bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Quantitative Evaluation of the Effects of Radiation Therapy on the Post-Surgical Breast.
Authors: Becker Miriam , Reese McKay , Yessaillian Andrea , Lopes Kelli , Harfouche Cyril , Leach Garrison , Blair Sarah , Yashar Catheryn , Ojeda-Fournier Haydee , Reid Chris M 
Published: September 2024

Background:
Radiation (RT) effects on breast volume may impact breast-conserving therapy (BCT) outcomes, but quantitative information is lacking regarding the extent/timing of volume loss. This study aimed to quantify volume loss by assessing changes in irradiated breasts.

Methods:
Breast volume changes were calculated for 113 patients (115 breasts) following T1 tumor lumpectomies. From preoperative baseline to seven years post-radiation, volumes were calculated from mammograms using π/3* height*radius2. Paired t-tests assessed change over time, with subset analyses of tumor/breast volumes of ≤ 10% (n=67) and > 10% (n=48). Multivariable regression assessed volume change as a function of age, smoking history, diabetes, radiation dosage, fractions, technique, treatment length, boost dose, chemotherapy (hormonal or cytotoxic), baseline breast volume, and time since treatment.

Results:
Patients lost 8.3% of breast volume during surgery. One year following BCT/RT, volume loss was 19.3%. By year five, total volume loss was 26.6%.
Subset analyses demonstrated that in addition to lumpectomy defects, five-year volume loss was 21.7% for tumor/ breast volume > 10% and 29.5 % for tumor/ breast volume ≤ 10%. Volume loss between subgroups was not significantly different (p=0.37). Larger breast volume was a significant predictor of greater volume loss for all five years (p<0.001), followed by diabetes and smoking history.

Conclusion:
Patients with T1 tumors undergoing BCT/RT may lose approximately 20% of breast volume (beyond specimens) within a year, with continued loss for five years. Volume change did not differ significantly according to baseline breast volume, although larger breasts may experience comparatively larger volume changes.
Postoperative Orbital Morphology Observations Following Fronto-Orbital Advancement and Cranial Vault Remodeling in Patients With Unilateral Coronal Synostosis
Authors: Zhang Songchunyuan , Fang Cheng , Lan Dongyi , Wang Yueqing , Dong Chenbin 
Published: September 2024

Object:
Observations of preoperative and postoperative orbital morphology following fronto-orbital advancement and cranial vault remodeling (FOA and CVR) in patients with unilateral coronal synostosis (UCS).

Methods:
This retrospective cohort included patients diagnosed with unilateral coronal synostosis and treated with fronto-orbital advancement and cranial vault remodeling at the Children’s Hospital of Fudan University. The orbital height, orbital width, and orbital volume were obtained from head 3-dimensional computed tomography of preoperation and postoperation. The DICOM data of CT were then imported into mimics research version 21.0. The authors measured OH and OW according to the bony landmarks, then reset the parameters of the soft tissue window, and conducted a 3-dimensional reconstruction of the orbital soft tissue to get OV. The preoperative and postoperative measurements of the intact side were compared with the affected side, respectively. Statistical analysis was performed using SPSS version 25.0 (Ρ=0.05).

Results:
Twelve patients with UCS (5 male, 7 female) meeting criteria were included in the study. There were 4 patients with UCS on the left and 8 on the right. The average age at initial surgery was 19.50 months. Before the operation, the data of the intact side and the affected side were compared, respectively, and the difference was found to be significant in OH (Ρ=0.005) and OW (Ρ=0.005), while the OV (Ρ=0.106) was not statistically significant. After procedures of FOA and CVR, the data of the intact side and the affected side were compared, respectively, the significant difference was found in OV (Ρ=0.002), while not in OH (Ρ=0.060) or OW (Ρ=0.066).

Conclusion:
After undergoing the operation of FOA and CVR, the OH and OW of the ipsilateral and contralateral sides of patients with UCS were basically symmetrical, while the volume of the affected orbit was still relatively smaller.
The association among multiple-site chronic pain, sedentary behavior, and major depressive disorders: a mendelian randomization study
Authors: Li Nan-Xi , Chen Cheng-Feng , Zhang Bin 
Published: September 2024

Objective
Observational studies have reported that major depressive disorder (MDD) is associated with sedentary behavior (SB) and multiple chronic pain (MCP), but their associations remain unclear. Mendelian randomization analysis was used to assess the association.

Methods
Single nucleotide polymorphisms (SNPs) associated with MCP, SB [time spent watching television (Tel), using a computer (Com), or driving (Dri)], and MDD were collected from genome-wide association studies and screened as instrumental variants with a threshold of 1 × 10−5. Mendelian randomization was performed to examine their associations. Sensitivity analyses were conducted to evaluate robustness.

