bluuebunny/crossref_metadata_2025 huggingface dataset:
Emission of PM2.5-Bound Polycyclic Aromatic Hydrocarbons from Biomass and Coal Combustion in China
Authors: Li Xinghua , Wang Zihao , Guo Tailun
Published: September 2021

Field measured PAH emissions from diverse sources in China are limited or even not available. In this study, the PM2.5-bound PAH emission factors (EFs) for typical biomass and coal combustion in China were determined on-site. The measured total PAH EFs were 24.5 mg/kg for household coal burning, 10.5–13.9 mg/kg for household biofuel burning, 8.1–8.6 mg/kg for biomass open burning, and 0.021–0.31 mg/kg for coal-fired boilers, respectively. These EF values were compared with previous studies. The sources profiles of PAHs for four sources were developed to use in chemical mass balance receptor modelling. BaP equivalent EFs (EFBaPeq) were calculated to evaluate PAH emission toxicity among different combustion sources, and were 6.81, 2.94–4.22, 1.59–3.62, and 0.0006–0.042 mg/kg for those four types of sources, respectively.
Analysis of Cooling and Heating Degree Days over Mexico in Present and Future Climate
Authors: Corrales-Suastegui Arturo , Ruiz-Alvarez Osias , Torres-Alavez José Abraham , Pavia Edgar G.
Published: September 2021

One simple way to estimate the relationship between air temperature and the energy needed for heating and cooling is to use the concept of degree day. Cooling degree days (CDD) and heating degree days (HDD) are indicators of the energy required to reach comfort levels and are related directly to energy demands. Therefore, using a novel approach, we examine the current conditions and future projections in degree days over Mexico using observations (Livneh and CPC), ERA5 reanalysis, and simulations from the Regional Climate Model (RegCM4). The RegCM4 experiments were driven by different General Circulation Models for two Representative Concentration Pathways scenarios. We consider three 20-year periods as “present conditions” (1995–2014), “near-future conditions” (2041–2060), and “far-future conditions” (2080–2099). The results suggest that in the future, under the lowest radiative forcing scenario there will be a smaller increase (decrease) in CDD (HDD) for the far-future, as compared to the near-future. This could represent the model’s response to the peak of radiative forcing at mid-century and its subsequent decline. For the highest radiative forcing scenario, we found a greater increase (decrease) in CDD (HDD) for the far-future, which could be explained by the response of the RegCM4 to the warming increase projected for 2100.
Fragility and Vulnerability Analysis of an RC Building with the Application of Nonlinear Analysis
Authors: Folić Radomir , Čokić Miloš
Published: September 2021

In this paper, the seismic response of a five-story reinforced concrete (RC) frame system building is analysed through fragility analysis. The structure is designed in accordance with structural Eurocodes EN1990, EN1991, EN1992 and EN1998, as a high-ductility (DCH) system. For the analysis of the response of a structural system to earthquake actions, the methods of nonlinear static (NSA) and nonlinear dynamic analyses (NDA) are applied and, based on the obtained results, fragility curves are constructed using statistical methods. A relationship between the intensity measure (IM) and engineering demand parameters (EDPs) is needed in order to estimate a fragility curve. Fragility functions represent a possibility for different states of damage to occur in a certain structural systems at the observed value of the specified IM. Ten accelerograms, used in NDA, are selected and scaled, according to EN1998 provisions, for the chosen elastic response spectrum and referent PGA. Obtained results are used for the statistical analysis and construction of fragility curves. Structural damage state threshold parameters are determined based on the Park and Ang modified damage index methodology and provisions given in FEMA, HAZUS, VISION 2000 and EN codes. Comparative analysis of the structural damage probability for the analysed RC building, calculated using different methodologies to determine damage states, is applied. The fragility analysis results showed the difference between the probabilities of the damage states to occur when different calculation methods are used. This reflects on the assessment of vulnerability curves as well. The obtained results, calculated using different methods, are analysed using comparative analysis.
Large Granular Lymphocytic Leukemia: From Immunopathogenesis to Treatment of Refractory Disease
Authors: Zawit Misam , Bahaj Waled , Gurnari Carmelo , Maciejewski Jaroslaw
Published: September 2021

Large Granular Lymphocyte Leukemia (LGLL) is a rare, chronic lymphoproliferative disorder of effector cytotoxic T-cells, and less frequently, natural killer (NK) cells. The disease is characterized by an indolent and often asymptomatic course. However, in roughly 50% of cases, treatment is required due to severe transfusion-dependent anemia, severe neutropenia, or moderate neutropenia with associated recurrent infections. LGLL represents an interesting disease process at the intersection of a physiological immune response, autoimmune disorder, and malignant (clonal) proliferation, resulting from the aberrant activation of cellular pathways promoting survival, proliferation, and evasion of apoptotic signaling. LGLL treatment primarily consists of immunosuppressive agents (methotrexate, cyclosporine, and cyclophosphamide), with a cumulative response rate of about 60% based on longitudinal expertise and retrospective studies. However, refractory cases can result in clinical scenarios characterized by transfusion-dependent anemia and severe neutropenia, which warrant further exploration of other potential targeted treatment modalities. Here, we summarize the current understanding of the immune-genomic profiles of LGLL, its pathogenesis, and current treatment options, and discuss potential novel therapeutic agents, particularly for refractory disease.
Moderate Altitude Residence Reduces Male Colorectal and Female Breast Cancer Mortality More Than Incidence: Therapeutic Implications?
Authors: Burtscher Johannes , Millet Grégoire P. , Renner-Sattler Kathrin , Klimont Jeannette , Hackl Monika , Burtscher Martin
Published: September 2021

