bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resilience and Protective Factors for Mental Health among Indigenous Youth in Canada: A Scoping Review
Authors: Shin Hwayeon Danielle , Carrier Leah , Dame Jessy , Padley Michelle , Daclan Anika , Wong Helen , Dass Ronessa , Dorey Rachel Anne , Stirling-Cameron Emma , Langley Jodi , Curran Janet A. 
Published: August 2024

AbstractIndigenous youth’s inherent strength and resilience play a vital role in their well-being and mental health. Protective factors, closely linked to resilience, spanning individual, family, and community levels reinforce positive mental health outcomes. The purpose of the present scoping review was to summarize the available literature that describes resilience and/or protective factors promoting mental health and well-being among Indigenous youth in Canada. As a secondary objective, this review investigated community involvement reported in the identified sources. JBI scoping review methodology was followed, and the search of PubMed, EMBASE, CINHAL, PsycINFO, ERIC, and Scopus commenced in August 2021, and was updated in February 2023. A targeted Google search was also conducted to identify eligible grey literature. A total of 61 papers were included in data extraction. The types of sources identified were observational (n=22), participatory action research (n=11), mixed/multi-methods (n=10), qualitative (n=9), case study (n=4), quasi-experimental (n=1), experimental (=1), and other designs such as quality improvement and program evaluation (n=3). Additionally, only a handful of included studies reported use of an Indigenous-specific approach, such as Two-Eyed seeing. Protective and resilience factors were identified across various levels such as individual (n=52), interpersonal (n=37), and wider environmental beyond social systems (n=37) levels. Forty studies described community involvement, which included non-specified community members, like friends or citizens (n=21), youth (n=19), Indigenous community members such as leaders and workers (n=14), and Elders (n=11). These groups were engaged to varying degrees, functioning either as equal collaborators, consultants, or, in some instances, as decision-makers.
Reduced Risk of Cardiovascular Diseases after Bariatric Surgery Based on the New PREVENT Equations
Authors: Wang Lei , Zhang Xinmeng , Chen You , Flynn Charles R. , English Wayne J. , Samuels Jason M. , Williams Brandon , Spann Matthew , Albaugh Vance L. , Shu Xiao-Ou , Yu Danxia 
Published: August 2024

AbstractBackgroundWe applied the novel Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations to evaluate cardiovascular-kidney-metabolic (CKM) health and estimated CVD risk, including heart failure (HF), after bariatric surgery.MethodsAmong 7804 patients (20–79 years) undergoing bariatric surgery at Vanderbilt University Medical Center during 1999–2022, CVD risk factors at pre-surgery, 1-year, and 2-year post-surgery were extracted from electronic health records. The 10- and 30-year risks of total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), stroke, and HF were estimated for patients without a history of CVD or its subtypes at each time point, using the social deprivation index-enhanced PREVENT equations. Paired t-tests or McNemar tests were used to compare pre- with post-surgery CKM health and CVD risk. Two-sample t-tests were used to compare CVD risk reduction between patient subgroups defined by age, sex, race, operation type, weight loss, and history of diabetes, hypertension, and dyslipidemia.ResultsCKM health was significantly improved after surgery with lower systolic blood pressure, non-high-density-lipoprotein cholesterol (non-HDL), and diabetes prevalence, but higher HDL and estimated glomerular filtration rate (eGFR). The 10-year total CVD risk decreased from 6.51% at pre-surgery to 4.81% and 5.08% at 1- and 2-year post-surgery (relative reduction: 25.9% and 16.8%), respectively. Significant risk reductions were seen for all CVD subtypes (i.e., ASCVD, CHD, stroke, and HF), with the largest reduction for HF (relative reduction: 55.7% and 44.8% at 1- and 2-year post-surgery, respectively). Younger age, White race, >30% weight loss, diabetes history, and no dyslipidemia history were associated with greater HF risk reductions. Similar results were found for the 30-year risk estimates.ConclusionsBariatric surgery significantly improves CKM health and reduces estimated CVD risk, particularly HF, by 45-56% within 1-2 years post-surgery. HF risk reduction may vary by patient’s demographics, weight loss, and disease history, which warrants further research.
Snapshots of acetyl-CoA synthesis, the final step of CO2fixation in the Wood-Ljungdahl pathway
Authors: Yin Max Dongsheng , Lemaire Olivier N. , Rosas Jiménez José Guadalupe , Belhamri Mélissa , Shevchenko Anna , Hummer Gerhard , Wagner Tristan , Murphy Bonnie J. 
Published: August 2024

