bluuebunny/crossref_metadata_2025 huggingface dataset:
The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules
Authors: Li Bin , Sun Wen-Xuan , Zhang Wan-Ying , Zheng Ye , Qiao Lu , Hu Yue-Ming , Li Wei-Qiang , Liu Di , Leng Bing , Liu Jia-Ren , Jiang Xiao-Feng , Zhang Yan
Published: October 2021

Rationale: Severe asthma is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of asthmatic bronchial epithelial cells have provided biological insights and underscored possible pathological mechanisms; however, the molecular basis in severe asthma is still poorly understood.

Objective: The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype.

Methods: The k-means clustering and differentially expressed genes (DEGs) were performed in 129 asthma individuals in the Severe Asthma Research Program. The DEG profiles were analyzed by weighted gene co-expression network analysis (WGCNA), and the expression value of each gene module in each individual was annotated by gene set variation analysis (GSVA).

Results: Expression analysis defined five stable asthma subtype (AS): 1) Phagocytosis-Th2, 2) Normal-like, 3) Neutrophils, 4) Mucin-Th2, and 5) Interferon-Th1 and 15 co-expressed gene modules. “Phagocytosis-Th2” enriched for receptor-mediated endocytosis, upregulation of Toll-like receptor signal, and myeloid leukocyte activation. “Normal-like” is most similar to normal samples. “Mucin-Th2” preferentially expressed genes involved in O-glycan biosynthesis and unfolded protein response. “Interferon-Th1” displayed upregulation of genes that regulate networks involved in cell cycle, IFN gamma response, and CD8 TCR. The dysregulation of neural signal, REDOX, apoptosis, and O-glycan process were related to the severity of asthma. In non-TH2 subtype (Neutrophils and Interferon-Th1) with severe asthma individuals, the neural signals and IL26-related co-expression module were dysregulated more significantly compared to that in non-severe asthma. These data infer differences in the molecular evolution of asthma subtypes and identify opportunities for therapeutic development.

Conclusions: Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity.
What Open Source Software Research Can Teach Us About Public Blockchain(s)?—Lessons for Practitioners and Future Research
Authors: Lindman Juho
Published: October 2021

Peer-to-peer governance of blockchain technology reemerges a number of interesting practical and theoretical questions. This article aims to bridge current research on blockchain technology to earlier research on open source software (OSS) and to suggest a number of concepts from OSS research that are useful in discussing governance of blockchain systems. Thus, the purpose of this article is to provide a theoretically oriented review of some of the earlier concepts and discuss their applicability in a novel context. Bridging these extending literatures and concepts accelerates theoretical development in the area of governance of technology, opening fertile avenues for future research and offering a variety of insights to both practitioners.
SARS-CoV-2 UK, South African and Brazilian Variants in Karachi- Pakistan
Authors: Khan Adnan , Hanif Muhammad , Ahmed Akhtar , Syed Sarosh , Ghazali Saqib , Khanani Rafiq
Published: October 2021

The COVID-19 pandemic has been evolving in Pakistan with the emergence of the United Kingdom, South African, and Brazilian variants. These variants of concern (VOC) are known for increased transmissibility and can also be responsible for avoiding immune responses. The gold standard to detect VOC is sequencing, however routine genomic surveillance in resource-limited countries like Pakistan is not always readily available. The inadvertent detection of the B.1.1.7 (United Kingdom) VOC by a target failure due to the key deletion in spike Δ69-70 by commercially available PCR assay helps to understand target failures as an alternative approach to detect variants. In pursuit of VOC it was further discovered that a deletion in the ORF1a gene (ORF1a Δ3675-3677) is common in B.1.1.7, B.1.351 (South African), and P.1 (Brazilian) VOC. The Real-Time Quantitative PCR (RT-qPCR) assay can distinguish target failures and can discriminate SARS-CoV-2 VOC. The study uses positive samples archived in respective labs. Samples were divided into two groups. Group I constitutes 261 positive samples out of total of 16,964 (1.53%) performed from August till September 2020, while group II consists of 3501 positive samples out of a total of 46,041 (7.60%) performed, from November 2020 till January 2021. The RT-qPCR analysis showed that no VOC was present in positive samples of group I. However, a staggering difference in results was noted in group II where the positivity ratio increased exponentially and the VOC started appearing in significant numbers (53.64%). This concludes that the third wave in Pakistan is due to the importation of SARS-CoV-2 variants.
Rapid and Sensitive Diagnosis of Drug-Resistant FLT3-F691L Mutation by CRISPR Detection
Authors: Liu Yin , Chen Yanling , Huang Shisheng , Ma Xiaodong , Huang Xingxu , Wang Xinjie , Zhou Fuling
Published: October 2021

Sensitive and efficient detection of drug-resistant mutations is essential in cancer precision medicine. In treating acute myeloid leukemia (AML), FLT3 gene F691L mutation shows universal resistance to all currently available FLT3 inhibitors. However, there is no particular detection method for FLT3-F691L. Commonly-used first-generation sequencing (FGS) approaches have low sensitivity, and next-generation sequencing (NGS) is time-consuming. Herein, we developed an accurate and sensitive FLT3-F691L diagnostic method by CRISPR detection. Briefly, the FLT3-691 region is amplified by recombinase polymerase amplification (RPA) and detected by L691-crRNA induced Cas12a reaction, and finally the result can be directly observed under a blue lamp or analyzed by a fluorescence reader. Confirmed by the tests on diluted plasmids and 120 AML patient samples, this method can achieve a sensitivity of 0.1% and complete the whole diagnosis process within 40 min. Potentially, this method will play an important role in point-of-care applications and guidance of AML treatment.
Advancement of Scaffold-Based 3D Cellular Models in Cancer Tissue Engineering: An Update
Authors: Unnikrishnan Kavitha , Thomas Lynda Velutheril , Ram Kumar Ram Mohan
Published: October 2021

