bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parent-of-Origin inference and its role in the genetic architecture of complex traits: evidence from ~265,000 individuals
Authors: Kutalik Zoltán , Hofmeister Robin , Cavinato Theo , Karimi Roya , Graaf Adriaan van der , Pajuste Fanny-Dhelia , Kronberg Jaanika , Taba Nele , Magi Reedik , Vaudel Marc , Rubinacci Simone , Johansson Stefan , Milani Lili , Delaneau Olivier 
Published: January 2025

Abstract

Parent-of-origin effects (POEs) occur when the impact of a genetic variant depends on its parental origin. Traditionally linked to genomic imprinting, these effects are believed to have evolved from parental conflict over resource allocation to offspring, which results in opposing parental genetic influences. Despite their potential importance, POEs remain heavily understudied in complex traits, largely due to the lack of parental genomes.
Here, we present a multi-step approach to infer the parent-of-origin of alleles without parental genomes, leveraging inter-chromosomal phasing, mitochondrial and chromosome X data, and sibling-based crossover inference. Applied to the UK Biobank (discovery cohort) and Estonian Biobank (replication cohort), this scalable approach enabled parent-of-origin inference for up to 221,062 individuals, representing the largest dataset of its kind.
GWAS scans in the UK Biobank for more than 60 complex traits and over 2,400 protein levels contrasting maternal and paternal effects identified over 30 novel POEs and confirmed more than 50% of testable known associations. Notably, approximately half of our POEs exhibited a bi-polar pattern, where maternal and paternal alleles exert conflicting effects. These effects were particularly prevalent for traits related to growth (e.g., IGF-1, height, fat-free mass) and metabolism (e.g., type 2 diabetes, triglycerides, glucose). Replication in the Estonian Biobank and in 45,402 offspring from the Norwegian Mother, Father and Child Cohort Study validated over 75% of testable associations.
Overall, our findings shed new light on the influence of POEs on diverse complex traits and align with the parental conflict hypothesis, providing compelling evidence for this understudied evolutionary phenomenon.
Differences in Gate Apraxia Due to Reduced Regional Cerebral Blood Flow in the Supplementary Motor Area in Corticobasal Syndrome: A Report of Two Cases
Authors: Igari Kota , Fujimaki Motoki , Mai Mera , Sakuma Moe , Saiki Shinji 
Published: January 2025

Abstract

Background
Gait apraxia, characterized by difficulties initiating and coordinating walking despite preserved conceptual movement abilities, is a distinct entity from lower limb apraxia. Although gait apraxia has been associated with dysfunction of the frontal lobe, particularly the supplementary motor area (SMA), the specific associated somatotopic organization phenotype remains poorly understood. Corticobasal syndrome (CBS), a clinical phenotype of corticobasal degeneration, commonly presents with upper limb apraxia, while lower limb or gait apraxia has rarely been reported. Herein, we describe two rare cases of CBS presenting with gait apraxia shown to be caused by SMA dysfunction, based on regional cerebral blood flow (rCBF) reduction on single-photon emission computed tomography (SPECT).
Case presentation:
Case 1 was of an 82-year-old man who exhibited right-sided apraxic gait with freezing and shuffling patterns, along with SMA hypoperfusion in both the dorsal and pre-SMA regions. Neurological examination revealed mild rigidity, right-sided Babinski sign, and clumsiness in mimicking leg movements. Gait patterns were inconsistent and unresponsive to levodopa or sensory cues. Case 2 was of an 80-year-old man who demonstrated a peculiar gait characterized by exaggerated right leg movements and everted ankle positioning. Hypoperfusion was localized to the left dorsal SMA. Examination findings included rigidity and impaired hand weight perception. Sensory tricks and levodopa provided no benefit.
Conclusion
These cases highlight the role of SMA dysfunction in the pathogenesis of gait apraxia. Variations in rCBF reduction correlated with distinct gait patterns. For example, the freezing gait shown in Case 1 likely resulted from pre-SMA impairment, which is critical for movement initiation, while the exaggerated leg movements in Case 2 reflected dorsal SMA dysfunction, involved in motor execution. These results indicate that gait apraxia, which is often underdiagnosed, should be recognized as a potential early indicator of CBS. Further, these cases suggest that SMA dysfunction, identified through SPECT imaging, underlies the distinct gait patterns seen in CBS patients with apraxic gait. Recognizing these symptoms, even in the absence of weakness or limb apraxia, may aid in early CBS diagnosis and improve clinical management.
Analysis of BGN and pan-cancer correlations: based a Mendelian randomisation and bioinformatics study
Authors: Min GuangTao , Tang Hao , Min GuangNing , Li YuMin 
Published: January 2025