Background: Living at moderate altitude may be associated with health benefits, including reduced mortality from male colorectal and female breast cancer. We aimed to determine altitude-dependent incidence and mortality rates of those cancers and put them in the context of altitude-associated lifestyle differences. Methods: Incidence cases and deaths of male colorectal cancer (n = 17,712 and 7462) and female breast cancer (n = 33,803 and 9147) from altitude categories between 250 to about 2000 m were extracted from official Austrian registries across 10 years (2008–2017). Altitude-associated differences in health determinants were derived from the Austrian Health Interview Survey (2014). Results: The age-standardized incidence and mortality rates of male colorectal cancer decreased by 24.0% and 44.2%, and that of female breast cancer by 6.5% and 26.2%, respectively, from the lowest to the highest altitude level. Higher physical activity levels and lower body mass index for both sexes living at higher altitudes were found. Conclusions: Living at a moderate altitude was associated with a reduced incidence and (more pronounced) mortality from colorectal and breast cancer. Our results suggest a complex interaction between specific climate conditions and lifestyle behaviours. These observations may, in certain cases, support decision making when changing residence.
Anthracyclines Strike Back: Rediscovering Non-Pegylated Liposomal Doxorubicin in Current Therapeutic Scenarios of Breast Cancer
Authors: Schettini Francesco , Giuliano Mario , Lambertini Matteo , Bartsch Rupert , Pinato David James , Onesti Concetta Elisa , Harbeck Nadia , Lüftner Diana , Rottey Sylvie , van Dam Peter A. , Zaman Khalil , Mustacchi Giorgio , Gligorov Joseph , Awada Ahmad , Campone Mario , Wildiers Hans , Gennari Alessandra , Tjan-Heijnen Vivianne C. G. , Cortes Javier , Locci Mariavittoria , Paris Ida , Del Mastro Lucia , De Placido Sabino , Martín Miguel , Jerusalem Guy , Venturini Sergio , Curigliano Giuseppe , Generali Daniele
Published: September 2021

Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non-pegylated liposomal doxorubicin (NPLD) has been developed to optimize the toxicity profile induced by anthracyclines, while maintaining its unquestionable therapeutic index, thanks to its delivering characteristics that increase its diffusion in tumor tissues and reduce it in normal tissues. This feature allows NPLD to be safely administered beyond the standard doxorubicin maximum cumulative dose of 450–480 mg/m2. Following three pivotal first-line phase III trials in HER2-negative metastatic BC (MBC), this drug was finally approved in combination with cyclophosphamide in this specific setting. Given the increasing complexity of the therapeutic scenario of HER2-negative MBC, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms.
Synergistic Drug Combinations Prevent Resistance in ALK+ Anaplastic Large Cell Lymphoma
Authors: Arosio Giulia , Sharma Geeta G. , Villa Matteo , Mauri Mario , Crespiatico Ilaria , Fontana Diletta , Manfroni Chiara , Mastini Cristina , Zappa Marina , Magistroni Vera , Ceccon Monica , Redaelli Sara , Massimino Luca , Garbin Anna , Lovisa Federica , Mussolin Lara , Piazza Rocco , Gambacorti-Passerini Carlo , Mologni Luca
Published: September 2021

Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is a subtype of non-Hodgkin lymphoma characterized by expression of the oncogenic NPM/ALK fusion protein. When resistant or relapsed to front-line chemotherapy, ALK+ ALCL prognosis is very poor. In these patients, the ALK inhibitor crizotinib achieves high response rates, however 30–40% of them develop further resistance to crizotinib monotherapy, indicating that new therapeutic approaches are needed in this population. We here investigated the efficacy of upfront rational drug combinations to prevent the rise of resistant ALCL, in vitro and in vivo. Different combinations of crizotinib with CHOP chemotherapy, decitabine and trametinib, or with second-generation ALK inhibitors, were investigated. We found that in most cases combined treatments completely suppressed the emergence of resistant cells and were more effective than single drugs in the long-term control of lymphoma cells expansion, by inducing deeper inhibition of oncogenic signaling and higher rates of apoptosis. Combinations showed strong synergism in different ALK-dependent cell lines and better tumor growth inhibition in mice. We propose that drug combinations that include an ALK inhibitor should be considered for first-line treatments in ALK+ ALCL.
Particle Radiotherapy for Skull Base Chondrosarcoma: A Clinical Series from Italian National Center for Oncological Hadrontherapy
Authors: Riva Giulia , Cavallo Iacopo , Gandini Sara , Ingargiola Rossana , Pecorilla Mattia , Imparato Sara , Rossi Eleonora , Mirandola Alfredo , Ciocca Mario , Orlandi Ester , Iannalfi Alberto
Published: September 2021

