bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a new serum granulocyte–macrophage colony-stimulating factor autoantibody testing kit
Authors: Nakata Koh , Sugi Tatsuki , Kuroda Keiko , Yoshizawa Kazutaka , Takada Toshinori , Tazawa Ryushi , Ueda Takahiro , Aoki Ami , Abe Mitsuhiro , Tatsumi Koichiro , Eda Ryosuke , Kondoh Shotaro , Morimoto Konosuke , Tanaka Takeshi , Yamaguchi Etsuro , Takahashi Ayumu , Oda Miku , Ishii Haruyuki , Izumi Shinyu , Sugiyama Haruhito , Nakagawa Atsushi , Tomii Keisuke , Suzuki Masaru , Konno Satoshi , Ohkouchi Shinya , Hirano Taizou , Handa Tomohiro , Hirai Toyohiro , Inoue Yoshikazu , Arai Toru , Asakawa Katsuaki , Sakagami Takuro , Tanaka Takahiro , Mikami Ayako , Kitamura Nobutaka 
Published: January 2020

Very recently, a modest but significant efficacy of granulocyte–macrophage colony-stimulating factor (GM-CSF) inhalation therapy for the treatment of mild to moderate autoimmune pulmonary alveolar proteinosis (aPAP) has been reported.As the ability to measure the level of GM-CSF autoantibody (GMAb) in the serum is required to decide the indication for this therapy, we developed a high-performance GMAb testing kit for clinical use.As the kit succeeded in reducing nonspecific IgG binding to the ELISA plate, the predictive performance shown in the training study to discriminate aPAP patients from healthy subjects was perfect, providing a cut-off value of 1.65 U·mL−1in 78 patients with aPAP and 90 healthy subjects in an operator-blinded manner using logistic regression analysis. As in the validation study, serum samples from another 213 patients with aPAP were also blinded and evaluated in an operator-blinded manner against external 207 samples from patients with other types of PAP and patients exhibiting various ground-glass opacities on chest high-resolution computed tomography that require discrimination from PAP.The logistic regression analysis of these validation data sets revealed values of 97.6% and 100% for specificity and sensitivity, respectively. Thus, this new GMAb testing kit is reliable for the diagnosis of aPAP and differential diagnosis of other lung diseases.
Validation of online Asthma Control Questionnaire and Asthma Quality of Life Questionnaire
Authors: Khusial Rishi J. , Honkoop Persijn J. , van der Meer Victor , Snoeck-Stroband Jiska B. , Sont Jacob K. 
Published: January 2020

ObjectiveSeveral newly developed eHealth applications use online questionnaires to monitor asthma control. The Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) are two such commonly used questionnaires. These questionnaires are validated for use on paper. This study aims to validate them by assessing the agreement between online and paper versions of the ACQ and AQLQ.MethodsPatients (aged 18 years and older) from the Self-Management in Asthma Supported by Hospitals, ICT, Nurses and General Practitioners (SMASHING)-trial and Davos@home study were included in this study. Patients completed both the paper and online Dutch versions of the ACQ and AQLQ in a random order within a 2-week interval. Agreement between the different versions was assessed with paired t-tests, intraclass correlation coefficients and Bland–Altman plots.ResultsIn total 44 patients were eligible for analysis. The mean difference between the paper and online versions of the ACQ was 0.04 (p=0.40) and for the AQLQ it was 0.08 (p=0.06). The intraclass correlation coefficient scores were 0.94 for the ACQ and 0.95 for the AQLQ.ConclusionThe online versions of the ACQ and AQLQ show high levels of agreement with the paper versions and can therefore be safely used in eHealth applications to respectively monitor asthma control and quality of life.
Necrotic scleral melt and fungal keratitis—a complication of subtenon triamcinolone acetonide injection
Authors: Agarwal Manisha , Ranjan Richa , Mathur Umang 
Published: January 2020

Abstract
Purpose
Subtenon triamcinolone acetonide injection (STAI) is a safe drug delivery method for various ocular conditions. We report two cases of necrotic scleral melt, a rare complication of STAI.

Methods
The first patient received STAI for post-operative inflammation control and developed necrotic scleral melt at the site of STAI with superadded fungal keratitis.
The second patient received three STAI for non-necrotizing, non-infectious anterior scleritis and developed scleral necrosis at the site of her last STAI. Noncompliance with medications resulted in the progression of scleral necrosis to a new area.