The lack of traditional cancer treatments has resulted in an increased need for new clinical techniques. Standard two-dimensional (2D) models used to validate drug efficacy and screening have a low in vitro-in vivo translation potential. Recreating the in vivo tumor microenvironment at the three-dimensional (3D) level is essential to resolve these limitations in the 2D culture and improve therapy results. The physical and mechanical environments of 3D culture allow cancer cells to expand in a heterogeneous manner, adopt different phenotypes, gene and protein profiles, and develop metastatic potential and drug resistance similar to human tumors. The current application of 3D scaffold culture systems based on synthetic polymers or selected extracellular matrix components promotes signalling, survival, and cancer cell proliferation. This review will focus on the recent advancement of numerous 3D-based scaffold models for cancer tissue engineering, which will increase the predictive ability of preclinical studies and significantly improve clinical translation.
High-Risk Features Are Prognostic in dMMR/MSI-H Stage II Colon Cancer
Authors: Mohamed Amr , Jiang Renjian , Philip Philip A. , Diab Maria , Behera Madhusmita , Wu Christina , Alese Olatunji , Shaib Walid L. , Gaines Tyra M. , Balch Glen G. , El-Rayes Bassel F. , Akce Mehmet
Published: October 2021

Background

High-risk features, such as T4 disease, bowel obstruction, poorly/undifferentiated histology, lymphovascular, perineural invasion, and <12 lymph nodes sampled, indicate poor prognosis and define high-risk stage II disease in proficient mismatch repair stage II colon cancer (CC). The prognostic role of high-risk features in dMMR/MSI-H stage II CC is unknown. Similarly, the role of adjuvant therapy in high-risk stage II CC with dMMR/MSI-H (≥1 high-risk feature) has not been studied in prospective trials. The aim of this analysis of the National Cancer Database is to evaluate the prognostic value of high-risk features in stage II dMMR/MSI-H CC.

Methods

Univariate (UVA) and multivariate (MVA) Cox proportional hazards (Cox-PH) models were built to assess the association between clinical and demographic characteristics and overall survival. Kaplan–Meier survival curves were generated with log-rank tests to evaluate the association between adjuvant chemotherapy in high-risk and low-risk cohorts separately.

Results

A total of 2,293 stage II CC patients have dMMR/MSI-H; of those, 29.5% (n = 676) had high-risk features. The high-risk dMMR/MSI-H patients had worse overall survival [5-year survival and 95%CI, 73.2% (67.3–78.1%) vs. 80.3% (76.7–83.5%), p = 0.0001]. In patients with stage II dMMR/MSI-H CC, the high-risk features were associated with shorter overall survival (OS) along with male sex, positive carcinoembryonic antigen, Charlson–Deyo score >1, and older age. Adjuvant chemotherapy administration was associated with better OS, regardless of the high-risk features in dMMR/MSI-H (log-rank test, p = 0.001) or not (p = 0.0006). When stratified by age, the benefit of chemotherapy was evident only in patients age ≥65 with high-risk features.

Conclusion

High-risk features are prognostic in the setting of dMMR/MSI-H stage II CC. Adjuvant chemotherapy may improve survival specifically in patients ≥65 years and with high-risk features.
Achieving NIR Light-Mediated Tumor-Specific Fenton Reaction-Assisted Oncotherapy by Using Magnetic Nanoclusters
Authors: Qin Shaoyou , Xue Jinru , Jia Erna , Ren Na , Dong Yongqiang , Zhou Changyu
Published: October 2021

As an emerging strategy for oncotherapy, Fenton chemistry can efficiently improve the conversion from endogenous H2O2 into highly toxic ·OH in the whole high-performance therapeutic process. Although promising, the efficiency of Fenton reaction in tumor regions is highly limited by the inefficient delivery of Fenton reagents and the restrictive conditions of tumor microenvironment. One promising strategy against the above limitations is to specifically increase the temperature around the tumor regions. In this study, a novel NIR light-mediated tumor-specific nanoplatform based on magnetic iron oxide nanoclusters (MNCs) was rationally designed and well developed for photothermally enhanced Fenton reaction-assisted oncotherapy. MNCs could accumulate into the tumor regions with the help of an external magnet field to enable T2-weighted magnetic resonance (MR) imaging of tumors and MR imaging-guided combined antitumor therapy. Our well-prepared MNCs also revealed excellent photothermal effect upon a NIR light irradiation, promising their further important role as a photothermal therapy (PTT) agent. More importantly, heat induced by the PTT of MNCs could accelerate the release of Fe from MNCs and enhance the efficiency of Fenton reaction under H2O2-enriched acidic tumor microenvironment. Results based on long-term toxicity investigations demonstrated the overall safety of MNCs after intravenous injection. This work therefore introduced a novel nanoplatform based on MNCs that exerted a great antitumor effect via photothermally enhanced tumor-specific Fenton chemistry.
Long-Term Functional Outcomes After Sepsis for Adult and Pediatric Critical Care Patients—Protocol for a Systematic Review
Authors: Simpson Adam , Long Deborah , Fleischmann-Struzek Carolin , Minogue Jessicah , Venkatesh Balasubramanian , Hammond Naomi E. , Tian David H. , Schlapbach Luregn J.
Published: October 2021

