bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is maternal diabetes during pregnancy associated with neurodevelopmental, cognitive and behavioural outcomes in children? Insights from individual participant data meta-analysis in ten birth cohorts
Authors: Pretorius Rachelle A. , Avraam Demetris , Guxens Mònica , Julvez Jordi , Harris Jennifer R. , Nader Johanna Thorbjornsrud , Cadman Tim , Elhakeem Ahmed , Strandberg-Larsen Katrine , Marroun Hanan El , Defina Serena , Yang Tiffany C. , McEachan Rosie , Wright John , Ibarluzea Jesús , Santa-Marina Loreto , Delgado Juana Mari , Rebagliato Marisa , Charles Marie-Aline , Vainqueur Chloe , Maritano Silvia , Zugna Daniela , Yuan Wen Lun , Heude Barbara , Huang Rae-Chi 
Published: January 2025

Abstract

Background
Growing evidence shows that dysregulated metabolic intrauterine environments can affect offspring’s neurodevelopment and behaviour. However, the results of individual cohort studies have been inconsistent. We aimed to investigate the association between maternal diabetes before pregnancy and gestational diabetes mellitus (GDM) with neurodevelopmental, cognitive and behavioural outcomes in children.

Methods
Harmonised data from > 200 000 mother-child pairs across ten birth cohorts in Europe and Australia were available. Mother-child pairs were included for analysis to determine whether GDM was recorded (yes or no) and whether at least one neurodevelopmental, cognitive and behavioural outcome was available in children aged 3 to 13 years. Confounder-adjusted regression models were used to estimate associations between maternal diabetes and child outcomes using two-stage individual participant data (IPD) meta-analysis. Model 1 included a crude estimate. The full adjustment model (model 2) included adjustment for child sex, maternal age, pre-pregnancy BMI, pregnancy weight gain, maternal smoking during pregnancy, plurality, parity and maternal education.

Results
Children (aged 7–10 years) born to mothers with GDM had higher attention-deficient hyperactive disorder (ADHD) symptoms compared to non-exposed controls (model 2, regression coefficient (β) 3.67 (95% CI 1.13, 6.20), P = 0.001). Moreover, children (aged 4–6 years) born to mothers with GDM exhibited more externalising problems than those born to mothers without GDM (model 2, β 2.77 (95% CI 0.52, 5.02), P = 0.01). A pre-existing maternal history of type 1 and type 2 diabetes mellitus was associated with ADHD symptoms at 4–6 years (model 1, β 8.82 (95% CI 2.21, 15.45, P = 0.009) and β 7.90 (95% CI 0.82, 14.98, P = 0.02), respectively). The association was no longer apparent in further adjustments.

Conclusions
This study found that children between 4 - 6 and 7–10 years of age born to mothers with GDM have a greater likelihood of developing externalising problems and ADHD symptoms, respectively. Externalising problems often co-exist with ADHD symptoms and precede formal ADHD diagnosis. Overall, this large-scale multi-cohort study suggested that a dysregulated metabolic environment during pregnancy may contribute to ADHD symptoms and externalising problems in young children.
Extracellular matrix stiffness regulates colorectal cancer progression via HSF4
Authors: Wang Kangtao , Ning Siyi , Zhang Shuai , Jiang Mingming , Huang Yan , Pei Haiping , Li Ming , Tan Fengbo 
Published: January 2025

Abstract

Background
Colorectal cancer (CRC) has high incidence and mortality rates, with severe prognoses during invasion and metastasis stages. Despite advancements in diagnostic and therapeutic technologies, the impact of the tumour microenvironment, particularly extracellular matrix (ECM) stiffness, on CRC progression and metastasis is not fully understood.

Methods
This study included 107 CRC patients. Tumour stiffness was assessed using magnetic resonance elastography (MRE), and collagen ratio was analysed with Masson staining. CRC cell lines were cultured on matrices of varying stiffness, followed by transcriptome sequencing to identify stiffness-related genes. An HSF4 knockout CRC cell model was cultured in different ECM stiffness to evaluate the effects of HSF4 on cell proliferation, migration, and invasion in vitro and in vivo.