Abstract

Background/Objectives: To preliminarily explore the significance of BGN in various cancers using pan-cancer analysis.
Methods: Transcriptome data of 33 cancers were downloaded from TCGA database, and the expression levels of BGN in 33 cancers were extracted using Perl software. The limma package of R software was used to identify differential genes in some tumour types (paraneoplastic samples ≥5), and the clinical prognostic significance of BGN was analysed using Kaplan-Meier and Cox in conjunction with clinical information from TCGA. Mendelian randomisation was used to test for causal associations between BGN and multiple malignancies. The correlation between BGN and the tumour immune infiltration microenvironment was explored by ESTIMATE package, and the relationship between BGN and immune subtypes, clinical stage and tumour immune infiltration microenvironment were analysed in conjunction with TCGA-GTEx data. Analysis of clinical data of 180 patients with gastric cancer and immunohistochemical verification of the poor prognosis of BGN in gastric cancer.
Results: BGN was significantly differentially expressed in most of the tumours, and MR analysis revealed potential causal associations with colorectal, lung and cervical cancers, etc. BGN showed prognostic correlations with a variety of cancers in survival analyses (P < 0.05). Single-tumour analyses showed correlations between BGN and TNM staging, immune subtypes, and the tumour microenvironment. BGN expression promotes immune cell infiltration and expression of immune checkpoint-associated genes in the tumour microenvironment, and the higher the level of expression, the greater the stromal component and the less the immune component.BGN may be expressed via ECM receptor interaction, BGN may be involved in the process of tumour immune and inflammatory responses through ECM receptor interaction, ascorbate and aldarate metabolism, and other signalling pathways.
Conclusion: BGN plays an important role in tumour development and is expected to become a new prognostic marker and a potential target for immunotherapy in many types of cancers.
Variation in Morphology of the Suprascapular Nerve and Vessels at the Suprascapular Notch: Clinical Implications for Suprascapular Nerve Release
Authors: Heins BS Robert J. , Konstanty BS Jordan , Hemaya BS Justine , Hodge BS Travis , Olinger Anthony 
Published: January 2025

Abstract

Purpose
This study aimed to classify variation in morphology of the suprascapular nerve (SSN), suprascapular artery (SSA), and suprascapular vein (SSV) in relation to the superior transverse scapular ligament (STSL) at the suprascapular notch (SN) to evaluate the risk of vascular injury during SSN release.
Methods
Dissections were performed on 104 shoulders to analyze the morphology of the SSN, SSA, and SSV at the SN. The superior transverse scapular ligament (STSL) was evaluated for dimensions, ossification, and impact on SN morphology Configurations of the nerve and vessels were categorized, and vascular injury risk was stratified as low, moderate, or high.
Results
The SSN passed beneath the STSL in 99% of shoulders, while the SSA and SSV configurations varied. Low vascular injury risk was identified in 82% of shoulders, moderate risk in 10.6%, and high risk in 7.4%, with female cadavers demonstrating higher risk anatomy (13.3%) compared to males (2.0%). Ossified STSLs were significantly associated with smaller SN dimensions, including reduced height and width (p < 0.001).
Conclusion
Anatomical variations at the SN play a critical role in determining the risk of vascular injury during SSN release. Surgeons should consider these morphological differences, particularly in cases involving ossified STSLs or higher-risk configurations, to optimize surgical planning. This study underscores the importance of precise anatomical knowledge for minimizing complications in suprascapular procedures at the SN.
Efficacy of Daily 50 mg Intramuscular Progesterone for Luteal Phase Support in Frozen Embryo Transfer Cycles: Analysis of Serum Levels and Pregnancy Outcomes
Authors: Hatami Robabeh , Tehraninejad Ensieh Shahrokh , Rashidi Batool Hossein , Keikha Fatemeh , Masoumi Masoumeh , Barkhordarioon Amirali , Tarafdari Azadeh 
Published: January 2025

