bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological Investigation of Meningeal Worm-Induced Mortalities in Small Ruminants and Camelids Over a 19 Year Period
Authors: Keane Charlena , Marchetto Katherine M. , Oliveira-Santos Luiz Gustavo R. , Wünschmann Arno , Wolf Tiffany M.
Published: April 2022

Meningeal worm, or Parelaphostrongylus tenuis (P. tenuis) is a nematode parasite that can invade the nervous system of small ruminant and camelid species such as alpaca, llama, goats and sheep. Limited reports exist on the epidemiology of disease caused by the nematode in susceptible livestock. We examined archived necropsy reports from small ruminant and camelid mortalities that were submitted, post mortem, to the University of Minnesota Veterinary Diagnostic Laboratory (MNVDL) during 2001–2019 for gross necropsy, histopathology, and pathogen screening. We estimated P. tenuis-induced mortality over time and developed temporal models to better understand patterns and drivers of P. tenuis-induced mortalities in these animals. During the period under examination, 5,617 goats, sheep, llamas and alpacas were necropsied, revealing an overall P. tenuis-induced mortality rate of 1.14% in the necropsy submission pool for these species. P. tenuis-induced mortality rates were highest in llamas (9.91%) and alpacas (5.33%) compared to sheep and goats (<1%), with rates in llamas and alpacas significantly higher than in sheep and goats. P. tenuis-induced mortalities exhibited one seasonal peak, around October to December. P. tenuis-induced mortality rates varied greatly between years, and have significantly increased over time. We also observed a positive correlation between summer temperature (range 20.4–22.4°C) and P. tenuis-induced mortality rates (range 0–3.9%), but not precipitation. This study demonstrates seasonal patterns and differences in mortality between alpacas, goats, llamas and sheep and helps us to better understand the epidemiology of P. tenuis mortality.
Comparative Analysis of the Fecal Microbiota of Relict Gull (Larus relictus) in Mu Us Desert (Hao Tongcha Nur) and Bojiang Haizi in Inner Mongolia, China
Authors: Liu Li , Du Chao , Liu Yunpeng , Gao Li
Published: April 2022

The gut microbiota contributes to host health by improving digestive efficiency and maintaining homeostasis. The relict gull (Larus relictus), a national first-class protected bird in China, is listed as vulnerable in the International Union for Conservation of Nature Red List. Here, 16S rRNA gene sequencing was performed to characterize and compare the community composition and diversity of the gut microbiota sampled from relict gulls in two breeding sites. In total, 418 operational taxonomic units (OUTs) were obtained and classified into 15 phyla and 228 genera. Alpha diversity analysis revealed no significant differences in community diversity among the two breeding sites. Beta diversity analyses showed that the microbial communities at the two sites were different. Six dominant phyla and fourteen dominant genera were identified. The most abundant bacterial genera had a significant relationship with the diet and living environment, and some bacterial genera were found to adapt to the plateau environment in which relict gulls live, which enables the relict gulls to use local resources effectively to accumulate energy. Simultaneously, a variety of highly abundant pathogenic bacteria were found, suggesting that these gulls may spread diseases among the local gull population. Certain measures should be taken to protect this species and to prevent the spread of diseases.
Predictors and Timing to Viral Suppression in HIV-Infected Pregnant Women in the University of Zimbabwe Birth Cohort Study During the Era of Lifelong Antiretroviral Therapy (Option B+ Treatment Strategy)
Authors: Duri Kerina , Munjoma Privilege Tendai , Mazhandu Arthur John , Marere Tarisai , Gomo Exnevia , Banhwa Simeon , Jordi Sebastian Bruno Ulrich , Misselwitz Benjamin , Mazengera Lovemore Ronald
Published: April 2022

Background

Achieving and maintaining viral suppression (VS) in people living with HIV/AIDS on antiretroviral therapy (ART) remains a crucial clinical goal, more so in pregnancy to prevent mother-to-child-transmission (MTCT). There is a need to understand VS kinetics and barriers to achieving it in order to meet the target of eliminating HIV-MTCT by 2030.

Methods

HIV-infected pregnant women ≥20 weeks of gestation with different durations of Tenofovir/Lamivudine/Efavirenz exposures seeking antenatal care services at four primary health centres in high-density residential areas in Harare, Zimbabwe were enrolled in the University of Zimbabwe Birth Cohort Study. Plasma viral load (VL) was quantified by reverse transcriptase–polymerase chain reaction. Demographic, clinical, socio-economic and HIV- and ART-related factors were tested in multivariable logistic regression analyses as potential predictors for VS and undetectable VL.

Results

From March 2016 to June 2019, 608 HIV-infected pregnant women were enrolled. 63 (10.4%) were self-reported-ART-naïve; 324 (53.3%) and 221 (36.3%) initiated ART pre- and post-conception, respectively. Time from ART initiation to VS (VL ≤ 1,000 copies/ml) in 95% of the women was 126 days. Overall lack of VS (VL > 1,000 copies/ml) was observed in 133 (21.9%) women being 76.2, 27.4 and 7.7% in self-reported-ART-naïve, post-conception and pre-conception groups, respectively. Undetectable VL (≤ 50 copies/ml) was observed in 371 (61.2%) and low-level viremia (51–1,000 copies/ml) in 102 (16.8%) women.