Results
CRC tumour stiffness was significantly higher than normal tissue and positively correlated with collagen content and TNM staging. High-stiffness matrices significantly regulated cell functions and signalling pathways. High HSF4 (heat shock transcriptional factor 4) expression was strongly associated with tumour stiffness and poor prognosis. HSF4 expression increased with higher TNM stages, and its knockout significantly inhibited cell proliferation, migration, and invasion, especially on high-stiffness matrices. In vivo experiments confirmed that HSF4 promoted tumour growth and metastasis, independent of collagen protein increase.

Conclusions
This study reveals that tumour stiffness promotes the proliferation and metastasis of CRC by regulating EMT-related signalling pathways through HSF4. Tumour stiffness and HSF4 could be valuable targets for prognostic assessment and therapeutic intervention in CRC.
Whole exome sequencing-based homologous recombination deficiency test for epithelial ovarian cancer
Authors: Chiang Ying-Cheng , Huang Hsien-Neng , Kuo Kuan-Ting , Hwu Wuh-Liang , Lin Po-Han 
Published: January 2025

Abstract

Background
The homologous recombination deficiency (HRD) test is an important tool for identifying patients with epithelial ovarian cancer (EOC) benefit from the treatment with poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi). Using whole exome sequencing (WES)-based platform can provide information of gene mutations and HRD score; however, the clinical value of WES-based HRD test was less validated in EOC.

Methods
We enrolled 40 patients with EOC in the training cohort and 23 in the validation cohort. The WES-based HRD score was calculated using the scarHRD software. We first evaluated the concordance of the HRD status defined by the Myriad MyChoice CDx and then assessed the value of HRD on clinical prognosis in patients with EOC.

Results
The HRD score defined by the WES-based test was positively correlated with that of the Myriad MyChoice® CDx test (r = 0.82, p < 0.01) in the training cohort. In compared to HRD status of Myriad test, the sensitivity, specificity, positive predictive value, and negative predictive value of the WES-based HRD test were 93.5% (29/31), 77.8% (7/9), 93.5% (29/31), and 77.8% (7/9), respectively. Patients with positive HRD status defined by WES-based scarHRD test and Myriad MyChoice® CDx test were both highly associated with platinum sensitive response (both Fisher’s exact test, p = 0.002) as well as the superior progression-free survival (both log-rank p = 0.002). The multi-variate Cox regression model incorporated with optimal debulking surgery showed that the recurrence risk was decreased in the patients with positive HRD status, either defined by Myriad MyChoice® CDx test (Hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.14–0.79, p = 0.013) or WES-based test Myriad MyChoice® CDx test (HR 0.34, 95% CI 0.14–0.80, p = 0.014). Nine patients had mutations in the genes involved in HR DNA repair, and all of them were positive for HRD. In the validation group, 23 patients were defined as positive HRD by WES-based testing. Six positive HRD patients and 5 negative HRD patients received maintenance PARPi. The median responsive interval of PARPi was 17 months in positive HRD patients and 3 months in negative HRD patients.

Conclusion
The WES-based test is a potential option for determining the HRD status in EOC patients, and desires for further validation in large-scale cohorts.
Decision tree-based learning and laboratory data mining: an efficient approach to amebiasis testing
Authors: Al-khlifeh Enas , Tarawneh Ahmad S. , Almohammadi Khalid , Alrashidi Malek , Hassanat Ramadan , Hassanat Ahmad B. 
Published: January 2025

Abstract

Background
Amebiasis represents a significant global health concern. This is especially evident in developing countries, where infections are more common. The primary diagnostic method in laboratories involves the microscopy of stool samples. However, this approach can sometimes result in the misinterpretation of amebiasis as other gastroenteritis (GE) conditions. The goal of the work is to produce a machine learning (ML) model that uses laboratory findings and demographic information to automatically predict amebiasis.

Method
Data extracted from Jordanian electronic medical records (EMR) between 2020 and 2022 comprised 763 amebic cases and 314 nonamebic cases. Patient demographics, clinical signs, microscopic diagnoses, and leukocyte counts were used to train eight decision tree algorithms and compare their accuracy of predictions. Feature ranking and correlation methods were implemented to enhance the accuracy of classifying amebiasis from other conditions.

