bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generalising uncertainty improves accuracy and safety of deep learning analytics applied to oncology
Authors: MacDonald Samual , Foley Helena , Yap Melvyn , Johnston Rebecca , Steven Kaiah , Koufariotis Lambros , Sharma Somwya , Wood Scott , Addala Venkateswar , Pearson John , Roosta Fred , Waddell Nicola , Kondrashova Olga , Trzaskowski Maciej 
Published: August 2022

Abstract
Trust and transparency are critical for deploying deep learning (DL) models into the clinic. DL application poses generalisation obstacles since training/development datasets often have different data distributions to clinical/production datasets that can lead to incorrect predictions with underestimated uncertainty. To investigate this pitfall, we benchmarked one pointwise and three approximate Bayesian DL models used to predict cancer of unknown primary with three independent RNA-seq datasets covering 10,968 samples across 57 primary cancer types. Our results highlight simple and scalable Bayesian DL significantly improves the generalisation of uncertainty estimation (e.g., p-value = 0.0013 for calibration). Moreover, we demonstrate Bayesian DL substantially improves accuracy under data distributional shifts when utilising ‘uncertainty thresholding’ by designing a prototypical metric that evaluates the expected (accuracy) loss when deploying models from development to production, which we call the Area between Development and Production curve (ADP). In summary, Bayesian DL is a hopeful avenue of research for generalising uncertainty, which improves performance, transparency, and therefore safety of DL models for deployment in real-world.
Age- and Sex-Specific Changes in visceral fat mass Throughout the Lifespan
Authors: Falkentoft Rikke , Jensen Mads , Hansen Ole , Haddock Bryan , Prescott Eva , Hovind Peter , Simonsen Lene , Bülow Jens , Suetta Charlotte 
Published: August 2022

Abstract
Background High visceral fat mass (VFM) is a risk factor for cardiovascular diseases, type 2 diabetes mellitus and malignancy, however, normative data are limited. The aim of this study was to provide reference data for VFM from a large apparently healthy Caucasian adult population. Materials and methods Volunteers aged 20-93 years from the Copenhagen City Heart Study had a standardized whole-body Dual-energy X-ray Absorptiometry (DXA) scan performed using the iDXA (GE Lunar). Total and regional fat mass was assessed, and VFM was quantified using the CoreScanTM application.Results We included 1277 participants [708 women (mean±SD age: 56 ± 19 years, height: 1.66 ± 0.07 m, body mass index: 24.64 ± 4.31 kg/m2 and 569 men, age: 57 ± 18 years, height: 1.80 ± 0.07 m, body mass index: 25.99 ± 3.86 kg/m2]. Visceral fat mass was associated with age in both sexess, but men had significantly higher VFM both in mass (g) and after normalization to body size (height, m2) and total fat mass (p<0.001). With the same BMI, body fat % (BF %) and fat mass index (total fat mass/height2 (FMI)), men had significantly higher VFM. In contrast, VFM increased more in women with high values of android-gynoid ratio, while this relationship was linear in men.Conclusion Normative data of visceral fat mass (VFM) from a large healthy Danish cohort aged 20-93 years are presented. Notably, VFM increased with age in both sexes, but men had significantly higher VFM compared to women with the same BMI, BF % and FMI.
A Feature Based Approach on Automatic Stopword Detection
Authors: Kucukyilmaz Tayfun , Akin Tayfun 
Published: August 2022

Abstract
In information retrieval, words that contribute little to the semantic information within a text are called stopwords. Identification of stopwords is considered an asset for many retrieval tasks as removal of such words from the text collection increase the regularization within the dataset and reduce the volume and computational complexity. Traditional techniques for identification of stopwords either involve manual construction of stopword lists by analyzing terms individually or employing sorting-based techniques that uses global term characteristics as a proxy. Due to the context-dependant and non-precise definition of what really classifies as a stopword, transfer and application of these traditional methodologies to different languages or domains leaves room for generalized and interpretable results. To address this concern, we propose a feature based supervised machine learning technique for automatic detection of stopwords. We have tested the validity of the proposed technique with extensive experiments and compared the results with a general English stopword list. Furthermore, we have evaluated the proposed technique with both formal written and social media text. The results reveal that the proposed technique leads to promising results and is also capable of addressing the changes in the dialect.
A robust procedure for determination of immunosuppressants Cyclosporine A and Tacrolimus in blood samples with detection of LC-MS/MS
Authors: Huo Yumei , Zhang Shangqing , Pan Chao , Shan Hongbo , Xu Yuxuan , Cai Xin 
Published: August 2022

