bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immediate Breast Reconstruction After Neoadjuvant Chemotherapy
Authors: Chi Weiru , Zhang Qi , Li Lun , Chen Ming , Xiu Bingqiu , Yang Benlong , Wu Jiong 
Published: May 2023

Background
Breast reconstruction has become an integral component of breast cancer treatment, especially for patients who are unable to undergo breast-conserving surgery after neoadjuvant chemotherapy (NAC). We analyzed factors influencing the type of immediate reconstruction surgery after NAC, as well as the complication rates for each surgery type.

Methods
The study included patients with breast cancer who underwent mastectomy following NAC from 2010 to 2021. Clinicopathological characteristics, unplanned reoperation rates, and the duration of postoperative hospitalization were analyzed in patients undergoing autologous tissue reconstruction (ATR, n = 127), implant-based reconstruction (IBR, n = 60), and combined autologous tissue and implant reconstruction (n = 60).

Results
A total of 1651 patients who received NAC before mastectomy were enrolled. Among them, 247 (15.0%) patients underwent immediate reconstruction (IR), whereas 1404 underwent mastectomy only. Patients in the IR group were younger (P < 0.001), had lower body mass index (P < 0.001), and exhibited earlier clinical (P = 0.003) and nodal (P < 0.001) stage than those in the non-IR group. Patients in the ATR group were older (P < 0.001) and had higher body mass index (P = 0.007), larger tumor size (P = 0.024), and more frequent childbearing history (P = 0.011) than those in the other groups. Complications resulting in unplanned reoperations were more frequent in the IBR group (P = 0.039). The duration of postoperative hospitalization was longest after ATR (P = 0.008).

Conclusions
Age and clinical tumor/nodal stage at presentation are associated with IR for patients undergoing mastectomy after NAC. For patients undergoing IR after NAC, ATR may be safer and more suitable than IBR.
Can Nonalcoholic Steatohepatitis Be Surgically Cured? Liver Histological Comparison after Metabolic Surgery versus Usual Care
Authors: Aminian Ali , Wilson Rickesha , Al-Kurd Abbas , Bena James , Fayazzadeh Hana , Alkhouri Naim , Nissen Steven E. , Dasarathy Srinivasan 
Published: May 2023

Objective:
To compare histological outcomes in patients with fibrotic nonalcoholic steatohepatitis (NASH) and obesity after metabolic surgery versus nonsurgical care.

Background:
There are no published data comparing the effects of metabolic surgery versus nonsurgical care on histological progression of NASH.

Methods:
Repeat liver biopsies were performed in patients with BMI >30 kg/m2 at a US health system whose baseline liver biopsy between 2004 and 2016 confirmed a histological diagnosis of NASH including presence of liver fibrosis, but without cirrhosis. Baseline characteristics of liver histology for patients who underwent simultaneous liver biopsy at the time of metabolic surgery were balanced with a nonsurgical control group using overlap weighting methods. The primary composite end point required both resolution of NASH and improvement of at least 1 fibrosis stage in the repeat liver biopsy.

Results:
133 patients (42 metabolic surgery and 91 nonsurgical controls) had a repeat liver biopsy with a median interval of 2 years. Overlap weighting provided balance for baseline histological disease activity, fibrosis stage, and time interval between liver biopsies. In overlap-weighted patients, 50.1% in the surgical and 12.1% in the nonsurgical group met the primary end point (odds ratio 7.3 [95% CI, 2.8-19.2], P<0.001). NASH resolution and fibrosis improvement occurred in 68.5% and 64.1% of surgical patients, respectively. Surgical and nonsurgical patients who met the primary end point lost more weight than their counterparts who did not meet the primary end point (mean weight loss difference in the surgical group 12.2% [95% CI, 7.3%-17.2%] and in the nonsurgical group 11.6% [95% CI, 6.2%-16.9%]).

