bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key challenges for in vitro testing of tobacco products for regulatory applications: Recommendations for dosimetry
Authors: Miller‐Holt Jacqueline , Behrsing Holger , Crooks Ian , Curren Rodger , Demir Kubilay , Gafner Jeremie , Gillman Gene , Hollings Michael , Leverette Robert , Oldham Michael , Simms Liam , Stankowski Leon F. , Thorne David , Wieczorek Roman , Moore Martha M. 
Published: July 2022

AbstractThe Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to develop recommendations for optimal scientific and technical approaches for conducting in vitro assays to assess potential toxicity within and across tobacco and various next‐generation products (NGPs) including heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDSs). This publication was developed by a working group of the workshop members in conjunction with the sixth workshop in that series entitled “Dosimetry for conducting in vitro evaluations” and focuses on aerosol dosimetry for aerosol exposure to combustible cigarettes, HTP, and ENDS aerosolized tobacco products and summarizes the key challenges as well as documenting areas for future research.
Tracking global invasion pathways of the spongy moth (Lepidoptera: Erebidae) to the United States using stable isotopes as endogenous biomarkers
Authors: Freistetter Nadine‐Cyra , Simmons Gregory S. , Wu Yunke , Finger David C. , Hood‐Nowotny Rebecca 
Published: July 2022

AbstractThe spread of invasive insect species causes enormous ecological damage and economic losses worldwide. A reliable method that tracks back an invaded insect's origin would be of great use to entomologists, phytopathologists, and pest managers. The spongy moth (Lymantria dispar, Linnaeus 1758) is a persistent invasive pest in the Northeastern United States and periodically causes major defoliations in temperate forests. We analyzed field‐captured (Europe, Asia, United States) and laboratory‐reared L. dispar specimens for their natal isotopic hydrogen and nitrogen signatures imprinted in their biological tissues (δ2H and δ15N) and compared these values to the long‐term mean δ2H of regional precipitation (Global Network of Isotopes in Precipitation) and δ15N of regional plants at the capture site. We established the percentage of hydrogen–deuterium exchange for L. dispar tissue (Pex = 8.2%) using the comparative equilibration method and two‐source mixing models, which allowed the extraction of the moth's natal δ2H value. We confirmed that the natal δ2H and δ15N values of our specimens are related to the environmental signatures at their geographic origins. With our regression models, we were able to isolate potentially invasive individuals and give estimations of their geographic origin. To enable the application of these methods on eggs, we established an egg‐to‐adult fraction factor for L. dispar (Δegg‐adult = 16.3 ± 4.3‰). Our models suggested that around 25% of the field‐captured spongy moths worldwide were not native in the investigated capture sites. East Asia was the most frequently identified location of probable origin. Furthermore, our data suggested that eggs found on cargo ships in the United States harbors in Alaska, California, and Louisiana most probably originated from Asian L. dispar in East Russia. These findings show that stable isotope biomarkers give a unique insight into invasive insect species pathways, and thus, can be an effective tool to monitor the spread of insect pest epidemics.
MODY probability calculator utility in individuals' selection for genetic testing: Its accuracy and performance
Authors: da Silva Santos Tiago , Fonseca Liliana , Santos Monteiro Sílvia , Borges Duarte Diana , Martins Lopes Ana , Couto de Carvalho André , Oliveira Maria João , Borges Teresa , Laranjeira Francisco , Couce María Luz , Cardoso Maria Helena 
Published: July 2022

