bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a TNIK-CDK9 axis as a targetable strategy for platinum-resistant ovarian cancer
Authors: Puleo Noah , Ram Harini , Dziubinski Michele L. , Carvette Dylan , Teitel Jessica , Sekhar Sreeja C. , Bedi Karan , Robida Aaron , Nakashima Michael M. , Farsinejad Sadaf , Iwanicki Marcin , Senkowski Wojciech , Ray Arpita , Bollerman TJ , Dunbar James , Richardson Peter , Taddei Andrea , Hudson Chantelle , DiFeo Analisa 
Published: January 2025

Abstract
Up to 90% of high-grade serous ovarian cancer (HGSC) patients will develop resistance to platinum-based chemotherapy, posing substantial therapeutic challenges due to a lack of universally druggable targets. Leveraging BenevolentAI’s AI-driven approach to target discovery, we screened potential AI-predicted therapeutic targets mapped to unapproved tool compounds in patient-derived 3D models. This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC. Targeting by this compound demonstrated efficacy across both in vitro and ex vivo organoid platinum-resistant models. Additionally, NCB-0846 treatment effectively decreased Wnt activity, a known driver of platinum resistance; however, we found that these effects were not solely mediated by TNIK inhibition. Comprehensive AI, in silico, and in vitro analyses revealed CDK9 as another key target driving NCB-0846’s efficacy. Interestingly, TNIK and CDK9 co-expression positively correlated, and chromosomal gains in both served as prognostic markers for poor patient outcomes. Combined knockdown of TNIK and CDK9 markedly diminished downstream Wnt targets and reduced chemotherapy-resistant cell viability. Furthermore, we identified CDK9 as a novel mediator of canonical Wnt activity, providing mechanistic insights into the combinatorial effects of TNIK and CDK9 inhibition and offering a new understanding of NCB-0846 and CDK9 inhibitor function. Our findings identified the TNIK-CDK9 axis as druggable targets mediating platinum resistance and cell viability in HGSC. With AI at the forefront of drug discovery, this work highlights how to ensure that AI findings are biologically relevant by combining compound screens with physiologically relevant models thus supporting the identification and validation of potential drug targets.
Figure 3 from Serially Quantifying <i>TERT</i> Rearrangement Breakpoints in ctDNA Enables Minimal Residual Disease Monitoring in Patients with Neuroblastoma
Authors: Hollander Jan F. , Szymansky Annabell , Wünschel Jasmin , Astrahantseff Kathy , Rosswog Carolina , Thorwarth Anne , Thole-Kliesch Theresa M. , Chamorro González Rocío , Hundsdörfer Patrick , Hauptmann Kathrin , Schmelz Karin , Gürgen Dennis , Rogasch Julian M.M. , Henssen Anton G. , Fischer Matthias , Schulte Johannes H. , Eckert Cornelia , Eggert Angelika , Lodrini Marco , Deubzer Hedwig E. 
Published: January 2025

<p>Targeted ctDNA-based <i>TERT</i> breakpoint and <i>ALK</i> p.R1275Q markers persist in patient P3. <b>A,</b> The graphical display integrates biosample and analysis type along the patient P3 course timeline for <i>TERT</i> rearrangement breakpoint (violet) and <i>ALK</i> p.R1275Q copies (green, top time line) and selected clinical case information (bottom time line). Light yellow and white backgrounds represent different treatment modules. <b>B, </b><i>TERT</i> breakpoint and <i>ALK</i> p.R1275Q quantification in tumor tissue-derived genomic DNA and murine blood-derived ctDNA from the PDX model of P3. BM, bone marrow; HVA, homovanillic acid in urine/g creatinine; INRC, International Neuroblastoma Response Criteria; max., maximum; mIBG, [<sup>123</sup>I]<i>meta</i>-iodobenzylguanidine; NDD, no detectable disease; NSE, neuron-specific enolase; PD, progressive disease; PDX, patient-derived xenograft; RIST, molecularly targeted multimodal therapy consisting of metronomic courses of rapamycin/dasatinib and irinotecan/temozolomide; SIOPEN, The European Association for Neuroblastoma Research; T, tumor; VMA, vanillylmandelic acid in urine/g creatinine.</p>
Residual Mitral Regurgitation Interacts With Transmitral Mean Pressure Gradient to Modify the Association With Mortality Following Transcatheter Edge-to-Edge Repair
Authors: Duggal Neal M. , Engoren Milo , Sorajja Paul , Lim D. Scott , Rogers Jason H. , Chadderdon Scott M. , Zahr Firas E. , Rodriguez Evelio , Morse M. Andrew , Garcia-Sayan Enrique , Sodhi Nishtha , Calfon Press Marcella A. , Ailawadi Gorav 
Published: January 2025