Objective: Sepsis is responsible for a massive burden of disease, with a global estimate of 48.9 million cases resulting in approximately 11 million deaths annually. Survivors of sepsis may also experience long-term impairments that can persist for years after hospital discharge. These cognitive, physical and/or psychosocial deficits may contribute to a lower health related quality of life and represent a significant ongoing burden to the individual, the community and the health care system. We aim to systematically review the available evidence on long-term functional and quality of life outcomes after sepsis in children and adults.

Data Sources: Medline, EMBASE, and CINAHL will be searched for eligible studies.

Study Selection: Studies of adult and pediatric survivors of sepsis who had required admission to intensive care will be included. A minimum 6 month prospective follow up will be required. Accepted outcomes will be any validated measure of health-related quality of life (HRQoL) or functional deficits, using the Post-Intensive Care Syndrome (PICS) framework of cognitive, physical or psychosocial outcomes.

Data Extraction: Data extraction will include information related to study characteristics, population characteristics, clinical criteria and outcomes.

Data Synthesis: Studies meeting the inclusion criteria will be presented descriptively separated for pediatric and adult age groups. Meta-analysis will be attempted if sufficient primary data from several studies applying the same tests and outcomes are available. The primary outcome is HRQoL after sepsis; secondary outcomes include the functional status at follow-up.

Conclusions: This systematic review will define the long-term impact of sepsis survivorship. The data will contribute to informing patient, clinician and stakeholder decisions and guide further research and resource management.
Development of a High Performance 1280×1024 InGaAs SWIR FPA Detector at Room Temperature
Authors: Zhang Jia-Xin , Wang Wei , Li Zai-Bo , Ye Hai-Feng , Huang Run-Yu , Hou Ze-Peng , Zeng Hui , Zhu Hong-xia , Liu Chen , Yang Xue-Yan , Shi Yan-Li
Published: October 2021

A 1280 × 1,024 In0.53Ga0.47As short wave infrared (SWIR) focal plane array (FPA) detector with a planar-type back-illuminated process has been fabricated. With indium bump flip-chip bonding techniques, the InGaAs photodiode arrays were hybrid-integrated to the CMOS readout integrated circuit (ROIC) with correlated double sampling (CDS). The response spectrum is 0.9–1.7 μm. The test results show that the dark current density is 2.25 nA/cm2 at 25 °C, the detectivity D* is up to 1.1 × 1013 cm · Hz1/2/W, the noise electron is as low as 48 e− under correlated double sampling mode, the quantum efficiency is 88% at 1550 nm, and the operability is more than 99.9%. Moreover, the dark current and noise electron have been studied theoretically in depth. The results indicate that the diffusion current is the main contribution of the dark current, and the readout integrated circuit noise electron is the main source of FPA noise.
Comparative Dynamic Transcriptome Reveals the Delayed Secondary-Cell-Wall Thickening Results in Altered Lint Percentage and Fiber Elongation in a Chromosomal Segment Substitution Line of Cotton (Gossypium hirsutum L.)
Authors: Gao Yang , Chen Yu , Song Zhangqiang , Zhang Jingxia , Lv Wanyu , Zhao Han , Huo Xuehan , Zheng Ling , Wang Furong , Zhang Jun , Zhang Tianzhen
Published: October 2021

Lint percentage (LP) is an important yield component in cotton that is usually affected by initial fiber number and cell wall thickness. To explore how fiber cell wall development affects LP, phenotypic identification and dynamic transcriptome analysis were conducted using a single segment substitution line of chromosome 15 (SL15) that harbors a major quantitative trait locus (QTL) for LP. Compared to its recurrent parent LMY22, SL15 did not differ in initial fiber number, but the fiber cell wall thickness and single-fiber weight decreased significantly, altering LP. The comparative transcriptome profiles revealed that the secondary cell wall (SCW) development phase of SL15 was relatively delayed. Meanwhile, the expression of genes related to cell expansion decreased more slightly in SL15 with fiber development, resulting in relatively higher expression at SL15_25D than at LMY22_25D. SCW development-related genes, such as GhNACs and GhMYBs, in the putative NAC-MYB-CESA network differentially expressed at SL15_25D, along with the lower expression of CESA6, CSLC12, and CSLA2. The substituted chromosomal interval was further investigated, and found 6 of 146 candidate genes were differentially expressed in all four cell development periods including 10, 15, 20 and 25 DPA. Genetic variation and co-expression analysis showed that GH_D01G0052, GH_D01G0099, GH_D01G0100, and GH_D01G0140 may be important candidate genes associated with qLP-C15-1. Our results provide novel insights into cell wall development and its relationship with LP, which is beneficial for lint yield and fiber quality improvement.
The Geographies and Politics of Gene Editing: Framing Debates Across Seven Countries
Authors: Meyer Morgan , Vergnaud Frédéric
Published: October 2021