Results
MCP was associated with a higher risk of MDD [odds ratio (OR) inverse variance weighting (IVW) = 1.88; 95% confidence interval (CI), 1.64–2.15; P = 4.26 × 10−8), and causally related to SB (Tel: ORIVW = 1.23; 95% CI, 1.19–1.26; P = 6.02 × 10−38) (Dri: ORIVW = 1.05; 95% CI, 1.03–1.08; P = 3.92 × 10−5). Causality of SB on MCP was detected for Tel (ORIVW = 1.46; 95% CI, 1.39–1.53; P = 1.40 × 10−54) and Com (ORIVW = 0.88; 95% CI, 0.83–0.93; P = 2.50 × 10−6). No association was observed for SB on MDD. There is currently insufficient evidence to support that leisure activities are a mediating factor in MCP-induced MDD.

Conclusion
There are complex relationships among MCP, SB, and MDD. More research and learning about potential relationships and mechanisms among these phenotypes should be supplied.
Prenatal diagnosis and molecular cytogenetic analyses of a homozygous Robertsonian translocation family with novel mosaic Robertsonian fission karyotype
Authors: Xu Zhen , Luo Huili , Li Manman , OuYang Liu , Xia Zhi 
Published: September 2024

Background
Approximately one person in 1000 is a Robertsonian translocation carrier. Errors in the formation of eggs (or more rarely of sperms) may be the cause of Robertsonian translocation. Most Robertsonian translocation carriers are healthy and have a normal lifespan, but do have an increased risk of offsprings with trisomies and pregnancy loss. The fitness of Robertsonian translocation carriers is reduced, but can provide material for evolution.

Materials and methods
We have done prenatal diagnosis and molecular cytogenetic analyses on this homozygous Robertson translocation family. We report a homozygous Robertson translocation family with previously undescribed mosaic Robertsonian fission karyotype.

Results
We identified six Robertsonian translocation carriers in this family. Four were heterozygous translocation carriers of 45,XX or XY,der(14;15)(q10;q10), one was a homozygous translocation carrier of a 44,XY,der(14;15)(q10;q10),der(14;15)(q10;q10), and one was a previously undescribed Robertsonian fission carrier of 45,XN,der(14;15)(q10;q10)[42]/46,XN[58] with normal phenotype.

Conclusion
We reported a previously undescribed mosaic Robertsonian fission karyotype. The homozygosity of Robertsonian translocation for speciation may be a potential mechanism of speciation in humans. In theory, the carriers of homologous Robertsonian translocation cannot produce normal gametes, but Robertson fission made it possible for them to produce normal gametes.
MYC plus class IIa HDAC inhibition potentiates mitochondrial dysfunction in non-small cell lung cancer
Authors: Park Jina , Chen Ying-Yu , Cao Jennie J. , An Julia , Yen Ray-Whay Chiu , Outen John D. , Baylin Stephen B. , Topper Michael J. 
Published: September 2024

ABSTRACTMYC is frequently activated in cancer, leading to significant efforts to develop MYC inhibitors. While much progress has been made in targeting MYC, combination treatment strategies are needed to exploit this molecular vulnerability. To this end, we interrogated transcriptome data from cancer cell lines treated with MYC inhibitors and identified HDAC5 and HDAC9, both class IIa HDACs, as therapeutic targets to inhibit concurrently. Notably, these HDAC isoforms, which can be specifically targeted by small molecules, are known augmenters of several hallmarks of cancer. The combination of MYC and class IIa HDAC inhibition induces a significant reduction in viability for NSCLC cell lines with high MYC and mitochondrial pathway activation. Additionally, combination treatment induces a robust reduction of MYC with concomitant elevation of mitochondrial ROS, both of which have a causal relationship with therapeutic efficacy. Confirmation of in vivo efficacy was pursued in several animal model systems, with subsequent molecular correlate derivation confirming the importance of MYC depletion and mitochondrial dysfunction in driving drug efficacy. Ultimately, we define a therapeutic approach combining MYCi and class IIa HDACi to potentiate anti-tumor efficacy in NSCLC.
A type 1 immune-stromal cell network mediates disease tolerance and barrier protection against intestinal infection
Authors: Westfall Susan , Gentile Maria E. , Olsen Tayla M. , Karo-Atar Danielle , Bogza Andrei , Röstel Franziska , Pardy Ryan D. , Mandato Giordano , Fontes Ghislaine , Herbert De’Broski , Melichar Heather J. , Abadie Valerie , Richer Martin J. , Vinh Donald C. , Koenig Joshua F. E. , Harrison Oliver J. , Divangahi Maziar , Weis Sebastian , Gregorieff Alex , King Irah L. 
Published: September 2024