Conclusions:
Among patients with fibrotic non-cirrhotic NASH, metabolic surgery resulted in simultaneous NASH resolution and fibrosis improvement in half of patients.
Low to moderate genetic influences on the rapid smell test SCENTinel™
Authors: Hunter Stephanie R. , Lin Cailu , Hannum Mackenzie E. , Bell Katherine , Huang Amy , Joseph Paule V. , Parma Valentina , Dalton Pamela H. , Reed Danielle R. 
Published: May 2023

AbstractSCENTinel™- a rapid, inexpensive smell test that measures odor detection, intensity, identification, and pleasantness - was developed for population-wide screening of smell function. SCENTinel™was previously found to screen for multiple types of smell disorders. However, the effect of genetic variability on SCENTinel™test performance is unknown, which could affect the test’s validity. This study assessed performance of SCENTinel™in a large group of individuals with a normal sense of smell to determine the test-retest reliability and the heritability of SCENTinel™test performance. One thousand participants (36 [IQR 26-52] years old, 72% female, 80% white) completed a SCENTinel™test at the 2021 and 2022 Twins Days Festivals in Twinsburg, OH, and 118 of those completed a SCENTinel™test on each of the festival’s two days. Participants comprised 55% percent monozygotic twins, 13% dizygotic twins, 0.4% triplets, and 36% singletons. We found that 97% of participants passed the SCENTinel™test. Test-retest reliability ranged from 0.57 to 0.71 for SCENTinel™subtests. Broad-sense heritability, based on 246 monozygotic and 62 dizygotic twin dyads, was low for odor intensity (r=0.03) and moderate for odor pleasantness (r=0.4). Together, this study suggests that SCENTinel™is a reliable smell test with only moderate heritability effects, which further supports its utility for population-wide screening for smell function.
Association of Baseline Cerebrovascular Reactivity and Longitudinal Development of Enlarged Perivascular Spaces in the Basal Ganglia
Authors: Libecap T.J. , Bauer Christopher E. , Zachariou Valentinos , Pappas Colleen A. , Raslau Flavius D. , Liu Peiying , Lu Hanzhang , Gold Brian T. 
Published: May 2023

1.AbstractBackgroundIncreasing evidence suggests that enlarged perivascular spaces (ePVS) are associated with cognitive dysfunction in aging. However, the etiology of ePVS remains unknown. Here we tested the possibility that baseline cerebrovascular dysfunction, as measured by an MRI measure of cerebrovascular reactivity (CVR), contributes to the later development of ePVS.MethodsA total of 79 cognitively normal, older adults (46 women, age range 60-84) were recruited to undergo MRI scanning at baseline and 50 participants returned for a follow-up scan approximately 2.5 years later. ePVS were counted in the basal ganglia, centrum semiovale, midbrain, and hippocampus. CVR, an index of the vasodilatory capacity of cerebral small vessels, was assessed using carbon-dioxide inhalation while acquiring blood oxygen-level dependent (BOLD) MR images.ResultsLow baseline CVR values in the basal ganglia were associated with increased follow-up ePVS counts in the basal ganglia after controlling for age, sex, and baseline ePVS values (coefficient estimate (SE) = -15.87 (3.92), p < 0.001, 95% confidence interval [CI] -23.68 to - 8.05). This effect remained significant after accounting for self-reported risk factors of cerebral small vessel disease (cSVD) (coefficient estimate (SE) = -15.03 (4.00), p < 0.001, CI -23.02 to - 7.05) and neuroimaging markers of cSVD (coefficient estimate (SE) = -13.99 (4.02), p < 0.001, CI -22.03 to -5.95).ConclusionsOur results demonstrate that low baseline CVR is a risk factor for later development of ePVS. MRI-based CVR may represent a promising biomarker of cSVD.
A reproducibility evaluation of the effects of MRI defacing on brain segmentation
Authors: Gao Chenyu , Landman Bennett A. , Prince Jerry L. , Carass Aaron 
Published: May 2023

AbstractPurposeRecent advances in magnetic resonance (MR) scanner quality and the rapidly improving nature of facial recognition software have necessitated the introduction of MR defacing algorithms to protect patient privacy. As a result, there are a number of MR defacing algorithms available to the neuroimaging community, with several appearing in just the last five years. While some qualities of these defacing algorithms, such as patient identifiability, have been explored in previous works, the potential impact of defacing on neuroimage processing has yet to be explored.ApproachWe qualitatively evaluate eight MR defacing algorithms on 179 subjects from the OASIS-3 cohort and the 21 subjects from the Kirby-21 dataset. We also evaluate the effects of defacing on two neuroimaging pipelines— SLANT and FreeSurfer—by comparing the segmentation consistency between the original and defaced images.ResultsDefacing can alter brain segmentation and even lead to catastrophic failures, which are more frequent with some algorithms such asQuickshear,MRI_Deface, andFSL_deface. Compared to FreeSurfer, SLANT is less affected by defacing. On outputs that pass the quality check, the effects of defacing are less pronounced than those of rescanning, as measured by the Dice similarity coefficient.ConclusionsThe effects of defacing are noticeable and should not be disregarded. Extra attention, in particular, should be paid to the possibility of catastrophic failures. It is crucial to adopt a robust defacing algorithm and perform a thorough quality check before releasing defaced datasets. To improve the reliability of analysis in scenarios involving defaced MRIs, it’s encouraged to include multiple brain segmentation pipelines.
Repurposing Non-pharmacological Interventions for Alzheimer’s Diseases through Link Prediction on Biomedical Literature
Authors: Xiao Yongkang , Hou Yu , Zhou Huixue , Diallo Gayo , Fiszman Marcelo , Wolfson Julian , Kilicoglu Halil , Chen You , Su Chang , Xu Hua , Mantyh William G. , Zhang Rui 
Published: May 2023