In multivariable models for all participants regardless of ART exposure, being on ART was the strongest predictor for both VS and undetectable VL (odds ratio 95% confidence interval, OR (CI): 8.9(4.2–19.5) and 8.1(3.2–24.4), respectively). For women on ART, duration of ART use >126 days was the strongest predictor with OR (CI): 6.7(3.3–14.0) for VS and 8.5(5.6–13.1) for undetectable VL. Other relevant predictors for favourable virological outcomes were older maternal age, HIV-status disclosure, absence of ART side effects and self-reported depression. Having a spouse/intimate partner on ART predicted a 4 times higher likelihood for VS.

Discussion

Lack of VS was frequently observed in this Harare cohort of pregnant women, mainly due to new HIV diagnosis, hence not being on ART and suboptimal duration of ART exposure. Since VS for 95% of women needed about 4 months of ART exposure, eliminating HIV-MTCT will require timely screening and commencing women together with their spouses/intimate partners on ART before pregnancy or early after conception.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier: NCT04087239.
Associations between Developing Sexuality and Mental Health in Heterosexual Adolescents: Evidence from Lower- and Middle-Income Countries—A Scoping Review
Authors: Punjani Neelam Saleem , Papathanassoglou Elizabeth , Hegadoren Kathleen , Hirani Saima , Mumtaz Zubia , Jackson Margot
Published: April 2022

Background: During puberty and emerging sexuality, adolescents experience important physical, mental, and social transformations. In the process of dealing with these changes, adolescents can become potentially vulnerable to mental health problems. Aim: The aim is to identify and synthesize published research evidence on sexuality-related mental health stressors among adolescent girls and boys, identify gaps (if any) in the current knowledge, and contribute to the knowledge about the experiences of emerging sexuality and health among adolescents, to further inform research, practice, and policy initiatives in sexual health. Design: A scoping literature review of peer-reviewed articles published between 1990 and 2021. MEDLINE, CINAHL, EMBASE, PsycINFO, Global health, ERIC, and Sociological Abstracts databases were searched for research studies that reported experiences of sexuality-related mental health issues and symptomatology of adolescents. We targeted studies conducted with adolescent populations between ages 10–19 years living in LMICs. Results: Data from 12 published research papers, including 8 qualitative studies, 3 quantitative studies, and 1 mixed method study, were systematically analyzed. Four major themes and four sub-themes were identified regarding the sexual and mental health of adolescents: (1) Relationship of sexuality and mental health; (2) Social and cultural influences; (3) Challenges in seeking sexuality information and services among adolescents; and (4) Educational needs among adolescents related to sexuality. Conclusions: Lack of social support, unmet needs for accessible adolescent-friendly sexual health services, counseling, and age-appropriate information may be associated with several mental health stressors and symptoms, such as sadness, depressive and anxiety symptomatology, regret, fear, embarrassment, low self-esteem, guilt, shame, and anger. Therefore, tackling sexuality-related stressors could play an important role in addressing the overall well-being of young people. Future studies need to generate a deeper understanding of the concept of sexual health and its relation to mental health in diverse contexts. Implications for Practice: Health care professionals need to be aware of sexuality-related experiences of adolescent girls and boys by offering effective youth-friendly sexual and reproductive health education to support overall mental health and improve the experiences of emerging sexuality in adolescents.
Spatial Modeling of Extreme Temperature in Northeast Thailand
Authors: Senapeng Prapawan , Prahadchai Thanawan , Guayjarernpanishk Pannarat , Park Jeong-Soo , Busababodhin Piyapatr
Published: April 2022

The objective of the present study was to examine and predict the annual maximum temperature in the northeast of Thailand by using data from 25 stations and employing spatial extreme modeling which is based on max-stable process (MSP) using schlatter’s method. We analyzed extreme temperature data using the MSP using latitude, longitude, and altitude variables. Our result showed that the maximum temperature has an increasing trend. The return level estimates of the study areas from both the local generalized extreme value (GEV) model and MSP models show that the Nong Khai, Maha Sarakham, and Khon Kaen stations had higher return levels than the other stations for every return period, whereas Pak Chong Agromet had the lowest return levels. Furthermore, the results showed that MSP modeling is more suitable than point-wise GEV distribution. We realize that the spatial extreme modeling based on MSP provides more precise and robust return levels as well as some indices of the maximum temperatures for both the observation stations and the locations with no observed data. The results of this study are consistent with those of some previous studies. The increasing trend in return levels could affect agriculture and the surrounding environment in northeast Thailand. Spatial extreme modeling can be beneficial in the impact management and vulnerability assessment under extreme event scenarios caused by climate change.
A Self-Consistent Return Stroke Model That Includes the Effect of the Ground Conductivity at the Strike Point
Authors: Cooray Vernon , Rubinstein Marcos , Rachidi Farhad
Published: April 2022