AbstractIntroductionMODY probability calculator (MPC) represents an easy‐to‐use tool developed by Exeter University to help clinicians prioritize which individuals should be oriented to genetic testing. We aimed to assess the utility of MPC in a Portuguese cohort with early‐onset monogenic diabetes.MethodsThis single‐centre retrospective study enrolled 132 participants submitted to genetic testing between 2015 and 2020. Automatic sequencing and, in case of initial negative results, generation sequencing were performed. MODY probability was calculated using the probability calculator available online. Positive and negative predictive values (PPV and NPV, respectively), accuracy, sensitivity and specificity of the calculator were determined for this cohort.ResultsSeventy‐three individuals were included according to inclusion criteria: 20 glucokinase (GCK‐MODY); 16 hepatocyte nuclear factor 1A (HNF1A‐MODY); 2 hepatocyte nuclear factor 4A (HNF4A‐MODY) and 35 DM individuals with no monogenic mutations found. The median probability score of MODY was significantly higher in monogenic diabetes‐positive subgroup (75.5% vs. 24.2%, p < .001). The discriminative accuracy of the calculator, as expressed by area under the curve, was 75% (95% CI: 64%–85%). In our cohort, the best cut‐off value for the MODY calculator was found to be 36%, with a PPV of 74.4%, NPV of 73.5% and corresponding sensitivity and specificity of 76.2% and 71.4%, respectively.ConclusionsIn a highly pre‐selected group of probands qualified for genetic testing, the Exeter MODY probability calculator provided a useful tool in individuals' selection for genetic testing, with good discrimination ability under an optimal probability cut‐off of 36%. Further geographical and population adjustments are warranted for general use.
Building energy model validation and estimation using heating and cooling degree days (HDD–CDD) based on accurate base temperature
Authors: Mehregan Mahmood , Naminezhad Alireza , Vakili Sajjad , Delpisheh Mostafa 
Published: July 2022

AbstractA great deal of energy used in buildings is directed toward heating, ventilation, and air‐conditioning (HVAC). The key procedure in reducing heating and cooling loads is the creation of a baseline model that represents a theoretical version of the building. This allows multiple scenarios to balance the lowest retrofit cost with the lowest annual energy cost. This study emphasizes establishing an energy consumption model and energy benchmarks for a commercial building located in Shiraz, Iran. The energy‐related data are gathered for 3 years based on real values from billing receipts. Herein, two distinct approaches are integrated; forward and inverse methods. In the forward method, building energy consumption is predicted based on building performance and specifications, geometry, location, and air conditioning system. In the reverse method, building energy consumption is evaluated using the building load coefficient and building base consumption according to effective factors such as weather data and appliance performance. Also, considering constant fixed temperatures as 18°C, and 21°C for calculating heating and cooling degree days is not correct. Thus, finding a proper and valid base temperature is the main aim of this study by examining this integrated method. The integrated application of these methods allowed determining the thermomechanical state of the building as a whole. To this end, base temperature boundaries are extracted from the energy consumption trend which grounds the need for cooling and heating. Eventually, the baseline for energy consumption of the building based on the proposed method is provided for calculating the development of methodological foundations for the design, construction, operation, and renovation of energy‐efficient buildings. The results show that according to an acceptable thermal building comfort zone of 14–18.6°C, the building achieves a 30 percent reduction in annual cooling and heating energy consumption compared to the base year.
Multivariate analysis of eshnan (Seidlitzia rosmarinus Boiss.) based on morphological characterizations
Authors: Mirheidari Farhad , Khadivi Ali 
Published: July 2022

AbstractSeidlitzia rosmarinus Boiss. has been identified as one of the potential species that could be used for rehabilitating degraded desert rangelands and salt‐affected soils due to its high salinity resistance and soil‐stabilizing ability. Morphological variation of 144 accessions of this species from 14 regions of the Isfahan province, Iran was investigated. The accessions studied were significantly different in terms of the traits recorded. Three forms of plant growth habit were observed, including spreading bush, erect bush, and shrub. The range of leaf dimensions was as follows: terminal leaf length: 1.57–7.22 mm, terminal leaf width: 0.91–3.34 mm, basal leaf length: 11.84–45.27 mm, and basal leaf width: 1.32–4.18 mm. Fruit diameter (with wings) ranged from 0.19 to 12.91 mm, and 100‐fruits dry weight varied between 0.11 and 0.76 g. A dendrogram created using Euclidean distances and the Ward's method revealed two main clusters. The obtained data revealed the morphological diversity within the studied populations. The reason for such a high diversity can be explained by a low probability of gene flow among the studied accessions. This is the first report on the application of morphological characteristics in the evaluation of the phenotypic variation of S. rosmarinus. This study presented a high phenotypic diversity of S. rosmarinus germplasm that could provide useful information for conservation and selection of cross‐parents in breeding.
Venturing into uncharted territory: An extensible implied volatility surface model
Authors: François Pascal , Galarneau‐Vincent Rémi , Gauthier Geneviève , Godin Frédéric 
Published: July 2022