AbstractRecently, computational drug repurposing has emerged as a promising method for identifying new pharmaceutical interventions (PI) for Alzheimer’s Disease (AD). Non-pharmaceutical interventions (NPI), such as Vitamin E and Music therapy, have great potential to improve cognitive function and slow the progression of AD, but have largely been unexplored. This study predicts novel NPIs for AD through link prediction on our developed biomedical knowledge graph. We constructed a comprehensive knowledge graph containing AD concepts and various potential interventions, called ADInt, by integrating a dietary supplement domain knowledge graph, SuppKG, with semantic relations from SemMedDB database. Four knowledge graph embedding models (TransE, RotatE, DistMult and ComplEX) and two graph convolutional network models (R-GCN and CompGCN) were compared to learn the representation of ADInt. R-GCN outperformed other models by evaluating on the time slice test set and the clinical trial test set and was used to generate the score tables of the link prediction task. Discovery patterns were applied to generate mechanism pathways for high scoring triples. Our ADInt had 162,213 nodes and 1,017,319 edges. The graph convolutional network model, R-GCN, performed best in both the Time Slicing test set (MR = 7.099, MRR = 0.5007, Hits@1 = 0.4112, Hits@3 = 0.5058, Hits@10 = 0.6804) and the Clinical Trials test set (MR = 1.731, MRR = 0.8582, Hits@1 = 0.7906, Hits@3 = 0.9033, Hits@10 = 0.9848). Among high scoring triples in the link prediction results, we found the plausible mechanism pathways of (Photodynamic therapy, PREVENTS, Alzheimer’s Disease) and (Choerospondias axillaris, PREVENTS, Alzheimer’s Disease) by discovery patterns and discussed them further. In conclusion, we presented a novel methodology to extend an existing knowledge graph and discover NPIs (dietary supplements (DS) and complementary and integrative health (CIH)) for AD. We used discovery patterns to find mechanisms for predicted triples to solve the poor interpretability of artificial neural networks. Our method can potentially be applied to other clinical problems, such as discovering drug adverse reactions and drug-drug interactions.
Correlation between life satisfaction and symptoms of attention deficit hyperactivity disorder (ADHD) in dental students: The mediation of resilience
Authors: Sun Yuwei , Miao Lei , Chen Siying , Piao Zhenya , Tong Chi 
Published: May 2023

AbstractThe aim of the study was to examine the morbidity of Attention Deficit Hyperactivity Disorder (ADHD) symptoms in dental students, explore the correlation between life satisfaction and ADHD symptoms. It also discusses whether resilience mediates the correlation between ADHD symptoms and life satisfaction. Self-report questionnaires consist of the Wender Utah Rating Scale (WURS), the Adult ADHD Self-Report Scale (ASRS), the Satisfaction With Life Scale (SWLS), the Conner-Davidson Resilience Scale (CD-RISC), and sociodemographic characteristics. The analyses with Hierarchical linear regression were operated to investigate the effect of ADHD symptoms on life satisfaction. The study used resampling and asymptotic strategies to discuss the mediation of resilience. 291 dental students became final objects. Twenty students (6.87%) may have ADHD. There were differences in ADHD prevalence among objects of diverse ages and with varying levels of paternal education. The ADHD asymptomatic group had distinctly higher resilience and life satisfaction degrees than the symptomatic group. Inattention and hyperactivity were both correlated negatively with life satisfaction and resilience. Life satisfaction was observably positively associated with resilience. Resilience serves as a mediating role between life satisfaction and the two symptoms of ADHD. Detecting ADHD symptoms earlier is helping improve mental health of future dentists. Resilience intervention programs can enhance life satisfaction of dental students.
The Association of QRS Duration with Risk of Adverse Outcomes in Sex- and Race- Based Subgroups: The Dallas Heart Study
Authors: Kondamudi Nitin , Zeleke Yihun , Rosenblatt Anna , Hu Gene , Grubb Christopher , Link Mark S. 
Published: May 2023