BACKGROUND:
The association, if any, between the transmitral mean pressure gradient (TMPG) after mitral transcatheter edge-to-edge repair and 1-year mortality is controversial in patients undergoing mitral transcatheter edge-to-edge repair with the MitraClip system. We sought to estimate the association between intraoperatively measured residual mitral regurgitation (rMR) and TMPG and 1-year mortality among patients undergoing mitral transcatheter edge-to-edge repair to facilitate decisions on additional devices.

METHODS:
In patients with severe secondary (functional) MR, we analyzed registry data using generalized estimating equations. Both rMR and TMPG were nonlinearly transformed using fractional polynomials.

RESULTS:

We studied 570 patients with secondary MR who underwent mitral transcatheter edge-to-edge repair in 11 centers. Most patients were men (61%) and averaged 72±12 years of age. Most (78%) patients had TMPG <5 mm Hg and 22% had TMPG ≥5 mm Hg. Postprocedural MR severity improved substantially, being ≤2+ in 95% (with ≤1+ in 76%), 3+ in 3%, and 4+ in 2%. 1-year mortality was 20%. After adjustment for confounders, rMR (odds ratio, 2.10 [95% CI, 1.88–2.35];
P
<0.001 for rMR
.5
) and TMPG remained associated with mortality, with odds ratios of 1.26 (95% CI, 1.19–1.32), 1.84 (1.58–2.10), and 3.13 (2.31–3.98) for TMPG values of 4, 6, and 8, respectively, compared with TMPG=2 mm Hg at rMR=1+.

CONCLUSIONS:
Both rMR and TMPG were nonlinearly associated with 1-year mortality. At low levels of rMR, changes in TMPG are associated with only small changes in the risk of death. Conversely, at higher levels of rMR, even small changes in TMPG are associated with larger changes in the absolute risk of death.
Modeling neural contrast sensitivity functions in human visual
cortex
Authors: Roelofzen Carlien , Daghlian Marcus , van Dijk Jelle A. , de Jong Maartje C. , Dumoulin Serge O. 
Published: January 2025

Abstract
The contrast sensitivity function (CSF) characterizes visual function, and is widely used in research on visual perception and ophthalmological disorders. The CSF describes the lowest contrast level that participants can perceive as a function of spatial frequency. Here, we present a new method to estimate the neural equivalent of the CSF that describes how a population of neurons responds to contrast as a function of spatial frequency. Using functional magnetic resonance imaging (fMRI) at 7 Tesla, we measured neural responses while participants viewed gratings that varied systematically in contrast and spatial frequency. We modeled the neural CSF (nCSF) using an asymmetric parabolic function, and we modeled the transition from no response to full response using a contrast response function (CRF). We estimated the nCSF parameters for every cortical location by minimizing the residual variance between the model predictions and the fMRI data. We validated the method using simulations and parameter recovery. We show that our nCSF model explains a significant amount of the variance in the fMRI time series. Moreover, the properties of the nCSF vary according to known systematic differences across the visual cortex. Specifically, the peak spatial frequency that a cortical location responds to decreases with eccentricity and across the visual hierarchy. This new method will provide valuable insights into the properties of the visual cortex and how they are altered in both healthy and clinical conditions.
Fast and reliable quantitative measures of white matter development
with magnetic resonance fingerprinting
Authors: Yablonski Maya , Zhou Zihan , Cao Xiaozhi , Schauman Sophie , Liao Congyu , Setsompop Kawin , Yeatman Jason D. 
Published: January 2025