ABSTRACTIn the ancient microbial Wood-Ljungdahl pathway, CO2is fixed in a multi-step process ending with acetyl-CoA synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). Here, we present catalytic snapshots of the CODH/ACS from the gas-converting acetogenClostridium autoethanogenum, characterizing the molecular choreography of the overall reaction including electron transfer to the CODH for CO2reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer and protect the reaction intermediates. Altogether, the structures allow us to draw a detailed reaction mechanism of this enzyme crucial for CO2fixation in anaerobic organisms.One-Sentence Summary:Structural description of key states of CO2fixation by the carbon monoxide dehydrogenase/acetyl-CoA synthase complex.
Variant-to-function dissection of rare non-coding GWAS loci with high impact on blood traits
Authors: Tardaguila Manuel , Schiller Dominique Von , Colombo Michela , Gori Ilaria , Coomber Eve L. , Vanderstichele Thomas , Benaglio Paola , Chiereghin Chiara , Gerety Sebastian , Vuckovic Dragana , Landini Arianna , Clerici Giuditta , Albers Patrick , Ray-Jones Helen , Burnham Katie L. , Tokolyi Alex , Persyn Elodie , Spivakov Mikhail , Sankaran Vijay G. , Walter Klaudia , Kundu Kousik , Pirastu Nicola , Inouye Michael , Paul Dirk S. , Davenport Emma E. , Sahlén Pelin , Watt Stephen , Soranzo Nicole 
Published: August 2024

AbstractTwo decades of Genome Wide Association Studies (GWAS) have yielded hundreds of thousands of robust genetic associations to human complex traits and diseases. Nevertheless, the dissection of the functional consequences of variants lags behind, especially for non-coding variants (RNVs). Here we have characterised a set of rare, non-coding variants with large effects on haematological traits by integrating (i) a massively parallel reporter assay with (ii) a CRISPR/Cas9 screen and (iii)in vivogene expression and transcript relative abundance analysis of whole blood and immune cells. After extensive manual curation we identify 22 RNVs with robust mechanistic hypotheses and perform an in-depth characterization of one of them, demonstrating its impact on megakaryopoiesis through regulation of theCUX1transcriptional cascade. With this work we advance the understanding of the translational value of GWAS findings for variants implicated in blood and immunity.
Scarless circular mRNA-based CAR-T cell therapy elicits superior anti-tumor efficacy
Authors: Hu Qinchao , Zhao Hui , Zhou Kaicheng , Hua Xianxin , Zhang Xuyao 
Published: August 2024

AbstractMessenger RNA (mRNA)-based transient expression of CAR shows optimal safety profiles and provides promising opportunities to address existing challenges of viral vector-based CAR-T therapies and to meet emerging medical needs in noncancerous indications. However, linear mRNAs are intrinsically unstable and thus just achieve compromised efficacy. Here, we engineered a permuted intron exon (PIE) platform to synthesize scarless circular mRNA (cmRNA) for potent CAR expression and long-lasting efficacy. cmRNA significantly increased amount and duration of anti-CD19 CAR expression on human T cells. cmRNA-based anti-CD19 CAR-T cells elicit superior anti-tumor efficacy over linear mRNA counterparts, demonstrated by parallel lines of evidence includingin vitrospecific cell-killing, cytokine release, transcriptomics patterns, andin vivotumor elimination and survival benefit. We found that cmRNA-based anti-CD19 CAR-T efficiently eliminated target cellsin vivoand provide long-lasting antitumor efficacy. These results suggested that cmRNA could be a potent platform for unleashing full potential of mRNA technologies in cell therapies.
The molecular basis of Human FN3K mediated phosphorylation of glycated substrate
Authors: Garg Ankur , On Kin Fan , Xiao Yang , Elkayam Elad , Cifani Paolo , David Yael , Joshua-Tor Leemor 
Published: August 2024

AbstractGlycation, a non-enzymatic post-translational modification occurring on proteins, can be actively reversed via site-specific phosphorylation of the fructose-lysine moiety by FN3K kinase, to impact the cellular function of target protein. A regulatory axis between FN3K and glycated protein targets has been associated with conditions like diabetes and cancer. However the molecular basis of this relationship has not been explored so far. Here, we determined a series of crystal structures of HsFN3K in apo-state, and in complex with different nucleotide analogs together with a sugar substrate mimic to reveal the features important for its kinase activity and substrate recognition. Additionally, the dynamics in sugar substrate binding during the kinase catalytic cycle provide important mechanistic insights into HsFN3K function. Our structural work provides the molecular basis for rationale small molecule design targeting FN3K.
Two structurally mobile regions control the conformation and function of metamorphic meiotic HORMAD proteins
Authors: Barroso Consuelo , Prince Josh P , Rattu Punam , Kundé Daimona , Ferrandiz Nuria , Khalid Syma , Martinez-Perez Enrique 
Published: August 2024

