bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chest radiograph reading panel performance in a Bangladesh pneumococcal vaccine effectiveness study
Authors: McCollum Eric D , Ahmed Salahuddin , Chowdhury Nabidul H , Rizvi Syed J R , Khan Ahad M , Roy Arun D , Hanif Abu AM , Pervaiz Farhan , Ahmed ASM Nawshad U , Farrukee Ehteshamul H , Monowara Mahmuda , Hossain Mohammad M , Doza Fatema , Tanim Bidoura , Alam Farzana , Simmons Nicole , Reller Megan E , Harrison Meagan , Schuh Holly B , Quaiyum Abdul , Saha Samir K , Begum Nazma , Santosham Mathuram , Moulton Lawrence H , Checkley William , Baqui Abdullah H 
Published: April 2019

IntroductionTo evaluate WHO chest radiograph interpretation processes during a pneumococcal vaccine effectiveness study of children aged 3–35 months with suspected pneumonia in Sylhet, Bangladesh.MethodsEight physicians masked to all data were standardised to WHO methodology and interpreted chest radiographs between 2015 and 2017. Each radiograph was randomly assigned to two primary readers. If the primary readers were discordant for image interpretability or the presence or absence of primary endpoint pneumonia (PEP), then another randomly selected, masked reader adjudicated the image (arbitrator). If the arbitrator disagreed with both primary readers, or concluded no PEP, then a masked expert reader finalised the interpretation. The expert reader also conducted blinded quality control (QC) for 20% of randomly selected images. We evaluated agreement between primary readers and between the expert QC reading and the final panel interpretation using per cent agreement, unadjusted Cohen’s kappa, and a prevalence and bias-adjusted kappa.ResultsAmong 9723 images, the panel classified 21.3% as PEP, 77.6% no PEP and 1.1% uninterpretable. Two primary readers agreed on interpretability for 98% of images (kappa, 0.25; prevalence and bias-adjusted kappa, 0.97). Among interpretable radiographs, primary readers agreed on the presence or absence of PEP in 79% of images (kappa, 0.35; adjusted kappa, 0.57). Expert QC readings agreed with final panel conclusions on the presence or absence of PEP for 92.9% of 1652 interpretable images (kappa, 0.75; adjusted kappa, 0.85).ConclusionPrimary reader performance and QC results suggest the panel effectively applied the WHO chest radiograph criteria for pneumonia.
Suicide rates in Zhejiang Province, China, from 2006 to 2016: a population-based study
Authors: Fei Fangrong , Liu Huixin , I Leuba Sequoia , Li Yichong , Hu Ruying , Yu Min , Pan Jin , Zhong Jieming 
Published: April 2019

BackgroundWe investigated the current temporal trends of suicide in Zhejiang, China, from 2006 to 2016 to determine possible health disparities in order to establish priorities for intervention.MethodsWe collected mortality surveillance data from 2006 to 2016 from the Zhejiang Chronic Disease Surveillance Information and Management System from the Zhejiang Provincial Centre for Disease Control and Prevention. We estimated region-specific and gender-specific suicide rates using joinpoint regression analyses to determine the average annual percentage change (AAPC) and its 95% CI.ResultsThe crude suicide rate declined from 9.64 per 100 000 people in 2006 to 4.86 per 100 000 in 2016, and the age-adjusted suicide rate decreased from 9.74 per 100 000 in 2006 to 4.14 per 100 000 in 2016. During 2006–2013, rural males had the highest suicide rate, followed by rural females, urban males, and urban females, while after 2013, urban males suicide rates surpassed rural female suicide rates, and became the second highest suicide rate subgroup. The rate of suicide declined in all region-specific and/or gender-specific subgroups except among urban males between 20 and 34 years of age. Their age-adjusted suicide rate AAPC greatly increased to 28.39 starting in 2013 compared with an AAPC of −13.47 from 2006 to 2013.ConclusionsThe suicide rate among young urban males has been alarmingly increasing since 2013, and thus, researchers must develop targeted effective strategies to mitigate this escalating loss of life.
Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes
Authors: Forsberg Karin , Graffmo Karin , Pakkenberg Bente , Weber Markus , Nielsen Martin , Marklund Stefan , Brännström Thomas , Andersen Peter Munch 
Published: April 2019