Abstract
Therapeutic monitoring of immunosuppressants is a key tool in the treatment of transplant patients. It is essential to develop accurate methods to obtain precise and reliable results. a simple protein precipitation method with absence of zinc sulfate was explored to pretreat blood samples, the influence of matrix was eliminated, Cyclosporine A and Tacrolimus were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The linearity, matrix effect, carry over, accuracy, intraday and interday precision of this method were investigated. The linear relationship of tacrolimus and cyclosporine were 1–40 ng/mL and 50-2000 ng/mL, respectively; The correlation coefficient (R2) was both greater than 0.995. The intraday and interday precision of cyclosporine and tacrolimus were ≤ 10%. The lower limit of quantitation (LLOQ) of tacrolimus and cyclosporine A were 1 ng mL− 1 and 50 ng mL− 1, respectively. The main features of this method are simplicity, promptness, robustness, high sensitivity and throughput and good selectivity. It is suitable for therapeutic drug monitoring of cyclosporine A and tacrolimus in routine clinical diagnostics.
Bibliometric Analysis to Assess the Relationship Between Foreign Direct Investment, Environmental Emissions, and Green Economy
Authors: Trinh Nguyen Thi Hoai 
Published: August 2022

Abstract
The green economy is an unavoidable shift in economic structures toward sustainability. Foreign direct investment drives the economic growth of a nation. However, the process of foreign direct investment always includes unintended repercussions, such as environmental pollution. This topic is the subject of several hypotheses, including the polluted aura and polluted paradise hypotheses. The author investigated the association between FDI, environmental emissions, and Green economy using a bibliometric analysis approach and two softwares, VOS viewer and Citespaces. The author conducted literature synthesis study by keyword search, analysis of keyword patterns over time, and analysis of co-citation networks to determine the development of research on foreign direct investment and how to establish a green economic model. The findings demonstrate a connection between foreign direct investment, environmental emissions, and the green economy. The purpose of this paper is to determine the relationship between foreign direct investment (FDI) and sustainable development; to propose solutions to restructure the economy from a brown economy to a green economy; to make rational use of FDI sources; and to provide researchers in this field with a framework for focusing future research on the relationship between FDI and sustainable development.
Long-term behavioral effects of social separation during early life in a social mammal, Octodon degus
Authors: Ukyo Rina , Shinohara Akio , Koshimoto Chihiro , Nagura-Kato Goro A. , Ieiri Seiji , Tsuzuki Yasuhiro , Sakamoto Shinsuke H. 
Published: August 2022

Abstract
Social separation is thought to induce a strong stress response in social juvenile mammals, but little is known about how this response might vary throughout the development. The present study examines the long-term effects of early-life stress (ELS) induced by social separation on individual behaviors later in life using the social and precocious species Octodon degus. Four experimental groups were established a positive control group of mothers and siblings from three litters comprised the socially housed (SH) group, while pups from six litters were randomly assigned to three treatments: pups experiencing no separation (NS) treatment while their siblings did; repeated bouts of consecutive separation (CS); intermittent separation (IS). We analyzed the effects of separation treatment on the frequency and duration of freezing, rearing and grooming behaviors. ELS was correlated with higher hyperactivity later in life, especially in developed males, and hyperactivity increased with more frequent separation. The SH group containing siblings that did not experience parental separation gained more weight than the other groups. The findings suggest that the NS group was indirectly affected by ELS, especially females. In summary, the long-term effects of ELS are more direct in males while those are more indirect in females.
Systemic mastocytosis mimicking blastic plasmacytoid dendritic cell neoplasm: A case report
Authors: Zhang Xin , Han Jing , Ji Yuan , Hou Yingyong 
Published: August 2022