This article traces the contours and dynamics of the debates about the politics of gene editing. It does so by providing both a quantitative and qualitative analysis of the publications on the topic. We present a scientometric analysis of scientific publications; we discuss the geographies of gene editing by analysing the scales and spatial terms mobilised; and we undertake a lexicometric analysis of how debates are framed and the public is positioned. Our scientometric analysis of scientific articles shows that the governance and regulation of gene editing is discussed across an increasing range of disciplines and countries over the years. Along with this internationalisation and “transdisciplinarisation,” we see a qualitative shift in the “grounding” of the debate: while initially, authors tend to reflect about gene editing, in more recent years, there are increasing calls to act upon current knowledge. Across the countries we studied (the United States, the United Kingdom, Germany, China, Australia, Japan, and Canada) our lexicometric analysis shows only a few differences in terms of how gene editing is discussed. While the general framing of the debate is widely shared, the differences that we observe concern for instance the applications or benefits of gene editing and the ways in which the importance of involving the public is worded. We hold that bringing together multiple methods allows a rich and multifaceted discussion of the politics of gene editing, and that this opens up fertile dialogues between geography, sociology and political science.
The ‘Comparative Logic’ and Why We Need to Explain Interlanguage Grammars
Authors: Domínguez Laura , Arche María J.
Published: October 2021

In this paper we argue that Bley-Vroman’s Comparative Fallacy, which warns against comparisons between native speakers and learners in second-language acquisition (SLA) research, is not justified on either theoretical or methodological grounds and should be abandoned as it contravenes the explanatory nature of SLA research. We argue that for SLA to be able to provide meaningful explanations, grammatical comparisons with a baseline (usually of native speakers although not always the case) are not only justified but necessary, a position which we call the ‘Comparative Logic’. The methodological choices assumed by this position ensure that interlanguage grammars are analysed in their own right and respecting their own principles. Related issues, such as why we focus on the native speaker and why investigating deficits in linguistic-cognitive SLA is essential in our field are discussed as well.
In the Pursuit of Green in COVID-19: Harnessing the Existing Talent to Pursue Green Corporate Entrepreneurship
Authors: Khan Essa , Mubarik Muhammad Shujaat , Shahid Zubair Ali
Published: October 2021

The study was conducted to ascertain the role of talent management practices in promoting green corporate entrepreneurship through the median of organizational engagement in the context of COVID-19. The study is quantitative and deductive in nature. The data was collected from 323 employees working in the large manufacturing industry. The data was collected through a self-administered survey and the data analysis was done through Smart-PLS, both measurement and structural models were evaluated. The study found that talent management is related to green corporate entrepreneurship. The study also confirmed the mediating role of organizational engagement relating talent management with green corporate entrepreneurship. This study will develop insight for the corporate managers and decision-makers to understand the intricacies of the talent management process and its interplay with green corporate entrepreneurship, and organizational engagement. Talent Management is concerned with the process of hiring, developing, and retaining highly competent incumbents for pivotal positions. Hence, the role of the talent management process invariably affects the organizational processes and outcomes like creativity and innovation, which come under the umbrella of corporate entrepreneurship. This study will not only add value in empirical research of the chosen concepts and constructs, but it will also bridge the theoretical gap between talent management and corporate entrepreneurship. It is the first study that related talent management practices to green corporate entrepreneurship. Furthermore, it is the first study that examined the mediating role of organizational engagement relating talent management to green corporate entrepreneurship.
Procedures Used in Managing SARS-CoV-2 Infected Dental Personnel or Patients: A Case Study From a Thai Dental Hospital
Authors: Pittayapat Pisha , Ampornaramveth Ruchanee , Jirachoksopon Chongpean , Suvarnbriksha Kanchana , Kattapong Siripun , Pethprasert Theerabhorn , Kungsadalpipob Kajorn , Chantarangsu Soranun , Thanyasrisung Panida , Koottathape Natthavoot , Tamsailom Suphot , Linsuwanont Pairoj , Kasevayuth Kasekarn , Sakoolnamarka Rangsima , Osathanon Thanaphum , Jansisyanont Pornchai
Published: October 2021

SARS-CoV-2 can transmit undetected from asymptomatic and pre-symptomatic patients in dental clinics. Triaging dental patients using temperature and questionnaire screening cannot completely exclude asymptomatic SARS-CoV-2 infected individuals. Hence, asymptomatic SARS-CoV-2 infected individuals might visit dental hospitals/clinics seeking dental treatment without knowing that they are infected and might infect others, especially in a pandemic area. Ideally, a nasopharyngeal swab for real-time polymerase chain reaction or rapid antigen screening for dental personnel and patients prior to their appointment should be done. However, the implementation of this approach is impractical in some situations. Here, we describe the procedures for dental hospitals/clinics in case of an asymptomatic SARS-CoV-2 infected individual involved in dental service/treatment and later after testing positive for SARS-CoV-2. Potential closely contacted individuals were traced and classified according to their exposure risk. The recommended course of action is to identify individuals based on their risk and take the risk-appropriate action. We also discuss the implementation of these procedures in a dental setting during the COVID-19 pandemic in our school as a case study.
Smallholder Farmer's Adaptability to Anthropogenic and Climate-Induced Variability in the Dhidhessa River Sub-basin, Ethiopia
Authors: Teweldebrihan Meseret Dawit , Lyu Haoyang , Pande Saket , McClain Michael E.
Published: October 2021