Results
In the first patient, surgical removal of triamcinolone deposit resulted in healing of the scleral melt while the second patient was managed conservatively with corticosteroids and immunosuppressants.

Conclusion
Scleral melt is a rare complication of STAI; however, an early diagnosis and management of any predisposing factor along with surgical debridement should be considered as a potential critical treatment option to salvage the eye.
Anticancer therapy within the last 30 days of life: results of an audit and re-audit cycle from an Australian regional cancer centre
Authors: Nguyen Mike , Ng Ying Kin Sean , Shum Evonne , Wann Alysson , Tamjid Babak , Sahu Arvind , Torres Javier 
Published: January 2020

Abstract
Background
The therapeutic landscape in medical oncology continues to expand significantly. Newer therapies, especially immunotherapy, offer the hope of profound and durable responses with more tolerable side effect profiles. Integrating this information into the decision making process is challenging for patients and oncologists. Systemic anticancer treatment within the last thirty days of life is a key quality of care indicator and is one parameter used in the assessment of aggressiveness of care.

Methods
A retrospective review of medical records of all patients previously treated at Goulburn Valley Health oncology department who died between 1 January 2015 and 30 June 2018 was conducted. Information collected related to patient demographics, diagnosis, treatment, and hospital care within the last 30 days of life. These results were presented to the cancer services meeting and a quality improvement intervention program was instituted. A second retrospective review of medical records of all patients who died between 1 July 2018 and 31 December 2018 was conducted in order to measure the effect of this intervention.

Results
The initial audit period comprised 440 patients. 120 patients (27%) received treatment within the last 30 days of life. The re-audit period comprised 75 patients. 19 patients (25%) received treatment within the last 30 days of life. Treatment rates of chemotherapy reduced after the intervention in contrast to treatment rates of immunotherapy which increased. A separate analysis calculated the rate of mortality within 30 days of chemotherapy from the total number of patients who received chemotherapy was initially 8% and 2% in the re-audit period. Treatment within the last 30 days of life was associated with higher use of aggressive care such as emergency department presentation, hospitalisation, ICU admission and late hospice referral. Palliative care referral rates improved after the intervention.

Conclusion
This audit demonstrated that a quality improvement intervention can impact quality of care indicators with reductions in the use of chemotherapy within the last 30 days of life. However, immunotherapy use increased which may be explained by increased access and a better risk benefit balance.
The mitochondrial HSP90 paralog TRAP1 forms an OXPHOS-regulated tetramer and is involved in mitochondrial metabolic homeostasis
Authors: Joshi Abhinav , Dai Li , Liu Yanxin , Lee Jungsoon , Ghahhari Nastaran Mohammadi , Segala Gregory , Beebe Kristin , Jenkins Lisa M. , Lyons Gaelyn C. , Bernasconi Lilia , Tsai Francis T. F. , Agard David A. , Neckers Len , Picard Didier 
Published: January 2020

AbstractBackgroundThe molecular chaperone TRAP1, the mitochondrial isoform of cytosolic HSP90, remains poorly understood with respect to its pivotal role in the regulation of mitochondrial metabolism. Most studies have found it to be an inhibitor of mitochondrial oxidative phosphorylation (OXPHOS) and an inducer of the Warburg phenotype of cancer cells. However, others have reported the opposite, and there is no consensus on the relevant TRAP1 interactors. This calls for a more comprehensive analysis of the TRAP1 interactome and of how TRAP1 and mitochondrial metabolism mutually affect each other.ResultsWe show that the disruption of the gene for TRAP1 in a panel of cell lines dysregulates OXPHOS by a metabolic rewiring that induces the anaplerotic utilization of glutamine metabolism to replenish TCA cycle intermediates. Restoration of wild-type levels of OXPHOS requires full-length TRAP1. Whereas the TRAP1 ATPase activity is dispensable for this function, it modulates the interactions of TRAP1 with various mitochondrial proteins. Quantitatively by far, the major interactors of TRAP1 are the mitochondrial chaperones mtHSP70 and HSP60. However, we find that the most stable stoichiometric TRAP1 complex is a TRAP1 tetramer, whose levels change in response to both a decline and an increase in OXPHOS.ConclusionsOur work provides a roadmap for further investigations of how TRAP1 and its interactors such as the ATP synthase regulate cellular energy metabolism. Our results highlight that TRAP1 function in metabolism and cancer cannot be understood without a focus on TRAP1 tetramers as potentially the most relevant functional entity.
Mental, behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies
Authors: Stein Dan J. , Szatmari Peter , Gaebel Wolfgang , Berk Michael , Vieta Eduard , Maj Mario , de Vries Ymkje Anna , Roest Annelieke M. , de Jonge Peter , Maercker Andreas , Brewin Chris R. , Pike Kathleen M. , Grilo Carlos M. , Fineberg Naomi A. , Briken Peer , Cohen-Kettenis Peggy T. , Reed Geoffrey M. 
Published: January 2020