Background: The standard treatment for skull base chondrosarcoma (SB-CHS) consists of surgery and high-dose radiation therapy. Our aim was to evaluate outcome in terms of local control (LC) and toxicity of proton therapy (PT) and carbon ion (CIRT) after surgery. Materials and methods: From September 2011 to July 2020, 48 patients underwent particle therapy (67% PT, 33% CIRT) for SB-CHS. PT and CIRT total dose was 70 GyRBE (relative biological effectiveness) in 35 fractions and 70.4 GyRBE in 16 fractions, respectively. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE v5). Results: After a median follow-up time of 38 months, one local failure (2%) was documented and the patient died for progressive disease. Overall, 3-year LC was 98%. One (2%) and 4 (8%) patients experienced G3 acute and late toxicity, respectively. White-matter brain changes were documented in 22 (46%) patients, but only 7 needed steroids (G2). No patients had G3 brain toxicity. No G4–5 complications were reported. We did not find any correlation between high-grade toxicity or white-matter changes and characteristics of patients, disease and surgery. Conclusions: PT and CIRT appeared to be effective and safe treatments for patients with SB-CHS, resulting in high LC rates and an acceptable toxicity profile.
Androgen Receptor-Mediated Nuclear Transport of NRDP1 in Prostate Cancer Cells Is Associated with Worse Patient Outcomes
Authors: Steele Thomas , Sam Anhao , Evans Shawna , Browning Elizabeth , Krig Sheryl , Macias Katelyn , Konda Adarsh , Siddiqui Salma , Durbin-Johnson Blythe , Ghosh Paramita , Vinall Ruth
Published: September 2021

To our knowledge, our group is the first to demonstrate that NRDP1 is located in the nucleus as well as the cytoplasm of CaP cells. Subcellular fractionation, immunohistochemistry, and immunofluorescence analysis combined with confocal microscopy were used to validate this finding. Subcellular fractionation followed by western blot analysis revealed a strong association between AR and NRDP1 localization when AR expression and/or cellular localization was manipulated via treatment with R1881, AR-specific siRNA, or enzalutamide. Transfection of LNCaP with various NRDP1 and AR constructs followed by immunoprecipitation confirmed binding of NRDP1 to AR is possible and determined that binding requires the hinge region of AR. Co-transfection with NRDP1 constructs and HA-ubiquitin followed by subcellular fractionation confirmed that nuclear NRDP1 retains its ubiquitin ligase activity. We also show that increased nuclear NRDP1 is associated with PSA recurrence in CaP patients (n = 162, odds ratio; 1.238, p = 0.007) and that higher levels of nuclear NRDP1 are found in castration resistant cell lines (CWR22Rv1 and PC3) compared to androgen sensitive cell lines (LNCaP and MDA-PCa-3B). The combined data indicate that NRDP1 plays a role in mediating CaP progression and supports further investigation of both the mechanism by which nuclear transport occurs and the identification of specific nuclear targets.
Current Management of Bone Metastases from Differentiated Thyroid Cancer
Authors: Kato Satoshi , Demura Satoru , Shinmura Kazuya , Yokogawa Noriaki , Shimizu Takaki , Tsuchiya Hiroyuki
Published: September 2021

After the lung, the skeleton is the second most common site of distant metastases in differentiated thyroid carcinoma (DTC). Patients with osteolytic bone metastases (BMs) from thyroid carcinoma often have significantly reduced performance status and quality of life. Recent advancements in cancer therapy have improved overall survival in multiple cancer subtypes, including thyroid cancer. Therefore, long-term local control of thyroid BMs is desired, especially in patients with a single metastasis or oligometastases. Here, we reviewed the current management options for DTC-BMs and especially focused on local treatments for long-term local tumor control from an orthopedic tumor surgeon’s point of view. Metastasectomy and stereotactic radiosurgery can be performed either alone or in combination with radioiodine therapy and kinase inhibitors to cure skeletal lesions in selected patients. Percutaneous procedures have been developed in recent years, and they can also have a curative role in small BMs. Recent advancements in local therapies have the potential to provide not only long-term local tumor control but also a better prognosis.
Prevalence of Germline Pathogenic Variants in Cancer Predisposing Genes in Czech and Belgian Pancreatic Cancer Patients
Authors: Wieme Greet , Kral Jan , Rosseel Toon , Zemankova Petra , Parton Bram , Vocka Michal , Van Heetvelde Mattias , Kleiblova Petra , Blaumeiser Bettina , Soukupova Jana , van den Ende Jenneke , Nehasil Petr , Tejpar Sabine , Borecka Marianna , Gómez García Encarna B. , Blok Marinus J. , Safarikova Marketa , Kalousova Marta , Geboes Karen , De Putter Robin , Poppe Bruce , De Leeneer Kim , Kleibl Zdenek , Janatova Marketa , Claes Kathleen B. M.
Published: September 2021

(1) Background: The proportion and spectrum of germline pathogenic variants (PV) associated with an increased risk for pancreatic ductal adenocarcinoma (PDAC) varies among populations. (2) Methods: We analyzed 72 Belgian and 226 Czech PDAC patients by multigene panel testing. The prevalence of pathogenic variants (PV) in relation to personal/family cancer history were evaluated. PDAC risks were calculated using both gnomAD-NFE and population-matched controls. (3) Results: In 35/298 (11.7%) patients a PV in an established PDAC-predisposition gene was found. BRCA1/2 PV conferred a high risk in both populations, ATM and Lynch genes only in the Belgian subgroup. PV in other known PDAC-predisposition genes were rarer. Interestingly, a high frequency of CHEK2 PV was observed in both patient populations. PV in PDAC-predisposition genes were more frequent in patients with (i) multiple primary cancers (12/38; 32%), (ii) relatives with PDAC (15/56; 27%), (iii) relatives with breast/ovarian/colorectal cancer or melanoma (15/86; 17%) but more rare in sporadic PDAC (5/149; 3.4%). PV in homologous recombination genes were associated with improved overall survival (HR = 0.51; 95% CI 0.34–0.77). (4) Conclusions: Our analysis emphasizes the value of multigene panel testing in PDAC patients, especially in individuals with a positive family cancer history, and underlines the importance of population-matched controls for risk assessment.
Primary Melanoma Characteristics of Metastatic Disease: A Nationwide Cancer Registry Study
Authors: Zhou Catherine , Louwman Marieke , Wakkee Marlies , van der Veldt Astrid , Grünhagen Dirk , Verhoef Cornelis , Mooyaart Antien , Nijsten Tamar , Hollestein Loes
Published: September 2021