Ethiopia depends on rain-fed agriculture with limited use of irrigation for agricultural production. More than 90% of the food supply in the country comes from low productivity rain-fed smallholder agriculture. Since the livelihoods of many farmers depend on rainfed agriculture, this paper investigates how smallholders adapt to climate variability. Dhidhessa sub-basin of the Blue Nile river basin is home to many vulnerable immigrant smallholders from other parts of Ethiopia. Our study focuses on this sub-basin to understand how crop production and patterns have depended on rainfall. Secondary data on land cover and croplands, the number of households growing crops, crop yields, crop prices and area covered by three major crops (teff, maize, and sorghum) are analyzed over a period 2000–2019 and interpreted in light of a primary household survey of 135 farmers in the basin. Results show that almost 40% of the basin is under crop cultivation, and the area under cultivation has been growing 8.6‰ per year. Irrespective of rainfall variability, the number of households practicing crop cultivation has also been growing over the years. This means that more farmers are moving into the basin to cultivate. Analysis reveals that adaptation strategies are at play. Farmer decisions to grow which crops are sensitive to rainfall and their expectations of crop prices resulting from rainfall variability. Their decisions and crop prices are endogenous to the smallholder sociohydrology of the basin, leading more farmers to grow Teff relative to other crops in years of lower rainfall. These decisions are due to the lower sensitivity of Teff prices to rainfall variability and farmers' expectations of higher Teff prices relative to other crops as rainfall decreases. Such behavior also induces climate resilience, enabling farmers to respond to climate variability rather than migrating out of the basin. Moreover, it allows more farmers to migrate in and engage in crop cultivation within the basin. Such an adaptive strategy based on past experiences offers a way forward to incorporating adaptation mechanisms in sociohydrological models to simulate and assess water futures for similar basins worldwide.
The Frequency of Communication Between the Synovial Compartments of the Equine Temporomandibular Joint: A Contrast-Enhanced Computed Tomographic Assessment
Authors: Pimentel Karen L. , Carmalt James L.
Published: October 2021

Background: There is conflicting evidence regarding communication between the two compartments of the equine temporomandibular joint (TMJ). Understanding the inter-relationship between TMJ compartments is critical for diagnostic and clinical management purposes.

Objective: To determine the frequency of communication between the discotemporal joint (DTJ) and the discomandibular joint (DMJ) of the equine TMJ in horses free of overt disease.

Study Design: A randomized, blinded, controlled cadaveric study.

Methods: Equine cadaver heads (n = 20), with no reported history of potential TMJ disease, were collected and stored frozen until use. Horses were randomized to the treatment group, such that Group A horses (n = 10) underwent arthrocentesis of the left DTJ and the right DMJ compartments, while Group B (n = 10) underwent arthrocentesis of the left DMJ and the right DTJ compartments of the TMJ, for a total of 40 joints. Computed tomography (CT) imaging was performed before, and after, intra-articular injection of contrast media in each head. Two observers, blinded to the treatment group, independently interpreted CT images.

Results: Communication between synovial compartments occurred in the left TMJ of two horses. Arthroscopic evaluation revealed that both horses had a perforation of the intra-articular disc in the region of the caudomedial fibrous expansion. Mild anterior displacement of the abnormal disc in the joint of one horse was demonstrated using magnetic resonance imaging (MRI).

Main Limitations: Sample size, the use of owner provided animals' history, and frozen specimens.

Conclusions: No physiological communication was present between the DTJ and the DMJ in the equine TMJ of the cases studied, regardless of which compartment underwent arthrocentesis. Two joints had pathological communications. These results suggest that diagnostic, and medical, treatment of intra-articular disease may be most effective when both joint compartments are injected. Furthermore, this study illustrates the value of contrast enhancement while imaging the equine TMJ.
Revisión de algunas creencias en el tratamiento cognitivo-conductual de la agorafobia.
Authors: Bados Arturo
Published: October 2021

Con mucha mayor frecuencia de la que se piensa, las intervenciones psicológicas se basan en creencias terapéuticas que se apoyan solamente en estudios aislados, estudios con resultados inconsistentes o, simplemente, en la experiencia y sabiduría clínicas. El objetivo del presente trabajo es revisar críticamente algunas de estas creencias en el tratamiento conductual de los trastornos de ansiedad en general y de la agorafobia en particular. Por ejemplo, ¿es más eficaz una intervención individualizada que una estandarizada? El resultado del análisis es que en muchos casos poseemos sólo conclusiones tentativas sobre aspectos técnicos que son muy importantes de cara al tratamiento.
A Parallel Algorithm for Dividing Octonions
Authors: Cariow Aleksandr , Paplinski Janusz P.
Published: October 2021

The article presents a parallel hardware-oriented algorithm designed to speed up the division of two octonions. The advantage of the proposed algorithm is that the number of real multiplications is halved as compared to the naive method for implementing this operation. In the synthesis of the discussed algorithm, the matrix representation of this operation was used, which allows us to present the division of octonions by means of a vector–matrix product. Taking into account a specific structure of the matrix multiplicand allows for reducing the number of real multiplications necessary for the execution of the octonion division procedure.
Circulating microRNAs as Diagnostic Markers in Primary Aldosteronism
Authors: MacKenzie Scott M. , Saunders Hannah , van Kralingen Josie C. , Robertson Stacy , Riddell Alexandra , Zennaro Maria-Christina , Davies Eleanor
Published: October 2021