A current generation type return stroke model which can take into account the possible modifications of the return stroke properties by the soil conductivity at the strike point of the lightning flash is introduced. The model is also capable of incorporating the reflection of the current at the ground end of the return stroke channel. In this paper, this return stroke model is used to investigate (a) the effect of the ground conductivity at the strike point on the source electromagnetic fields generated by return strokes and (b) the effect of current reflection at ground level on the electromagnetic field generated by return strokes. The source electromagnetic fields are the electromagnetic fields generated by lightning flashes calculated in such a way that they are not distorted by propagation effects. The results obtained show that the ground conductivity at the strike point does not significantly influence the return stroke current peak or the radiation field peak for ground conductivities higher than about 0.001 S/m. However, strike points with very poor conductivities (lower than 0.001 S/m) would result in a decrease of the peak electric field. In contrast to the peak values of the lightning current and the electric field, the peak values of the time derivatives of the lightning current and electric field are significantly reduced when the strike point of the lightning flash is located over a finitely conducting ground. The inclusion of the current reflection at ground level influences significantly the saturation of the close electric fields. The current reflection also gives rise to residual electric fields, a difference in the field levels generated by the dart leader and the return stroke. The residual field decreases as the fraction of the reflected current decreases.
Lymphatic Tissue Bioengineering for the Treatment of Postsurgical Lymphedema
Authors: Sung Cynthia J. , Gupta Kshitij , Wang Jin , Wong Alex K.
Published: April 2022

Lymphedema is characterized by progressive and chronic tissue swelling and inflammation from local accumulation of interstitial fluid due to lymphatic injury or dysfunction. It is a debilitating condition that significantly impacts a patient’s quality of life, and has limited treatment options. With better understanding of the molecular mechanisms and pathophysiology of lymphedema and advances in tissue engineering technologies, lymphatic tissue bioengineering and regeneration have emerged as a potential therapeutic option for postsurgical lymphedema. Various strategies involving stem cells, lymphangiogenic factors, bioengineered matrices and mechanical stimuli allow more precisely controlled regeneration of lymphatic tissue at the site of lymphedema without subjecting patients to complications or iatrogenic injuries associated with surgeries. This review provides an overview of current innovative approaches of lymphatic tissue bioengineering that represent a promising treatment option for postsurgical lymphedema.
Towards Automated Structural Stability Design of Buildings—A BIM-Based Solution
Authors: Khattra Satinder Kaur , Rai Hardeep Singh , Singh Jagbir
Published: April 2022

Building information modelling (BIM) is a revolution in the architectural, engineering, and construction (AEC) industry. In the AEC industry, several interesting innovations are being introduced every day. Most of the code compliance work, which is time-consuming and quite multifaceted, is now performed manually. The number of unwanted errors is increasing, and any suspension of the project is led by the structural code-checking system, and is a tiresome process. Subsequently, the BIM-based model is presented to automate the structural stability design of buildings. The Industry Foundation Classes (IFC) specification is introduced in this work, and is used to automate the building design processes to achieve design correctness and efficiency. The IFC-based interoperability framework is presented to automate the design of structural elements of RC buildings. Consequently, a deep multi-perception-based generalized adaptive framework (DMPBGAF) is presented for the automated code compliance checking process. The concepts and relationships in the building code were automatically matched to their equivalent concepts. A building code was checked against the Indian seismic code IS 13920, and when shear wall data were presented in this IFC file, it exchanged the data with the custom engine. It is possible to eliminate the unwanted issues based on the automated code compliance system with BIM. This goal can be accomplished by using a coding rule-based engine to compile the BIM model and store the design code of the specific country with its clauses. After generating the Python file to code all of the prepared checks, the python file in the form of functions was obtained from the IfcOpenShell library. Finally, a rule engine was developed for interpretation of the checks; the three model IFC files were tested on this, and it gave satisfactory results. The FreeCAD software was employed in this research for the IFC-based BIM model to automate the design. The shear wall data were presented in the first IFC model; all of the code checks were passed based on this modelled design, and when given to the rule engine, it gave a 100% compliance report. Insufficiently reinforced shear wall data contained in the other two IFC files were purposely created to fail some of the code checks. This method significantly reduces the time by eliminating the duplication of efforts. From the viewpoint of accuracy and reliability, the proposed method is more accurate and results in enhanced reliability as compared to manual design methods.
N, LNR or LODDS: Which Is the Most Appropriate Lymph Node Classification Scheme for Patients with Radically Resected Pancreatic Cancer?
Authors: Prassas Dimitrios , Safi Sami Alexander , Stylianidi Maria Chara , Telan Leila Anne , Krieg Sarah , Roderburg Christoph , Esposito Irene , Luedde Tom , Knoefel Wolfram Trudo , Krieg Andreas
Published: April 2022

Background: Even though numerous novel lymph node (LN) classification schemes exist, an extensive comparison of their performance in patients with resected pancreatic ductal adenocarcinoma (PDAC) has not yet been performed. Method: We investigated the prognostic performance and discriminative ability of 25 different LN ratio (LNR) and 27 log odds of metastatic LN (LODDS) classifications by means of Cox regression and C-statistic in 319 patients with resected PDAC. Regression models were adjusted for age, sex, T category, grading, localization, presence of metastatic disease, positivity of resection margins, and neoadjuvant therapy. Results: Both LNR or LODDS as continuous variables were associated with advanced tumor stage, distant metastasis, positive resection margins, and PDAC of the head or corpus. Two distinct LN classifications, one LODDS and one LNR, were found to be superior to the N category in the complete patient collective. However, only the LODDS classification exhibited statistically significant, gradually increasing HRs of their subcategories and at the same time significantly higher discriminative potential in the subgroups of patients with PDAC of the head or corpus and in patients with tumor free resection margins or M0 status, respectively. On this basis, we built a clinically helpful nomogram to estimate the prognosis of patients after radically resected PDAC. Conclusion: One LNR and one LODDS classification scheme were found to out-perform the N category in terms of both prognostic performance and discriminative ability, in distinct patient subgroups, with reference to OS in patients with resected PDAC.
Neuroendocrine Neoplasms of the Gynecologic Tract
Authors: Virarkar Mayur , Vulasala Sai Swarupa , Morani Ajaykumar C. , Waters Rebecca , Gopireddy Dheeraj R. , Kumar Sindhu , Bhosale Priya , Lall Chandana
Published: April 2022