Abstract
Background: Systemic mastocytosis (SM), a rare myeloid neoplasm, is defined as a clonal and neoplastic proliferation of mast cells in at least one extracutaneous organ(s). The pathologic diagnosis and treatment of SM are challenging. Case presentation: We presented a 44-year-old male patient who had endured abdomen discomfort for 4 years and diarrhea for 5 months. Colonoscopy and PET/CT found a protuberant lesion in the cecum with adjacent lymphadenopathy. Histopathology of the cecum biopsy showed diffuse infiltration of medium-sized round/oval cells in lamina propria with immunohistochemical expressions of CD45, CD117, CD25, CD123, CD56, CD4, CD35, CD68, and CD163, mimicking blastic plasmacytoid dendritic cell neoplasm. Molecular analysis revealed missense mutation (D816V) in the exon 17 of KIT gene. Serum tryptase level was 38.56 ng/ml. No abnormality was found in skin examination and bone marrow biopsy. The diagnosis of aggressive SM with intestinal tract involvement was established. The patient received avapritinib treatment at an initial dosage of 200 mg once daily and exhibited dramatic clinical improvement but memory impairment within 1 month. No recurrence was observed in 1-year follow-up at the adjusted avapritinib dose (75 mg once daily). Conclusions: SM is very rare and should be considered in patients with long-term diarrhea symptoms and hematopoietic/lymphoid-appearing tumors. KIT D816V mutation contributes to the differentiation of CD123, CD4, and CD56 immunoreactive SM from blastic plasmacytoid dendritic cell neoplasm. The rare side-effect of memory impairment in this case helps to accumulate the experience of avapritinib in treating KIT D816V-mutant SM.
Occurrence of Research Misconduct and Institutional Capacity to Prevent and Manage Research Misconduct-Perspectives from Kenyan Research Regulators
Authors: Were Edwin , Kiplagat Jepchirchir , Kaguiri Eunice , Ayikukwei Rose , Naanyu Violet 
Published: August 2022

Abstract
Background
Research misconduct is often defined as fabrication, falsification and plagiarism. Its occurrence is associated with individual, institutional, national and global factors. Researcher perceptions of weak or non-existent institutional guidelines on prevention and management of research misconduct encourage these practices. Few countries in Africa have clear guidance on research misconduct. In Kenya, the capacity to prevent or manage research misconduct in academic and research institutions has not been assessed. The objective of this study was to explore the perceptions of Kenyan research regulators on the occurrence of and institutional capacity to prevent or manage research misconduct.
Methods
Key informant interviews with open-ended questions were conducted with 27 research regulators (chairs and secretaries of ethics committees, research directors of academic and research institutions, and national regulatory bodies). Among other questions to explore their perceptions on occurrence of research misconduct and existing institutional capacity to prevent or manage research misconduct, participants were asked: (1) How common is research misconduct in your view? (2) Does your institution have capacity to Prevent research misconduct? (3) Does your institution have capacity to manage research misconduct?. Their responses were audiotaped, transcribed and coded using NVivo software. Deductive coding covered predefined themes including occurrence, prevention detection, investigation and management of research misconduct and illustrative quotes were identified.
Results
Respondents perceived research misconduct to be very common among students. Their responses suggested there was no dedicated capacity to prevent or manage research misconduct at the institutional and national levels. The national research regulator had no specific guidelines on research misconduct. At the institutional level, the only capacity / efforts mentioned were directed at reducing, detecting and managing student plagiarism. There was no direct mention of capacity to manage fabrication and falsification or misconduct by non-student researchers.
Conclusions and Recommendations
Our respondents perceived research misconduct to be common mostly pointing to student plagiarism but not by non-student researchers. Additionally, fabrication and falsification were not mentioned among the concerns. We recommend development of Kenya guidelines, at national and institutional levels, on research misconduct in all its nuances, addressing all potential perpetrators and underpinned by relevant laws.
Observing volcanoes with drones: studies of volcanic plume chemistry with ultralight sensor systems
Authors: Karbach Niklas , Bobrowski Nicole , Hoffmann Thorsten 
Published: August 2022