SUMMARYType 1 immunity mediates host defense through pathogen elimination, but whether this pathway also impacts tissue function is unknown. Here we demonstrate that rapid induction of IFNγ signaling coordinates a multi-cellular response that is critical to limit tissue damage and maintain gut motility following infection of mice with a tissue-invasive helminth. IFNγ production is initiated by antigen-independent activation of lamina propria CD8+T cells following MyD88-dependent recognition of the microbiota during helminth-induced barrier invasion. IFNγ acted directly on intestinal stromal cells to recruit neutrophils that limited parasite-induced tissue injury. IFNγ sensing also limited the expansion of smooth muscle actin-expressing cells to prevent pathological gut dysmotility. Importantly, this tissue-protective response had limited impact on parasite burden, indicating that IFNγ supports a disease tolerance defense strategy. Our results have important implications for managing the pathophysiological sequelae of post-infectious gut dysfunction and chronic inflammatory diseases associated with stromal remodelling.HIGHLIGHTSType 1 immunity is required for disease tolerance to tissue-invasive infection.Gut-resident CD8+T cells produce IFNγ in an antigen-independent, yet microbiota-dependent manner.IFNγ signaling recruits neutrophils in a cell-extrinsic manner to limit helminth-induced tissue injury.Direct sensing of IFNγ by intestinal stroma is essential to limit tissue damage and maintain gut motility during infection.
TGFβ primes alveolar-like macrophages to induce type I IFN following TLR2 activation
Authors: Thomas Sean M. , Ankley Laurisa M. , Conner Kayla N. , Rapp Alexander W. , McGee Abigail P. , LeSage Francois , Tanner Christopher D. , Vielma Taryn E. , Scheeres Eleanor C. , Obar Joshua J. , Olive Andrew J. 
Published: September 2024

ABSTRACTAlveolar macrophages (AMs) are key mediators of lung function and are potential targets for therapies during respiratory infections. TGFβ is an important regulator of AM differentiation and maintenance, but how TGFβ directly modulates the innate immune responses of AMs remains unclear. This shortcoming prevents effective targeting of AMs to improve lung function in health and disease. Here we leveraged an optimizedex vivoAM model system, fetal-liver derived alveolar-like macrophages (FLAMs), to dissect the role of TGFβ in AMs. Using transcriptional analysis, we first globally defined how TGFβ regulates gene expression of resting FLAMs. We found that TGFβ maintains the baseline metabolic state of AMs by driving lipid metabolism through oxidative phosphorylation and restricting inflammation. To better understand inflammatory regulation in FLAMs, we next directly tested how TGFβ alters the response to TLR2 agonists. While both TGFβ (+) and TGFβ (−) FLAMs robustly responded to TLR2 agonists, we found an unexpected activation of type I interferon (IFN) responses in FLAMs and primary AMs in a TGFβ-dependent manner. Surprisingly, mitochondrial antiviral signaling protein and the interferon regulator factors 3 and 7 were required for IFN production by TLR2 agonists. Together, these data suggest that TGFβ modulates AM metabolic networks and innate immune signaling cascades to control inflammatory pathways in AMs.
Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation
Authors: Liu Kevin , Titt Uwe , Esplen Nolan , Connell Luke , Konradsson Elise , Yang Ming , Wang Xiaochun , Takaoka Takeshi , Li Ziyi , Koong Albert C. , Mitra Devarati , Mohan Radhe , Loo Billy W. , Lin Steven H. , Schüler Emil 
Published: September 2024

