bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linked-read genome sequencing identifies biallelic pathogenic variants in DONSON as a novel cause of Meier-Gorlin syndrome
Authors: Knapp Karen M , Sullivan Rosie , Murray Jennie , Gimenez Gregory , Arn Pamela , D'Souza Precilla , Gezdirici Alper , Wilson William G , Jackson Andrew P , Ferreira Carlos , Bicknell Louise S 
Published: November 2019

MaterialLinked-read whole genome sequencing (WGS) presents a new opportunity for cost-efficient singleton sequencing in place of traditional trio-based designs while generating informative-phased variants, effective for recessive disorders when parental DNA is unavailable.MethodsWe have applied linked-read WGS to identify novel causes of Meier-Gorlin syndrome (MGORS), a condition recognised by short stature, microtia and patella hypo/aplasia. There are eight genes associated with MGORS to date, all encoding essential components involved in establishing and initiating DNA replication.ResultsOur successful phasing of linked-read data led to the identification of biallelic rare variants in four individuals (24% of our cohort) in DONSON, a recently established DNA replication fork surveillance factor. The variants include five novel missense and one deep intronic variant. All were demonstrated to be deleterious to function; the missense variants all disrupted the nuclear localisation of DONSON, while the intronic variant created a novel splice site that generated an out-of-frame transcript with no residual canonical transcript produced.ConclusionVariants in DONSON have previously been associated with extreme microcephaly, short stature and limb anomalies and perinatal lethal microcephaly-micromelia syndrome. Our novel genetic findings extend the complicated spectrum of phenotypes associated with DONSON variants and promote novel hypotheses for the role of DONSON in DNA replication. While our findings reiterate that MGORS is a disorder of DNA replication, the pathophysiology is obviously complex. This successful identification of a novel disease gene for MGORS highlights the utility of linked-read WGS as a successful technology to be considered in the genetic studies of recessive conditions.
Retesting of women who are negative for aBRCA1andBRCA2mutation using a 20-gene panel
Authors: Lerner-Ellis Jordan , Sopik Victoria , Wong Andrew , Lázaro Conxi , Narod Steven A , Charames George S 
Published: November 2019

BackgroundThe value of retesting women who previously tested negative for a pathogenic variant (mutation) inBRCA1andBRCA2using an expanded panel of breast and ovarian cancer genes is unclear.MethodsWe studied 110BRCA1/2-negative women who were retested using a panel of 20 breast and/or ovarian cancer susceptibility genes at the Advanced Molecular Diagnostics Laboratory (AMDL) at Mount Sinai Hospital in Toronto between March 2017 and March 2019. All patients had previously tested negative forBRCApathogenic variants at the AMDL between January 2012 and March 2018 and were subsequently referred for retesting by their physician.ResultsOverall, six pathogenic variants in genes other thanBRCA1andBRCA2were found (prevalence 5.5%). There were two pathogenic variants found inRAD51C, and one found in each ofBRIP1,PALB2,PMS2andPTEN. The prevalence of pathogenic variants was 6.5% for women affected with cancer (6 of 93), including 4.9% for women with breast cancer (4 of 82) and 22.2% for women with ovarian cancer (2 of 9). None of the 17 unaffected women had a clinically significant or pathogenic variant. There were 44 women (40%) for whom the result of the panel test was inconclusive due to the detection of a variant of uncertain significance.ConclusionsOur findings indicate that the retesting ofBRCA1/2-negative individuals with an expanded panel of 20 breast and ovarian cancer genes can produce clinically relevant results, with a yield of 5.5% for pathogenic variants in genes other thanBRCA1andBRCA2.
Three-step site-directed mutagenesis screen identifies pathogenic MLH1 variants associated with Lynch syndrome
Authors: Houlleberghs Hellen , Dekker Marleen , Lusseveld Jarnick , Pieters Wietske , van Ravesteyn Thomas , Verhoef Senno , Hofstra Robert M W , te Riele Hein 
Published: November 2019