Abstract
Developmental cognitive neuroscience aims to shed light on evolving relationships between brain structure and cognitive development. To this end, quantitative methods that reliably measure individual differences in brain tissue properties are fundamental. Standard qualitative MRI sequences are influenced by scan parameters and hardware-related biases, and also lack physical units, making the analysis of individual differences problematic. In contrast, quantitative MRI can measure physical properties of the tissue but with the cost of long scan durations and sensitivity to motion. This poses a critical limitation for studying young children. Here, we examine the reliability of an efficient quantitative multiparameter mapping method—magnetic resonance fingerprinting (MRF)—in children scanned longitudinally. We focus on T1 values in white matter, since quantitative T1 values are known to primarily reflect myelin content, a key factor in brain development. Forty-nine children aged 8–13 years (mean 10.3 years ± 1.4) completed 2 scanning sessions 2–4 months apart. In each session, two 2-min 3D-MRF scans at 1 mm isotropic resolution were collected to evaluate the effect of scan duration on image quality and scan–rescan reliability. A separate calibration scan was used to measure B0 inhomogeneity and correct for bias. We examined the impact of scan time and B0 inhomogeneity correction on scan–rescan reliability of values in white matter, by comparing single 2-min and combined two 2-min scans, with and without B0 correction. Whole-brain voxel-based reliability analysis showed that combining two 2-min MRF scans improved reliability (Pearson’s r = 0.87) compared with a single 2-min scan (r = 0.84), while B0 correction had no effect on reliability in white matter (r = 0.86 and 0.83 4- vs. 2-min). Using diffusion tractography, we segmented major white matter fiber tracts and examined the profiles of MRF-derived T1 values along each tract. We found that T1 values from MRF showed similar or greater reliability compared with diffusion parameters. Lastly, we found that R1 (1/T1) values in multiple white matter tracts were significantly correlated with age. In sum, MRF-derived T1 values were highly reliable in a longitudinal sample of children and replicated known age effects. Reliability in white matter was improved by longer scan duration but was not affected by B0 correction, making it a quick and straightforward scan to collect. We propose that MRF provides a promising avenue for acquiring quantitative brain metrics in children and patient populations where scan time and motion are of particular concern.
Selenium nanoparticles enhance metabolic and nutritional profile in Phaseolus vulgaris: comparative metabolomic and pathway analysis with selenium selenate
Authors: Abdelsalam Asmaa , Gharib Fatma Abd El Lateef , Boroujerdi Arezue , Abouelhamd Nada , Ahmed Eman Zakaria 
Published: January 2025

Abstract
Selenium is a beneficial element in agriculture, particularly for its potential to improve plant growth and stress tolerance at suitable concentrations. In this study, Phaseolus vulgaris was foliar-sprayed with selenium selenate (Se) or selenium nanoparticles (SeNP) at different concentrations during the vegetative stage; afterward, the seed yield was analyzed for metabolomics using 1H, J-resolved and HSQC NMR data, and NMR databases. A total of 47 metabolites were identified with sugars being the major chemical class. In the control sample, the most abundant sugar was stachyose (14.6 ± 0.8 mM). Among the identified alkaloids, the concentration of trigonelline was the highest (0.6 ± 0.08 mM). Chemometric and cluster analyses distinctly differentiated the control from the Se and SeNP-treated samples. Treatments with SeNP resulted in elevated concentrations of sugars, carboxylic acids, and sulfur-containing amino acids compared to control and Se treated samples. Conversely, betaine levels were higher in Se samples. The presence of Se and SeNP significantly decreased the levels of several aliphatic amino acids, e.g. alanine. The addition of 50 µM SeNP upregulated the levels of trigonelline and syringate by 2-fold and 1.75-fold, respectively, relative to the control. Pathway analysis indicated the most significantly altered pathways due to SeNP addition were arginine biosynthesis and nitrogen metabolism. The pathways influenced by Se addition were glyoxylate and dicarboxylate metabolism as well as glycine-serine and threonine metabolism. This study proved that SeNP are more efficient than Se in enhancing the metabolic profile of Phaseolus vulgaris which will have implications for agricultural practices, focusing on the sustainability and nutritional enhancement of crops.
Resilience-based interventions in the public sector workplace: a systematic review
Authors: Hollaar Malin H. L. , Kemmere Bram , Kocken Paul L. , Denktaş Semiha 
Published: January 2025

Abstract

Background
Previous studies have advocated the benefits of resilience-based interventions for creating a healthy and sustainable workforce. However, resilience is defined and measured in diverse ways. Therefore, the aim of this systematic review is (1) to identify how resilience is defined within different workplace interventions, translated into intervention content, and measured in these interventions; and (2) to synthesize the effectiveness of these interventions.