ABSTRACTPurposeProton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs. spread-out-Bragg-peak [SOBP]) on acute radiation-induced gastrointestinal toxicity (RIGIT) in mice. We also compared RIGIT between synchrotron-based protons and linac-based electrons with matched mean dose rates.Methods and MaterialsWe administered abdominal irradiation (12-14 Gy single fraction) to female C57BL/6J mice with an 87 MeV synchrotron-based proton beamline (2 cm diameter field size as a lateral beam). Dose rates were 0.2 Gy/s (S-T pCONV), 0.3 Gy/s (SOBP pCONV), 150 Gy/s (S-T pFLASH), and 230 Gy/s (SOBP pFLASH). RIGIT was assessed by the jejunal regenerating crypt assay and survival. We also compared responses to proton [pFLASH and pCONV] with responses to electron CONV (eCONV, 0.4 Gy/s) and electron FLASH (eFLASH, 188-205 Gy/s).ResultsThe number of regenerating jejunal crypts at each matched dose was lowest for pFLASH (similar between S-T and SOBP), greater and similar between pCONV (S-T and SOBP) and eCONV, and greatest for eFLASH. Correspondingly, mice that received pFLASH SOBP had the lowest survival rates (50% at 50 days), followed by pFLASH S-T (80%), and pCONV SOBP (90%), but 100% of mice receiving pCONV S-T survived (log-rankP= 0.047 for the four groups).ConclusionsOur findings are consistent with an increase in RIGIT after synchrotron-based pFLASH versus pCONV. This negative proton-specific FLASH effect versus linac-based electron irradiation underscores the importance of understanding the physical and biological factors that will allow safe and effective clinical translation.
Dynamic cycles between idea generation and evaluation during creative storytelling
Authors: Liang Xitong , Cai Mingnan , Jing Gaohan , Zhang Chengming , Nichols Emily S , Liu Li 
Published: September 2024

AbstractMany theories support the notion that creative thinking involves a dynamic transition between idea generation and evaluation, but there is limited evidence of how these two stages interact. The dual process model proposes that spontaneous thinking and deliberate thinking drive these stages and the transitions between them, but there is a debate over whether they operate in parallel or in sequence. To address these gaps, we conducted a functional magnetic resonance imaging (fMRI) study in 41 college students during a creative storytelling task. By analyzing the dynamic brain state, we link the brain states with idea generation and evaluation. The transition patterns between brain states provide evidence for dynamic circulation between idea generation and evaluation during creative storytelling. Using a deep learning approach, we demonstrate an alternating interaction between spontaneous and deliberate thinking, driving the idea generation and evaluation stages and the transitions between them. These findings deepen our understanding of the cognitive and neural mechanisms underlying creative thinking.
MaskMol: Knowledge-guided Molecular Image Pre-Training Framework for Activity Cliffs with Pixel Masking
Authors: Cheng Zhixiang , Xiang Hongxin , Ma Pengsen , Zeng Li , Jin Xin , Yang Xixi , Lin Jianxin , Deng Yang , Song Bosheng , Feng Xinxin , Deng Changhui , Zeng Xiangxiang 
Published: September 2024

AbstractActivity cliffs, which refer to pairs of molecules that are structurally similar but show significant differences in their potency, can lead to model representation collapse and make the model challenging to distinguish them. Our research indicates that as molecular similarity increases, graph-based methods struggle to capture these nuances, whereas imagebased approaches effectively retain the distinctions. Thus, we developed MaskMol, a knowledge-guided molecular image selfsupervised learning framework. MaskMol accurately learns the representation of molecular images by considering multiple levels of molecular knowledge, such as atoms, bonds, and substructures. By utilizing pixel masking tasks, MaskMol extracts fine-grained information from molecular images, overcoming the limitations of existing deep learning models in identifying subtle structural changes. Experimental results demonstrate MaskMol’s high accuracy and transferability in activity cliff estimation and compound potency prediction across 20 different macromolecular targets, outperforming 25 state-of-the-art deep learning and machine learning approaches. Visualization analyses reveal MaskMol’s high biological interpretability in identifying activity cliff-relevant molecular substructures. Notably, through MaskMol, we identified candidate EP4 inhibitors that could be used to treat tumors. This study not only raises awareness about activity cliffs but also introduces a novel method for molecular image representation learning and virtual screening, advancing drug discovery and providing new insights into structure-activity relationships (SAR). Code is available athttps://github.com/ZhixiangCheng/MaskMol.
Deciphering transcriptional programming during lupin (Lupinus angustifolius) seed development using RNA-seq
Authors: Wainaina Virginia , Rathjen Tina , Hughes Trijntje , Marquardt Annelie , Fletcher Natalie , Casarotto Hayley , McNeil Meredith , McElroy Kerensa , Gao Ling-Ling 
Published: September 2024