The characteristics and disease patterns of primary stage I and II cutaneous melanomas that progress to stage III or IV disease were investigated based on data from the Netherlands Cancer Registry (NCR). Data on stage III or IV melanomas at first diagnosis or during follow-up between 2017 and 2019 were retrieved. Patient and primary tumour characteristics were investigated in relation to time to disease progression and the number of organ sites with metastatic disease using regression models. In total, 2763 patients were included, of whom 1613 were diagnosed with stage IV disease. Among the patients with stage IV disease, 60% (n = 963) were initially diagnosed with stage I or II disease. The proportion of patients who received a sentinel lymph node biopsy increased after the introduction of adjuvant therapy in 2019 from 61% to 87%. Among all patients with stage III disease who were eligible for adjuvant systemic therapy (n = 453) after 2019, 37% were not treated with this therapy. Among patients with stage IV disease, lung metastases were most often detected as the first metastatic site and females presented with more metastatic sites than males. Most patient and primary tumour characteristics were not associated with the distant metastatic organ site, except melanoma localisation in the lower extremities and the head or neck. Our observation that most stage IV patients were initially diagnosed with early-stage disease highlights the need for more accurate risk prediction models.
Per-Feature Accuracy of Liver Imaging Reporting and Data System Locoregional Treatment Response Algorithm: A Systematic Review and Meta-Analysis
Authors: Huh Yeon Jong , Kim Dong Hwan , Kim Bohyun , Choi Joon-Il , Rha Sung Eun
Published: September 2021

We aimed to investigate the accuracy of each imaging feature of LI-RADS treatment response (LR-TR) viable category for diagnosing tumor viability of locoregional therapy (LRT)-treated HCC. Studies evaluating the per feature accuracy of the LR-TR viable category on dynamic contrast-enhanced CT or MRI were identified in databases. A bivariate random-effects model was used to calculate the pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of LR-TR viable features. Ten studies assessing the accuracies of LR-TR viable features (1153 treated observations in 971 patients) were included. The pooled sensitivities and specificities for diagnosing viable HCC were 81% (95% confidence interval [CI], 63–92%) and 95% (95% CI, 88–98%) for nodular, mass-like, or irregular thick tissue (NMLIT) with arterial phase hyperenhancement (APHE), 55% (95% CI, 34–75%) and 96% (95% CI, 94–98%) for NMLIT with washout appearance, and 21% (95% CI, 6–53%) and 98% (95% CI, 92–100%) for NMLIT with enhancement similar to pretreatment, respectively. Of these features, APHE showed the highest pooled DOR (81 [95% CI, 25–261]), followed by washout appearance (32 [95% CI, 13–82]) and enhancement similar to pretreatment (14 [95% CI, 5–39]). In conclusion, APHE provided the highest sensitivity and DOR for diagnosing viable HCC following LRT, while enhancement similar to pretreatment showed suboptimal performance.
Expression Pattern of T-Type Ca2+ Channels in Cerebellar Purkinje Cells after VEGF Treatment
Authors: Tjaden Jonas , Eickhoff Annika , Stahlke Sarah , Gehmeyr Julian , Vorgerd Matthias , Theis Verena , Matschke Veronika , Theiss Carsten
Published: September 2021

T-type Ca2+ channels, generating low threshold calcium influx in neurons, play a crucial role in the function of neuronal networks and their plasticity. To further investigate their role in the complex field of research in plasticity of neurons on a molecular level, this study aimed to analyse the impact of the vascular endothelial growth factor (VEGF) on these channels. VEGF, known as a player in vasculogenesis, also shows potent influence in the central nervous system, where it elicits neuronal growth. To investigate the influence of VEGF on the three T-type Ca2+ channel isoforms, Cav3.1 (encoded by Cacna1g), Cav3.2 (encoded by Cacna1h), and Cav3.3 (encoded by Cacna1i), lasermicrodissection of in vivo-grown Purkinje cells (PCs) was performed, gene expression was analysed via qPCR and compared to in vitro-grown PCs. We investigated the VEGF receptor composition of in vivo- and in vitro-grown PCs and underlined the importance of VEGF receptor 2 for PCs. Furthermore, we performed immunostaining of T-type Ca2+ channels with in vivo- and in vitro-grown PCs and showed the distribution of T-type Ca2+ channel expression during PC development. Overall, our findings provide the first evidence that the mRNA expression of Cav3.1, Cav3.2, and Cav3.3 increases due to VEGF stimulation, which indicates an impact of VEGF on neuronal plasticity.
Ion Channels in Epithelial Dynamics and Morphogenesis
Authors: Roy Choudhury Ankit , Großhans Jörg , Kong Deqing
Published: September 2021