ObjectiveA hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase-1 (SOD1) are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.MethodsA panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue.ResultsThe 18 patients with hexanucleotide-repeat-expansions in C9orf72 had inclusions of misfolded wild type (WT) SOD1WT in spinal motor neurons. Similar inclusions were occasionally observed in medulla oblongata and in the motor cortex and frontal lobe. Patients with mutations in FUS, KIF5A, NEK1, ALSIN or VAPB, carried similar SOD1WT inclusions. Minute amounts of misSOD1WT inclusions were detected in 2 of 20 patients deceased from non-neurological causes and in 4 of 10 patients with other neurodegenerative diseases. Comparison was made with 17 patients with 9 different SOD1 mutations. Morphologically, the inclusions in patients with mutations in C9orf72HRE, FUS, KIF5A, NEK1, VAPB and ALSIN resembled inclusions in patients carrying the wildtype-like SOD1D90A mutation, whereas patients carrying unstable SOD1 mutations (A4V, V5M, D76Y, D83G, D101G, G114A, G127X, L144F) had larger skein-like SOD1-positive inclusions.Conclusions and relevanceAbundant inclusions containing misfolded SOD1WT are found in spinal and cortical motor neurons in patients carrying mutations in six ALS-causing genes other than SOD1. This suggests that misfolding of SOD1WT can be part of a common downstream event that may be pathogenic. The new anti-SOD1 therapeutics in development may have applications for a broader range of patients.
Noise-induced hearing loss in the military dental setting: a UK legislative perspective
Authors: Ramsey Richard , Greenough J , Breeze J 
Published: April 2019

IntroductionHealth professionals working in the dental environment are potentially at risk of noise-induced hearing loss (NIHL) due to the use of clinical and laboratory equipment. Workplaces engaging in the practice of dentistry within the UK are subject to legislation from the Control of Noise at Work (CNW) regulations 2005. Clinicians working in the military are at further increased risk of NIHL due to exposure from additional risk factors such as rifles or aircraft engines. To our knowledge, no authors have previously studied the noise levels experienced in a military dental setting or compared noise levels in a typical dental practice with current UK legislation.MethodMeasurements of noise levels experienced by a dentist, dental nurse and dental hygienist during a standard conservation procedure were assessed using wearable noise dose-badges. Furthermore, noise levels within a dental technician’s work space were also assessed. Noise levels produced by representative clinical and laboratory equipment were assessed and compared with CNW legislation.ResultsThe highest level for clinical equipment was produced by the suction apparatus while aspirating up a cup of water at 76 dB. For laboratory equipment, the lower exposure action value (LEAV) of 80 dB would be exceeded in 2.1 hours’ use of the trimmer, 3.6 hours’ use of the vibrating table and 9 min use of the airline.ConclusionsNoise levels experienced by clinicians within the dental surgery were well below the legislative LEAV thresholds for both peak and continuous noise. However, noise levels produced by laboratory equipment were far higher and there is clearly the potential for excessive noise exposure for dental professional in the everyday setting. Dental professionals responsible for dental laboratory settings must be familiar with the CNW regulations and measures put in place that control the inadvertent breach of legislation. Hearing protection must be mandated when using equipment that exceeds the LEAV and an educational programme is required to explain both their correct use and the rationale behind it. Methods of mitigating that risk further require exploration such as alternative methods of completing the tasks performed by the airline or reducing the noise generated by it, such as by reducing the supply pressure or using an alternative nozzle design.
Surgical outcomes for chronic exertional compartment syndrome following improved diagnostic criteria
Authors: Simpson Christopher , Roscoe D , Hughes S , Hulse D , Guthrie H 
Published: April 2019

IntroductionChronic exertional compartment syndrome (CECS) presents with pain during exercise, most commonly within the anterior compartment of the lower limb. A diagnosis is classically made from a typical history and the measurement of intramuscular compartmental pressure (IMCP) testing. Improved, more specific diagnostic criteria for IMCP testing allow clinicians to now be more certain of a diagnosis of CECS. Outcomes following surgical treatment in patients diagnosed using these more robust criteria are unknown.MethodsAll patients undergoing fasciectomy for anterior compartment CECS at a single rehabilitation unit were identified between 2014 and 2017. Wilcoxen signed-rank test was used to compare military fitness grading and paired t-test was used to compare Foot and Ankle Ability Measure, FAAM Sport Specific and Exercise-Induced LimbPain-G outcome measures, presurgery and postsurgery.ResultsThere was a significant difference in fitness grading between presurgical and postsurgical intervention (Z = −2.68, p < 0.01) with 46 % of patients improving their occupational medical grading. All secondary measures of outcome, looking at clinical symptoms, also improved.ConclusionAlmost half of the patients undergoing fasciectomy, following diagnosis using more specific criteria, will have an improvement in occupational medical grading. These outcomes represent the lower end of those reported in civilian populations. This is likely a result of a combination of factors, most notably the different diagnostic criteria followed and the more stringent criteria applied to military occupational grading, compared with civilian practice. Further work is now required to evaluate the impact of differing rehabilitation regimes on postoperative patients identified through this more specific diagnostic testing.
Conceptual design study of iron-based superconducting dipole magnets for SPPC
Authors: Kong Ershuai , Wang Chengtao , Wang Lin , Wang Xiangqi , Cheng Da , Zhang Kai , Wang Yingzhe , Peng Quanling , Xu Qingjin 
Published: April 2019