Results
The primary dependent variables distinguishing amebiasis include the percentage of neutrophils, mucus presence, and the counts of red blood cells (RBCs) and white blood cells (WBCs) in stool samples. Prediction accuracy and precision ranged from 92% to 94.6% when employing decision tree classifiers including decision tree (DT), random forest (RF), XGBoost, AdaBoost, and gradient boosting (GB). However, the optimized RF model demonstrated an area under the curve (AUC) of 98% for detecting amebiasis from laboratory data, utilizing only 300 estimators with a max depth of 20. This study highlights that amebiasis is a significant health concern in Jordan, responsible for 17.22% of all gastroenteritis episodes in this study. Male sex and age were associated with higher incidence of amebiasis (P = 0.014), with over 25% of cases occurring in infants and toddlers.

Conclusions
The application of ML to EMR can accurately predict amebiasis. This finding significantly contributes to the emerging use of ML as a decision support system in parasitic disease diagnosis.

Graphical Abstract
Gene expression of psychiatric disorder-related kinesin superfamily proteins (Kifs) is potentiated in alternatively activated primary cultured microglia
Authors: Iwata Suguru , Hyugaji Mitsuhiro , Soga Yohei , Morikawa Momo , Sasaki Tetsuya , Takei Yosuke 
Published: January 2025

Abstract

Objective
Reactivity of microglia, the resident cells of the brain, underlies innate immune mechanisms (e.g., injury repair), and disruption of microglial reactivity has been shown to facilitate psychiatric disorder dysfunctions. Although cellular analyses based on cultured microglia have been conducted, the molecular mechanism regulating microglial polarization remains elusive. We established a primary microglia culture that enabled manipulation of the substate of cells. This allowed us to investigate the expression levels of psychiatric disorder-related Kifs messenger RNA (mRNA) in each condition. Kifs encode molecular motor proteins that transport cargo along microtubules, which are thought to dynamically reorganize during a substate change.

Results
As a candidate for a crucial Kifs gene that is associated with microglia polarization, we selected psychiatric disorder-related Kifs including Kif17. We found that the relative amounts of Kif3a, Kif17, and Kif13a mRNA were potentiated in alternatively activated microglia, whereas there were no significant changes in activated microglia. Furthermore, the microglia derived from a mouse line which possesses a mutation inducing truncated KIF17 indicated disrupted morphological phenotype of alternatively activated microglia. These results suggest that the potentiation of specific molecular motor expression is required to maintain the function of alternatively activated microglia.
Biofilm characterisation of Mycoplasma bovis co-cultured with Trueperella pyogenes
Authors: Nishi Koji , Gondaira Satoshi , Hirano Yuki , Ohashi Masahide , Sato Ayano , Matsuda Kazuya , Iwasaki Tomohito , Kanda Takuya , Uemura Ryoko , Higuchi Hidetoshi 
Published: January 2025

Abstract

Mycoplasma pneumonia, caused by Mycoplasma bovis (Mycoplasmopsis bovis; M. bovis), is linked with severe inflammatory reactions in the lungs and can be challenging to treat with antibiotics. Biofilms play a significant role in bacterial persistence and contribute to the development of chronic lesions. A recent study has shown that polymicrobial interactions between species are an important factor in biofilm formation, yet the precise mechanism of biofilm formation in M. bovis remains unknown. By assuming multiple pathogen infections in the bovine respiratory disease complex (BRDC), this study examined the characterisation of the polymicrobial relationship between M. bovis and Trueperella pyogenes (T. pyogenes) during biofilm formation. Autopsies were performed on four Holstein calves (two chronic Mycoplasma pneumonia calves and two control calves). Bacterium-like aggregation structures (> 10 μm), which were assumed to be biofilms of M. bovis in vivo, were observed adhering to the cilia in calves with Mycoplasma pneumonia. M. bovis released an extracellular matrix to connect with neighbouring bacteria and form a mature biofilm on the plate. Biofilm formation in the co-culture of M. bovis and T. pyogenes (strain T1: 1 × 105 and 1 × 106 CFU/well) significantly increased (p < 0.05 and p < 0.01; 64.1% and 64.8% increase) compared to that in a single culture of these bacteria. Furthermore, some large aggregates (> 40 μm), composed of M. bovis and T. pyogenes, were observed. The morphological characteristics of this biofilm were similar to those observed in vivo compared to a single culture. In conclusion, the polymicrobial interaction between M. bovis and T. pyogenes induces biofilm formation, which is associated with increased resistance to antimicrobial agents, and this exacerbates the progression of chronic Mycoplasma pneumonia.
Influence of mechanical stress on biomass allocation in three species (Pachira aquatica Aubl., Sextonia rubra (Mez) van der Werff and Simarouba amara Aubl.) with contrasting posture control mechanisms
Authors: Ghislain Barbara , Coste Sabrina , Faure Grégory , Cazal Jocelyn , Prunier Jonathan , Clair Bruno 
Published: January 2025