Mechanosensitive ion channels mediate the neuronal sensation of mechanical signals such as sound, touch, and pain. Recent studies point to a function of these channel proteins in cell types and tissues in addition to the nervous system, such as epithelia, where they have been little studied, and their role has remained elusive. Dynamic epithelia are intrinsically exposed to mechanical forces. A response to pull and push is assumed to constitute an essential part of morphogenetic movements of epithelial tissues, for example. Mechano-gated channels may participate in sensing and responding to such forces. In this review, focusing on Drosophila, we highlight recent results that will guide further investigations concerned with the mechanistic role of these ion channels in epithelial cells.
Hepatitis E Virus Infection—Immune Responses to an Underestimated Global Threat
Authors: Kupke Paul , Werner Jens M.
Published: September 2021

Infection with the hepatitis E virus (HEV) is one of the main ubiquitous causes for developing an acute hepatitis. Moreover, chronification plays a predominant role in immunocompromised patients such as transplant recipients with more frequent severe courses. Unfortunately, besides reduction of immunosuppression and off-label use of ribavirin or pegylated interferon alfa, there is currently no specific anti-viral treatment to prevent disease progression. So far, research on involved immune mechanisms induced by HEV is limited. It is very difficult to collect clinical samples especially from the early phase of infection since this is often asymptomatic. Nevertheless, it is certain that the outcome of HEV-infected patients correlates with the strength of the proceeding immune response. Several lymphoid cells have been identified in contributing either to disease progression or achieving sustained virologic response. In particular, a sufficient immune control by both CD4+ and CD8+ T cells is necessary to prevent chronic viral replication. Especially the mechanisms underlying fulminant courses are poorly understood. However, liver biopsies indicate the involvement of cytotoxic T cells in liver damage. In this review, we aimed to highlight different parts of the lymphoid immune response against HEV and point out questions that remain unanswered regarding this underestimated global threat.
Preimplantation Genetic Testing for Aneuploidy Improves Live Birth Rates with In Vitro Produced Bovine Embryos: A Blind Retrospective Study
Authors: Silvestri Giuseppe , Canedo-Ribeiro Carla , Serrano-Albal María , Labrecque Remi , Blondin Patrick , Larmer Steven G. , Marras Gabriele , Tutt Desmond A.R. , Handyside Alan H. , Farré Marta , Sinclair Kevin D. , Griffin Darren K.
Published: September 2021

Approximately one million in vitro produced (IVP) cattle embryos are transferred worldwide each year as a way to improve the rates of genetic gain. The most advanced programmes also apply genomic selection at the embryonic stage by SNP genotyping and the calculation of genomic estimated breeding values (GEBVs). However, a high proportion of cattle embryos fail to establish a pregnancy. Here, we demonstrate that further interrogation of the SNP data collected for GEBVs can effectively remove aneuploid embryos from the pool, improving live births per embryo transfer (ET). Using three preimplantation genetic testing for aneuploidy (PGT-A) approaches, we assessed 1713 cattle blastocysts in a blind, retrospective analysis. Our findings indicate aneuploid embryos have a 5.8% chance of establishing a pregnancy and a 5.0% chance of given rise to a live birth. This compares to 59.6% and 46.7% for euploid embryos (p < 0.0001). PGT-A improved overall pregnancy and live birth rates by 7.5% and 5.8%, respectively (p < 0.0001). More detailed analyses revealed donor, chromosome, stage, grade, and sex-specific rates of error. Notably, we discovered a significantly higher incidence of aneuploidy in XY embryos and, as in humans, detected a preponderance of maternal meiosis I errors. Our data strongly support the use of PGT-A in cattle IVP programmes.
Novel, Fully Characterised Bovine Taste Bud Cells of Fungiform Papillae
Authors: Ftuwi Habtom , Parri Rheinallt , Mohammed Afzal R.
Published: September 2021

Current understanding of functional characteristics and biochemical pathways in taste bud cells have been hindered due the lack of long-term cultured cells. To address this, we developed a holistic approach to fully characterise long term cultured bovine taste bud cells (BTBCs). Initially, cultured BTBCs were characterised using RT-PCR gene expression profiling, immunocytochemistry, flowcytometry and calcium imaging, that confirmed the cells were mature TBCs that express taste receptor genes, taste specific protein markers and capable of responding to taste stimuli, i.e., denatonium (2 mM) and quinine (462.30 μM). Gene expression analysis of forty-two genes implicated in taste transduction pathway (map04742) using custom-made RT-qPCR array revealed high and low expressed genes in BTBCs. Preliminary datamining and bioinformatics demonstrated that the bovine α-gustducin, gustatory G-protein, have higher sequence similarity to the human orthologue compared to rodents. Therefore, results from this work will replace animal experimentation and provide surrogate cell-based throughput system to study human taste transduction.
Omega-3 Fatty Acids DHA and EPA Reduce Bortezomib Resistance in Multiple Myeloma Cells by Promoting Glutathione Degradation
Authors: Chen Jing , Zaal Esther A. , Berkers Celia R. , Ruijtenbeek Rob , Garssen Johan , Redegeld Frank A.
Published: September 2021