Abstract
The study of the chemical composition of volcanic emissions is an important method for obtaining information about volcanic systems and providing indirect and unique insights into magmatic processes. However, there is a non-negligible risk associated with sampling directly at volcanic craters or maintaining geochemical monitoring stations at such locations. Spectroscopic remote sensing methods, in turn, can measure only a few species. Here, drones offer the opportunity to bring measurement systems to the scene. Standard parameters that are commonly measured are SO2 and CO2 concentrations, as well as a number of meteorological parameters. The in-flight transmission of data by radio telemetry plays an important role, since visual localization of the volcanic plume from a distance of several kilometers is practically impossible. Until now, larger and quite cost-intensive drones have been used for this purpose, which must first be transported to the site of operation at great expense. Here, we present the development and successful deployment of a very small drone system (empty weight < 0.9 kg) for chemical characterization of volcanic plumes that can be easily transported on foot to difficult-to-access terrain and, moreover, requires only minimal flight and administrative preparations for operation as an aerial observation platform.
Progression of Sarcomatoid Mesothelioma from Mesothelioma In Situ: A Case Report on Morphologic Changes during a Nine-month Interval and Careful Observation of Cytology in Early- stage Mesothelioma
Authors: Yoshida Miho , Jimbo Naoe , Tsukamoto Ryuko , Itoh Tomoo , Kawahara Kunimitsu , Mitsui Suguru , Tanaka Yugo , Maniwa Yoshimasa 
Published: August 2022

Abstract
Background: It had been difficult to distinguish between reactive and malignant conditions due to overlapping morphological characteristics. The development of methods based on detecting genomic abnormalities using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have contributed greatly to solving this problem. In order to lead it to efficient IHC and/or FISH and final diagnosis of mesothelioma, it is important to pick up bland mesothelioma cells on cytological screening because the first clinical manifestation of pleural mesothelioma (PM) is pleural effusion, which is first sample available for pathological diagnosis.Case presentation: This report describes a case of a 72-year-old man with a history of asbestos exposure presented with pleural effusion as first symptoms and was eventually diagnosed as mesothelioma. He was suspected for mesothelioma on cytology due to prominent cell-in-cell engulfment in mesothelial cells, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, the lesion progressed to sarcomatoid mesothelioma with 9 months interval. Both the initial mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy after the diagnosis of sarcomatoid mesothelioma, but the disease progressed and died 12 months after the diagnosis of sarcomatoid mesothelioma.Conclusion: Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early progression to invasive lesions and/or sarcomatoid changes. Although interest in and knowledge regarding mesothelioma in situ has been increasing, some diagnostic problems can be challenging even for experts. In our opinion, it is important to consider genetic abnormalities when deciding on individual patient management. At least, we believe that cases of mesothelioma, even if in situ lesion, with MTAP loss and/or CDKN2A deletion should be performed carefully followed up or early treatment intervention.
Local Control of Brain Metastases with Osimertinib Alone in Patients with EGFR-mutant Non- Small Cell Lung Cancer
Authors: Hui Caressa , Qu Vera , Wang Jen-Yeu , Eyben Rie , Chang Yu-Cheng , Chiang Po-Lin , Liang Chih-Hung , Lu Jen-Tang , Li Gordon , Hayden-Gephart Melanie , Wakelee Heather , Neal Joel , Ramchandran Kavitha , Das Millie , Nagpal Seema , Soltys Scott , Myall Nathaniel , Pollom Erqi 
Published: August 2022