Abstract

Key message
The posture control in Pachira aquatica, Sextonia rubra and Simarouba amara is achieved through contrasted mechanisms involving tensile stress in wood only, bark only or both. This study evidenced that the restoration of verticality does not imply an overall cost for trees but modifies growth kinetics and biomass allocation to organs and tissues, improving the posture control of the trees in the three species.

Context
All trees need a motor system to correct their position through the generation of asymmetric tensile stress around the stem, leading to active bending. In angiosperms, depending on the species, tensile stress is generated either in wood (tension wood), in bark or in both.

Aims
Here, we investigated how gravitropic stimuli (tilted stems without any movement) may affect growth and biomass allocation and whether this process depends on the posture control mechanism of the species.

Methods
Tree growth kinetics, final biomass allocation and wood and bark proportion, localisation and density were measured on young tilted plants and straight plants as controls. Pachira aquatica, Sextonia rubra and Simarouba amara were selected according to the location of their their motor system within bark only, wood only or both wood and bark, respectively.

Results
In response to tilting, trees from the three species increased their diameter and decreased their slenderness, but the total biomass (including stem and roots) was not different from that in the control trees, suggesting that reaction to artificial tilting does not imply a specific cost for the plant. However, the species exhibited strong differences in growth kinetics, in the amount and organisation of the tissues or in biomass allocation to different organs (root vs shoot, wood vs bark), adapted to the specificity of the posture control mechanisms and improving their motor function.

Conclusion
Whatever the posture control mechanism, uprighting does not modify the total biomass invested. However, allocation of biomass to different organs is strongly modified to obtain an efficient control of the posture.
Surrogate End Points for Overall Survival in Neoadjuvant Randomized Clinical Trials for Early Breast Cancer
Authors: Conforti Fabio , Nekljudova Valentina , Sala Isabella , Ascari Roberto , Solbach Christine , Untch Michael , Denkert Carsten , Bagnardi Vincenzo , Pala Laura , Fasching Peter A. , Schneeweiss Andreas , Lück Hans-Joachim , Pagan Eleonora , De Pas Tommaso , van Mackelenbergh Marion , Huober Jens , Müller Volkmar , Link Theresa , Karn Thomas , Reinisch Mattea , Marmé Frederik , Bjelic-Radisic Vesna , Schem Christian , Hartkopf Andreas , Stickeler Elmar , Hanusch Claus , Blohmer Jens-Uwe , Fehm Tanja , Rhiem Kerstin , Holtschmidt Johannes , Gelber Richard D. , Loibl Sibylle 
Published: January 2025

PURPOSE
To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC).

METHODS

Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination
R
2
from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points.

RESULTS

Eleven RCTs, for a total of 15 treatment comparisons and 12,247 patients, were included in the analysis. There was a weak association between hazard ratios (HRs) for OS and odds ratio of pCR overall (
R
2
, 0.07; 95% CI, 0.00 to 0.48), as well as in all the subgroups explored. Overall, the
R
2
for the association between HR OS and HR iDFS was 0.46 (95% CI, 0.08 to 0.71), which is just below the cutoff of 0.5 for moderate surrogacy. In the majority of subgroups explored, the
R
2
ranged from 0.5 to <0.7, while in hormone receptor–/human epidermal growth factor receptor 2– subtype, histologic grade 1-2 tumors, and lobular tumors, surrogacy was strong (ie,
R
2
≥0.7). The surrogacy value of iDFS for OS was affected by follow-up (FUP) length:
R
2
substantially increased up to 36 months of FUP, with little further improvement after 48 months of FUP.