Methods
A systematic literature search was conducted and included articles from 2013 – 2023. Twenty-four studies met the inclusion criteria, covering a total of 26 unique interventions. Definitions were categorized as: resilience as a trait, process, or outcome. Cohen’s D was calculated to depict the effect sizes within the intervention groups from pre-test to post-test and, when possible, from pre-test to 3-month follow-up.

Results
Included studies applied a wide range of definitions; most definitions fitted within the trait-orientation, conceptualizing resilience as an individual characteristic or ability, or the process-orientation, conceptualizing resilience as a dynamic process. No studies solely used the outcome-orientation, but some did combine elements of all three orientations. Various definitions, measures and intervention strategies were applied, however, almost half of the studies (46%) showed inconsistencies within these choices. Furthermore, findings show that most resilience-based interventions in the workplace have a positive impact. While educational workshops with a higher frequency and duration had medium to large effects, solely digital interventions had small effects, changing to small to medium when combined with non-digital elements.

Conclusions
Findings suggest that resilience-based can benefit employees by enhancing their psychological well-being. This, in turn, can lead to improved work-related outcomes such as productivity, thereby offering advantages to employers as well. This underscores the growing recognition that resilience should be viewed as a shared responsibility between the individual and the organization. Further advancement in the field of resilience-based interventions in the workplace calls for future research to focus on maintaining consistency when choosing a definition of resilience, developing intervention content, and choosing an outcome measure.

Preregistration
The search protocol was preregistered in the Open Science Framework, see Hollaar et al. (2023). https://doi.org/10.17605/OSF.IO/UKYF7.
Community benefits of mass distribution of three types of dual-active-ingredient long-lasting insecticidal nets against malaria prevalence in Tanzania: evidence from a 3-year cluster-randomized controlled trial
Authors: Lukole Eliud Andrea , Cook Jackie , Mosha Jacklin F , Matowo Nancy S , Kulkarni Manisha A , Mallya Elizabeth , Aziz Tatu , Martin Jacklin , Rowland Mark , Kleinschmidt Immo , Manjurano Alphaxard , Mosha Franklin W , Protopopoff Natacha 
Published: January 2025

Abstract

Background
Long-lasting insecticidal nets (LLINs) were once fully effective for the prevention of malaria; however, mosquitoes have developed resistance to pyrethroids, the main class of insecticides used on nets. Dual active ingredient LLINs (dual-AI LLINs) have been rolled out as an alternative to pyrethroid (PY)-only LLINs to counteract this. Understanding the minimum community usage at which these LLINs elicit an effect that also benefits non-users against malaria infection is important.

Methods
We conducted a secondary analysis of a 3-year randomized controlled trial (RCT) in 84 clusters in North-western Tanzania to evaluate the effectiveness of three dual-AI LLINs: pyriproxyfen and alpha(α)-cypermethrin, chlorfenapyr and α-cypermethrin, and the piperonyl-butoxide (PBO) and permethrin compared to α-cypermethrin only LLINs. We measured malaria infection prevalence using 5 cross-sectional surveys between 2020 and 2022. We assessed net usage at the cluster level and malaria infection in children aged from 6 months to 14 years in 45 households per cluster. The trial was registered as a clinical trial on www.clinicaltrials.gov: ClinicalTrials.gov (NCT03554616) on 2018-06-13.

Results
A total of 22,479 children from 12,654 households were tested for malaria using rapid diagnostic tests in January 2020, 2021, & 2022 and July 2020 & 2021. Among non-users, community-level usage of > 40% of dual-AI LLIN was significantly associated with protection against malaria infection: chlorfenapyr arm (OR: 0.44 (95% CI: 0.27–0.71), p = 0.0009), PBO arm (OR: 0.55 (95% CI: 0.33–0.94), p = 0.0277) and pyriproxyfen arm (OR: 0.61 (95% CI: 0.37–0.99), p = 0.0470) compared with non-users in clusters with > 40% usage of pyrethroid-only LLINs. There were indications of some protection against malaria infection to non-users in the chlorfenapyr arm when community-level usage was ≤ 40% (OR: 0.65 (95% CI: 0.42–1.01), p = 0.0528) compared to those living in clusters with > 40% usage of pyrethroid-only LLINs.