BackgroundInactivating mutations in the MLH1 DNA mismatch repair (MMR) gene underlie 42% of Lynch syndrome (LS) cases. LS is a cancer predisposition causing early onset colorectal and endometrial cancer. Nonsense and frameshift alterations unambiguously cause LS. The phenotype of missense mutations that only alter a single amino acid is often unclear. These variants of uncertain significance (VUS) hinder LS diagnosis and family screening and therefore functional tests are urgently needed. We developed a functional test for MLH1 VUS termed ‘oligonucleotide-directed mutation screening’ (ODMS).MethodsThe MLH1 variant was introduced by oligonucleotide-directed gene modification in mouse embryonic stem cells that were subsequently exposed to the guanine analogue 6-thioguanine to determine whether the variant abrogated MMR.ResutsIn a proof-of-principle analysis, we demonstrate that ODMS can distinguish pathogenic and non-pathogenic MLH1 variants with a sensitivity of >95% and a specificity of >91%. We subsequently applied the screen to 51 MLH1 VUS and identified 31 pathogenic variants.ConclusionODMS is a reliable tool to identify pathogenic MLH1 variants. Implementation in clinical diagnostics will improve clinical care of patients with suspected LS and their relatives.
Single-Cell Gene Expression Analyses Reveal Distinct Self-Renewing and Proliferating Subsets in the Leukemia Stem Cell Compartment in Acute Myeloid Leukemia
Authors: Sachs Karen , Sarver Aaron L. , Noble-Orcutt Klara E. , LaRue Rebecca S. , Antony Marie Lue , Chang Daniel , Lee Yoonkyu , Navis Connor M. , Hillesheim Alexandria L. , Nykaza Ian R. , Ha Ngoc A. , Hansen Conner J. , Karadag Fatma K. , Bergerson Rachel J. , Verneris Michael R. , Meredith Matthew M. , Schomaker Matthew L. , Linden Michael A. , Myers Chad L. , Largaespada David A. , Sachs Zohar 
Published: November 2019

Abstract

Standard chemotherapy for acute myeloid leukemia (AML) targets proliferative cells and efficiently induces complete remission; however, many patients relapse and die of their disease. Relapse is caused by leukemia stem cells (LSC), the cells with self-renewal capacity. Self-renewal and proliferation are separate functions in normal hematopoietic stem cells (HSC) in steady-state conditions. If these functions are also separate functions in LSCs, then antiproliferative therapies may fail to target self-renewal, allowing for relapse. We investigated whether proliferation and self-renewal are separate functions in LSCs as they often are in HSCs. Distinct transcriptional profiles within LSCs of Mll-AF9/NRASG12V murine AML were identified using single-cell RNA sequencing. Single-cell qPCR revealed that these genes were also differentially expressed in primary human LSCs and normal human HSPCs. A smaller subset of these genes was upregulated in LSCs relative to HSPCs; this subset of genes constitutes “LSC-specific” genes in human AML. To assess the differences between these profiles, we identified cell surface markers, CD69 and CD36, whose genes were differentially expressed between these profiles. In vivo mouse reconstitution assays resealed that only CD69High LSCs were capable of self-renewal and were poorly proliferative. In contrast, CD36High LSCs were unable to transplant leukemia but were highly proliferative. These data demonstrate that the transcriptional foundations of self-renewal and proliferation are distinct in LSCs as they often are in normal stem cells and suggest that therapeutic strategies that target self-renewal, in addition to proliferation, are critical to prevent relapse and improve survival in AML.

Significance:
These findings define and functionally validate a self-renewal gene profile of leukemia stem cells at the single-cell level and demonstrate that self-renewal and proliferation are distinct in AML.
Association Between Ambulatory Care Utilization and Coronary Artery Disease Outcomes by Race/Ethnicity
Authors: Kim Eun Ji , Parker Victoria A. , Liebschutz Jane M. , Conigliaro Joseph , DeGeorge Jean , Hanchate Amresh D. 
Published: November 2019

Background

Coronary artery disease is common, and there exist disparities in management and outcomes. The purpose of this study is to examine the association between ambulatory care utilizations and inpatient acute myocardial infarction (
AMI
) mortality.