Abstract
Purpose: Although osimertinib has excellent intracranial activity in metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion or L858R EGFR alterations, measures of local control of brain metastases are less well-reported. We describe lesion-level outcomes of brain metastases treated with osimertinib alone.Methods: We retrospectively reviewed patients with EGFR-mutant NSCLC with untreated brain metastasis measuring ≥5 mm at the time of initiating osimertinib. Cumulative incidence of local recurrence in brain (LRiB) was calculated with death as a competing risk, and univariable and multivariable analyses were conducted to identify factors associated with LRiB. Results: We included 284 brain metastases from 37 patients. Median follow-up was 20.1 months. On initial MRI after starting osimertinib, patient-level response was complete response (CR) in 11 (15%), partial response (PR) in 33 (45%), stable disease (SD) in 18 (25%) and progressive disease (PD) in 11 (15%). The 1-year cumulative incidence of LRiB was 14% (95% CI 9.9-17.9) and was significantly different in patients with a CR (0%), PR (4%), and SD (11%; p=0.02). Uncontrolled primary tumor (adjusted hazard ratio [aHR] 3.78, 95% CI 1.87-7.66; p<0.001), increasing number of prior systemic therapies (aHR 2.12, 95% CI 1.49-3.04; p<0.001), and higher ECOG score (aHR 7.8, 95% CI 1.99-31.81; p=0.003) were associated with LRiB. Conclusions: Although 1-year risk of LRiB is <4% with a CR or PR, 1-year risk of LRiB is over 10% for patients with less than a PR to osimertinib. These patients should be followed closely for need for additional treatment such as stereotactic radiosurgery.
First ancient DNA analysis of mummies from the post-Scythian Oglakhty cemetery in South Siberia
Authors: Nedoluzhko Artem , Pankova Svetlana , Vergasova Ekaterina , Plotnikov Nikolay , Kim Anna , Shulpin Mikhail , Nenasheva Natalia , Adameyko Kim , Poliakov Andrei , Pogodina Nadezhda , Rakitko Alexander , Ilinskaya Anna , Ilinsky Valery 
Published: August 2022

Abstract
The Minusinsk Basin in Southern Siberia had unique conditions for the development of ancient societies, thanks to its geographical location, favorable climatic conditions, and relative isolation. Located at the northern periphery of the eastern Eurasian steppe, surrounded by the Altai-Sayan Mountains this area witnessed numerous ancient human migrations with specific types of interaction between outside and local archaeological cultures. The genomic history of the human population of Southern Siberia from the Chalcolithic to the middle Bronze Age has been relatively well described in the recent genome-wide studies, while the genetic ancestry of populations, represented by diverse archaeological cultures of the Late Bronze and Early Iron Ages, remains a blank spot for modern paleogenomics. Here, for the first time, we present two ancient nuclear genomes of the individuals buried in the Oglakhty cemetery (early Tashtyk culture, 2nd to 4th centuries AD). Our pilot study is undertaken within a multidisciplinary project on this noteworthy site with well-preserved organic remains and provides fresh paleogenomic data on the ancient societies of Southern Siberia.
Maternal RBPMS2 protein plays a crucial role in mouse blastocyst formation
Authors: Zhou Cheng , Zheng Lu , Teng Hui , Yang Ye , Ma Rujun , Wang Shuxian , Yang Yang , Jing Jun , Li Meiling , Cheng Xi , Lin Ying , Xu Juanjuan , Wu Ronghua , Chen Li , Yao Bing 
Published: August 2022

AbstractBackground Maternal factors that accumulate and stored in the cytoplasm of mature oocytes regulate preimplantation embryogenesis through many aspects, like pronuclear formation, genome reprogramming, zygotic genome activation and cell fate determination. However, most of maternal factors are still unknown. We investigated the role of the maternal protein RBPMS2 during early embryo development in mice and explored the underlying mechanisms. Methods The expression pattern of rbpms2 in mouse were analyzed by qRT-PCR and immunofluorescence staining. The effect of knockdown of RBPMS2 on embryo development was evaluated through microinjection of specific morpholino. RNA sequencing was performed for mechanistic analysis. The interaction between RBPMS2 and BMP pathway was studied using BMP inhibitor and activator. The effect of the localization of E-cadherin was determined by immunofluorescence staining. Results The maternal protein RBPMS2 is highly expressed in mouse oocytes and knockdown of RBPMS2 inhibits embryo development from the morula to blastocyst stage. Mechanically, RNA sequencing showed the differentially expressed genes were enriched in TGF-β signaling pathway. We then found embryo arrested in morula stage by adding BMP inhibitor into KSOM medium. And the morula-stage arrest defect caused by RBPMS2 knockdown was partially rescued by BMP activator. Furthermore, localization of E-cadherin in the membrane was impaired in response to knockdown of RBPMS2 or inhibition of BMP pathway. Conclusion Our study suggests that RBPMS2 activates the BMP pathway and thus influences the localization of E-cadherin, which is important for early mouse embryo development during compaction.