Primary aldosteronism (PA) is a common and highly treatable condition, usually resulting from adrenocortical tumorous growth or hyperplasia. PA is currently underdiagnosed owing to its complex and protracted diagnostic procedures. A simplified biomarker-based test would be highly valuable in reducing cardiovascular morbidity and mortality. Circulating microRNAs are emerging as potential biomarkers for a number of conditions due to their stability and accessibility. PA is known to alter microRNA expression in adrenocortical tissue; if these changes or their effects are mirrored in the circulating miRNA profile, then this could be exploited by a diagnostic test. However, the reproducibility of studies to identify biomarker-circulating microRNAs has proved difficult for other conditions due to a series of technical challenges. Therefore, any studies seeking to definitively identify circulating microRNA biomarkers of PA must address this in their design. To this end, we are currently conducting the circulating microRNA arm of the ongoing ENS@T-HT study. In this review article, we present evidence to support the utility of circulating microRNAs as PA biomarkers, describe the practical challenges to this approach and, using ENS@T-HT as an example, discuss how these might be overcome.
3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset
Authors: Kim Hugh Andrew Jinwook , Shaikh Mushfiq Hassan , Lee Mark , Zeng Peter Y. F. , Sorgini Alana , Akintola Temitope , Deng Xiaoxiao , Jarycki Laura , Khan Halema , MacNeil Danielle , Khan Mohammed Imran , Mendez Adrian , Yoo John , Fung Kevin , Lang Pencilla , Palma David A. , Patel Krupal , Mymryk Joe S. , Barrett John W. , Boutros Paul C. , Morris Luc G. T. , Nichols Anthony C.
Published: October 2021

Loss of the 3p chromosome arm has previously been reported to be a biomarker of poorer outcome in both human papillomavirus (HPV)-positive and HPV-negative head and neck cancer. However, the precise operational measurement of 3p arm loss is unclear and the mutational profile associated with the event has not been thoroughly characterized. We downloaded the clinical, single nucleotide variation (SNV), copy number aberration (CNA), RNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Atlas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. In addition, we report the inclusion of an independent Memorial Sloan Kettering cohort. We assessed the frequency of loci deletions across the 3p arm separately in HPV-positive and -negative disease. We found that deletions on chromosome 3p were almost exclusively an all or none event in the HPV-negative cohort; patients either had <1% or >97% of the arm deleted. 3p arm loss, defined as >97% deletion in HPV-positive patients and >50% in HPV-negative patients, had no impact on survival (p > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases (p < 0.05). They were enriched for SNVs in TP53, and depleted for point mutations in CASP8, HRAS, HLA-A, HUWE1, HLA-B, and COL22A1 (false discovery rate, FDR < 0.05). 3p arm loss was associated with CNAs across the whole genome (FDR < 0.1), and pathway analysis revealed low lymphoid–non-lymphoid cell interactions and cytokine signaling (FDR < 0.1). In the tumor microenvironment, 3p arm lost tumors had low immune cell infiltration (FDR < 0.1) and elevated hypoxia (FDR < 0.1). 3p arm lost tumors had lower abundance of proteins phospho-HER3 and ANXA1, and higher abundance of miRNAs hsa-miR-548k and hsa-miR-421, which were all associated with survival. There were no molecular differences by 3p arm status in HPV-positive patients, at least at our statistical power level. 3p arm loss is largely an all or none phenomenon in HPV-negative disease and does not predict poorer survival from the time of diagnosis in TCGA cohort. However, it produces tumors with distinct molecular characteristics and may represent a clinically useful biomarker to guide treatment decisions for HPV-negative patients.
Radiological Patterns of Uveal Melanoma Liver Metastases in Correlation to Genetic Status
Authors: Yavuzyigitoglu Serdar , Tang Michael C. Y. , Jansen Miguel , Geul Kaspar W. , Dwarkasing Roy S. , Vaarwater Jolanda , Drabarek Wojtek , Verdijk Robert M. , Paridaens Dion , Naus Nicole C. , Brosens Erwin , de Klein Annelies , Kilic Emine
Published: October 2021

This study reports the role played by the mutation status of Uveal Melanoma (UM) in relation to hepatic metastatic patterns as seen on imaging modalities. Radiological images were obtained from 123 patients treated at the Erasmus Medical Center Rotterdam or the Rotterdam Eye Hospital. Radiological images were derived from either computed tomography or magnetic resonance imaging. Hepatic metastatic patterns were classified by counting the number of metastases found in the liver. Miliary metastatic pattern (innumerable small metastases in the entire liver) was analyzed separately. Mutation status was determined in 85 patients. Median disease-free survival (DFS) and survival with metastases differed significantly between each of the metastatic patterns (respectively, p = 0.009, p < 0.001), both in favor of patients with less hepatic metastases. The mutation status of the primary tumor was not correlated with any hepatic tumor profiles (p = 0.296). Of the patients who had a solitary metastasis (n = 18), 11 originated from a primary BAP1-mutated tumors and one from a primary SF3B1-mutated tumor. Of the patients who had a miliary metastasis pattern (n = 24), 17 had a primary BAP1-mutated tumor and two had a primary SF3B1-mutated tumor. Chromosome 8p loss was significantly more in patients with more metastases (p = 0.045). Moreover, the primary UMs of patients with miliary metastases harbored more chromosome 8p and 1p loss, compared to patients with single solitary metastasis (p = 0.035 and p = 0.026, respectively). In conclusion, our study shows that there is an inverse correlation of the number of metastasis with the DFS and metastasized survival, indicating separate growth patterns. We also revealed that the number and type of metastases is irrelevant to the prognostic mutation status of the tumor, showing that both BAP1- and SF3B1-mutated UM can result in solitary and miliary metastases, indicating that other processes lay ground to the different metastatic patterns.
New Markers of Disease Progression in Myelofibrosis
Authors: Campanelli Rita , Massa Margherita , Rosti Vittorio , Barosi Giovanni
Published: October 2021