AbstractMetamorphic HORMA domain proteins (HORMADs) nucleate protein complex formation by refolding their mobile safety belt region to bind short motifs on interactors. Meiotic HORMADs (mHORMADs) bind proteinaceous axial elements to orchestrate complex chromosomal events that underpin fertility, including pairing and recombination between homologous chromosomes. However, the mechanisms supporting the diverse roles of mHORMADs remain unclear. Here, we show that mHORMADs have a second structurally mobile region, the β5-αC loop, which controls mHORMAD conformation and function. Molecular dynamics and in vivo approaches show that functional specialisation ofC. elegansparalogs HTP-1 and HTP-2 depends on the interplay between their β5-αC loop and safety belt. The β5-αC loop can interact with the same HORMA core surface as the safety belt, forming a “loop engaged” conformation. The β5-αC loop HORMA core interaction is essential for axis loading of HTP-1 and its paralog HTP-3, and is also present in yeast, plant, and mammalian mHORMADs, suggesting that it represents a conserved functional feature of mHORMADs. Our study reveals that mHORMADs have expanded the bimodal folding landscape first identified in Mad2, paving the way to elucidate how non-canonical HORMAD conformations control meiotic chromosome function to ensure fertility.
Aversion-induced drug taking and escape behavior involve similar nucleus accumbens core dopamine signaling signatures
Authors: Grafelman Elaine M , Côté Bridgitte E , Vlach Lisa , Geise Ella , Padula G. Nino , Wheeler Daniel S , Hearing Matthew , Mantsch John , Wheeler Robert A 
Published: August 2024

AbstractDopamine release in the nucleus accumbens core (NAcC) has long been associated with the promotion of motivated behavior. However, inhibited dopamine signaling can increase behavior in certain settings, such as during drug self-administration. While aversive environmental stimuli can reduce dopamine, it is unclear whether such stimuli reliably engage this mechanism in different contexts. Here we compared the physiological and behavioral responses to the same aversive stimulus in different designs to determine if there is uniformity in the manner that aversive stimuli are encoded and promote behavior. NAcC dopamine was measured using fiber photometry in male and female rats during cocaine self-administration sessions in which an acutely aversive 90 dB white noise was intermittently presented. In a separate group of rats, aversion-induced changes in dopamine were measured in an escape design in which operant responses terminated aversive white noise. Aversive white noise significantly reduced NAcC dopamine and increased cocaine self-administration in both male and female rats. The same relationship was observed in the escape design, in which white noise reduced dopamine and promoted escape attempts. In both designs, the magnitude of the dopamine reduction predicted behavioral performance. While prior research demonstrated that pharmacologically reduced dopamine signaling can promote intake, this report demonstrates that this physiological mechanism is naturally engaged by aversive environmental stimuli and generalizable to non-drug contexts. These findings illustrate a common physiological signature in response to aversion that may promote both adaptive and maladaptive behavior.
EXOSC4 is recruited by histone H3 co-modified with K9me3 and acetylations to surveil non-coding transcription
Authors: Stransky Stephanie , Cutler Ronald , Aguilan Jennifer , DeAngelo Joseph D. , Shechter David , Sidoli Simone 
Published: August 2024

AbstractHistones are hyper modified proteins that regulate chromatin accessibility and DNA readout. Co-existing post-translational modifications (PTMs) on histones affect interaction affinities of chromatin-associated proteins in ways that are still mostly unexplored. Here, we focus on the biological role of a specific histone code made of two PTMs with supposedly opposing biological functions, i.e. H3K9me3 marker of constitutive heterochromatin and H3K14ac benchmarking accessible chromatin. By applying multi-dimensional mass spectrometry, we demonstrated that EXOSC4 interacts with H3K9me3 + acetyls and affects post-transcriptional regulation. Specifically, EXOSC4 depletion leads to down-regulation of the RNA surveillance machinery and increased expression of non-coding transcripts, including anti-sense RNAs. Together, we elucidate the role of a co-modified histone tail and demonstrate its involvement in the RNA machinery and spurious transcription surveillance.
Mfn2 induces NCLX-mediated calcium release from mitochondria
Authors: Kolitsida Panagiota , Saha Akash , Caliri Andrew , Assali Essam , Riera Alejandro Martorell , Itskanov Samuel , Magana Catalina S. , Stork Björn , Shirihai Orian , Sekler Israel , Koehler Carla M. , van der Bliek Alexander M. 
Published: August 2024

