bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the parameters for endovenous microwave ablation to achieve equivalence with endovenous laser ablation, using the porcine liver model.
Authors: Bachetta Anjali , Cheung Simon , Moore Emma , Nguyen Danny , Kiely Melissa , Whiteley Mark 
Published: October 2022

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<p><strong>ABSTRACT</strong></p>
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<p>Aims: Endovenous microwave ablation (EMWA) is a relatively new catheter-based endovenous thermoablation (EVTA) system to ablate incompetent truncal veins. Early results suggest that EMWA uses more power than endovenous laser ablation (EVLA) to get the same results. Therefore, we aimed to define the parameters for EMWA, which give the same tissue ablation as EVLA, using the previously validated porcine liver model.</p>
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<p>Methods: EVLA (1470nm and 600micron radial fibre) treatments were performed at 6W, 8W and 10W, at each pullback speed of 6, 7, 8 and 9 s/cm, giving a range of Linear Endovenous Energy Densities (LEEDs) between 36 – 90 J/cm. We repeated each combination of power and pullback five times. Following a preliminary screening process to identify parameters that gave similar results, we used EMWA in the same model. Powers of 35-75W and pullback speeds of 4-9 s/cm were used (LEEDs 140-675 J/cm). Ablation tracts from both devices were analysed by two blinded observers, noting thermal spread and carbonisation. </p>
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<p>Results: For each of the commonly used parameters for EVLA, we identified a range of power and pullback parameters for EMWA that produced similar tissue ablation in the porcine liver model. To keep the pullback speeds within the usual range, we used powers of 35-75W with EMWA, with mean EMWA LEEDs 3.9 - 5.8 times higher than EVLA LEEDs. We found the quicker the pullback speed, the higher the multiple of EMWA LEED we needed to get the same effect.</p>
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<p>Conclusion: We have identified parameters for EMWA that gave equivalent tissue ablation in the validated porcine liver model to commonly used parameters and LEEDs for EVLA. As the power during EMWA is higher than EVLA, EVMA LEEDs are approximately 4-6 times higher than EVLA LEEDs to achieve the same thermal effect on the tissues.</p>
Morphologic and Morphometric Measurements of the Foramen Ovale: Comparing Digitized Measurements Performed on Dried Human Crania With Computed Tomographic Imaging. An Observational Anatomic Study
Authors: Héréus Savanah , Lins Bjarne , Van Vlasselaer Nicolas , Van Buyten Jean-Pierre , Cattrysse Erik 
Published: October 2022

The foramen ovale (FO) of the sphenoid bone is clinically important for the interventional treatment of trigeminal neuralgia. Percutaneous procedures applied to treat the chronic pain condition typically involve the cannulation of this oval-like foramen located at the base of the skull. Anatomic variations of the FO have been reported to contribute to difficulties in the cannulation of this structure. Computed tomography (CT) can help the surgeon improve the accuracy and safety of the intervention. However, even with navigation technology, unsuccessful cannulation of the FO has been reported. The aim of this observational anatomic study was to define morphometric and morphologic data of the FO and to investigate for potential differences between measurements taken on dried human crania and digitized measurements of the FO measured on CT images. One hundred eighteen FOs were evaluated. Twenty FOs underwent CT scanning. The mean length of the foramen was 7.41±1.3 mm on the left side and 7.57±1.07 mm on the right. The mean width of the foramen was 4.63±0.86 mm on the left side and 4.33±0.99 on the right. The mean area on the left side was 27.11±7.58 and 25.73±6.64 mm2 on the right. No significant left-right differences were found for any of these dimensions. The most important conclusion that we can draw is that the measurements can indeed be performed on CT images to obtain an accurate picture of the morphology. Considering the surgical importance of the FO and taking into consideration the limitations this study added to scientific knowledge, this study was constructive as far as neurosurgeons and anatomists are concerned.
Understanding the stability and structural properties of ordered nanoporous metals towards their rational synthesis
Authors: Ortiz-Roldan Jose M. , Balestra Salvador R. G. , Bueno-Perez Rocio , Calero Sofía , Garcia-Perez Elena , Catlow C. Richard A. , Ruiz-Salvador A. Rabdel , Hamad Said 
Published: October 2022