Gynecological tract neuroendocrine neoplasms (NEN) are rare, aggressive tumors from endocrine cells derived from the neuroectoderm, neural crest, and endoderm. The primary gynecologic NENs constitute 2% of gynecologic malignancies, and the cervix is the most common site of NEN in the gynecologic tract. The updated WHO classification of gynecologic NEN is based on the Ki-67 index, mitotic index, and tumor characteristics such as necrosis, and brings more uniformity in the terminology of NENs like other disease sites. Imaging plays a crucial role in the staging, triaging, restaging, and surveillance of NENs. The expression of the somatostatin receptors on the surface of neuroendocrine cells forms the basis of increasing evaluation with functional imaging modalities using traditional and new tracers, including 68Ga-DOTA-Somatostatin Analog-PET/CT. Management of NENs involves a multidisciplinary approach. New targeted therapies could improve the paradigm of care for these rare malignancies. This article focuses on the updated staging classifications, clinicopathological characteristics, imaging, and management of gynecologic NENs of the cervix, ovary, endometrium, vagina, and vulva, emphasizing the relatively common cervical neuroendocrine carcinomas among these entities.
Melanin and Melanin-Functionalized Nanoparticles as Promising Tools in Cancer Research—A Review
Authors: Marcovici Iasmina , Coricovac Dorina , Pinzaru Iulia , Macasoi Ioana Gabriela , Popescu Roxana , Chioibas Raul , Zupko Istvan , Dehelean Cristina Adriana
Published: April 2022

Cancer poses an ongoing global challenge, despite the substantial progress made in the prevention, diagnosis, and treatment of the disease. The existing therapeutic methods remain limited by undesirable outcomes such as systemic toxicity and lack of specificity or long-term efficacy, although innovative alternatives are being continuously investigated. By offering a means for the targeted delivery of therapeutics, nanotechnology (NT) has emerged as a state-of-the-art solution for augmenting the efficiency of currently available cancer therapies while combating their drawbacks. Melanin, a polymeric pigment of natural origin that is widely spread among many living organisms, became a promising candidate for NT-based cancer treatment owing to its unique physicochemical properties (e.g., high biocompatibility, redox behavior, light absorption, chelating ability) and innate antioxidant, photoprotective, anti-inflammatory, and antitumor effects. The latest research on melanin and melanin-like nanoparticles has extended considerably on many fronts, allowing not only efficient cancer treatments via both traditional and modern methods, but also early disease detection and diagnosis. The current paper provides an updated insight into the applicability of melanin in cancer therapy as antitumor agent, molecular target, and delivery nanoplatform.
Cost-Effectiveness of Genetic Testing for All Women Diagnosed with Breast Cancer in China
Authors: Sun Li , Cui Bin , Wei Xia , Sadique Zia , Yang Li , Manchanda Ranjit , Legood Rosa
Published: April 2022

Unselected multigene testing for all women with breast cancer (BC) identifies more cancer susceptibility gene (CSG) carriers who can benefit from precision prevention compared with family history (FH)/clinical-criteria-based guidelines. Very little CSG testing is undertaken in middle-income countries such as China, and its cost-effectiveness remains unaddressed. We aimed to estimate cost-effectiveness and population impact of multigene testing for all Chinese BC patients. Data from 8085 unselected BC patients recruited to a Peking University Cancer Hospital study were used for microsimulation modeling, comparing three strategies in the Chinese setting: all BC women undergo BRCA1/BRCA2/PALB2 genetic testing, only BC women fulfilling FH/clinical criteria undergo BRCA testing, and no genetic testing. Prophylactic mastectomy and salpingo-oophorectomy would be adopted where appropriate. Societal and payer perspectives with a lifetime horizon along with sensitivity analyses were presented. Incremental cost-effectiveness ratio (ICER): incremental cost per quality-adjusted life-year (QALY) gained is compared to the USD 10,260/QALY (one-times GDP per capita) willingness-to-pay threshold. BC incidence, ovarian cancer (OC) incidence, and related deaths were also estimated. FH/clinical-criteria-based BRCA testing was ruled out on the principle of extensive dominance. Compared with no genetic testing, multigene testing for all BC patients had an ICER = USD 4506/QALY (societal perspective) and USD 7266/QALY (payer perspective), well below our threshold. Probabilistic sensitivity analysis showed unselected multigene testing remained cost-effective for 94.2%/86.6% of simulations from the societal and payer perspectives. One year’s unselected multigene testing could prevent 7868 BC/OC cases and 5164 BC/OC deaths in China. Therefore, unselected multigene testing is extremely cost-effective and should be offered to all Chinese women with BC.
How AI Can Help in the Diagnostic Dilemma of Pulmonary Nodules
Authors: Fahmy Dalia , Kandil Heba , Khelifi Adel , Yaghi Maha , Ghazal Mohammed , Sharafeldeen Ahmed , Mahmoud Ali , El-Baz Ayman
Published: April 2022

