over a 3-year period (February 2019–January 2022), 2446 patients 65 years old or older were assessed in the preoperative clinic prior. Of those 1956 patients underwent cognitive screening. Eighty-nine percent of English-speaking patients underwent preoperative cognitive screening, compared to 58% of LOE patients. The odds of having a Mini-Cog assessment were 5.6 times higher (95% confidence interval [CI], 4.6–7.0) P < .001 for English-speaking patients compared to LOE patients. In English-speaking patients with a positive Mini-Cog screen, the odds of having postop delirium were 3.5 times higher (95% CI, 2.6–4.8) P < .001 when compared to negative Mini-Cog. In LOE patients, the odds of having postop delirium were 3.9 times higher (95% CI, 2.1–7.3) P < .001 for those with a positive Mini-Cog compared to a negative Mini-Cog. The difference between these 2 odds ratios was not significant (P = .753).

CONCLUSIONS:
We observed a disparity in the rates LOE patients were cognitively screened before surgery, despite the Mini-Cog being associated with POD in both English-speaking and LOE patients. Efforts should be made to identify barriers to cognitive screening in limited English-proficient older adults.
Filopodial protrusion driven by density-dependent Ena–TOCA-1 interactions
Authors: Blake Thomas C. A. , Fox Helen M. , Urbančič Vasja , Ravishankar Roshan , Wolowczyk Adam , Allgeyer Edward S. , Mason Julia , Danuser Gaudenz , Gallop Jennifer L. 
Published: February 2024

ABSTRACT
Filopodia are narrow actin-rich protrusions with important roles in neuronal development where membrane-binding adaptor proteins, such as I-BAR- and F-BAR-domain-containing proteins, have emerged as upstream regulators that link membrane interactions to actin regulators such as formins and proteins of the Ena/VASP family. Both the adaptors and their binding partners are part of diverse and redundant protein networks that can functionally compensate for each other. To explore the significance of the F-BAR domain-containing neuronal membrane adaptor TOCA-1 (also known as FNBP1L) in filopodia we performed a quantitative analysis of TOCA-1 and filopodial dynamics in Xenopus retinal ganglion cells, where Ena/VASP proteins have a native role in filopodial extension. Increasing the density of TOCA-1 enhances Ena/VASP protein binding in vitro, and an accumulation of TOCA-1, as well as its coincidence with Ena, correlates with filopodial protrusion in vivo. Two-colour single-molecule localisation microscopy of TOCA-1 and Ena supports their nanoscale association. TOCA-1 clusters promote filopodial protrusion and this depends on a functional TOCA-1 SH3 domain and activation of Cdc42, which we perturbed using the small-molecule inhibitor CASIN. We propose that TOCA-1 clusters act independently of membrane curvature to recruit and promote Ena activity for filopodial protrusion.
The Dilute domain in Canoe is not essential for linking cell junctions to the cytoskeleton but supports morphogenesis robustness
Authors: McParland Emily D. , Butcher T. Amber , Gurley Noah J. , Johnson Ruth I. , Slep Kevin C. , Peifer Mark 
Published: February 2024

ABSTRACT
Robust linkage between adherens junctions and the actomyosin cytoskeleton allows cells to change shape and move during morphogenesis without tearing tissues apart. The Drosophila multidomain protein Canoe and its mammalian homolog afadin are crucial for this, as in their absence many events of morphogenesis fail. To define the mechanism of action for Canoe, we are taking it apart. Canoe has five folded protein domains and a long intrinsically disordered region. The largest is the Dilute domain, which is shared by Canoe and myosin V. To define the roles of this domain in Canoe, we combined biochemical, genetic and cell biological assays. AlphaFold was used to predict its structure, providing similarities and contrasts with Myosin V. Biochemical data suggested one potential shared function – the ability to dimerize. We generated Canoe mutants with the Dilute domain deleted (CnoΔDIL). Surprisingly, they were viable and fertile. CnoΔDIL localized to adherens junctions and was enriched at junctions under tension. However, when its dose was reduced, CnoΔDIL did not provide fully wild-type function. Furthermore, canoeΔDIL mutants had defects in the orchestrated cell rearrangements of eye development. This reveals the robustness of junction–cytoskeletal connections during morphogenesis and highlights the power of natural selection to maintain protein structure.
Energy allocation is revealed while behavioural performance persists after fire disturbance
Authors: Iwińska Karolina , Wirowska Martyna , Borowski Zbigniew , Boratyński Zbyszek , Solecki Paweł , Ciesielski Mariusz , Boratyński Jan S. 
Published: February 2024

ABSTRACT
Metabolic physiology and animal behaviour are often considered to be linked, positively or negatively, according to either the performance or allocation models. Performance seems to predominate over allocation in natural systems, but the constraining environmental context may reveal allocation limitations to energetically expensive behaviours. Habitat disturbance, such as the large-scale fire that burnt wetlands of Biebrza National Park (NE Poland), degrades natural ecosystems. It arguably reduces food and shelter availability, modifies predator–prey interactions, and poses a direct threat for animal survival, such as that of the wetland specialist root vole Microtus oeconomus. We hypothesized that fire disturbance induces physiology–behaviour co-expression, as a consequence of changed environmental context. We repeatedly measured maintenance and exercise metabolism, and behavioural responses to the open field, in a root voles from post-fire and unburnt locations. Highly repeatable maintenance metabolism and distance moved during behavioural tests correlated positively, but relatively labile exercise metabolism did not covary with behaviour. At the same time, voles from a post-fire habitat had higher maintenance metabolism and moved shorter distances than voles from unburnt areas. We conclude there is a prevalence of the performance mechanism, but simultaneous manifestation of context-dependent allocation constraints of the physiology–behaviour covariation after disturbance. The last occurs at the within-individual level, indicating the significance of behavioural plasticity in the context of environmental disturbance.