Ordered Nanoporous Metals (ONMs) form a new family of nanoporous materials composed only of pure metals. The expected impact is considerable from combining the ordered nanopore structure of MOFs, zeolites and carbon schwartzites with the robustness and electronic conductivity of metals. Little is known about their stability and structural features. Here we address these points to provide clues toward their rational synthesis, introducing an automatic atomistic design that uses model building and molecular dynamics structural relaxation, and is validated against the experimentally known ONMs. Analysing the properties of the 10 stable structures out of the 17 studied (14 of which are designed in this work) using four noble metals (Pt, Pd, Au and Ag), we have deciphered some key elements and structural descriptors that provide guidelines for the experimental synthesis of ONMS. The long-lived metastability of the stable ONMs is evidenced by the high free energy landscape, computed via Metadynamic simulations. The new ONMs permit molecular diffusion of various molecules of industrial relevance, increasing the expectation for their use in catalysis, separation, nanofiltration, batteries, fuel cells, etc. Stable low-cost ONMs are predicted using Earth-abundant Ni metal, which maintains the main features of their relative noble metal forms.
Effect of WASH/MNCH Integrated interventions on skilled birth attendance and incidence of neonatal Sepsis in Amuru District, Uganda; A quasi-experimental study
Authors: Mukasa Comfort Hajra , Nankanja Maureen , Mugisa Margaret , Valentine Ojoro , Kagurusi Patrick 
Published: October 2022

AbstractBackgroundEvidence on the impact of Maternal Newborn and child health (MNCH) and Water, Sanitation and Hygiene (WASH) interventions on skilled birth attendance and neonatal sepsis remains unclear. We assessed the effect of WASH/MNCH integrated interventions on skilled birth attendance and incidence of neonatal Sepsis in a resource-constrained setting in Uganda.MethodsA quasi-experimental study design was conducted in Amuru district. The package of interventions implemented included; training of health workers, facilitation of integrated outreach services, construction of WASH facilities, and health education of communities. A digitized structured questionnaire was used to obtain data on ANC and skilled birth attendance, WASH practices and prevalence of pneumonia and diarrhea among 466 expectant mothers and caretakers of under-fives at baseline, midterm and endline. Data on the incidence of sepsis, ANC and skilled birth attendance, and WASH status was also obtained from 6 healthcare facilities. A total of 12 key informant interviews and 12 Focus group discussions were also conducted. Data were imported into STATA 15 for analysis. Two sample tests of proportions were used to compare findings at baseline and endline. Qualitative was analyzed using thematic content analysis.ResultsThere was a significant increase in the number of women delivering at the health facilities that were supported by the project from 41.4% at baseline to 63.0% at endline (p= <0.0001). There was a reduction in the incidence of neonatal sepsis from 0.6% to 0.2% (p = 0.0687), although the difference was not significant. There was an increase in the percentage of households with sanitation facilities and improved hygiene practices. Community-level findings also indicated a decline in cases of water-borne illnesses; cases of dysentery decreased from 10.0% at baseline to 0.6% at endline, cases of cholera decreased from 8.9% to 1.9% at endline, cases of typhoid decreased from 26.5% to 12.7% at endline.ConclusionThis study revealed that integrated WASH/MNCH interventions can significantly increase ANC and skilled birth attendance, reduce incidences of neonatal sepsis, diarrhea, pneumonia, and other related diseases and improve WASH practices in communities. Significant improvements in WASH/IPC in the maternity wards and the capacity of healthcare workers to deliver clean and safe MNCH services can also be realized. We recommend the integration of WASH/MNCH interventions for projects aimed at improving skilled birth attendance and WASH practices and reduction of childhood infections.
Deep Learning model accurately classifies metastatic tumors from primary tumors based on mutational signatures
Authors: Zheng Weisheng , Pu Mengchen , Li Xiaorong , Jin Sutong , Li Xingshuai , Zhou Jielong , Zhang Yingsheng 
Published: October 2022