AbstractAn update of the chapter on Mental, Behavioral and Neurodevelopmental Disorders in the International Classification of Diseases and Related Health Problems (ICD) is of great interest around the world. The recent approval of the 11th Revision of the ICD (ICD-11) by the World Health Organization (WHO) raises broad questions about the status of nosology of mental disorders as a whole as well as more focused questions regarding changes to the diagnostic guidelines for specific conditions and the implications of these changes for practice and research. This Forum brings together a broad range of experts to reflect on key changes and controversies in the ICD-11 classification of mental disorders. Taken together, there is consensus that the WHO’s focus on global applicability and clinical utility in developing the diagnostic guidelines for this chapter will maximize the likelihood that it will be adopted by mental health professionals and administrators. This focus is also expected to enhance the application of the guidelines in non-specialist settings and their usefulness for scaling up evidence-based interventions. The new mental disorders classification in ICD-11 and its accompanying diagnostic guidelines therefore represent an important, albeit iterative, advance for the field.
FGFR3 signaling and function in triple negative breast cancer
Authors: Chew Nicole J. , Nguyen Elizabeth V. , Su Shih-Ping , Novy Karel , Chan Howard C. , Nguyen Lan K. , Luu Jennii , Simpson Kaylene J. , Lee Rachel S. , Daly Roger J. 
Published: January 2020

Abstract
Background
Triple negative breast cancer (TNBC) accounts for 16% of breast cancers and represents an aggressive subtype that lacks targeted therapeutic options. In this study, mass spectrometry (MS)-based tyrosine phosphorylation profiling identified aberrant FGFR3 activation in a subset of TNBC cell lines. This kinase was therefore evaluated as a potential therapeutic target.

Methods
MS-based tyrosine phosphorylation profiling was undertaken across a panel of 24 TNBC cell lines. Immunoprecipitation and Western blot were used to further characterize FGFR3 phosphorylation. Indirect immunofluorescence and confocal microscopy were used to determine FGFR3 localization. The selective FGFR1–3 inhibitor, PD173074 and siRNA knockdowns were used to characterize the functional role of FGFR3 in vitro. The TCGA and Metabric breast cancer datasets were interrogated to identify FGFR3 alterations and how they relate to breast cancer subtype and overall patient survival.

Results
High FGFR3 expression and phosphorylation were detected in SUM185PE cells, which harbor a FGFR3-TACC3 gene fusion. Low FGFR3 phosphorylation was detected in CAL51, MFM-223 and MDA-MB-231 cells. In SUM185PE cells, the FGFR3-TACC3 fusion protein contributed the majority of phosphorylated FGFR3, and largely localized to the cytoplasm and plasma membrane, with staining at the mitotic spindle in a small subset of cells. Knockdown of the FGFR3-TACC3 fusion and wildtype FGFR3 in SUM185PE cells decreased FRS2, AKT and ERK phosphorylation, and induced cell death. Knockdown of wildtype FGFR3 resulted in only a trend for decreased proliferation. PD173074 significantly decreased FRS2, AKT and ERK activation, and reduced SUM185PE cell proliferation. Cyclin A and pRb were also decreased in the presence of PD173074, while cleaved PARP was increased, indicating cell cycle arrest in G1 phase and apoptosis. Knockdown of FGFR3 in CAL51, MFM-223 and MDA-MB-231 cells had no significant effect on cell proliferation. Interrogation of public datasets revealed that increased FGFR3 expression in breast cancer was significantly associated with reduced overall survival, and that potentially oncogenic FGFR3 alterations (eg mutation and amplification) occur in the TNBC/basal, luminal A and luminal B subtypes, but are rare.