IntroductionWe explored sex and race differences in the prognostic implications of QRS prolongation among healthy adults.MethodsParticipants from the Dallas Heart Study (DHS) free of cardiovascular (CV) disease who underwent ECG testing and cMRI evaluation were included. Multivariable linear regression was used to examine the cross-sectional association of QRS duration with left ventricular (LV) mass, LV ejection fraction (LVEF), and LV end diastolic volume (LVEDV). Association of QRS duration with risk of MACE was evaluated using Cox models. Interaction testing was performed between QRS duration and sex/race respectively for each outcome of interest. QRS duration was log transformed.ResultsThe study included 2,785 participants. Longer QRS duration was associated with higher LV mass, lower LVEF, and higher LVEDV, independent of CV risk factors ([β: 0.21, P<0.001], [β: - 0.13, P<0.001], [β: 0.22, P<0.001] respectively). Men with longer QRS duration were more likely to have higher LV mass and higher LVEDV compared to women (P-int=0.012, P-int=0.01, respectively). Black participants with longer QRS duration were more likely to have higher LV mass as compared to White participants (P-int<0.001). In Cox analysis, QRS prolongation was associated with higher risk of MACE in women (HR = 6.66 [95% CI: 2.32, 19.1]) but not men. This association was attenuated after adjustment for CV risk factors, with a trend toward significance (HR = 2.45 [95% CI: 0.94, 6.39]). Longer QRS duration was not associated with risk of MACE in Black or White participants in the adjusted models. No interaction between sex/race and QRS duration for risk of MACE was observed.DiscussionIn healthy adults, QRS duration is differentially associated with abnormalities in LV structure and function. These findings inform the use of QRS duration in identifying subgroups at risk for CV disease, and caution against using QRS duration cut offs uniformly for clinical decision making.What is known?QRS prolongation in healthy adults is associated with higher risk of death, cardiovascular disease, and left ventricular hypertrophy.What the study adds?QRS prolongation may reflect a higher degree of underlying LV hypertrophy in Blacks compared to Whites. Longer QRS interval may reflect higher risk of adverse cardiac events, driven by prevalent cardiovascular risk factors.Graphic AbstractRisk of underlying left ventricular hypertrophy in demographic groups based on QRS prolongation
Genomic and transcriptomic analysis revealed new insights into the influence of key T6SS geneshcpandvgrGon drug resistance and interbacterial competition inKlebsiella pneumoniae
Authors: Li Wanzhen , Huang Xiaolan , Li Dan , Liu Xiaofen , Jiang Xiaoying , Bian Xingchen , Li Xin , Zhang Jing 
Published: May 2023

AbstractType VI secretion systems (T6SSs) act as a molecular weapon in interbacterial competition and play an important role in cell-cell interactions. Different species of bacteria use their T6SSs to perform a variety of functions according to ecological niche. Therefore, it is necessary to better understand the T6SS potential ofKlebsiella pneumoniae(K. pneumoniae), a common clinical opportunistic pathogen. Here, we conducted a genomic analysis on the evolution, T6SS, virulence and antimicrobial resistance of 65K. pneumoniaein patients with different infections. And we combined transcriptome analysis after knockout of key gene in T6SS of this species. Results showed that genes encoding a T6SS were present in allK. pneumoniaein this study, and there was no correlation was found between T6SS cluster and carbapenem resistance and virulence genes. Differentially expressed genes (DEGs) including 1298 co-upregulated and 1714 co-downregulated were identified afterhcporvgrGdeletion. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis have demonstrated common changes in quorum sensing, propionate metabolism and other pathways. And we found that the deletion ofhcporvgrGgenes up-regulated of beta-lactam (blaKPC-2) and other resistance genes. Interbacterial competition experiments showed thathcpandvgrGare essential genes for competitive ability of ST11K. pneumoniae. Taken together, the entire study provides further insight into the investigation of T6SS inK. pneumoniaethrough genomic and transcriptomic analysis.ImportanceGram-negative bacteria use T6SS to deliver toxin effectors to interact with neighboring cells for niche advantage.K. pneumoniaeis an opportunistic nosocomial pathogen that often carriers multiple cope T6SSs, but the function of its T6SS has not yet elucidated. Here, we performed a genomic analysis of 65 clinicalK. pneumoniaestrains, in order to explore the relationship between T6SS and virulence and resistance genes. We also study the repertoire after knockout of key gene in T6SS of this species by transcriptomics. It was suggested that T6SS is associated with drug resistance, and its key geneshcpandvgrGare critical for the interspecies competition ofK. pneumoniae.
Oncogenic reactivation of young L1s is a hallmark of colon cancer
Authors: Neu Devin , Hung Stevephen , Bartels Cynthia F. , Faber Zachary J. , Lovrenert Katreya , Pontius W. Dean , Morgan Laura , Chakraborty Maharshi , Liao Will , Chin Diana , Hong Ellen S. , Gray Jeremy , Moreno Victor , Kalady Matthew , Peters Ulrike , Gryder Berkley , Sallari Richard C. , Scacheri Peter C. 
Published: May 2023