A conceptual design study of 12-T two-in-one dipole magnets is ongoing with the iron-based superconducting (IBS) technology, as a candidate option for Super Proton Proton Collider (SPPC), which is designed with a circumference of 100 km and a center-of-mass energy of 70 TeV. Compared with Nb3Sn, the IBS design is competitive because of the potential much higher performance and lower cost of IBS conductors in the future. The design study is carried out with an expected Je level of IBS in 10 years. Besides, we also expect the IBS superconductor to have much better mechanical properties compared to stress-sensitive conductors like Nb3Sn and Bi-2212 wires. The 12-T dipole magnet is designed with common-coil configuration. We have optimized the field uniformity with two different layouts of the coil ends, including the soft-way bending and the hard-way bending. We also have explored the influence of a mid-plane gap on the field uniformity. The main parameters, the coil layouts, and the optimization of the field quality are presented.
The energy sawtooth effects in the partial double ring scheme of CEPC
Authors: Wang Yiwei , Bai Sha , Yu Chenghui , Gao Jie 
Published: April 2019

The energy sawtooth will be significant in the future circular Higgs factory with beam energy as high as 120 GeV. For the partial double ring scheme, unlike the double ring scheme, the effects of energy sawtooth cannot be corrected by tapering the magnet strength with beam energy along the beamline. In this paper, the energy sawtooth effects in the partial double ring scheme and its mitigation methods are presented. As an example, the study of the energy sawtooth effects of the CEPC advanced partial double ring scheme is presented.
Providing multidisciplinary scientific advice for coastal planning in Kitimat Arm, British Columbia
Authors: Lintern Gwyn , Blais-Stevens Andrée , Stacey Cooper , Shaw John , Bobrowsky Peter , Conway Kim , Huntley David , Mackillop Kevin , Overeem Irina , Scherwath Martin 
Published: April 2019

Abstract

A 6.3 m tsunami swept through Kitimat Arm, British Columbia in 1974. An even larger wave struck and damaged the Northlands Navigation dock at Kitimat and the Haisla First Nation docks at Kitamaat Village the following year. Further down the fjord, two large coastal block failures were observed on the fjord walls across from the Gitga'at village of Hartley Bay. Several large infrastructure projects have recently been proposed for the Kitimat Arm coastal areas. The Geological Survey of Canada has therefore embarked on a five-year project to understand the magnitude and frequency of submarine mass movements in this fjord system to provide information regarding the risks from these events and to propose mitigation measures that may reduce these risks. We provide here an overview and the main results to date of an ongoing multidisciplinary study, which includes palaeotsunami studies, geomorphological and sub-seabed mapping, subaerial landslide hazard assessment, tsunami modelling,
in situ
and laboratory geotechnical testing, and the real-time tracking of seismic activity and seafloor movement. Some of these activities are reported in greater detail elsewhere in this book. The results of this research are summarized as a list of conclusions and recommendations to the Government of Canada.
ROCK Inhibition Induces Terminal Adipocyte Differentiation and Suppresses Tumorigenesis in Chemoresistant Osteosarcoma Cells
Authors: Takahashi Nobuhiro , Nobusue Hiroyuki , Shimizu Takatsune , Sugihara Eiji , Yamaguchi-Iwai Sayaka , Onishi Nobuyuki , Kunitomi Haruko , Kuroda Tatsuo , Saya Hideyuki 
Published: April 2019