AbstractMfn2 is a mitochondrial outer membrane fusion protein with the additional role of tethering mitochondria to the ER. Here, we describe a novel connection between Mfn2 and calcium release from mitochondria. We show that Mfn2 controls the mitochondrial inner membrane sodium-calcium exchange protein NCLX, which is a major source for calcium release from mitochondria. This discovery was made with the fungal toxin Phomoxanthone (PXA), which induces calcium release from mitochondria. PXA-induced calcium release is blocked by a chemical inhibitor of NCLX, while NCLX and Mfn2 deletions both also prevent PXA-induced calcium release. CETSA experiments show that PXA directly targets Mfn2, which likely controls NCLX through physical interactions since co-immunoprecipitation and proximity ligation assays show increased association between Mfn2 and NCLX upon treatment with PXA. Interactions between Mfn2 and NCLX also increase when cells are treated with mitochondrial ROS-inducing conditions, such as oligomycin treatment of respiring cells, while the interactions do not increase in Oma1 -/-cells. It seems likely that opening of cristae by Oma1-mediated cleavage of Opa1 promotes translocation of NCLX from cristae to the rim where it can come into contact with Mfn2 thus promoting PXA-induced calcium release from mitochondria. These results therefore delineate a pathway that connects ROS produced inside mitochondria with calcium release and signaling in the cytosol.
A biodegradable and restorative peripheral neural interface for the interrogation of neuropathic injuries
Authors: Wang Liu , Zhang Tieyuan , Lei Jiaxin , Wang Shirong , Guan Yanjun , Chen Kuntao , Li Chaochao , Song Yahao , Li Weining , Wang Shimeng , Jia Zhibo , Chen Shengfeng , Bai Jun , Yu Bingbing , Yang Can , Sun Pengcheng , Wang Qingyun , Sheng Xing , Peng Jiang , Fan Yubo , Wang Lizhen , Zhang Milin , Wang Yu , Yin Lan 
Published: August 2024

AbstractMonitoring the early-stage healing of severe traumatic nerve injuries is essential to gather physiological and pathological information for timely interventions and optimal clinical outcomes. While implantable peripheral nerve interfaces provide direct access to nerve fibers for precise interrogation and modulation, conventional non-degradable designs pose limited utilization in nerve injury rehabilitation. Here, we introduce a biodegradable and restorative neural interface for wireless real-time tracking and recovery of long-gap nerve injuries. Leveraging machine learning techniques, this electronic platform deciphers nerve recovery status and identifies traumatic neuroma formation at the early phase, enabling timely intervention and significantly improved therapeutic outcomes. The biodegradable nature of the device eliminates the need for retrieval procedures, reducing infection risks and secondary tissue damage. This research sheds light on bioresorbable multifunctional peripheral nerve interfaces for probing neuropathic injuries, offering vital information for early diagnosis and therapeutic intervention.
Photon-Counting Detector Computed Tomography Angiography to assess intracranial stents and flowdiverters - in vivo study comprising ultra-high resolution spectral reconstructions
Authors: De Beukelaer Frederic , De Beukelaer Sophie , Wuyts Laura L , Nikoubashman Omid , El Halal Mohammed , Kantzeli Iliana , Wiesmann Martin , Ridwan Hani , Weyland Charlotte S. 
Published: August 2024