Abstract

Background
Frozen embryo transfer (FET) success depends on adequate luteal phase support (LPS), with serum progesterone (P4) levels on embryo transfer (ET) day being a critical factor. While serum P4 levels have been probably associated with improved outcomes, there is ongoing debate regarding the most effective route and dosage of P4 supplementation. This prospective cohort study aimed to (1) evaluate the efficacy of 50 mg/day intramuscular (IM) progesterone in achieving optimal serum P4 levels during endometrial preparation and (2) investigate the association between serum P4 levels on ET day and subsequent fertility outcomes in hormone replacement therapy (HRT) FET cycles.
Methods
The study included 121 women (aged 22–45 years) undergoing HRT-FET at Imam Khomeini Hospital Complex from December 2022 to January 2024. Endometrial preparation began with oral estradiol valerate (6 mg/day) on cycle day 2, followed by daily IM P4 (50 mg) upon achieving endometrial thickness ≥ 8 mm. Serum P4 levels were measured on ET day, and oral dydrogesterone (20 mg/day) was added for patients with P4 levels < 10.0 ng/mL. Primary outcomes included chemical pregnancy, clinical pregnancy, miscarriage, and ongoing pregnancy rates.
Results
The mean serum P4 level on ET day was 22.8 ± 10.1 ng/mL, with 78.5% of participants achieving the target range (10-32.5 ng/mL) following IM P4 administration. Overall chemical pregnancy, clinical pregnancy, and ongoing pregnancy rates were 23.1%, 18.2%, and 14.1%, respectively, with a miscarriage rate of 5.0%. Multivariate analysis revealed that P4 levels > 27.8 ng/mL were associated with reduced odds of chemical pregnancy (OR = 0.22; 95% CI: 0.05–0.92; p = 0.04), while no significant differences were observed in other pregnancy outcomes across P4 quartiles.
Conclusion
Daily administration of 50 mg IM P4 effectively achieved optimal serum P4 levels in most patients. While higher P4 levels (> 27.8 ng/mL) were associated with reduced chemical pregnancy rates, the absence of significant correlations with other pregnancy outcomes highlights the multifactorial nature of embryo implantation success. These findings emphasize the need for further research to refine P4 thresholds and identify additional predictive factors influencing pregnancy outcomes in FET cycles.
Topography-induced TKE budget behavior over an Amazon Forest
Authors: Laba Paulo Henrique , Dias Nelson Luís da Costa , Chamecki Marcelo , Dias Cléo Quaresma , Torkelson Gregory 
Published: January 2025

Abstract

Data from three different heights (35, 50 and 81 meters) of one of the ATTO Project towers in the Amazon forest were used to calculate the TKE (turbulence kinetic energy) budget and some other statistics within the RSL (roughness sublayer). In addition, the results obtained from the data were compared with large eddy simulation (LES). The analyses were carried out for unstable and stable cases. The vertical turbulence transport (Tv) and the vertical advection (Av) terms do not explain the imbalances found in the TKE budget, highlighting the importance of horizontal terms in complex terrain. Indeed, patterns independent of the time of day were found for Tv, horizontal and vertical velocity skewness, the vertical component velocity (w), and momentum and vertical TKE flux. The highest values of w were observed from the direction where there is a valley near the tower, which may indicate a topographical effect. Monin-Obukhov Similarity Theory (MOST) predictions, strictly applicable only in the inertial sublayer (ISL), gave reasonable predictions at the 35 m level. At 81 m, there were clear deviations from MOST, disclosing the effect of topography. Finally, the results obtained with LES were in general agreement with tower observations.
Transforming Alzheimer's Treatment: Unveiling New Potential with Drug Repurposing Strategies
Authors: Mishra Ashish Sriram , Vasantham Manimaran , Ghosh Bhavna , Malliappan Sivakumar Ponnurengam 
Published: January 2025