Abstract

Tumors comprise heterogeneous cell types including cancer stem cells (CSC), progenitor cells, and differentiated cells. Chemoresistance is a potential cause of relapse and a key characteristic of CSC, but the development of novel therapeutic approaches for targeting these cells has been limited. We previously established osteosarcoma-initiating (OSi) cells by introducing the gene for c-Myc into bone marrow stromal cells of Ink4a/Arf knockout mice. These OSi cells are composed of two distinct clones: highly tumorigenic cells (AX cells), similar to bipotent committed osteochondral progenitor cells, and tripotent cells of low tumorigenicity (AO cells), similar to mesenchymal stem cells. Here we show that depolymerization of the actin cytoskeleton induces terminal adipocyte differentiation and suppresses tumorigenesis in chemoresistant OSi cells. In contrast to AX cells, AO cells were highly resistant to conventional chemotherapeutic agents such as doxorubicin and were thus identified as chemoresistant cells. Inhibition of Rho-associated coiled-coil containing protein kinase (ROCK) elicited terminal adipocyte differentiation in chemoresistant AO cells through negative regulation of the transcriptional coactivator megakaryoblastic leukemia 1 associated with actin depolymerization. The clinically administered ROCK inhibitor fasudil significantly suppressed growth in vitro and tumorigenicity in vivo of chemoresistant AO cells as well as of OSi cells. Our findings thus suggest a new therapeutic strategy based on the induction of trans-terminal differentiation via modulation of actin cytoskeleton dynamics for therapy-resistant osteosarcoma stem cells.

Significance:
These findings suggest that induction of trans-terminal differentiation through regulation of actin dynamics is a potential novel therapeutic approach for targeting chemoresistant stem-like tumor cells.
BRCA1—No Matter How You Splice It
Authors: Li Dan , Harlan-Williams Lisa M. , Kumaraswamy Easwari , Jensen Roy A. 
Published: April 2019

AbstractBRCA1 (breast cancer 1, early onset), a well-known breast cancer susceptibility gene, is a highly alternatively spliced gene. BRCA1 alternative splicing may serve as an alternative regulatory mechanism for the inactivation of the BRCA1 gene in both hereditary and sporadic breast cancers, and other BRCA1-associated cancers. The alternative transcripts of BRCA1 can mimic known functions, possess unique functions compared with the full-length BRCA1 transcript, and in some cases, appear to function in opposition to full-length BRCA1. In this review, we will summarize the functional “naturally occurring” alternative splicing transcripts of BRCA1 and then discuss the latest next-generation sequencing–based detection methods and techniques to detect alternative BRCA1 splicing patterns and their potential use in cancer diagnosis, prognosis, and therapy.
Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence
Authors: Coombes Raoul Charles , Page Karen , Salari Raheleh , Hastings Robert K. , Armstrong Anne , Ahmed Samreen , Ali Simak , Cleator Susan , Kenny Laura , Stebbing Justin , Rutherford Mark , Sethi Himanshu , Boydell Anna , Swenerton Ryan , Fernandez-Garcia Daniel , Gleason Kelly L.T. , Goddard Katie , Guttery David S. , Assaf Zoe J. , Wu Hsin-Ta , Natarajan Prashanthi , Moore David A. , Primrose Lindsay , Dashner Scott , Tin Antony S. , Balcioglu Mustafa , Srinivasan Ramya , Shchegrova Svetlana V. , Olson Alexander , Hafez Dina , Billings Paul , Aleshin Alexey , Rehman Farah , Toghill Bradley J. , Hills Allison , Louie Maggie C. , Lin Cheng-Ho Jimmy , Zimmermann Bernhard G. , Shaw Jaqueline A. 
Published: April 2019

Abstract

Purpose:
Up to 30% of patients with breast cancer relapse after primary treatment. There are no sensitive and reliable tests to monitor these patients and detect distant metastases before overt recurrence. Here, we demonstrate the use of personalized circulating tumor DNA (ctDNA) profiling for detection of recurrence in breast cancer.

Experimental Design:
Forty-nine primary patients with breast cancer were recruited following surgery and adjuvant therapy. Plasma samples (n = 208) were collected every 6 months for up to 4 years. Personalized assays targeting 16 variants selected from primary tumor whole-exome data were tested in serial plasma for the presence of ctDNA by ultradeep sequencing (average &gt;100,000X).

Results:
Plasma ctDNA was detected ahead of clinical or radiologic relapse in 16 of the 18 relapsed patients (sensitivity of 89%); metastatic relapse was predicted with a lead time of up to 2 years (median, 8.9 months; range, 0.5–24.0 months). None of the 31 nonrelapsing patients were ctDNA-positive at any time point across 156 plasma samples (specificity of 100%). Of the two relapsed patients who were not detected in the study, the first had only a local recurrence, whereas the second patient had bone recurrence and had completed chemotherapy just 13 days prior to blood sampling.