AbstractLupin (Lupinus spp.)seeds are valued for their high protein content (35-40%) for both human and animal consumption. Seed development in crop plants is a critical factor influencing both seed fate and yield, hence, understanding the molecular mechanisms of seed development is essential. This study conducted a transcriptome analysis of Narrow Leaf Lupin (NLL) during seed development stages (3, 6, 9, 12, 15, 18, and 21 days after flowering) to investigate transcriptional dynamics and identify key candidate genes that control seed development. Approximately 357 million sequencing reads were generated from nine samples from leave, flower and seed tissues, enabling the identification of 34,769 expressed genes. The analysis revealed dynamic gene expression, with early stages marked by high metabolic activity and later stages focusing on storage protein synthesis and nutrient reservoir formation. The differential expression patterns of seed storage protein genes, including cupin groups (α, β, γ, and δ conglutins), were notable. The expression of α and β conglutins increased at later stages (15-21 days after flowering), supporting their role in grain filling and nutrient storage. Genes related to quinolizidine alkaloid biosynthesis, such as lysine/ornithine decarboxylase and purine permease transporter 1, showed late expression patterns suggesting alkaloid synthesis and transport during later stages. Many of the well-established transcription factors (TFs) known for their roles in seed development (bHLH, AP2, MYB, ERF, C2H2, NAC, WRKY, and C3H zinc finger families) showed differential expression, thus reinforcing the validity of our findings. These findings lay the groundwork for understanding the genetic and molecular mechanisms of seed development in lupin, contributing to enhanced crop management and breeding programs.
Photochemical processes drive thermal responses of dissolved organic matter in the dark ocean
Authors: Hu Ang , Cui Yifan , Bercovici Sarah , Tanentzap Andrew J. , Lennon Jay T. , Lin Xiaopei , Yang Yuanhe , Liu Yongqin , Osterholz Helena , Dong Hailiang , Lu Yahai , Jiao Nianzhi , Wang Jianjun 
Published: September 2024

AbstractHow dissolved organic matter (DOM) responds to climate warming is critical for understanding its effectiveness as a natural climate solution. Here, we use a highly resolved dataset of 821 DOM samples covering the surface waters to the deep Atlantic, Southern, and Pacific oceans to examine molecular-level responses to warming water temperatures, i.e. their thermal responses. In general, the strength and diversity of thermal responses among individual molecules both decline towards the deep waters, but they show decreasing and increasing trends with more recalcitrant molecules in concentration, respectively. Their contrasting trends concur with the more important role of photochemical processes in explaining the diversity of thermal responses than the strength. By projecting global ocean thermal responses from 1950-2020, we predict increases in the diversity are unexpectedly largest at deeper depths (> 1,000 m). Such increases could elevate recalcitrant deep-ocean carbon sink by approximately 10 Tg C yr-1which accounts for > 5% of the carbon flux survived to the deep ocean. Our findings highlight the importance of photochemical legacies in driving DOM thermal responses and further help predict the future oceanic carbon sink under global change.
Genomic characterization of plasmids harboringblaNDM-1,-5,-7carbapenemase alleles in clinicalKlebsiella pneumoniaein Pakistan
Authors: Qamar Muhammad Usman , Sierra Roberto , Jabeen Kokab , Rizwan Muhammad , Rashid Ayesha , Dar Yumna Fatima , Andrey Diego O. 
Published: September 2024

ABSTRACTKlebsiella pneumoniaeis notorious for causing healthcare-associated infections, which become more complicated by the acquisition ofblaNDMgenes via mobile genetic elements. Although Pakistan is a well-established hot spot ofblaNDM-positiveK. pneumoniae, detailed molecular descriptions ofblaNDM-carrying plasmids are scarce. SevenK. pneumoniaeisolates harboringblaNDMwere recovered from clinical sample sources during a six-month period and tested for antimicrobial susceptibility. A long-read approach was used for whole genome sequencing to obtain circularized plasmids and chromosomes for typing, annotation, and comparative analysis. The isolates were susceptible to colistin and tigecycline only among the tested antibiotics. We identified five STs: ST11, ST16, ST716, ST464, and ST2856. Notably, three strains possessed the hypervirulent capsule KL2, while five were classified as O locus type O2a. Evidence of genetic diversity was further highlighted by the presence of four IncC plasmids harboringblaNDM-1, two IncX3 plasmids harboringblaNDM-5, and a single hybrid IncFIB/IncHI1B plasmid harboringblaNDM-7. These plasmids also carried additional ARGs conferring resistance to aminoglycosides, cephalosporins, and fluoroquinolones. We identified the plasmidome of theK. pneumoniaeisolates and characterized the NDM-carrying plasmids. Genetic analysis confirmed the presence ofblaNDM-1andblaNDM-5on broad host range plasmids andblaNDM-7in a previously unreported hybrid plasmid backbone. We emphasized the critical role of plasmids in spreadingblaNDMin the clinical setting in Pakistan. Hence, we stressed the urgent need for enhanced surveillance, not least in LMICs, infection control measures, and adherence to the AWaRe guidelines in antibiotics use.