AbstractMetastatic propagation is the leading cause of death for most cancers. Prediction and elucidation of metastatic process is crucial for the therapeutic treatment of cancers. Even though somatic mutations have been directly linked to tumorigenesis and metastasis, it is less explored whether the metastatic events can be identified through genomic mutation signatures, a concise representation of the mutational processes. Here, applying mutation signatures as input features calculated from Whole-Exome Sequencing (WES) data of TCGA and other metastatic cohorts, we developed MetaWise, a Deep Neural Network (DNN) model. This model accurately classified metastatic tumors from primary tumors. Signatures of non-coding mutations also have a major impact on the model performance. SHapley Additive exPlanations (SHAP) and Local Surrogate (LIME) analysis into the MetaWise model identified several mutational signatures directly correlated to metastatic spread in cancers, including APOBEC-mutagenesis, UV-induced signatures and DNA damage response deficiency signatures.
The power of TOPMed imputation for the discovery of Latino enriched rare variants associated with type 2 diabetes
Authors: Huerta-Chagoya Alicia , Schroeder Philip , Mandla Ravi , Deutsch Aaron J. , Zhu Wanying , Petty Lauren , Yi Xiaoyan , Cole Joanne B. , Udler Miriam S. , Dornbos Peter , Porneala Bianca , DiCorpo Daniel , Liu Ching-Ti , Li Josephine H. , Szczerbiński Lukasz , Kaur Varinderpal , Kim Joohyun , Lu Yingchang , Martin Alicia , Eizirik Decio L. , Marchetti Piero , Marselli Lorella , Chen Ling , Srinivasan Shylaja , Todd Jennifer , Flannick Jason , Gubitosi-Klug Rose , Levitsky Lynne , Shah Rachana , Kelsey Megan , Burke Brian , Dabelea Dana M. , Divers Jasmin , Marcovina Santica , Stalbow Lauren , Loos Ruth J.F. , Darst Burcu F. , Kooperberg Charles , Raffield Laura M. , Haiman Christopher , Sun Quan , McCormick Joseph B. , Fisher-Hoch Susan P. , Ordoñez Maria L. , Meigs James , Baier Leslie J. , González-Villalpando Clicerio , González-Villalpando Maria Elena , Orozco Lorena , Moreno Andrés , Aguilar-Salinas Carlos A. , Tusié Teresa , Dupuis Josée , Ng Maggie C.Y. , Manning Alisa , Highland Heather M. , Cnop Miriam , Hanson Robert , Below Jennifer , Florez Jose C. , Leong Aaron , Mercader Josep M. 
Published: October 2022

ABSTRACTHypothesisThe prevalence of type 2 diabetes is higher in Latino populations compared with other major ancestry groups. Not only has the Latino population been systematically underrepresented in large-scale genetic analyses, but previous studies relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation reference panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The NHLBI Trans-Omics for Precision Medicine (TOPMed) reference panel represents a unique opportunity to analyze rare genetic variations in the Latino population.MethodsWe evaluate the TOPMed imputation performance using genotyping array and whole-exome sequence data in 6 Latino cohorts. To evaluate the ability of TOPMed imputation of increasing the identified loci, we performed a Latino type 2 diabetes GWAS meta-analysis in 8,150 type 2 diabetes cases and 10,735 controls and replicated the results in 6 additional cohorts including whole-genome sequence data from the All of Us cohort.ResultsWe show that, compared to imputation with 1000G, the TOPMed panel improves the identification of rare and low-frequency variants. We identified 26 distinct signals including a novel genome-wide significant variant (minor allele frequency 1.6%, OR=2.0, P=3.4×10−9) near ORC5. A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improves the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance.ConclusionsOur results demonstrate the utility of TOPMed imputation for identifying low-frequency variation in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores.
A comprehensive view of cell-type-specific temporal dynamics in human and mouse brains
Authors: Lu Ziyu , Zhang Melissa , Lee Jasper , Sziraki Andras , Anderson Sonya , Ge Shaoyu , Nelson Peter T. , Zhou Wei , Cao Junyue 
Published: October 2022