Methods and Results

This is a retrospective analysis of a stratified national sample of Medicare fee‐for‐service enrollees aged 66 years and older from January 1, 2010 to December 31, 2011. We measured both number of ambulatory visits and presence of ambulatory cardiac tests. The primary outcome was inpatient
AMI
mortality. Using multivariate logistic regression models, we estimated the association between ambulatory care utilization and the main patient outcomes, adjusting for patient‐ and area‐level demographic, geographical, and clinical characteristics. We found that a significantly lower percentage of Hispanics and Asians, relative to whites, had frequent ambulatory care visits. Among the largest 4 race/ethnic groups, Asians had the highest observed inpatient mortality rate (15.9%). Overall, low ambulatory utilization was associated with higher odds (odds ratio=1.85 [95% confidence interval: 1.11‐3.08]), and ambulatory cardiac testing was associated with lower odds (odds ratio=0.73 [0.55‐0.95]) of inpatient
AMI
mortality, after adjustment for covariates. Asians had higher odds of inpatient
AMI
mortality even after adjustment for covariates.

Conclusions

Among Medicare fee‐for‐service enrollees, Hispanics and Asians had lower rates of ambulatory care visits, and all minority groups had higher odds of hospitalization for
AMI
. Ambulatory care utilization, including both ambulatory clinic visits and outpatient cardiac tests, were associated with
AMI
mortality. Further research is needed to understand the causal relationship between ambulatory care utilization and cardiovascular outcomes.
To Bear the Past as a Living Wound: William James and the Philosophy of History
Authors: Sheehey Bonnie 
Published: November 2019

Abstract
Philosophers generally recognize pragmatism as a philosophy of progress. For many commentators, pragmatism is linked to a notion of historical progress through its embrace of meliorism – a forward-looking philosophy that places hope in the future possibility of improvement. This paper calls pragmatism’s progressivism into question by outlining an alternative account of meliorism in the work of William James. Drawing on his ethical writings from the 1870s and 1880s, I argue that James’s concept of hope does not imply an embrace of historical progress, but remains detached from such a notion precisely insofar as it relies on a non-progressive temporality that encourages a rethinking of historical change. This form of hope is significant, I suggest, for the work of conceptualizing a non-progressive pragmatist approach to history and historiography.
How does mindful eating without non-judgement, mindfulness and self-compassion relate to motivations to eat palatable foods in a student population?
Authors: Keyte Rebecca , Egan Helen , Mantzios Michail 
Published: November 2019

Background: Previous research acknowledges the impact mindfulness, mindful eating and self-compassion has upon weight regulation and motives to eat palatable foods, with mindful eating showing an increased impact of eating behaviours. Some research has identified that present moment awareness should be the primary focus of mindful eating. Aim: This research aimed to explore the relationship between mindfulness, self-compassion and mindful eating with motivations to eat palatable food. Methods: A cross-sectional study was conducted to investigate this relationship among university students ( n = 211), utilizing a newly developed mindful eating scale primarily focusing on present moment awareness. Results: Results indicated significant negative correlations between both self-compassion and mindful eating and motives to eat palatable foods. Mindful eating positively correlated with self-compassion and other mindfulness elements that are suggesting indirect acceptance measurements of the mindful eating scale. Conclusion: Possible explanations and future directions are discussed further with an emphasis on the need for more empirical work. In addition, suggestions are provided regarding the reinterpretation of elements that are investigated and explored in eating literature.
3D, Weightbearing Topographical Study of Periprosthetic Cysts and Alignment in Total Ankle Replacement
Authors: Lintz François , Mast Jef , Bernasconi Alessio , Mehdi Nazim , de Cesar Netto Cesar , Fernando Céline ,   International Weight-Bearing CT Society, Buedts Kristian 
Published: November 2019

Background: We investigated the association between hindfoot residual malalignment assessed on weightbearing computed tomography (WBCT) images and the development of periprosthetic cysts (PPCs) after total ankle replacement (TAR). We hypothesized that PPCs would be found predominantly medially in the varus configuration and laterally in the valgus configuration. Methods: Cases of primary TAR with available WBCT imaging of the ankle were included in this retrospective study. The location of the PPC was marked and the following volumes were calculated: total (TCV), medial (MCV), central (CCV), and lateral (LCV) cyst volumes. Hindfoot alignment was measured as Foot and Ankle Offset (FAO), with 95% confidence intervals (95% CIs) calculated to define varus (<95% CI) and valgus (>95% CI) groups. Cyst volumes were compared between these 2 groups. The American Orthopaedic Foot & Ankle Society (AOFAS) score at the time of the WBCT was also retrieved. Receiver operating characteristic (ROC) curves were used to determine FAO thresholds for predicting an increased risk of PPC. Results: Forty-eight TARs (mean follow-up, 44.6 months) were included, 81% of which had at least 1 PPC. The mean FAO was 0.12% (95% CI, –1.12 to 1.36). Patients with greater residual malalignment ( P < .001) and those with longer follow-up ( P < .001) presented with increased TCV. In varus cases, the MCV was greater than the LCV ( P = .042), with a threshold FAO value of −2.75% or less predicting an increased MCV. In valgus cases, the LCV was greater than the MCV ( P = .049), with a FAO threshold value of 4.5% or more predicting an increased LCV. Conclusion: In this series, the PPC volume after primary TAR significantly correlated with postoperative hindfoot malalignment and longer follow-up. Level of Evidence: Level III, retrospective comparative series.
Ultrasound-guided removal of organized thrombi using biopsy forceps in dialysis patients with arterio-venous access occlusion
Authors: Wakabayashi Masanori 
Published: November 2019