CONCLUSION
iDFS with sufficient FUP is an acceptable surrogate end point to confidently anticipate final OS results of neoadjuvant RCTs for early BC. This recommendation holds true across many subgroups, with the notable exception of HR+ disease. There is definite need to reassess whether OS is the optimal end point for treatment efficacy measurement in HR+ early BC.
Results From First-in-Human Phase I Study of a Novel CD19-1XX Chimeric Antigen Receptor With Calibrated Signaling in Large B-Cell Lymphoma
Authors: Park Jae H. , Palomba M. Lia , Perica Karlo , Devlin Sean M. , Shah Gunjan , Dahi Parastoo B. , Lin Richard J. , Salles Gilles , Scordo Michael , Nath Karthik , Valtis Yannis K. , Lynch Alec , Cathcart Elizabeth , Zhang Honglei , Schoder Heiko , Leithner Doris , Liotta Kelly , Yu Alina , Stocker Kelsey , Li Jia , Dey Agnish , Sellner Leopold , Singh Reshma , Sundaresan Varsha , Tong Xin , Zhao Faye , Mansilla-Soto Jorge , He Changhao , Meyerson Joel , Hosszu Kinga , McAvoy Devin , Wang Xiuyan , Rivière Isabelle , Sadelain Michel 
Published: January 2025

PURPOSE
We designed a CD19-targeted chimeric antigen receptor (CAR) comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3ζ and 4-1BB/CD3ζ CARs. Preclinical data demonstrated that 1XX CARs generated potent effector function without undermining T-cell persistence. We hypothesized that 1XX CAR T cells may be effective at low doses and elicit minimal toxicities.

METHODS

In this first-in-human, phase I, dose escalation and expansion clinical trial, patients with relapsed or refractory large B-cell lymphoma received 19(T2)28z-1XX CAR T cells at four dose levels (DLs), ranging from 25 to 200 × 10
6
.

RESULTS

Twenty-eight patients underwent apheresis and received CAR T cells. Sixteen and 12 patients were treated in the dose escalation and expansion cohorts, respectively. The overall response rate (ORR) was 82% and complete response (CR) rate was 71% in the entire cohort. The lowest dose of 25 × 10
6
was selected for dose expansion. In 16 patients treated at this DL, 88% achieved ORR and 75% CR. With the median follow‐up of 24 months, the 1-year event-free survival was 61% (95% CI, 45 to 82) and 14 patients remain in continuous CR beyond 12 months. In all cohorts, grade ≥3 cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome rates were low at 4% and 7%, respectively. 1XX CAR T-cell products contain a higher proportion of CD8 T cells with memory features, and CAR T-cell persistence has been detected beyond 1-2 years in patients with ongoing remission.

CONCLUSION
The calibrated potency of the 1XX CAR affords excellent efficacy at low cell doses with favorable toxicity profiles and may benefit the treatment of other hematologic malignancies, solid tumors, and autoimmunity.
Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions
Authors: Choi Wangsun , Goldfarb Dennis , Yan Feng , Major Michael B. , Fanning Alan S. , Peifer Mark 
Published: January 2025

ABSTRACT
The network of proteins at the interface between cell-cell adherens junctions and the actomyosin cytoskeleton provides robust yet dynamic connections that facilitate cell shape change and motility. While this was initially thought to be a simple linear connection via classic cadherins and their associated catenins, we now have come to appreciate that many more proteins are involved, providing robustness and mechanosensitivity. Defining the full set of proteins in this network remains a key objective in our field. Proximity proteomics provides a means to define these networks. Mammalian Afadin and its Drosophila homolog Canoe are key parts of this protein network, facilitating diverse cell shape changes during gastrulation and other events of embryonic morphogenesis. Here we report results of several proximity proteomics screens, defining proteins in the neighborhood of both the N- and C-termini of mammalian Afadin in the premier epithelial model, MDCK cells. We compare our results with previous screens done in other cell types, and with proximity proteomics efforts with other junctional proteins. These reveal the value of multiple screens in defining the full network of neighbors and offer interesting insights into the overlap in protein composition between different epithelial cell junctions.