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm due to the clonal proliferation of a hematopoietic stem cell. The vast majority of patients harbor a somatic gain of function mutation either of JAK2 or MPL or CALR genes in their hematopoietic cells, resulting in the activation of the JAK/STAT pathway. Patients display variable clinical and laboratoristic features, including anemia, thrombocytopenia, splenomegaly, thrombotic complications, systemic symptoms, and curtailed survival due to infections, thrombo-hemorrhagic events, or progression to leukemic transformation. New drugs have been developed in the last decade for the treatment of PMF-associated symptoms; however, the only curative option is currently represented by allogeneic hematopoietic cell transplantation, which can only be offered to a small percentage of patients. Disease prognosis is based at diagnosis on the classical International Prognostic Scoring System (IPSS) and Dynamic-IPSS (during disease course), which comprehend clinical parameters; recently, new prognostic scoring systems, including genetic and molecular parameters, have been proposed as meaningful tools for a better patient stratification. Moreover, new biological markers predicting clinical evolution and patient survival have been associated with the disease. This review summarizes basic concepts of PMF pathogenesis, clinics, and therapy, focusing on classical prognostic scoring systems and new biological markers of the disease.
Assessment of Radiation-Induced Optic Neuropathy in a Multi-Institutional Cohort of Chordoma and Chondrosarcoma Patients Treated with Proton Therapy
Authors: Köthe Andreas , Feuvret Loïc , Weber Damien Charles , Safai Sairos , Lomax Antony John , Fattori Giovanni
Published: October 2021

Radiation-induced optic neuropathy (RION) is a rare side effect following radiation therapy involving the optic structures whose onset is, due to the low amount of available data, challenging to predict. We have analyzed a multi-institutional cohort including 289 skull-base cancer patients treated with proton therapy who all received >45 GyRBE to the optic apparatus. An overall incidence rate of 4.2% (12) was observed, with chordoma patients being at higher risk (5.8%) than chondrosarcoma patients (3.2%). Older age and arterial hypertension, tumor involvement, and repeated surgeries (>3) were found to be associated with RION. Based on bootstrapping and cross-validation, a NTCP model based on age and hypertension was determined to be the most robust, showing good classification ability (AUC-ROC 0.77) and calibration on our dataset. We suggest the application of this model with a threshold of 6% to segment patients into low and high-risk groups before treatment planning. However, further data and external validation are warranted before clinical application.
Dietary Factors and Breast Cancer Prognosis among Breast Cancer Survivors: A Systematic Review and Meta-Analysis of Cohort Studies
Authors: Park Sin-Hye , Hoang Tung , Kim Jeongseon
Published: October 2021

Few studies have summarized the association between dietary factors and breast cancer (BC) prognosis among breast cancer survivors (BCS). Therefore, we carried out a systematic review and meta-analysis to determine the associations between dietary factors and BC prognosis among BCS. We performed a literature search in PubMed and Embase to investigate the association between dietary factors and BC prognosis. We applied a random-effects model to compute the hazard ratio/relative risk and their 95% confidence intervals and heterogeneity (Higgins I2) and to generate forest plots using STATA. Among the 2279 papers identified, 63 cohort studies were included in the systematic review and meta-analysis. Our main finding was that higher consumption of beer and saturated fat negatively affected BC prognosis. However, the intake of lignans, fiber, multivitamins, and antioxidants was negatively associated with the risk of mortality. Furthermore, we performed subgroup analyses by menopausal status and dietary or supplementary micronutrient intake. Most trends were similar to the main findings; in particular, the vitamin C, vitamin D, and vitamin E supplements decreased the risk of mortality. This study’s current systematic review and meta-analysis provide comprehensive dietary information for the development of dietary guidelines/recommendations to improve prognosis among BCS.
Anticancer Activity of Biogenic Selenium Nanoparticles: Apoptotic and Immunogenic Cell Death Markers in Colon Cancer Cells
Authors: Spyridopoulou Katerina , Aindelis Georgios , Pappa Aglaia , Chlichlia Katerina
Published: October 2021