Introduction: As a countermeasure against the organized thrombi frequently observed in vascular access occlusion, we devised a percutaneous excision method for organized thrombi under superficial ultrasound guidance using biopsy forceps. The Radial JawTM 3 (2 mm) biopsy forceps of Boston Scientific Corporation was used. The usefulness of this method was investigated. Method: The following protocol, which is suitable for endovascular treatment, was prepared and used: (1) all procedures were performed under ultrasound guidance and (2) use of the forceps was assisted via a long sheath in cases involving a complicated bloodstream. Subjects: Among 564 cases of arterio-venous access occlusion that received treatment at this hospital between May 2014 and April 2017, the subjects of this study were 468 cases who could be followed up. Thrombectomy of an organized thrombus using the biopsy forceps was performed 194 times in 138 cases. Biopsy forceps were used in the initial treatment in a total of 115 cases, including 71 cases of acute occlusion of an autologous vein, 3 cases of chronic occlusion of an autologous vein, and 41 cases of acute occlusion of a prosthetic vessel. Results: The initial success rate for all cases of occlusion was 97.2%. The initial success rate for cases in which biopsy forceps were used was 98.2%. For cases using biopsy forceps, the primary patency rates were 47.1% at 3 months, and the secondary patency rates (until occlusion) were 89.1% at 3 months. Conclusion: This method was considered to be a valuable choice as a countermeasure against organized thrombi.
Prescription Value-Based Automatic Optimization of Importance Factors in Inverse Planning
Authors: Guo Caiping , Zhang Pengcheng , Gui Zhiguo , Shu Huazhong , Zhai Lihong , Xu Jinrong 
Published: November 2019

Objective: An automatic method for the optimization of importance factors was proposed to improve the efficiency of inverse planning. Methods: The automatic method consists of 3 steps: (1) First, the importance factors are automatically and iteratively adjusted based on our proposed penalty strategies. (2) Then, plan evaluation is performed to determine whether the obtained plan is acceptable. (3) If not, a higher penalty is assigned to the unsatisfied objective by multiplying it by a compensation coefficient. The optimization processes are performed alternately until an acceptable plan is obtained or the maximum iteration N max of step (3) is reached. Results: Tested on 2 kinds of clinical cases and compared with manual method, the results showed that the quality of the proposed automatic plan was comparable to, or even better than, the manual plan in terms of the dose–volume histogram and dose distributions. Conclusions: The proposed algorithm has potential to significantly improve the efficiency of the existing manual adjustment methods for importance factors and contributes to the development of fully automated planning. Especially, the more the subobjective functions, the more obvious the advantage of our algorithm.
The Impact of Infusion Center Layout on Workflow and Satisfactions in Two Cancer Infusion Centers: A Case Study on Staff and Patients
Authors: Jalalianhosseini Mahshid , Freihoefer Kara , Doyle Nancy , Simpson Amanda 
Published: November 2019