Pulmonary nodules are the precursors of bronchogenic carcinoma, its early detection facilitates early treatment which save a lot of lives. Unfortunately, pulmonary nodule detection and classification are liable to subjective variations with high rate of missing small cancerous lesions which opens the way for implementation of artificial intelligence (AI) and computer aided diagnosis (CAD) systems. The field of deep learning and neural networks is expanding every day with new models designed to overcome diagnostic problems and provide more applicable and simply used models. We aim in this review to briefly discuss the current applications of AI in lung segmentation, pulmonary nodule detection and classification.
Associations of Computed Tomography Image-Assessed Adiposity and Skeletal Muscles with Triple-Negative Breast Cancer
Authors: Aduse-Poku Livingstone , Bian Jiang , Gopireddy Dheeraj R. , Hernandez Mauricio , Lall Chandana , Falzarano Sara M. , Masood Shahla , Jo Ara , Cheng Ting-Yuan David
Published: April 2022

Obesity measured by anthropometrics is associated with increased risk of triple-negative breast cancer (TNBC). It is unclear to what extent specific adipose tissue components, aside from muscle, are associated with TNBC. This retrospective study included 350 breast cancer patients who received treatment between October 2011 and April 2020 with archived abdominal or pelvic computed tomography (CT) images. We measured the areas of adipose tissue and five-density levels of skeletal muscle on patients’ third lumbar vertebra (L3) image. Logistic regression was performed to examine the associations of specific adiposity and skeletal muscles components and a four-category body composition phenotype with the TNBC subtype. Results showed that higher vs. lower areas (3rd vs. 1st tertiles) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were associated with increased odds of TNBC vs. non-TNBC after adjusting for age, race, stage, tumor grade, tumor size, and skeletal muscle areas (adjusted odds ratio [AOR], 11.25 [95% CI = 3.46–36.52]) and (AOR, 10.34 [95% CI = 2.90–36.90]) respectively. Higher areas of low density muscle was also associated with increased odds of TNBC (AOR, 3.15 [95% CI = 1.05–10.98]). Compared to normal body composition (low adipose tissue/high muscle), high adiposity/high muscle was associated with higher odds of TNBC (AOR, 5.54 [95% CI = 2.12–14.7]). These associations were mainly in premenopausal women and among patients with the CT performed after breast cancer surgery. Specific adipose tissue and low-density muscle can be associated with the TNBC subtype in breast cancer patients. The direction of association warrants confirmation by prospective studies.
Biological Role of Tumor/Stromal CXCR4-CXCL12-CXCR7 in MITO16A/MaNGO-OV2 Advanced Ovarian Cancer Patients
Authors: D’Alterio Crescenzo , Spina Anna , Arenare Laura , Chiodini Paolo , Napolitano Maria , Galdiero Francesca , Portella Luigi , Simeon Vittorio , Signoriello Simona , Raspagliesi Francesco , Lorusso Domenica , Pisano Carmela , Colombo Nicoletta , Zannoni Gian Franco , Losito Nunzia Simona , De Cecio Rossella , Scognamiglio Giosuè , Califano Daniela , Russo Daniela , Tuninetti Valentina , Piccirillo Maria Carmela , Gargiulo Piera , Perrone Francesco , Pignata Sandro , Scala Stefania
Published: April 2022

This study investigated the prognostic role of the CXCR4-CXCL12-CXCR7 axis in advanced epithelial ovarian cancer (EOC) patients receiving first-line treatment within the MITO16A/MaNGO-OV2 phase-IV trial. CXCR4-CXCL12-CXCR7 expression was evaluated in the epithelial and stromal component of 308 EOC IHC-stained tumor samples. The statistical analysis focused on biomarkers’ expression, their association with other variables and prognostic value. Zero-inflated tests, shrinkage, bootstrap procedures, and multivariable models were applied. The majority of EOC (75.0%) expressed CXCR4 and CXCR7, 56.5% expressed the entire CXCR4-CXCL12-CXCR7 axis, while only 4.6% were negative for CXCL12 and its cognate receptors, in regard to the epithelial component. Stromal CXCL12 and CXCR7, expressed in 11.2% and 65.5%, respectively, were associated with the FIGO stage. High CXCL12 in epithelial cancer cells was associated with shorter progression-free and overall survival. However, after adjusting for overfitting due to best cut-off multiplicity testing, the significance was lost. This is a wide-ranging, prospective study in which CXCR4-CXCL12-CXCR7 were systematically evaluated in epithelial and stromal components, in selected stage III-IV EOC. Although CXCL12 was not prognostic, epithelial expression identified high-risk FIGO stage III patients for PFS. These data suggest that it might be worth studying the CXCL12 axis as a therapeutic target to improve treatment efficacy in EOC patients.
Enhancer RNA Transcription Is Essential for a Novel CSF1 Enhancer in Triple-Negative Breast Cancer
Authors: Lewis Michael W. , Wisniewska Kamila , King Caitlin M. , Li Shen , Coffey Alisha , Kelly Michael R. , Regner Matthew J. , Franco Hector L.
Published: April 2022