SummaryProgenitor cells play fundamental roles in preserving optimal organismal functions under normal, aging, and disease conditions. However, progenitor cells are incompletely characterized, especially in the brain, partly because conventional methods are restricted by inadequate throughput and resolution for deciphering cell-type-specific proliferation and differentiation dynamicsin vivo. Here, we developedTrackerSci, a new technique that combinesin vivolabeling of newborn cells with single-cell combinatorial indexing to profile the single-cell chromatin landscape and transcriptome of rare progenitor cells and track cellular differentiation trajectoriesin vivo. We appliedTrackerScito analyze the epigenetic and gene expression dynamics of newborn cells across entire mouse brains spanning three age stages and in a mouse model of Alzheimer’s disease. Leveraging the dataset, we identified diverse progenitor cell types less-characterized in conventional single cell analysis, and recovered their unique epigenetic signatures. We further quantified the cell-type-specific proliferation and differentiation potentials of progenitor cells, and identified the molecular programs underlying their aging-associated changes (e.g.,reduced neurogenesis/oligodendrogenesis). Finally, we expanded our analysis to study progenitor cells in the aged human brain through profiling ∼800,000 single-cell transcriptomes across five anatomical regions from six aged human brains. We further explored the transcriptome signatures that are shared or divergent between human and mouse oligodendrogenesis, as well as the region-specific down-regulation of oligodendrogenesis in the human cerebellum. Together, the data provide an in-depth view of rare progenitor cells in mammalian brains. We anticipateTrackerSciwill be broadly applicable to characterize cell-type-specific temporal dynamics in diverse systems.
Hypothesis-driven probabilistic modelling enables a principled perspective of genomic compartments
Authors: Kariti Hagai , Feld Tal , Kaplan Noam 
Published: October 2022

AbstractThe Hi-C method has revolutionized the study of genome organization, yet interpretation of Hi-C interaction frequency maps remains a major challenge. Genomic compartments are a checkered Hi-C interaction pattern suggested to represent the partitioning of the genome into two self-interacting states associated with active and inactive chromatin. Based on a few elementary mechanistic assumptions, we derive a generative probabilistic model of genomic compartments, called deGeco. Testing our model, we find it can explain observed Hi-C interaction maps in a highly robust manner, allowing accurate inference of interaction probability maps from extremely sparse data without any training of parameters. Taking advantage of the interpretability of the model parameters, we then test hypotheses regarding the nature of genomic compartments. We find clear evidence of multiple states, and that these states self-interact with different affinities. We also find that the interaction rules of chromatin states differ considerably within and between chromosomes. Inspecting the molecular underpinnings of a four-state model, we show that a simple classifier can use histone marks to predict the underlying states with 87% accuracy. Finally, we observe instances of mixed-state loci and analyze these loci in single-cell Hi-C maps, finding that mixing of states occurs mainly at the population level.
Beyond BRCA: Discovery of novel causes and consequences of homologous recombination deficiencies
Authors: McGrail Daniel J. , Li Yang , Smith Roger S. , Feng Bin , Dai Hui , Li Yongsheng , Hu Limei , Dennehey Briana , Awasthi Sharad , Mendillo Marc L. , Mills Gordon B. , Lin Shiaw-Yih , Yi S. Stephen , Sahni Nidhi 
Published: October 2022

SUMMARYSince the discovery of BRCA1 and BRCA2 mutations as cancer risk factors, we have gained substantial insight into their role in maintaining genomic stability through homologous recombination (HR) DNA repair. However, upon pan-cancer analysis of tumors from The Cancer Genome Atlas (TCGA), we found that mutations in BRCA1/2 and other classical HR genes only identified 10-20% of tumors that display genomic evidence of HR deficiency (HRD), suggesting that the cause of the vast majority of HR defects in tumors is unknown. As HRD both predisposes individuals to cancer development and leads to therapeutic vulnerabilities, it is critical to define the spectrum of genetic events that drive HRD. Here, we employed a network-based approach leveraging the abundance of molecular characterization data from TCGA to identify novel drivers of HRD. We discovered that over half of putative genes driving HRD originated outside of canonical DNA damage response genes, with a particular enrichment for RNA binding protein (RBP)-encoding genes. These novel drivers of HRD were cross-validated using an independent ICGC cohort, and were enriched in GWAS loci associated with cancer risk. Experimental approaches validated over 90% of our predictions in a panel of 50 genes tested by siRNA and 31 additional engineered mutations identified from TCGA patient tumors. Moreover, genetic suppression of identified RBPs or pharmacological inhibition of RBPs induced PARP inhibition. Further mechanistic studies indicate that some RBPs are recruited to sites of DNA damage to facilitate repair, whereas others control the expression of canonical HR genes. Overall, this study greatly expands the repertoire of known drivers of HRD and their contributions to DNA damage repair, which has implications for not only future mechanistic studies, but also for genetic screening and therapy stratification.HIGHLIGHTSThe majority of HR deficiencies detected cannot be directly attributed to aberrations in canonical HR genes.Integrated network analysis identifies RNA binding proteins (RBPs) as a novel driver of HR deficiency in patient tumors.RBP dysfunction can produce HR deficiencies through both dysregulation of canonical HR genes and action at sites of DNA damage.
Risk Ratio (Relative Risk) And Odds Ratio For Radiologically Visible Intracranial Air After Neuraxial Access Attempts Among Our Peri-Partum Patients Were Undefined Although One In Forty Of Them Had Radiologically Visible Intracranial Air On CT/MR Of Head/Brain
Authors: Gupta Deepak 
Published: October 2022