Conclusions
These results indicate that targeting FGFR3 may represent a therapeutic option for TNBC, but only for patients with oncogenic FGFR3 alterations, such as the FGFR3-TACC3 fusion.
Cell death induced by the ER stressor thapsigargin involves death receptor 5, a non-autophagic function of MAP1LC3B, and distinct contributions from unfolded protein response components
Authors: Lindner Paula , Christensen Søren Brøgger , Nissen Poul , Møller Jesper Vuust , Engedal Nikolai 
Published: January 2020

Abstract
Background
Cell death triggered by unmitigated endoplasmic reticulum (ER) stress plays an important role in physiology and disease, but the death-inducing signaling mechanisms are incompletely understood. To gain more insight into these mechanisms, the ER stressor thapsigargin (Tg) is an instrumental experimental tool. Additionally, Tg forms the basis for analog prodrugs designed for cell killing in targeted cancer therapy. Tg induces apoptosis via the unfolded protein response (UPR), but how apoptosis is initiated, and how individual effects of the various UPR components are integrated, is unclear. Furthermore, the role of autophagy and autophagy-related (ATG) proteins remains elusive.

Methods
To systematically address these key questions, we analyzed the effects of Tg and therapeutically relevant Tg analogs in two human cancer cell lines of different origin (LNCaP prostate- and HCT116 colon cancer cells), using RNAi and inhibitory drugs to target death receptors, UPR components and ATG proteins, in combination with measurements of cell death by fluorescence imaging and propidium iodide staining, as well as real-time RT-PCR and western blotting to monitor caspase activity, expression of ATG proteins, UPR components, and downstream ER stress signaling.

Results
In both cell lines, Tg-induced cell death depended on death receptor 5 and caspase-8. Optimal cytotoxicity involved a non-autophagic function of MAP1LC3B upstream of procaspase-8 cleavage. PERK, ATF4 and CHOP were required for Tg-induced cell death, but surprisingly acted in parallel rather than as a linear pathway; ATF4 and CHOP were independently required for Tg-mediated upregulation of death receptor 5 and MAP1LC3B proteins, whereas PERK acted via other pathways. Interestingly, IRE1 contributed to Tg-induced cell death in a cell type-specific manner. This was linked to an XBP1-dependent activation of c-Jun N-terminal kinase, which was pro-apoptotic in LNCaP but not HCT116 cells. Molecular requirements for cell death induction by therapy-relevant Tg analogs were identical to those observed with Tg.

Conclusions
Together, our results provide a new, integrated understanding of UPR signaling mechanisms and downstream mediators that induce cell death upon Tg-triggered, unmitigated ER stress.

Graphical abstract
Measurement error and reliability of three available 3D superimposition methods in growing patients
Authors: Ponce-Garcia Cecilia , Ruellas Antonio Carlos de Oliveira , Cevidanes Lucia Helena Soares , Flores-Mir Carlos , Carey Jason P. , Lagravere-Vich Manuel 
Published: January 2020

Abstract
Introduction
Cone-Beam Computed Tomography (CBCT) images can be superimposed, allowing three-dimensional (3D) evaluation of craniofacial growth/treatment effects. Limitations of 3D superimposition techniques are related to imaging quality, software/hardware performance, reference areas chosen, and landmark points/volumes identification errors. The aims of this research are to determine/compare the intra-rater reliability generated by three 3D superimposition methods using CBCT images, and compare the changes observed in treated cases by these methods.

Methods
Thirty-six growing individuals (11–14 years old) were selected from patients that received orthodontic treatment. Before and after treatment (average 24 months apart) CBCTs were analyzed using three superimposition methods. The superimposed scans with the two voxel-based methods were used to construct surface models and quantify differences using SlicerCMF software, while distances in the landmark-derived method were calculated using Excel. 3D linear measurements of the models superimposed with each method were then compared.

Results
Repeated measurements with each method separately presented good to excellent intraclass correlation coefficient (ICC ≥ 0.825). ICC values were the lowest when comparing the landmark-based method and both voxel-based methods. Moderate to excellent agreement was observed when comparing the voxel-based methods against each other. The landmark-based method generated the highest measurement error.

Conclusions
Findings indicate good to excellent intra-examiner reliability of the three 3D superimposition methods when assessed individually. However, when assessing reliability among the three methods, ICC demonstrated less powerful agreement. The measurements with two of the three methods (CMFreg/Slicer and Dolphin) showed similar mean differences; however, the accuracy of the results could not be determined.
Coupled cycling and regulation of metazoan morphogenesis
Authors: Rezaei-Lotfi Saba , Farahani Ramin M. 
Published: January 2020