Enhancers are critical regulatory elements in the genome that help orchestrate spatiotemporal patterns of gene expression during development and normal physiology. In cancer, enhancers are often rewired by various genetic and epigenetic mechanisms for the activation of oncogenes that lead to initiation and progression. A key feature of active enhancers is the production of non-coding RNA molecules called enhancer RNAs, whose functions remain unknown but can be used to specify active enhancers de novo. Using a combination of eRNA transcription and chromatin modifications, we have identified a novel enhancer located 30 kb upstream of Colony Stimulating Factor 1 (CSF1). Notably, CSF1 is implicated in the progression of breast cancer, is overexpressed in triple-negative breast cancer (TNBC) cell lines, and its enhancer is primarily active in TNBC patient tumors. Genomic deletion of the enhancer (via CRISPR/Cas9) enabled us to validate this regulatory element as a bona fide enhancer of CSF1 and subsequent cell-based assays revealed profound effects on cancer cell proliferation, colony formation, and migration. Epigenetic silencing of the enhancer via CRISPR-interference assays (dCas9-KRAB) coupled to RNA-sequencing, enabled unbiased identification of additional target genes, such as RSAD2, that are predictive of clinical outcome. Additionally, we repurposed the RNA-guided RNA-targeting CRISPR-Cas13 machinery to specifically degrade the eRNAs transcripts produced at this enhancer to determine the consequences on CSF1 mRNA expression, suggesting a post-transcriptional role for these non-coding transcripts. Finally, we test our eRNA-dependent model of CSF1 enhancer function and demonstrate that our results are extensible to other forms of cancer. Collectively, this work describes a novel enhancer that is active in the TNBC subtype, which is associated with cellular growth, and requires eRNA transcripts for proper enhancer function. These results demonstrate the significant impact of enhancers in cancer biology and highlight their potential as tractable targets for therapeutic intervention.
CFTR Modulator Therapies: Potential Impact on Airway Infections in Cystic Fibrosis
Authors: Saluzzo Francesca , Riberi Luca , Messore Barbara , Loré Nicola Ivan , Esposito Irene , Bignamini Elisabetta , De Rose Virginia
Published: April 2022

Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding for the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein, expressed on the apical surface of epithelial cells. CFTR absence/dysfunction results in ion imbalance and airway surface dehydration that severely compromise the CF airway microenvironment, increasing infection susceptibility. Recently, novel therapies aimed at correcting the basic CFTR defect have become available, leading to substantial clinical improvement of CF patients. The restoration or increase of CFTR function affects the airway microenvironment, improving local defence mechanisms. CFTR modulator drugs might therefore affect the development of chronic airway infections and/or improve the status of existing infections in CF. Thus far, however, the full extent of these effects of CFTR-modulators, especially in the long-term remains still unknown. This review aims to provide an overview of current evidence on the potential impact of CFTR modulators on airway infections in CF. Their role in affecting CF microbiology, the susceptibility to infections as well as the potential efficacy of their use in preventing/decreasing the development of chronic lung infections and the recurrent acute exacerbations in CF will be critically analysed.
Urine-Derived Kidney Progenitor Cells in Cystinosis
Authors: Veys Koenraad , Berlingerio Sante Princiero , David Dries , Bondue Tjessa , Held Katharina , Reda Ahmed , Broek Martijn van den , Theunis Koen , Janssen Mirian , Cornelissen Elisabeth , Vriens Joris , Diomedi-Camassei Francesca , Gijsbers Rik , Heuvel Lambertus van den , Arcolino Fanny O. , Levtchenko Elena
Published: April 2022

Nephropathic cystinosis is an inherited lysosomal storage disorder caused by pathogenic variants in the cystinosin (CTNS) gene and is characterized by the excessive shedding of proximal tubular epithelial cells (PTECs) and podocytes into urine, development of the renal Fanconi syndrome and end-stage kidney disease (ESKD). We hypothesized that in compensation for epithelial cell losses, cystinosis kidneys undertake a regenerative effort, and searched for the presence of kidney progenitor cells (KPCs) in the urine of cystinosis patients. Urine was cultured in a specific progenitor medium to isolate undifferentiated cells. Of these, clones were characterized by qPCR, subjected to a differentiation protocol to PTECs and podocytes and assessed by qPCR, Western blot, immunostainings and functional assays. Cystinosis patients voided high numbers of undifferentiated cells in urine, of which various clonal cell lines showed a high capacity for self-renewal and expressed kidney progenitor markers, which therefore were assigned as cystinosis urine-derived KPCs (Cys-uKPCs). Cys-uKPC clones showed the capacity to differentiate between functional PTECs and/or podocytes. Gene addition with wild-type CTNS using lentiviral vector technology resulted in significant reductions in cystine levels. We conclude that KPCs present in the urine of cystinosis patients can be isolated, differentiated and complemented with CTNS in vitro, serving as a novel tool for disease modeling.
Alteration of Mitochondrial Integrity as Upstream Event in the Pathophysiology of SOD1-ALS
Authors: Günther René , Pal Arun , Williams Chloe , Zimyanin Vitaly L. , Liehr Maria , von Neubeck Cläre , Krause Mechthild , Parab Mrudula G. , Petri Susanne , Kalmbach Norman , Marklund Stefan L. , Sterneckert Jared , Munch Andersen Peter , Wegner Florian , Gilthorpe Jonathan D. , Hermann Andreas
Published: April 2022