Abstract:
Alzheimer's disease (AD) remains a significant challenge in neurology,
marked by progressive cognitive decline and neurodegeneration. Despite extensive research
efforts, effective treatments are still lacking. Traditional drug discovery is often
slow and costly, frequently resulting in limited success. Drug repurposing, which identifies
new therapeutic uses for existing medications, has emerged as a promising approach
to expedite AD treatment development. This review examines the potential of drug repurposing
to transform AD therapy by utilizing the established safety profiles and
known mechanisms of current drugs. We explore various repurposed drugs under investigation
for AD, originally intended for cardiovascular, metabolic, and psychiatric conditions.
Detailed discussions include how these drugs provide neuroprotective benefits by
inhibiting amyloid-beta aggregation, reducing tau phosphorylation, and modulating neuroinflammation.
Additionally, we emphasize the benefits of drug repurposing, such as
shortened development timelines, lower costs, and increased chances of clinical success.
By integrating current research findings, this review offers a thorough overview of the
most promising repurposed drug candidates and their potential impact on AD treatment
strategies. It stresses the importance of innovative approaches in AD research and calls
for greater investment in drug repurposing initiatives. Through these strategies, we aim
to accelerate the availability of effective treatments, providing renewed hope and a
brighter future for those affected by this devastating disease.
CERVIXNET: An Efficient Approach for the Detection and Classifications of the Cervigram Images Using Modified Deep Learning Architecture
Authors: Karthikeyan N. , Chandrasekaran Gokul , Sudha S. 
Published: January 2025

Introduction:
The earlier detection of cervical cancer in women patients can save human life. This article proposes a novel methodology for detecting abnormal
cervigram images from healthy cervigram images and segments the cancer regions in the abnormal cervigram images using the deep learning
method. The conventional deep learning architecture has been modified into the proposed CervixNet architecture to improve the cervical cancer
detection rate.

Methods:
This methodology is constituted of a training and testing process, where the training process generates the training sequences individually for
healthy cervigram images and the cancer case cervigram images. The testing process tests the cervigram images into either a healthy or cancer
cases using the training sequences generated through the training process. During the testing process of the proposed system, the cancer
segmentation algorithm was applied on the abnormal cervigram image to detect and segment the pixels belonging to cancer. Finally, the
performance has been carried out on the segmented cancer cervical images for the ground truth images. This proposed methodology has been
evaluated on the cervigrams on IMODT and Guanacaste databases. Its performance has been analyzed concerning cancer pixel sensitivity, cancer
pixel specificity and cancer pixel accuracy.

Results:
This research work obtains 98.69% Cancer Pixel Sensitivity (CPS), 98.76% Cancer Pixel Specificity (CPSP), and 99.27% Cancer Pixel Accuracy
(CPA) for the set of cervigram images in the IMODT database. This research work obtains 99.22% CPS, 99.03% CPSP, and 99.01% CPA for the
set of cervigram images in Guanacaste database.

Conclusion:
These experimental results of the proposed work have been significantly compared with the state-of-the-art methods and show the significance and
novelty of the proposed works.
Synthetic Strategies for the Development of Novel Heterocycles as Larvicides Targeting Aedes aegypti Linn.
Authors: Brito Thaysnara Batista , Oliveira Luana Marília Santos , Nunes Rafaela Karolina Viana , Maistro Edson Luis , Cavalcanti Socrates Cabral de Holanda 
Published: January 2025

Background:
Owing to their extensive utilization as pesticides, heterocycles assume a
fundamental role in the management of vector-borne diseases. Despite the presence of numerous
heterocyclic compounds in commercial insecticides and larvicides, resistance to pesticides still
demands novel strategies to current pest control methods. Considering these facts, this review
aims to survey the synthesis and SAR of heterocyclic molecules with larvicidal activity against
Aedes aegypti Linn.