AbstractTransposable elements become increasingly active in both cancerous and aging cells, driven by loss of DNA methylation as cells divide. Here we leverage the epigenomes of colon cancers with matched adjacent tissue, in addition to non-cancerous normals and cell line models, to assess the role of transposable elements as drivers or passengers in cancer development. Using the baseline of activity from normal and adjacent tissue, we show that the youngest subfamilies of the LINE1 (L1) family exhibit a degree of activity and recurrence across patients that goes beyond what is expected from hypomethylation and cell division, suggesting an additional mechanism of oncogenic reactivation. We characterize this mechanism and find that the loss of the tumor suppressor PLZF drives young L1 reactivation in a cell-division-independent manner. PLZF de-repression exposes abundant motifs for tumor core factors in the L1 5’UTR. Active young L1s act as oncogenic enhancers, interacting with oncogenes via gained chromatin loops. We uncover oncogenic L1 reactivation as a hallmark of colon cancer, where young L1s activate universally in our cohort at high levels of recurrence, act as enhancers to oncogenes, and become wired into the core regulatory circuitry of colon cancer.
Computational modeling of methylation impact of AML drivers reveals new pathways and refines AML risk-stratification
Authors: Gurun Burcu , Tyner Jeffrey W. , Demir Emek , Druker Brian J. , Spellman Paul T. 
Published: May 2023

ABSTRACTDecades before its clinical onset, epigenetic changes start to accumulate in the progenitor cells of Acute Myelogenous Leukemia (AML). Delineating these changes can improve risk-stratification for patients and shed insights into AML etiology, dynamics and mechanisms. Towards this goal, we extracted “epigenetic signatures” through two parallel machine learning approaches: a supervised regression model using frequently mutated genes as labels and an unsupervised topic modeling approach to factorize covarying epigenetic changes into a small number of “topics”. First, we created regression models forDNMT3AandTET2, the two most frequently mutated epigenetic drivers in AML. Our model differentiated wild-type vs. mutant genotypes based on their downstream epigenetic impacts with very high accuracy: AUROC 0.9 and 0.8, respectively. Methylation loci frequently selected by the models recapitulated known downstream pathways and identified several novel recurrent targets. Second, we used topic modeling to systematically factorize the high dimensional methylation profiles to a latent space of 15 topics. We annotated identified topics with biological and clinical features such as mutation status, prior malignancy and ELN criteria. Topic modeling successfully deconvoluted the combined effects of multiple upstream epigenetic drivers into individual topics including relatively infrequent cytogenetic events, improving the methylation-based subtyping of AML. Furthermore, they revealed complimentary and synergistic interactions between drivers, grouped them based on the similarity of their downstream methylation impact and linked them to prognostic criteria. Our models identify new signatures and methylation pathways, refine risk-stratification and inform detection and drug response studies for AML patients.KEY POINTSSupervised and unsupervised models reveal new methylation pathways of AML driver events and validate previously known associations.IndividualDNMT3AandTET2signatures are accurate and robust, despite the complex genetic and epigenetic make-up of samples at diagnosis.Unsupervised topic modeling factorizes covarying methylation changes and isolates methylation signatures caused by rare mutations.Topic modeling reveals a group of mutations with similar downstream methylation impacts and mapped to adverse-risk class by ELN.Topic modeling uncovers methylation signatures of infrequent cytogenetic events, significantly improving methylation-based subtyping.Our models can be leveraged to build predictive models for AML-risk.Our models show that cytogenetic events, such as t(15;17) have widespreadtransdownstream methylation impacts.