Conclusions:
This study demonstrates that patient-specific ctDNA analysis can be a sensitive and specific approach for disease surveillance for patients with breast cancer. More importantly, earlier detection of up to 2 years provides a possible window for therapeutic intervention.
Multidrug Cancer Therapy in Metastatic Castrate-Resistant Prostate Cancer: An Evolution-Based Strategy
Authors: West Jeffrey B. , Dinh Mina N. , Brown Joel S. , Zhang Jingsong , Anderson Alexander R. , Gatenby Robert A. 
Published: April 2019

Abstract

Purpose:
Integration of evolutionary dynamics into systemic therapy for metastatic cancers can prolong tumor control compared with standard maximum tolerated dose (MTD) strategies. Prior investigations have focused on monotherapy, but many clinical cancer treatments combine two or more drugs. Optimizing the evolutionary dynamics in multidrug therapy is challenging because of the complex cellular interactions and the large parameter space of potential variations in drugs, doses, and treatment schedules. However, multidrug therapy also represents an opportunity to further improve outcomes using evolution-based strategies.

Experimental Design:
We examine evolution-based strategies for two-drug therapy and identify an approach that divides the treatment drugs into primary and secondary roles. The primary drug has the greatest efficacy and/or lowest toxicity. The secondary drug is applied solely to reduce the resistant population to the primary drug.

Results:
Simulations from the mathematical model demonstrate that the primary–secondary approach increases time to progression (TTP) compared with conventional strategies in which drugs are administered without regard to evolutionary dynamics. We apply our model to an ongoing adaptive therapy clinical trial of evolution-based administration of abiraterone to treat metastatic castrate-resistant prostate cancer. Model simulations, parameterized with data from individual patients who progressed, demonstrate that strategic application of docetaxel during abiraterone therapy would have significantly increased their TTP.

Conclusions:
Mathematical models can integrate evolutionary dynamics into multidrug cancer clinical trials. This has the potential to improve outcomes and to develop clinical trials in which these mathematical models are also used to estimate the mechanism(s) of treatment failure and explore alternative strategies to improve outcomes in future trials.
Dual TGFβ/BMP Pathway Inhibition Enables Expansion and Characterization of Multiple Epithelial Cell Types of the Normal and Cancerous Breast
Authors: Prasad Mayuri , Kumar Brijesh , Bhat-Nakshatri Poornima , Anjanappa Manjushree , Sandusky George , Miller Kathy D. , Storniolo Anna Maria , Nakshatri Harikrishna 
Published: April 2019

Abstract

Functional modeling of normal breast epithelial hierarchy and stromal–epithelial cell interactions have been difficult due to inability to obtain sufficient stem-progenitor-mature epithelial and stromal cells. Recently reported epithelial reprogramming assay has partially overcome this limitation, but cross-contamination of cells from the feeder layer is a concern. The purpose of this study was to develop a feeder-layer–independent and inexpensive method to propagate multiple cell types from limited tissue resources. Cells obtained after enzymatic digestion of tissues collected at surgery or by core-needle biopsies were plated on tissue culture dishes precoated with laminin-5-rich–conditioned media from the rat bladder tumor cell line 804G and a defined growth media with inhibitors of ROCK, TGFβ, and BMP signaling. Cells were characterized by flow cytometry, mammosphere assay, 3D cultures, and xenograft studies. Cells from the healthy breasts included CD10+/EpCAM− basal/myoepithelial, CD49f+/EpCAM+ luminal progenitor, CD49f−/EpCAM+ mature luminal, CD73+/EpCAM+/CD90− rare endogenous pluripotent somatic stem, CD73+/CD90+/EpCAM−, estrogen receptor alpha–expressing ALCAM (CD166)+/EpCAM+, and ALDFLUOR+ stem/luminal progenitor subpopulations. Epithelial cells were luminal (KRT19+), basal (KRT14+), or dual-positive luminal/basal hybrid cells. While breast cells derived from BRCA1, BRCA2, and PALB2 mutation carriers did not display unique characteristics, cells from women with breast cancer–protective alleles showed enhanced differentiation. Cells could also be propagated from primary tumors and metastasis of breast, ovarian, and pancreatic cancer–neuroendocrine subtype. Xenograft studies confirmed tumorigenic properties of tumor-derived cells.

Implications:
Our method expands the scope of individualized studies of patient-derived cells and provides resources to model epithelial–stromal interactions under normal and pathologic conditions.