Conclusion
Our study demonstrated that at a community usage of 40% or more of dual-AI LLINs non-users benefited from the presence of these nets. Noticeably, even when usage was ≤ 40% in the chlorfenapyr arm, non-users were better protected than non-users in the higher coverage pyrethroid-only arm. The greater difference in malaria risk observed between users and non-users indicates that LLINs play a crucial role in providing personal protection against malaria infection for the people using the net.
Falls and balance impairment; what and how has this been measured in adults with joint hypermobility? A scoping review
Authors: Wang Yiduo , Strutton Paul H. , Alexander Caroline M. 
Published: January 2025

Abstract

Background
People with joint hypermobility have excessive joint flexibility, which is more common in young women. The people with symptomatic hypermobility report poor balance and even falls. This scoping review aims to identify and map the available evidence related to balance and falling in adults with joint hypermobility to support research planning and ideas for treatment direction.

Methods
A framework for the search was constructed using the Joanna Briggs Institute (JBI) approach. Electronic searches of primary evidence were performed using the following databases: Medline, Web of Science, CINAHL, Scopus and EMBASE. Papers written in English and published between 1946 and November 2023 were included. Titles, abstracts, and full papers were independently screened by two reviewers. Data extracted related to the population, the concept under investigation, the method of measurement, the level of evidence and the result.

Results
Nineteen of 1,950 screened articles were included. In terms of the population, details related to ethnicity of the research participants was missing. The hypermobility classification criteria varied; it was not always clear if people who were hypermobile had symptoms. Concepts related to fear of falling, balance and adaptive strategies prompted by different postural tasks with and without vision were explored. Centre of pressure, muscle activity, kinematics and psychological factors were measured using force plates, electromyography (EMG), motion capture, patient and clinician reported outcome measures, focus groups and interviews. Most papers were low on the hierarchy of evidence (i.e. equal or lower than a case control study). The participants with joint hypermobility had increased sway, different muscle activity, and different kinematics compared to people without hypermobility. When surveyed, they commonly fell and had a fear of falling.

Conclusions
It is unclear whether the participants represent the population of people with hypermobility. Different classification systems were used making it difficult to generalise the results. Although the methods used suggest a low level of evidence, it seems clear that people who are hypermobile have poor balance. The underlying mechanisms driving poor balance have not been explored in depth.
Mental health literacy among primary care providers in Hungary: a vignette-based survey
Authors: Swisher Valerie S. , Őri Dorottya , Rihmer Zoltán , Wernigg Róbert 
Published: January 2025

Abstract

Objective
This study examined mental health literacy and predictors of disorder recognition among primary care providers (PCPs) in Hungary.

Methods
208 PCPs in Hungary completed a survey assessing demographics, mental health stigma, and exposure to mental health (i.e., personal experiences and having a family member/friend with a mental health condition). Participants read six vignettes describing obsessive-compulsive disorder (OCD) harm/aggression subtype (OCD-Aggression), OCD order/symmetry subtype (OCD-Order), generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder (PD), and major depressive disorder (MDD) and were asked to identify each condition, perceived disorder causes, and provide treatment referrals. Descriptive analyses were used to characterize disorder recognition rates, perceived disorder causes, and treatment referrals. Binary logistic regression analyses were conducted to examine the degree to which demographic characteristics, mental health stigma, and exposure to mental health conditions predict accurate disorder recognition.

Results
Identification rates for each vignette were: OCD-Aggression (27.9%), OCD-Order (75.5%), SAD (34.1%), GAD (76.0%), PD (78.8%), and MDD (91.3%). First-choice treatment referrals were a psychiatrist for OCD-Aggression (63.0%), OCD-Order (53.8%), and MDD (46.6%), a psychologist/therapist for SAD (58.7%) and GAD (48.6%), and a PCP for PD (39.9%). Mislabeling conditions was significantly associated with older age (for GAD, OCD-Aggression, PD and MDD), male gender (for GAD), greater mental health stigma (for OCD-Order), and lack of exposure to mental health conditions (for SAD).

Conclusions
Findings highlight strengths (e.g., depression recognition) and limitations in knowledge of mental health conditions among PCPs in Hungary and identifies targets to address to improve mental health literacy.