Objective: The objective of this empirical research is to compare nurses’ operational workflow and nurses’ and patients’ satisfactions of two different infusion center designs. One center has a traditional open bay design and the other has semi-private bays. This study also intends to gather baseline data to compare to a future post-occupancy evaluation of a new infusion center where the two existing centers will be combined. Background: The increasing number of patients with cancer diagnosis who refer to infusion centers highlights the importance of design of these centers. Method: The mixed-method approach of this study involves shadowing nurses and surveying nurses and patients. Data collection captured nurses’ activities, activity durations, and nurses’ and patients’ satisfaction with the design of clinics. Results: Comparison of shadowing data indicated that although the infusion centers have different layouts, there are no significant differences in the activities or time spent by nurses in different areas among the centers. Staff, however, have different satisfaction levels with visual and speech privacy, ability to concentrate without distraction, collaboration with other staff, and the process of medication delivery. Patients also had slightly different satisfaction levels with their ability to communicate with staff and design of bays. Conclusion: This research sheds light on operational workflows and satisfaction of staff and patients in two different infusion center design. Considering the limited studies on these settings, this study serves as baseline data to compare to other studies on cancer infusion centers and addresses issues of benchmarking and staff and patient satisfaction.
Too Hot to Handle—Quantifying Temperature Variations in the Nasal Endoscope Ocular Assembly and Light Post
Authors: Lewis Trevor , Levin Marc , Sommer Doron D. 
Published: November 2019

Background Nasal endoscopes have transformed and improved the safety of intranasal and transnasal surgery. The heat they can produce may, however, reach dangerous levels for surgeons. Studies have not previously assessed the temperature of the nasal endoscope light post/ocular assembly (LP/OA)—where the surgeon usually holds the endoscope. Objective This study aims to understand the effect of different nasal endoscopes, light sources, and light cords on the LP/OA temperature. Methods We measured the temperature at the LP/OA of various rigid nasal endoscopes at multiple time intervals over 30 minutes, as well as after turning off the light source and irrigating the LP/OA with 10 mL of saline. Results The highest temperature recorded was 67.37°C at the LP/OA at 30 minutes, using a new light cord, older endoscope, and 184-hour xenon light bulb. In every trial, the temperature of the LP/OA continually increased until 30 minutes when the light source was turned off. Statistically significant ( P < .001) temperature differences were seen in trials using the older xenon light sources. The light-emitting diode light source was significantly cooler with an older light cord regardless of the age of the scope ( P = .003). Conclusion Endoscope temperatures during sinus surgery may reach potentially dangerous levels at the LP/OA region. These temperatures may be sufficient to cause second-degree burns during normal usage. Factors associated with higher endoscope temperatures include longer times with the light source on and xenon light bulbs.
Ultrasonic Welding of Magnesium–Titanium Dissimilar Metals: A Study on Thermo-mechanical Analyses of Welding Process by Experimentation and Finite Element Method
Authors: Zhao Dewang , Ren Daxin , Zhao Kunmin , Sun Pan , Guo Xinglin , Liu Liming 
Published: November 2019

AbstractUltrasonic welding is an effective ways to achieve a non-reactive/immiscible heterogeneous metal connection, such as the connection of magnesium alloy and titanium alloy. But the thermal mechanism of magnesium alloy/titanium alloy ultrasonic welding has not been defined clearly. In this paper, the experimental and the finite element analysis were adopted to study the thermal mechanism during welding. Through the test, the temperature variation law during the welding process is obtained, and the accuracy of the finite element model is verified. The microscopic analysis indicates that at the welding time of 0.5 s, the magnesium alloy in the center of the solder joint is partially melted and generates the liquid phase. Through the finite element analysis, the friction coefficient of the magnesium–titanium ultrasonic welding interface can be considered as an average constant value of 0.28. The maximum temperature at the interface can exceed 600 °C to reach the melting point temperature of the magnesium alloy. The plastic deformation begins after 0.35 s and occurs at the magnesium side at the center of the interface.
Shape Stability of Metallic Nanoplates: A Molecular Dynamics Study
Authors: Chen Xiwen , Huang Rao , Shih Tien-Mo , Wen Yu-Hua 
Published: November 2019

AbstractMetallic nanoplates have attracted widespread interests owing to their functional versatility, which relies heavily on their morphologies. In this study, the shape stability of several metallic nanoplates with body-centered-cubic (bcc) lattices is investigated by employing molecular dynamics simulations. It is found that the nanoplate with (110) surface planes is the most stable compared to the ones with (111) and (001) surfaces, and their shapes evolve with different patterns as the temperature increases. The formation of differently orientated facets is observed in the (001) nanoplates, which leads to the accumulation of shear stress and thus results in the subsequent formation of saddle shape. The associated shape evolution is quantitatively characterized. Further simulations suggest that the shape stability could be tuned by facet orientations, nanoplate sizes (including diameter and thickness), and components.