AbstractBackgroundDuring neuraxial access attempts, loss-of-resistance technique with air may inadvertently become injection-of-air technique potentially leading to intracranial air.ObjectiveThe purpose of this retrospective study was to ascertain the incidence of radiologically visible intracranial air among peri-partum patients admitted to local Women’s Hospital who underwent computed tomography/magnetic resonance imaging (CT/MR) of head/brain during their hospital stay at peri-partum floors over a seven-year period of July 1, 2015-June 30, 2022.MethodsAfter Institutional Review Board approval for exempt research, medical records of patients who underwent CT/MR of head/brain during their hospital stay at peri-partum floors over a seven-year period of July 1, 2015-June 30, 2022 were reviewed to see whether they had neuraxial access attempts (epidurals, spinals, combined spinal-epidurals, epidural blood patches) before their CT/MR of head/brain. Subsequently, such patients CT/MR of head/brain were reviewed to ascertain the evidence of any radiologically visible intracranial air.ResultsOnly 69 peri-partum patients underwent CT/MR of head/brain during the seven-year period with 40 of them receiving neuraxial access attempts before their CT/MR of head/brain. Only one labor epidural analgesia patient had radiologically visible intracranial air.ConclusionIn seven-year period sample among our peri-partum patients at local Women’s Hospital, risk ratio (relative risk) and odds ratio for radiologically visible intracranial air after neuraxial access attempts were undefined although one in forty had radiologically visible intracranial air on CT/MR of head/brain after neuraxial access attempts and that intracranial air was 100% attributable to neuraxial access attempts.
A Protocol for Single Nucleus RNAseq from Frozen Skeletal Muscle
Authors: Soule Tyler GB , Pontifex Carly S , Rosin Nicole , Joel Matthew M , Lee Sukyoung , Nguyen Minh Dang , Chhibber Sameer , Pfeffer Gerald 
Published: October 2022

AbstractSingle cell technologies are a method of choice to obtain vast amounts of cell-specific transcriptional information under physiological and diseased states. Myogenic cells are resistant to single nucleus RNA sequencing (snRNAseq) due to their large, multinucleated nature. Here, we report a novel, reliable, and cost-effective method to analyze frozen human skeletal muscle by snRNAseq. This method yields all expected cell types for human skeletal muscle and works on tissue frozen for long periods of time and with significant pathological changes. Our method is ideal for studying banked samples with the intention of studying human muscle disease.
Potential limitations of micro-dystrophin gene therapy for Duchenne muscular dystrophy
Authors: Hart Cora C. , Lee Young il , Xie Jun , Gao Guangping , Hammers David W. , Sweeney H. Lee 
Published: October 2022

ABSTRACTAdeno-associated viruses (AAVs) expressing versions of truncated dystrophin (micro-dystrophins) are being delivered at high doses to patients with Duchenne muscular dystrophy (DMD) in clinical trials. We examined this strategy with two different micro-dystrophins, similar to those currently in clinical trials, in a severe mouse model of DMD, the D2.mdx mouse, using doses of AAV comparable to those used in the clinical trials. We achieved high levels of micro-dystrophin expression in striated muscle with cardiac expression ∼10 fold higher than that observed in skeletal muscle. Significant, albeit incomplete, correction of the skeletal muscle disease is observed. Surprisingly, a lethal acceleration of cardiac disease progression occurs with one of the micro-dystrophins, while the second appears to benefit the heart. The detrimental impact on the heart in the first case appears to be caused by the high levels of micro-dystrophin in the heart resulting in competition between micro-dystrophin and utrophin at the cardiomyocyte membrane. While the significance of these observations for patients currently being treated with AAV-micro-dystrophin therapies is unclear since the levels of expression being achieved in the DMD hearts are unknown, it suggests that micro-dystrophin treatments may need to be carefully titrated to avoid high levels of expression in the heart.