AbstractA new factor‐based representation of implied volatility (IV) surfaces is proposed. The factors adequately capture the moneyness and maturity slopes, the smile attenuation, and the smirk. Furthermore, the IV specification is twice continuously differentiable and well‐behaved asymptotically, allowing for clean interpolation and extrapolation over a wide range of moneyness and maturity. Fitting performance on Standard and Poor's 500 options compares favorably with existing benchmarks. The benefits of a smoothed IV surface are illustrated through the valuation of illiquid index derivatives, the extraction of the risk‐neutral density and risk‐neutral moments, and the calculation of option price sensitivities.
3′RNA and whole‐genome sequencing of archival uterine leiomyomas reveal a tumor subtype with chromosomal rearrangements affecting either HMGA2, HMGA1, or PLAG1
Authors: Jokinen Vilja , Mehine Miika , Reinikka Siiri , Khamaiseh Sara , Ahvenainen Terhi , Äyräväinen Anna , Härkki Päivi , Bützow Ralf , Pasanen Annukka , Vahteristo Pia 
Published: July 2022

AbstractUterine leiomyomas, or fibroids, are very common smooth muscle tumors that arise from the myometrium. They can be divided into distinct molecular subtypes. We have previously shown that 3′RNA‐sequencing is highly effective in classifying archival formalin‐fixed paraffin‐embedded (FFPE) leiomyomas according to the underlying mutation. In this study, we performed 3′RNA‐sequencing with 111 FFPE leiomyomas previously classified as negative for driver alterations in mediator complex subunit 12 (MED12), high mobility group AT‐hook 2 (HMGA2), and fumarate hydratase (FH) by Sanger sequencing and immunohistochemistry. This revealed 43 tumors that displayed expression features typically seen in HMGA2‐positive tumors, including overexpression of PLAG1. We explored 12 such leiomyomas by whole‐genome sequencing to identify their underlying genomic drivers and to evaluate the feasibility of detecting chromosomal driver alterations from FFPE material. Four tumors with significant HMGA2 overexpression at the protein‐level served as controls. We identified chromosomal rearrangements targeting either HMGA2, HMGA1, or PLAG1 in all 16 tumors, demonstrating that it is possible to detect chromosomal driver alterations in archival leiomyoma specimens as old as 18 years. Furthermore, two tumors displayed biallelic loss of DEPDC5 and one tumor harbored a COL4A5–COL4A6 deletion. These observations suggest that instead of only HMGA2‐positive leiomyomas, a distinct leiomyoma subtype is characterized by rearrangements targeting either HMGA2, HMGA1, or PLAG1. The results indicate that the frequency of HMGA2‐positive leiomyomas may be higher than estimated in previous studies where immunohistochemistry has been used. This study also demonstrates the feasibility of detecting chromosomal driver alterations from archival FFPE material.
Outcomes of curative treatment for head and neck squamous cell carcinoma in very elderly adults ≥80 years old
Authors: Wilson Traeden , Fleischer Lindsay , Patel Shivam , Bhatnagar Anil , Ahmad Nadir , Kubicek Gregory 
Published: July 2022

AbstractBackgroundHead and neck cancer treatment can be difficult and advancing age is associated with greater frailty. It is unclear if curative treatment for very elderly patients is beneficial. This study compared outcomes to curative treatment in patients ≥80 aged with HNSCC to patients aged 70–79.MethodsRetrospective study of 114 patients diagnosed with HNSCC. Overall survival (OS), Disease‐Free Survival (DFS), and local‐regional control (LRC) were compared and adjusted for confounders.ResultsPatients aged 70–79 had a higher median OS (35 months [95% CI, 19.58–50.42]) compared with patients aged ≥80 (19 months [11.72–26.28]; p = 0.008) but similar DFS and LRC. KPS < 90 was the stand‐alone independent prognostic factor for OS (HR = 2.14 [1.05–4.38]).ConclusionVery elderly HNSCC patients (aged ≥80) can have favorable outcomes with curative therapy and advanced chronological age alone should not prohibit patients from receiving treatment. Performance status may be a greater predictor of survival outcome than age alone.Level of EvidenceLevel III.
Oral application of vancomycin alters murine lung microbiome and pulmonary immune responses
Authors: Pfeiffer Stefan , Jatzlauk Gregor , Lund Joni V. , Boateng Eistine , Kovacevic Draginja , N. Hylkema Machteld , Bartel Sabine , Schloter Michael , Krauss‐Etschmann Susanne 
Published: July 2022