Multiple myeloma (MM) is a hematological malignancy that exhibits aberrantly high levels of proteasome activity. While treatment with the proteasome inhibitor bortezomib substantially increases overall survival of MM patients, acquired drug resistance remains the main challenge for MM treatment. Using a combination treatment of docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) and bortezomib, it was demonstrated previously that pretreatment with DHA/EPA significantly increased bortezomib chemosensitivity in MM cells. In the current study, both transcriptome and metabolome analysis were performed to comprehensively evaluate the underlying mechanism. It was demonstrated that pretreating MM cells with DHA/EPA before bortezomib potently decreased the cellular glutathione (GSH) level and altered the expression of the related metabolites and key enzymes in GSH metabolism, whereas simultaneous treatment only showed minor effects on these factors, thereby suggesting the critical role of GSH degradation in overcoming bortezomib resistance in MM cells. Moreover, RNA-seq results revealed that the nuclear factor erythroid 2-related factor 2 (NRF2)-activating transcription factor 3/4 (ATF3/4)-ChaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1) signaling pathway may be implicated as the central player in the GSH degradation. Pathways of necroptosis, ferroptosis, p53, NRF2, ATF4, WNT, MAPK, NF-κB, EGFR, and ERK may be connected to the tumor suppressive effect caused by pretreatment of DHA/EPA prior to bortezomib. Collectively, this work implicates GSH degradation as a potential therapeutic target in MM and provides novel mechanistic insights into its significant role in combating bortezomib resistance.
Adipose Tissue Immunometabolism and Apoptotic Cell Clearance
Authors: Röszer Tamás
Published: September 2021

The safe removal of apoptotic debris by macrophages—often referred to as efferocytosis—is crucial for maintaining tissue integrity and preventing self-immunity or tissue damaging inflammation. Macrophages clear tissues of hazardous materials from dying cells and ultimately adopt a pro-resolving activation state. However, adipocyte apoptosis is an inflammation-generating process, and the removal of apoptotic adipocytes by so-called adipose tissue macrophages triggers a sequence of events that lead to meta-inflammation and obesity-associated metabolic diseases. Signals that allow apoptotic cells to control macrophage immune functions are complex and involve metabolites released by the apoptotic cells and also metabolites produced by the macrophages during the digestion of apoptotic cell contents. This review provides a concise summary of the adipocyte-derived metabolites that potentially control adipose tissue macrophage immune functions and, hence, may induce or alleviate adipose tissue inflammation.
Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus
Authors: Tan Xiaohui , Ren Shuyang , Yang Canyuan , Ren Shuchang , Fu Melinda Z. , Goldstein Amelia R. , Li Xuelan , Mitchell Leia , Krapf Jill M. , Macri Charles J. , Goldstein Andrew T. , Fu Sidney W.
Published: September 2021

Lichen sclerosus (LS) is a chronic inflammatory skin disorder with unknown pathogenesis. The aberrant expression of microRNAs (miRNAs) is considered to exert a crucial role in LS. We used the next-generation sequencing technology (RNASeq) for miRNA profiling and Ingenuity Pathway Analysis (IPA) for molecular network analysis. We performed qRT-PCR, miRNA transfection and Matrigel assays for functional studies. We identified a total of 170 differentially expressed miRNAs between female LS and matched adjacent normal tissue using RNASeq, with 119 upregulated and 51 downregulated. Bioinformatics analysis revealed molecular networks that may shed light on the pathogenesis of LS. We verified the expression of a set of miRNAs that are related to autoimmunity, such as upregulated miR-326, miR-142-5p, miR-155 and downregulated miR-664a-3p and miR-181a-3p in LS tissue compared to the matched adjacent normal tissue. The differentially expressed miRNAs were also verified in blood samples from LS patients compared to healthy female volunteers. Functional studies demonstrated that a forced expression of miR-142-5p in human dermal fibroblast PCS-201-010 cells resulted in decreased cell proliferation and migration. These findings suggest that differentially expressed miRNAs may play an important role in LS pathogenesis; therefore, they could serve as biomarkers for LS management.
The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization
Authors: Turathum Bongkoch , Gao Er-Meng , Chian Ri-Cheng
Published: September 2021

Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location. CCs are supporting cells of the oocyte that protect the oocyte from the microenvironment, which helps oocyte growth and maturation in the follicles. Bi-directional communications between an oocyte and CCs are necessary for the oocyte for the acquisition of maturation and early embryonic developmental competence following fertilization. Follicle-stimulation hormone (FSH) and luteinizing hormone (LH) surges lead to the synthesis of an extracellular matrix in CCs, and CCs undergo expansion to assist meiotic resumption of the oocyte. The function of CCs is involved in the completion of oocyte meiotic maturation and ovulation, fertilization, and subsequent early embryo development. Therefore, understanding the function of CCs during follicular development may be helpful for predicting oocyte quality and subsequent embryonic development competence, as well as pregnancy outcomes in the field of reproductive medicine and assisted reproductive technology (ART) for infertility treatment.
Biological and Clinical Factors Contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19
Authors: D’Alessandro Angelo , Thomas Tiffany , Akpan Imo J. , Reisz Julie A. , Cendali Francesca I. , Gamboni Fabia , Nemkov Travis , Thangaraju Kiruphagaran , Katneni Upendra , Tanaka Kenichi , Kahn Stacie , Wei Alexander Z. , Valk Jacob E. , Hudson Krystalyn E. , Roh David , Moriconi Chiara , Zimring James C. , Hod Eldad A. , Spitalnik Steven L. , Buehler Paul W. , Francis Richard O.
Published: September 2021