Little is known about the early pathogenic events by which mutant superoxide dismutase 1 (SOD1) causes amyotrophic lateral sclerosis (ALS). This lack of mechanistic understanding is a major barrier to the development and evaluation of efficient therapies. Although protein aggregation is known to be involved, it is not understood how mutant SOD1 causes degeneration of motoneurons (MNs). Previous research has relied heavily on the overexpression of mutant SOD1, but the clinical relevance of SOD1 overexpression models remains questionable. We used a human induced pluripotent stem cell (iPSC) model of spinal MNs and three different endogenous ALS-associated SOD1 mutations (D90Ahom, R115Ghet or A4Vhet) to investigate early cellular disturbances in MNs. Although enhanced misfolding and aggregation of SOD1 was induced by proteasome inhibition, it was not affected by activation of the stress granule pathway. Interestingly, we identified loss of mitochondrial, but not lysosomal, integrity as the earliest common pathological phenotype, which preceded elevated levels of insoluble, aggregated SOD1. A super-elongated mitochondrial morphology with impaired inner mitochondrial membrane potential was a unifying feature in mutant SOD1 iPSC-derived MNs. Impaired mitochondrial integrity was most prominent in mutant D90Ahom MNs, whereas both soluble disordered and detergent-resistant misfolded SOD1 was more prominent in R115Ghet and A4Vhet mutant lines. Taking advantage of patient-specific models of SOD1-ALS in vitro, our data suggest that mitochondrial dysfunction is one of the first crucial steps in the pathogenic cascade that leads to SOD1-ALS and also highlights the need for individualized medical approaches for SOD1-ALS.
The Cell Biology of Heterochromatin
Authors: Warecki Brandt , Sullivan William
Published: April 2022

A conserved feature of virtually all higher eukaryotes is that the centromeres are embedded in heterochromatin. Here we provide evidence that this tight association between pericentric heterochromatin and the centromere is essential for proper metaphase exit and progression into telophase. Analysis of chromosome rearrangements that separate pericentric heterochromatin and centromeres indicates that they must remain associated in order to balance Cohesin/DNA catenation-based binding forces and centromere-based pulling forces during the metaphase–anaphase transition. In addition, a centromere embedded in heterochromatin facilitates nuclear envelope assembly around the entire complement of segregating chromosomes. Because the nuclear envelope initially forms on pericentric heterochromatin, nuclear envelope formation proceeds from the pole, thus providing time for incorporation of lagging and trailing chromosome arms into the newly formed nucleus. Additional analysis of noncanonical mitoses provides further insights into the functional significance of the tight association between heterochromatin and centromeres.
Polymerisation Kinetics on FT-IR and Colorimetric Changes under UV Irradiation for a Commercial Polycyanoacrylate Adhesive, Addressed to Glass Restoration
Authors: Vouvoudi Evangelia C. , Morfis Panagiotis D. , Verros George D. , Achilias Dimitris S.
Published: April 2022

This study evaluates a commercial polycyanoacrylate adhesive of medium viscosity regarding its suitability for the restoration of glass objects of cultural heritage in a museum environment (exhibition/storage). Loctite® Super Attak was investigated in terms of (a) its polymerisation rate and degree of conversion, using Infrared Spectroscopy FT-IR by monitoring the change of the C=C peak vs. C=O peak and (b) the alteration of the colour parameters of its films after its submission to UVC irradiation for several time intervals. It was confirmed that within 6 h, a thin-layered adhesive film acquires 80–85% of its polymerization in ambient conditions, while the reaction continues for up to 12–18 h in the conditions examined. The progress of the reaction is slower when the adhesive is in a protected environment. On the other hand, the effect of UVC rays on the glue is destructive and oxidative, provoking a yellow shade/colour from the first hours of exposure. The intensity of the yellowness becomes higher after 6 h of exposure, showing shifts in the absorption peaks of C–O/C=O groups of the initial IR spectrum and the augmentation of –OH absorptions. It was concluded that the adhesive is suitable for glass restoration, especially for instant, rapid, applications, under mild conditions of maintenance and exposure.
Immunogenicity and Reactogenicity of CoronaVac: A Cohort Study
Authors: Masyeni Sri , Johar Edison , Budhitresna Anak Agung Gede , Mahardika Nyoman , Dewi Nyoman Ratna Kartika , Widiana I Gde Raka , Yudhaputri Frilasita Aisyah , Myint Khin Saw Aye
Published: April 2022

The ongoing COVID-19 pandemic remained a major public health concern despite a large-scale deployment of vaccines. One of the vaccines is CoronaVac, an inactivated vaccine. The efficacy of the vaccine was estimated at 50.7–83.5% in clinical trials. However, the real-world efficacy often differed. This study described CoronaVac post-vaccination reactogenicity and immunogenicity. Serum was collected on days 0, 28, 56 and 84 from participants who received CoronaVac in March–May 2021. Anti-SARS-CoV-2 Spike receptor binding domain was measured using an Elecsys® quantitative assay. Participants were interviewed for adverse events (AEs) one week after vaccination. Reported AEs were fatigue, fever, runny nose, headache, muscle pain, pain at injection site, and paresthesia. Females reported more incidents than males. However, the frequency was similar between immunologically naïve and pre-immune participants. In the naïve group, the antibody titer was 61.7 ± 84.2 U/mL (mean ± SD) on day 28 and increased to 99.3 ± 91.9 U/mL on day 56. The titer peaked on day 56 across all age groups, but a reduction of 18.0–26.3% was observed on day 84. A titer-boosting effect was observed in pre-immune participants with a baseline titer of 139.0 ± 101.0 U/mL, which increased to 206.7 ± 77.4 U/mL on day 28, and remained steady until day 84. Hence, CoronaVac elicited an antibody response in naïve and pre-immune participants, with mild AEs.
New, Spherical Solutions of Non-Relativistic, Dissipative Hydrodynamics
Authors: Kasza Gábor , Csernai László P. , Csörgő Tamás
Published: April 2022