AbstractEarly life exposures to antibiotics negatively impact respiratory health and are associated with an increased risk of childhood asthma. It is explained that the lung is inclined to develop chronic inflammatory phenotypes due to early antibiotic alteration in the gut microbiome. We investigated whether a gut‐targeted antibiotic has an impact on the lung microbiome and on pulmonary immunity. Fourteen‐day old C57BL/6 mice were administered with vancomycin via oral gavage for 3 days (1 time/day). Control groups were treated with clarithromycin and phosphate‐buffered saline (PBS), respectively. Five days after treatment, the cecum and lung microbiome, and pulmonary immune response were analyzed. Vancomycin treatment decreased the relative abundance of the genera Clostridium XIVa and Alistipes and the family Lachnospiraceae in the cecum. Furthermore, the relative abundance of the family Parabacteroidetes and the genus Lactobacillus were increased, whereas the abundance of the phylum Firmicutes was decreased. In the lung, vancomycin treatment reduced bacteria belonging to Clostridium XIVa and the family Lachnospiraceae as compared to those in the clarithromycin treated group. Lung cells from the vancomycin‐treated mice released higher levels of interleukin (IL)‐4 and IL‐13 compared to those from the PBS group, and increased levels of IL‐6, IFN‐γ, and TNFα compared to lung cells from the clarithromycin and PBS treated mice. Our pilot study suggests that alteration in the gut microbiome could affect bacterial composition and immunity of the lung hence proposes a gut–lung microbiome axis in early life.
PPARgamma agonism inhibits progression of premalignant lesions in a murine lung squamous cell carcinoma model
Authors: Dwyer‐Nield Lori D. , McArthur Debbie G. , Hudish Tyler M. , Hudish Laura I. , Mirita Carol , Sompel Kayla , Smith Alex J. , Alavi Kiana , Ghosh Moumita , Merrick Daniel T. , Tennis Meredith A. , Keith Robert L. 
Published: July 2022

AbstractThe N‐nitroso‐trischloroethylurea (NTCU)‐induced mouse model of squamous lung carcinoma recapitulates human disease from premalignant dysplasia through invasive tumors, making it suitable for preclinical chemoprevention drug testing. Pioglitazone is a peroxisome proliferator‐activated receptor γ (PPARγ) agonist shown to prevent lung tumors in preclinical models. We investigated pioglitazone's effect on lesion development and markers of potential preventive mechanisms in the NTCU model. Female FVB/N mice were exposed to vehicle, NTCU or NTCU + oral pioglitazone for 32 weeks. NTCU induces the appearance of basal cells in murine airways while decreasing/changing their epithelial cell makeup, resulting in development of bronchial dysplasia. H&E and keratin 5 (KRT5) staining were used to detect and grade squamous lesions in formalin fixed lungs. mRNA expression of epithelial to mesenchymal transition (EMT) markers and basal cell markers were measured by qPCR. Dysplasia persistence markers desmoglein 3 and polo like kinase 1 were measured by immunohistochemistry. Basal cell markers KRT14 and p63, club cell specific protein and ciliated cell marker acetylated tubulin were measured by immunofluorescence. Pioglitazone treatment significantly reduced squamous lesions and the presence of airway basal cells, along with increasing normal epithelial cells in the airways of NTCU‐exposed mice. Pioglitazone also significantly influenced EMT gene expression to promote a more epithelial, and less mesenchymal, phenotype. Pioglitazone reduced the presence of squamous dysplasia and maintained normal airway cell composition. This work increases the knowledge of mechanistic pathways in PPARγ agonism for lung cancer interception and provides a basis for further investigation to advance this chemoprevention strategy.
Clear cell carcinoma of the seminal vesicle in a young adult
Authors: Murakami Hidetoshi , Motoshima Takanobu , Kurahashi Ryoma , Murakami Yoji , Sugiyama Yutaka , Yamaguchi Takahiro , Yatsuda Junji , Asato Tsuguharu , Mikami Yoshiki , Kamba Tomomi 
Published: July 2022