AbstractMetazoan animals are characterized by restricted phenotypic heterogeneity (i.e. morphological disparity) of organisms within various species, a feature that contrasts sharply with intra-species morphological diversity observed in the plant kingdom. Robust emergence of morphogenic blueprint in metazoan animals reflects restricted autonomy of individual cells in adoption of fate outcomes such as differentiation. Fates of individual cells are linked to and influenced by fates of neighboring cells at the population level. Such coupling is a common property of all self-organising systems and propels emergence of order from simple interactions between individual cells without supervision by external directing forces. As a consequence of coupling, expected functional relationship between the constituent cells of an organ system is robustly established concurrent with multiple rounds of cell division during morphogenesis. Notably, the molecular regulation of multicellular coupling during morphogenic self-organisation remains largely unexplored. Here, we review the existing literature on multicellular self-organisation with particular emphasis on recent discovery that β-catenin is the key coupling factor that programs emergence of multi-cellular self-organisation by regulating synchronised cycling of individual cells.
Colistin-resistant Escherichia coli carrying mcr-1 in food, water, hand rinse, and healthy human gut in Bangladesh
Authors: Johura Fatema-Tuz , Tasnim Jarin , Barman Indrajeet , Biswas Sahitya Ranjan , Jubyda Fatema Tuz , Sultana Marzia , George Christine Marie , Camilli Andrew , Seed Kimberley D. , Ahmed Niyaz , Alam Munirul 
Published: January 2020

Abstract
Background
One of the most significant public health concerns in today’s world is the persistent upsurge of infections caused by multidrug resistant bacteria. As a result, clinicians are being forced to intervene with either less effective backup drugs or ones with substantial side-effects. Colistin is a last resort antimicrobial agent for the treatment of infections caused by multi-drug resistant gram-negative bacteria.

Methods
Escherichia coli (n = 65) isolated from street food (n = 20), hand rinse (n = 15), surface water (n = 10), and healthy human stool (n = 20) were tested for colistin resistance gene mcr-1 and response to antimicrobial agents. Antimicrobial resistance genes and virulence genes were detected by employing polymerase chain reaction. DNA fingerprinting of the strains were determined by pulsed-field gel electrophoresis.

Results
Screening of E. coli allowed us to confirm colistin resistance marker gene mcr-1 in 13 strains (street food, n = 4; hand rinse, n = 2; surface water, n = 4; and stool, n = 3); and two of these E. coli strains carrying mcr-1 harbored blaTEM gene encoding extended spectrum beta lactamase. Antibiotic assay results revealed all 13 E. coli strains carrying mcr-1 to be multi-drug resistant (MDR), including to colistin. The minimum inhibitory concentration (MIC) for colistin ranged from 2 to 6 μg/ml. DNA sequencing confirmed homogeneity of the nucleotide sequence for mcr-1, but the E. coli strains were heterogenous, as confirmed by pulsed-field gel electrophoresis suggesting horizontal transmission of colistin resistance in Bangladesh.

Conclusion
Widespread dissemination of E. coli strains carrying mcr-1 encoding resistance to colistin in the present study is alarming as this is the last resort drug for the treatment of infections caused by MDR gram-negative bacteria resistant to almost all drugs used commonly.
A patient with left-sided inferior vena cava who received oblique lumbar interbody fusion surgery: a case report
Authors: Liu Chen , Zhai Jian , Yuan Quan , Zhang Yu , Xu Hongguang 
Published: January 2020

Abstract
Background
Oblique lateral interbody fusion surgery has become increasingly popular for lumbar degenerative diseases. The oblique corridor is between the psoas muscle and the retroperitoneal vessels, and its use could result in decreased tissue trauma, minimal blood loss, and short operation times. Patients who undergo oblique lateral interbody fusion surgery are always placed in the right lateral position to avoid damage to the inferior vena cava, which is typically a right-sided vessel. There is a substantial risk of vascular injury during the operation if there are anatomical variations in the vessels.

Case presentation
A 77-year-old man, of the Han nationality, with lumbar spinal stenosis underwent stand-alone oblique lateral interbody fusion surgery. Transverse magnetic resonance imaging of the lumbar spine indicated that his inferior vena cava was left-sided. A three-dimensional reconstructed image of abdominal computed tomography angiography showed that the inferior vena cava was located on the left side. Finally, the surgeon decided to change the position of our patient from a right lateral position to a left lateral position before the surgery.

Conclusions
To date, this is the first reported case where a patient underwent oblique lateral interbody fusion surgery in a left lateral decubitus position due to a left-sided inferior vena cava. This case demonstrates that carefully reading radiological results is important for operation planning and avoiding anatomical complications.