Methods:
Comprehensive searches across the major databases were conducted to identify heterocyclic
compounds exhibiting larvicidal efficacy against Ae. aegypti with the goal to unveil the
main characteristics that are essential for exhibiting larvicidal activity.

Results:
Active compounds display LC50 values varying from 0.36 to 2907 μM. Fifteen heterocyclic
compounds displayed larvicidal activities below 20 μM. Five-membered ring molecules containing
nitrogen and oxygen have displayed larvicidal activity according to the position of heteroatoms
in the ring. Molecules bearing 1,2,4-oxadiazole and 1,2-oxazole moieties have been
shown to be more active than 1,3,4-oxadiazole derivatives. Compounds possessing the indole
scaffold have proven to be more potent than isatin and pyrimidine derivatives. Structural characteristics
other than a heterocyclic moiety, such as the presence of halogens and less ionized and
polar molecules, may also play a role in determining the final larvicidal activity.

Conclusion:
The rationale behind this review is to stimulate the discovery of innovative heterocyclic
larvicides. Thus, it is important to continue synthesizing new scaffolds to comprehensively
elucidate the structure-activity relationship for each heterocyclic moiety outlined in this investigation.
Anti-arthritic Effects of Undifferentiated and Chondrogenic Differentiated MSCs in MIA-induced Osteoarthritis in Wistar Rats: Involvement of Oxidative Stress and Immune Modulation
Authors: Saleh Ablaa S. , Abdel-Gabbar Mohammed , Gabr Hala , Shams Anwar , Tamur Shadi , Mahdi Emad A. , Ahmed Osama M. 
Published: January 2025

Introduction:
Osteoarthritis (OA) is a degenerative joint disease that can affect the
many tissues of the joint. There are no officially recognized disease-modifying therapies for clinical
use at this time probably due to a lack of complete comprehension of the pathogenesis of the
disease. In recent years, emerging regenerative therapy and treatments with stem cells both undifferentiated
and differentiated cells have gained much attention as they can efficiently promote tissue
repair and regeneration.

Methods:
To determine how bone marrow-derived mesenchymal stem cells (BM-MSCs) and
chondrogenic differentiated MSCs (CD-MSCs) can treat OA in rats, OA was induced in Wistar
rats by injecting three doses of 100 μL physiological saline containing 1 mg of MIA into rat ankle
joint of the right hind leg for three consecutive days. Following the induction, the osteoarthritic
rats were injected weekly with BM-MSCs or CD-MSCs at a dose of 1x106 cells/rat/dose for three
weeks. In addition to morphological and histological investigations of the ankle, spectrophotometric,
ELISA, and Western blot analyses were applied to detect various immunological and molecular
parameters in serum and ankle.

Results:
The results of the study showed that in osteoarthritic rats, BM-MSCs and CD-MSCs significantly
reduced right hind paw circumference, total leucocyte count (TLC), differential leukocyte
count (DLC) of neutrophils, monocytes, lymphocytes, and eosinophils, serum rheumatoid factor
(RF), prostaglandin E2 (PGE2) and interleukin (IL-) 1β levels, while they elevated serum
IL-10 level. Additionally, BM-MSCs and CD-MSCs markedly reduced lipid peroxides (LPO) levels
while they elevated superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities.
The monocyte chemoattractant protein-1 (MCP-1) level was significantly downregulated in
ankle joint articular tissues by treatment with BM-MSCs or CD-MSCs while nuclear factor erythroid
2-related factor 2 (Nrf2) was upregulated; CD-MSCs treatment was more effective.

Conclusion:
According to these findings, it can be inferred that BM-MSCs and CD-MSCs have
anti-arthritic potential in MIA-induced OA; CD-MSCs therapy is more effective than MSCs. The
ameliorative anti-arthritic effects may be mediated by suppressing inflammation and oxidative
stress through the downregulation of MCP-1 and upregulation of Nrf2. Based on the obtained results,
BM-MSCs and CD-MSCs therapies are promising new options that can be associated with
other clinical treatments to improve cartilage regeneration and joint healing. However, more preclinical
and clinical research is required to assess the benefits and safety of treating osteoarthritic
patients with BM-MSCs and CD-MSCs.