IntroductionMost seminal vesicle malignancies are secondary to prostate or bladder cancer. Herein, we report a case of primary clear cell carcinoma of the seminal vesicle.Case presentationA 27‐year‐old man was referred to our department for hematospermia and macroscopic hematuria. A digital rectal examination showed a soft elastic prostatic mass. Cystoscopy showed no bladder abnormalities, and tumor marker tests were unremarkable. Contrast‐enhanced computed tomography and magnetic resonance imaging revealed a cystic tumor containing an enhanced nodule near the prostate and seminal vesicle. The tumor was removed en bloc with the prostate and seminal vesicle through a laparoscopic radical prostatectomy. A histopathologic examination confirmed the diagnosis, with the tumor likely arising from a remnant Müllerian epithelium. A 1‐year follow‐up revealed local tumor recurrence, prompting laparoscopy.ConclusionA standard therapy for primary seminal vesicle carcinoma has not been established. Further studies are necessary to determine the optimal treatment strategy.
Decreased differentiation capacity and altered expression of extracellular matrix components in irradiation‐mediated senescent human breast adipose‐derived stem cells
Authors: Papadopoulou Adamantia , Kalodimou Vasiliki E. , Mavrogonatou Eleni , Karamanou Konstantina , Yiacoumettis Andreas M. , Panagiotou Petros N. , Pratsinis Harris , Kletsas Dimitris 
Published: July 2022

AbstractRadiotherapy is widely used for the treatment of breast cancer. However, we have shown that ionizing radiation can provoke premature senescence in breast stromal cells. In particular, breast stromal fibroblasts can become senescent after irradiation both in vitro and in vivo and they express an inflammatory phenotype and an altered profile of extracellular matrix components, thus facilitating tumor progression. Adipose‐derived stem cells (ASCs) represent another major component of the breast tissue stroma. They are multipotent cells and due to their ability to differentiate in multiple cell lineages they play an important role in tissue maintenance and repair in normal and pathologic conditions. Here, we investigated the characteristics of human breast ASCs that became senescent prematurely after their exposure to ionizing radiation. We found decreased expression levels of the specific mesenchymal cell surface markers CD105, CD73, CD44, and CD90. In parallel, we demonstrated a significantly reduced expression of transcription factors regulating osteogenic (i.e., RUNX2), adipogenic (i.e., PPARγ), and chondrogenic (i.e., SOX9) differentiation; this was followed by an analogous reduction in their differentiation capacity. Furthermore, they overexpress inflammatory markers, that is, IL‐6, IL‐8, and ICAM‐1, and a catabolic phenotype, marked by the reduction of collagen type I and the increase of MMP‐1 and MMP‐13 expression. Finally, we detected changes in proteoglycan expression, for example, the upregulation of syndecan 1 and syndecan 4 and the downregulation of decorin. Notably, all these alterations, when observed in the breast stroma, represent poor prognostic factors for tumor development. In conclusion, we showed that ionizing radiation‐mediated prematurely senescent human breast ASCs have a decreased differentiation potential and express specific changes adding to the formation of a permissive environment for tumor growth.
Neuroprotective effect of quercetin against rotenone‐induced neuroinflammation and alterations in mice behavior
Authors: Jain Juli , Hasan Whidul , Biswas Pronit , Yadav Rajesh S. , Jat Deepali 
Published: July 2022

AbstractVarious studies suggested that neuroinflammation leads to the development of several neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). Rotenone is an organic pesticide and potent inhibitor of complex I of electron transport chain widely used to develop the PD model. Numerous studies reported rotenone toxicity in the dopaminergic system but very few studies are available on rotenone‐induced glial cell activation and subsequent neurodegeneration and alterations in various types of behavior. Therefore, the present study was designed to explore the effect of rotenone on neuroinflammation and its deleterious effect on the behavior of mice, and also how these effects can be protected through quercetin. Quercetin, a natural flavonoid having strong antioxidant and anti‐inflammatory properties, is found in vegetables and fruits. The finding of the study indicated that rotenone 5 mg/kg body weight for 60 days through oral gavage leads to the release of inflammatory markers in blood serum, astrocytes activation in substantia nigra and hippocampus, and subsequently decreased density of dopaminergic fibers in the striatum. Rotenone also altered the memory of the mice as indicated by decreased spontaneous alteration in Y‐maze and T‐maze tests and reduction in exploration time in novel object recognition, increased immobility time in the forced swim test and reduced muscular strength. Co‐treatment of quercetin 30 mg/kg/day through oral gavage for 60 days along with rotenone significantly reversed all these adverse effects, suggesting that quercetin could reduce neuroinflammation, and improve memory, and cognitive function.