The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. The present large study sought to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831) that tested positive (n = 543) or negative (n = 288) for COVID-19. High-throughput metabolomics analyses were complemented with antigen and enzymatic activity assays on plasma from acutely ill patients collected while in the emergency department, at admission, or during hospitalization. Lipidomics analyses were also performed on COVID-19-positive or -negative subjects with the lowest and highest body mass index (n = 60/group). Significant changes in amino acid and fatty acid/acylcarnitine metabolism emerged as highly relevant markers of disease severity, progression, and prognosis as a function of biological and clinical variables in these patients. Further, machine learning models were trained by entering all metabolomics and clinical data from half of the COVID-19 patient cohort and then tested on the other half, yielding ~78% prediction accuracy. Finally, the extensive amount of information accumulated in this large, prospective, observational study provides a foundation for mechanistic follow-up studies and data sharing opportunities, which will advance our understanding of the characteristics of the plasma metabolism in COVID-19 and other acute critical illnesses.
Dietary Habits and Choices of 4-to-6-Year-Olds: Do Children Have a Preference for Sweet Taste?
Authors: Kostecka Malgorzata , Kostecka-Jarecka Joanna , Kowal Mariola , Jackowska Izabella
Published: September 2021

Children develop food preferences by coming into direct contact with various food products through the senses of taste, touch, sight and smell. The aim of this study was to analyze the food preferences of children aged 4 to 6 years and to determine whether age and gender influence children’s food preferences and whether the preference for sweet taste changes with age. The study involved a paper questionnaire containing images of 115 different food products and dishes. The respondents expressed their preferences by choosing the appropriate emoji (happy, sad or neutral face). The study was conducted between 2018 and 2020, and it involved 684 children from 10 kindergartens. Girls chose a significantly higher number of foods and dishes they liked than boys (p = 0.002), and 4-year-olds gave a higher number of “neutral” responses than 5- and 6-year-olds (p = 0.001). Dietary diversity increased with age, and younger children were familiar with fewer foods than 6-year-olds (p = 0.002). Children had a clear preference for sweet taste, regardless of age and gender. Young children (4-year-olds) were more likely to accept healthy foods despite the fact that they were familiar with fewer products and dishes.
Self-Cleaning Performance of Super-Hydrophilic Coatings for Dust Deposition Reduction on Solar Photovoltaic Cells
Authors: Zhao Wenjun , Lu Hao
Published: September 2021

Dust deposition on solar photovoltaic (PV) cell surface will significantly decrease the PV power efficiency, as the transmittance of the solar cells would be greatly decreased by the deposited dust particles. This paper aims to study the anti-dust performance of super-hydrophilic coatings for the solar PV cells with water spraying condition. The solar cell covering glass was treated to be super-hydrophilic and compared with the bare glass sample. It was found that many dust particles adhere and aggregate on the uncoated glass while the particles deposited on the super-hydrophilic glass surface are densely distributed. When the water spraying process was conducted, the dust deposition mass for the bare and the coated glass samples are both reduced obviously with the increase time of water spraying. In addtion, dust deposition mass is significantly reduced with the increase of deposition and spraying tilt angles. The self-cleaning efficiency of super-hydrophilic coating on dust deposition is 92% higher than the bare glass cases. The spectral transmittance of glass samples for all the coated cases are significantly higher than that for all the bare cases. The maximum transmittance improvement can reach 26.5% when the deposition tilt angle is 30° and the spraying tilt angle is 60°.
Fluid Flow Behavior of Sheared Rough Fractures Subjected to Different Stress State
Authors: Wang Min , Guo Qifeng , Shan Pengfei , Tian Yakun , Dai Bing
Published: September 2021

The hydraulic properties of fractures are greatly affected by the stress. Knowing the fluid flow behavior of fractures is of great importance to underground engineering construction and environmental safety. The main purpose of this paper is to study the fluid flow characteristics of rough fractures under different stress states. First, rough fracture surfaces were generated by using the corrected successive random addition (SRA) algorithm. Then, the sheared fracture models subjected to different stress condition were obtained under the boundary condition of constant normal stiffness (CNS). Finally, the hydraulic characteristics of the three-dimensional rough rock fractures were analyzed by numerically solving the full Navier–Stokes equation. It has been found that (1) the aperture of fractures all obeys the Gaussian distribution. The dilatancy effect is gradually obvious and aperture becomes larger with the increase of shear displacement. (2) When the initial normal stress increases, the contact area of fracture becomes larger and the reverse flow can be observed around the contact area. (3) The relationship between hydraulic gradient and flowrate exhibits nonlinearity which can be described by the Forchheimer’s law. The linear coefficient a and the nonlinear coefficient b gradually decrease with the increase of shear displacement and finally stabilize. The values of a and b are reduced by 1–2 and 1–3 orders of magnitude respectively during the shear. The critical Reynolds number increases with the increase of shear displacement and decrease as the initial normal stress increases.
Numerical Simulation of Three-Dimensional Dendrite Movement Based on the CA–LBM Method
Authors: Wang Qi , Wang Yingming , Zhang Shijie , Guo Binxu , Li Chenyu , Li Ri
Published: September 2021