ABSTRACTBACKGROUND AND PURPOSENeuroimaging of intracranial vessels with implanted stents (ICS) and flowdiverters (FD) is limited by artifacts. Photon-Counting-Detector-Computed Tomography (PCD-CT) is characterized by a higher resolution. The purpose of this study was to assess the image quality of ultra-high-resolution (UHR) PCD-CT-Angiography (PCD-CTA) and spectral reconstructions to define the best imaging parameters for the evaluation of vessel visibility in ICS and FD.MATERIALS AND METHODSRetrospective analysis of consecutive patients with implanted ICS or FD, who received a PCD-CTA between April 2023 and March 2024. Polyenergetic (PE), virtual monoenergetic imaging (VMI), pure lumen (PL) and iodine (I) reconstructions with different kiloelectron volt (keV) levels (keV 40, 60 and 80) and reconstruction kernels (Body vascular kernel (Bv) 48, Bv56, Bv64, Bv72, Bv76) were acquired to evaluate image quality and assessed by 2 independent radiologists using a 5-point Likert scale and regions of interest (ROI). The different kernels, keV and the optimized spectral reconstructions were compared in descriptive analysis.RESULTSIn total, 12 patients with 9 FDs and 6 ICSs were analyzed. In terms of quantitative image quality, sharper kernels as Bv64 and Bv72 yielded increased image noise, and decreased signal to noise (SNR) and contrast to noise ratio (CNR) compared to the smoothest kernel Bv48, (p<0.01). Among the different keV levels and kernels, readers selected the 40 keV level (p<0.01) and sharper kernels (in the majority of cases Bv72) as the best to visualize the in-stent vessel lumen. Assessing the different spectral reconstructions virtual monoenergetic and iodine reconstructions proved to be best to evaluate in-stent vessel lumen (p<0.01).CONCLUSIONSOur preliminary study suggests that PCD-CTA and spectral reconstructions with sharper reconstruction kernels and a low keV level of 40 seem to be beneficial to achieve optimal image quality for the evaluation of ICS and FD. Iodine and virtual monoenergetic reconstructions were superior to pure lumen and polyenergetic reconstructions to evaluate in-stent vessel lumen.Key pointsPCD-CTA imaging quality can be advanced by image post processing with spectral reconstructions and certain reconstruction kernels.Intracranial in-stent vessel lumen visibility significantly improves using sharp reconstruction kernels (Bv72) and low keV level in high-resolution mode in photon-counting detector computed tomography. Regarding the different optimized spectral reconstructions virtual monoenergetic and iodine reconstructions proved to be best to evaluate in-stent vessel lumen.
Circulating Lipids as Biomarkers for Diagnosis of Tuberculosis: A Multi-cohort, Multi-omics Data Integration Analysis
Authors: Tien Nguyen Tran Nam , Yen Nguyen Thi Hai , Phat Nguyen Ky , Anh Nguyen Ky , Thu Nguyen Quang , Dinh Hoa Vu , Eunsu Cho , Kim Ho-Sook , Nguyen Duc Ninh , Kim Dong Hyun , Oh Jee Youn , Long Nguyen Phuoc 
Published: August 2024

ABSTRACTBackgroundCirculating immunometabolic biomarkers show promise for the diagnosis and treatment monitoring of tuberculosis (TB). However, biomarkers that can distinguish TB from nontuberculous mycobacteria (NTM) infections, latent tuberculosis infection (LTBI), and other lung diseases (ODx) have not been elucidated. This study utilized a multi-cohort, multi-omics approach combined with predictive modeling to identify, validate, and prioritize biomarkers for the diagnosis of active TB.MethodsFunctional omics data were collected from two discovery cohorts (76 patients in the TB-NTM cohort and 72 patients in the TB-LTBI-ODx cohort) and one validation cohort (68 TB patients and 30 LTBI patients). An integrative multi-omics analysis was performed to identify the plasma multi-ome biosignatures. Machine learning-based predictive modeling was then applied to assess the performance of these biosignatures and prioritize the most promising candidates.ResultsConventional statistical analyses of immune profiling and metabolomics indicated minor differences between active TB and non-TB groups, whereas the lipidome showed significant alteration. Muti-omics integrative analysis identified three multi-ome biosignatures that could distinguish active TB from non-TB with promising performance, achieving area under the ROC curve (AUC) values of 0.7–0.9 across groups in both the discovery and validation cohorts. The lipid PC(14:0_22:6) emerged as the most important predictor for differentiating active TB from non-TB controls, consistently presenting at lower levels in the active TB group compared with counterparts. Further validation using two independent external datasets demonstrated AUCs of 0.77–1.00, confirming the biomarkers’ efficacy in distinguishing TB from other non-TB groups.ConclusionOur integrative multi-omics reveals significant immunometabolic alteration in TB. Predictive modeling suggests lipids as promising biomarkers for TB-NTM differential diagnosis and TB-LTBI-ODx diagnosis. External validation further indicates PC(14:0_22:6) as a potential diagnostic marker candidate for TB.SummaryOur multi-cohort, multi-omics data integration and predictive modeling identified reliable biomarkers and highlighted the importance of circulating lipids for distinguishing tuberculosis (TB) from complex conditions with similar clinical manifestations, latent infections, and healthy individuals.