Colorectal cancer is a health problem with high mortality rates and prevalence. Thus, innovative treatment approaches need to be developed. Biogenic nanoparticles are nanomaterials that can be synthesised in biological systems and, compared to chemically synthesised nanoparticles, have better bioavailability while being more cost-effective, eco-friendlier, and less toxic. In our previous studies, the probiotic strain Lactobacillus casei ATCC 393 was used to synthesise selenium nanoparticles (SeNps), which were shown to inhibit colon cancer cell growth in vitro and in vivo. Herein, we have further investigated SeNps’ pro-apoptotic activity and their ability to induce immunogenic cell death (ICD) in colon cancer cells. The SeNps’ effect on Caco-2 cells growth was examined along with their potential to induce caspase activation. Moreover, the expression of typical pro-apoptotic and ICD markers were examined in SeNps-treated HT29 and CT26 cells by flow cytometry, Western blot, ELISA and fluorescence microscopy. Elevated caspase-3 activation and surface phosphatyldoserine, that subsided upon co-incubation with a pan-caspase inhibitor, were detected in SeNps-treated cells. Furthermore, nanoparticles induced modulation of the expression of various apoptosis-related proteins. We also report the detection of biomarkers involved in ICD, namely the translocation of calreticulin and ERp57, the release of HMGB1 and ATP, and the secretion of pro-inflammatory cytokines from SeNps-treated cells. Moreover, RAW246.7 macrophages exhibited a higher rate of phagocytosis against treated CT26 when compared to control cells. Taken together, our findings indicate that treatment with SeNps might be an efficient strategy to destroy tumour cells by inducing apoptotic cell death and triggering immune responses.
A New Look into Cancer—A Review on the Contribution of Vibrational Spectroscopy on Early Diagnosis and Surgery Guidance
Authors: Mamede Adriana P. , Santos Inês P. , Batista de Carvalho Ana L. M. , Figueiredo Paulo , Silva Maria C. , Tavares Mariana V. , Marques Maria P. M. , Batista de Carvalho Luís A. E.
Published: October 2021

In 2020, approximately 10 million people died of cancer, rendering this disease the second leading cause of death worldwide. Detecting cancer in its early stages is paramount for patients’ prognosis and survival. Hence, the scientific and medical communities are engaged in improving both therapeutic strategies and diagnostic methodologies, beyond prevention. Optical vibrational spectroscopy has been shown to be an ideal diagnostic method for early cancer diagnosis and surgical margins assessment, as a complement to histopathological analysis. Being highly sensitive, non-invasive and capable of real-time molecular imaging, Raman and Fourier transform infrared (FTIR) spectroscopies give information on the biochemical profile of the tissue under analysis, detecting the metabolic differences between healthy and cancerous portions of the same sample. This constitutes tremendous progress in the field, since the cancer-prompted morphological alterations often occur after the biochemical imbalances in the oncogenic process. Therefore, the early cancer-associated metabolic changes are unnoticed by the histopathologist. Additionally, Raman and FTIR spectroscopies significantly reduce the subjectivity linked to cancer diagnosis. This review focuses on breast and head and neck cancers, their clinical needs and the progress made to date using vibrational spectroscopy as a diagnostic technique prior to surgical intervention and intraoperative margin assessment.
IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth
Authors: Li Jiahui , Wu Xiaolin , Schiffmann Lars , MacVicar Thomas , Zhou Chenghui , Wang Zhefang , Li Dai , Camacho Oscar Velazquez , Heuchel Reiner , Odenthal Margarete , Hillmer Axel , Quaas Alexander , Zhao Yue , Bruns Christiane J. , Popp Felix C.
Published: October 2021

In pancreatic ductal adenocarcinoma (PDAC), the tumor stroma constitutes most of the cell mass and contributes to therapy resistance and progression. Here we show a hitherto unknown metabolic cooperation between pancreatic stellate cells (PSCs) and tumor cells through Interleukin 17B/Interleukin 17B receptor (IL-17B/IL-17RB) signaling. Tumor-derived IL-17B carrying extracellular vesicles (EVs) activated stromal PSCs and induced the expression of IL-17RB. PSCs increased oxidative phosphorylation while reducing mitochondrial turnover. PSCs activated tumor cells in a feedback loop. Tumor cells subsequently increased oxidative phosphorylation and decreased glycolysis partially via IL-6. In vivo, IL-17RB overexpression in PSCs accelerated tumor growth in a co-injection xenograft mouse model. Our results demonstrate a tumor-to-stroma feedback loop increasing tumor metabolism to accelerate tumor growth under optimal nutritional conditions.
Varietal Threat Index for Monitoring Crop Diversity on Farms in Five Agro-Ecological Regions in India
Authors: Dulloo Mohammad Ehsan , Estrada Carmona Natalia , Rana Jai C. , Yadav Rashmi , Grazioli Francesca
Published: October 2021

Our knowledge about the status of agrobiodiversity on farms is still very limited. While several studies to assess the crop genetic diversity on farms have been undertaken, there are no systematic documentation and monitoring practices for varietal diversity in space and time. Achievement of the agrobiodiversity Aichi Target 13, established under the Biodiversity Strategy Plan 2011–2020, have failed due to the lack of existing data on varietal diversity at country, regional and global levels. Here, we propose a method for calculating the Varietal Threat Index using the four-cell analysis (FCA) participatory methodology at different geographical scales to monitor changes in the varietal diversity on farms and to compare between areas. We tested the method with datasets collected from the UN-Environment GEF project implemented in India, in which data on crop and varietal diversity were collected across seven states in India, covering five agroecological regions. Results showed that landraces are still commonly grown in the study sites, especially in the central and western regions, and that more than 50% of landraces are considered threatened, suggesting that conservation interventions are required to prevent large-scale genetic erosion. A long-term monitoring framework for varietal diversity in India is proposed.