We present a new family of exact solutions of dissipative fireball hydrodynamics for arbitrary bulk and shear viscosities. The main property of these solutions is a spherically symmetric, Hubble flow field. The motivation of this paper is mostly academic: we apply non-relativistic kinematics for simplicity and clarity. In this limiting case, the theory is particularly clear: the non-relativistic Navier–Stokes equations describe the dissipation in a well-understood manner. From the asymptotic analysis of our new exact solutions of dissipative fireball hydrodynamics, we can draw a surprising conclusion: this new class of exact solutions of non-relativistic dissipative hydrodynamics is asymptotically perfect.
On Positive Definite Kernels of Integral Operators Corresponding to the Boundary Value Problems for Fractional Differential Equations
Authors: Aleroev Mukhamed , Aleroev Temirkhan
Published: April 2022

In the spectral analysis of operators associated with Sturm–Liouville-type boundary value problems for fractional differential equations, the problem of positive definiteness or the problem of Hermitian nonnegativity of the corresponding kernels plays an important role. The present paper is mainly devoted to this problem. It should be noted that the operators under study are non-self-adjoint, their spectral structure is not well investigated. In this paper we use various methods to prove the Hermitian non-negativity of the studied kernels; in particular, a study of matrices that approximate the Green’s function of the boundary value problem for a differential equation of fractional order is carried out. Using the well-known Livshits theorem, it is shown that the system of eigenfunctions of considered operator is complete in the space L2(0,1). Generally speaking, it should be noted that this very important problem turned out to be very difficult.
Maximum Correntropy with Variable Center Unscented Kalman Filter for Robust Power System State Estimation
Authors: Sun Zhenglong , Liu Chuanlin , Peng Siyuan
Published: April 2022

The robust Kalman filter with correntropy loss has received much attention in recent years for forecasting-aided state estimation in power systems, since it efficiently reduces the negative influence of various abnormal situations, such as non-Gaussian communication, changing environment, and instrument failures, and obviously improves the stability of power systems. However, the existing correntropy-based robust Kalman filters usually use the Gaussian function with a fixed center as the kernel function in correntropy, which may not be a suitable choice in practical applications of power system forecasting-aided state estimation (PSSE). To address this issue, a new and robust unscented Kalman filter, called the maximum correntropy with variable center unscented Kalman filter (MCVUKF), is proposed in this paper for PSSE. Specifically, MCVUKF adopts an extended version of correntropy, whose center can be located at any position, to replace the original correntropy in an unscented Kalman filter to improve the performance in PSSE. Moreover, by using an exponential function of the innovation vector to adjust a covariance matrix, an enhanced MCVUKF (En-MCVUKF) method is also developed for suppressing the influence of bad data to the innovation vector and further improving the accuracy of PSSE. Finally, extensive simulations have been conducted on IEEE 14-bus, 30-bus, and 57-bus test power systems, and the simulation results have shown the superiority of the proposed MCVUKF and En-MCVUKF methods compared with several related state-of-the-art Kalman filter methods.
Recasting the (Synchrosqueezed) Short-Time Fourier Transform as an Instantaneous Spectrum
Authors: Sandoval Steven , De Leon Phillip L.
Published: April 2022

In a previous work, we proposed a time-frequency analysis called instantaneous spectral analysis (ISA), which generalizes the notion of the Fourier spectrum and in which instantaneous frequency is utilized to the fullest extent. In this paper, we recast both the Fourier transform (FT) and filterbank (FB) interpretations of the short-time Fourier transform (STFT) as instantaneous spectra. We show that to recast the FB interpretation of STFT as an instantaneous spectrum with valid structure, frequency reassignment is a fundamental necessity, thus demonstrating that this IS is closely related to the synchrosqueezed STFT. This result provides a new theoretical motivation for the synchrosqueezed STFT. Finally, we illustrate through example the instantaneous spectra corresponding to the FT and FB interpretations of STFT using two closed-form examples.
Towards Secure Big Data Analysis via Fully Homomorphic Encryption Algorithms
Authors: Hamza Rafik , Hassan Alzubair , Ali Awad , Bashir Mohammed Bakri , Alqhtani Samar M. , Tawfeeg Tawfeeg Mohmmed , Yousif Adil
Published: April 2022

Privacy-preserving techniques allow private information to be used without compromising privacy. Most encryption algorithms, such as the Advanced Encryption Standard (AES) algorithm, cannot perform computational operations on encrypted data without first applying the decryption process. Homomorphic encryption algorithms provide innovative solutions to support computations on encrypted data while preserving the content of private information. However, these algorithms have some limitations, such as computational cost as well as the need for modifications for each case study. In this paper, we present a comprehensive overview of various homomorphic encryption tools for Big Data analysis and their applications. We also discuss a security framework for Big Data analysis while preserving privacy using homomorphic encryption algorithms. We highlight the fundamental features and tradeoffs that should be considered when choosing the right approach for Big Data applications in practice. We then present a comparison of popular current homomorphic encryption tools with respect to these identified characteristics. We examine the implementation results of various homomorphic encryption toolkits and compare their performances. Finally, we highlight some important issues and research opportunities. We aim to anticipate how homomorphic encryption technology will be useful for secure Big Data processing, especially to improve the utility and performance of privacy-preserving machine learning.