At present, the calculation of three-dimensional (3D) dendrite motion using the cellular automata (CA) method is still in its infancy. In this paper, a 3D dendrite motion model is constructed. The heat, mass, and momentum transfer process in the solidification process of the alloy melt are calculated using a 3D Lattice–Boltzmann method (LBM). The growth process for the alloy microstructure is calculated using the CA method. The interactions between dendrites and the melt are assessed using the Ladd method. The solid–liquid boundary of the solute field in the movement process is assessed using the solute extrapolation method. The translational velocity of the equiaxed crystals in motion is calculated using the classical mechanical law. The rationality of the model is verified and the movement of single and multiple 3D equiaxed crystals is simulated. Additionally, the difference between 3D dendrite movement and two-dimensional (2D) dendrite movement is analyzed. The results demonstrate that the growth of moving dendrites is asymmetric. The growth velocity and falling velocity of the dendrite in the 3D model are faster than that in 2D model, while the simulation result is more realistic than that of the 2D model. When multiple dendrites move, the movement direction of the dendrites will change due to the merging of flow fields and other factors.
Synthesis of GaN Crystals by Nitrogen Pressure-Controlled Recrystallization Technique in Na Alloy Melt
Authors: Wu Xi , Wang Hongcheng , Ling Dongxiong , Jia Chuanyu , Lü Wei , Liu Ye , Zhou Fei , Li Zhenrong
Published: September 2021

GaN crystals are synthesized by recrystallization technique in Na-Li-Ca alloy melt under different N2 pressure. X-ray powder diffraction results confirm that the structure of crystals is GaN with wurtzite type and there still have raw powders remaining. The total mass of GaN decreases with the nitrogen pressure reduces. No GaN crystals are found in the solution under N2 pressure of 0.4 MPa. The morphologies of the crystal are mainly prism and pyramid. The size of the crystal increases when closer to the liquid surface. Raman spectra indicates that these crystals are stress-free and crystal grown at 3.6 MPa has high structural quality or low impurity concentrations. The results reveal that the solubility and supersaturation of the solution are controlled by N2 pressure. The principle of GaN crystal synthesis by recrystallization is discussed.
Diversity Aspects in Bats: Genetics, Morphology, Community Structure
Authors: Kruskop Sergei V.
Published: September 2021

Bats are the second largest order of mammals, with about 1400 known species [...]
Complex Regional Pain Syndrome Type I Following Non-Orthopedic Surgery: Case Report and Narrative Review
Authors: Moretti Antimo , Gimigliano Francesca , Paoletta Marco , Bertone Matteo , Liguori Sara , Toro Giuseppe , Iolascon Giovanni
Published: September 2021

Complex regional pain syndrome type I (CRPS I)—or algodystrophy—is a rare disease that usually occurs after a traumatic event. It is characterized by typical clinical findings such as severe and disabling pain disproportionate to the injury, functional limitations, as well as sensory and vasomotor alterations. However, some people do not report any injury associated with algodystrophy onset in personal history. We describe the management of an unusual case of CRPS I which occurred during the long-term follow-up of percutaneous transluminal coronary angioplasty (PTCA) and performed a narrative review of algodystrophy in non-orthopedic surgery. A clinical case of a 44-year-old man with a spontaneous onset of CRPS I of the right ankle is presented. He did not refer to history of any memorable significant trigger event. Approximately 5 months before the onset of clinical manifestations, he received a PTCA via the right femoral approach. We suppose an association between CRPS and this procedure and propose a possible pathophysiologic mechanism. The patient was treated with intramuscular neridronate, which resulted in significant pain relief and improved his quality of life. A comprehensive clinical and instrumental evaluation in patients with CRPS is challenging but mandatory for a correct diagnosis. An extensive analysis of patient history is important for identifying any potential trigger event, including non-orthopedic procedures. Bone scan could have a pivotal role for improving diagnostic sensitivity and specificity in CRPS I. Neridronate was a safe and effective therapeutic approach for this patient, confirming the results of the high-quality evidence available.
Sequential Application of Lugol’s Iodine Test after Acetic Acid for Detecting Cervical Dysplasia: A Prospective Cohort Study
Authors: Rezniczek Günther A. , Ertan Samira , Rehman Sadia , Tempfer Clemens B.
Published: September 2021

Applying Lugol’s iodine solution to the cervix followed by colposcopic assessment is an established standard test to identify low grade/high grade squamous intraepithelial lesions (LSIL/HSIL). Here, we assessed the performance of Lugol’s iodine test during colposcopy using a standardized protocol with 5% acetic acid followed by 5% Lugol’s iodine solution and recording the most severe acetowhite (MSAWL) and iodine-negative (MSINL) lesions in a prospective cohort of consecutive women referred to our specialized colposcopy unit. The primary study endpoint was the sensitivity/specificity of MSINL for the detection of LSIL/HSIL. Secondary endpoints were the time to first appearance of the MSINL, MSINL staining intensity, and fading of MSINL. Three hundred and twenty women were included. The sensitivity and specificity of MSINL for the detection of LSIL/HSIL was 81.4 (95%—confidence interval (CI) 77.3–85.0)% and 29.5 (24.2–35.5)%, respectively. Ninety-six MSINL were identified exclusively by Lugol’s iodine test (no pathology, n = 46; LSIL, n = 29; HSIL, n = 21) (number needed to biopsy to identify one additional LSIL/HSIL = 1.9). In 17/320 (5.3%) patients, the clinical management was changed based on the result of Lugol’s iodine test. Video analysis showed an instant appearance of the MSINL within 10 s in 100% of cases. Intensity of MSINL significantly correlated with the presence/absence of LSIL/HSIL (Spearman rank order correlation; p < 0.0001). Fading of iodine-induced staining intensity over time was not observed. Thus, Lugol’s iodine showed moderate sensitivity and poor specificity, but changed clinical management in 5% of cases when used in addition to acetic acid.