bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Association Analysis Reveals Novel Loci Related with Visual Score Traits in Nellore Cattle Raised in Pasture–Based Systems
Authors: Machado Pamela C. , Brito Luiz F. , Martins Rafaela , Pinto Luis Fernando B. , Silva Marcio R. , Pedrosa Victor B.
Published: December 2022

Body conformation traits assessed based on visual scores are widely used in Zebu cattle breeding programs. The aim of this study was to identify genomic regions and biological pathways associated with body conformation (CONF), finishing precocity (PREC), and muscling (MUSC) in Nellore cattle. The measurements based on visual scores were collected in 20,807 animals raised in pasture-based systems in Brazil. In addition, 2775 animals were genotyped using a 35 K SNP chip, which contained 31,737 single nucleotide polymorphisms after quality control. Single-step GWAS was performed using the BLUPF90 software while candidate genes were identified based on the Ensembl Genes 69. PANTHER and REVIGO platforms were used to identify key biological pathways and STRING to create gene networks. Novel candidate genes were revealed associated with CONF, including ALDH9A1, RXRG, RAB2A, and CYP7A1, involved in lipid metabolism. The genes associated with PREC were ELOVL5, PID1, DNER, TRIP12, and PLCB4, which are related to the synthesis of long-chain fatty acids, lipid metabolism, and muscle differentiation. For MUSC, the most important genes associated with muscle development were SEMA6A, TIAM2, UNC5A, and UIMC1. The polymorphisms identified in this study can be incorporated in commercial genotyping panels to improve the accuracy of genomic evaluations for visual scores in beef cattle.
GPX2 Gene Affects Feed Efficiency of Pigs by Inhibiting Fat Deposition and Promoting Muscle Development
Authors: Pu Lei , Luo Yunyan , Wen Zuochen , Dai Yuxin , Zheng Chunting , Zhu Xueli , Qin Lei , Zhang Chunguang , Liang Hong , Zhang Jianbin , Guo Liang , Wang Lixian
Published: December 2022

GPX2 has been recognized as a potential candidate gene for feed efficiency in pigs. This article aimed to elucidate polymorphism of GPX2 associated with feed efficiency and its related molecular mechanism. In this study, seven single nucleotide polymorphisms (SNP) of GPX2 were found among 383 Duroc pigs. In addition, seven SNPs and ALGA0043483 (PorcineSNP60 BeadChip data in 600 Duroc pigs), which are near the GPX2 gene, were identified in one haplotypes block. Furthermore, associated studies showed that the genotype of GPX2 has significant association with weaning weight and 100 kg BF in Duroc pigs. In addition, the AG had no effect when the backfat became thinner, and the FCR and RFI traits had a tendency to decrease in the G3 + TT combination genotype, accompanied by an increase of GPX2 expression in backfat and muscle tissues. At the cellular level, the adipocyte proliferation and ability of adipogenic differentiation were reduced, and the lipid degradation increased in 3T3-L1 when there was overexpression of GPX2. In contrast, overexpression of the GPX2 gene can promote the muscle cell proliferation and myogenic differentiation in C2C12 cells. In other words, GPX2 has the effect of reducing fat deposition and promoting muscle development, and it is a candidate gene for backfat and feed efficiency.
Current Situation and Utilization of Velvet Deer Germplasm Resources in China
Authors: Tang Lixin , Wen Xiaobin , Zhang Ranran , Xing Xiumei
Published: December 2022

Velvet deer are not only a representative special economic animal but also an important part of livestock. With the increasing awareness of international competition for germplasm resources in China, more and more attention has been paid to the protection and utilization of germplasm resources. However, there is poor understanding about velvet deer resources. Therefore, we are providing a comprehensive introduction of Chinese velvet deer germplasm resources from the aspects of ecological distribution, domestication and breeding.
Short-Term Efficacy of Capacitive-Resistive Electrical Transfer Therapy in Short-Haired Sled Dogs in Middle-Distance Competition
Authors: Benito Mila , Jasny Tania , Roger Vinciane , Pflieger Christophe , Grandjean Dominique
Published: December 2022

Achieving the successful recovery of sled dogs is one of the key tasks for veterinary teams involved in clinical care for middle-distance sled dog competitions. This study compares the efficacy of capacitive-resistive electrical transfer (CRet) with that of massage in the treatment of lower back pain in 40 short-haired sled dogs during a medium-distance snow sled race (LekkarodTM-2021). The dogs were divided into two groups: a CRet group (20 dogs) and a massage group (20 dogs). All subjects received a single 18 min treatment session and were evaluated one hour after the end of the treatment. A multivariate analysis of variance (MANOVA) was performed in which pre- and post-treatment pain measures were evaluated in relation to age and type of treatment. Older dogs were found to have higher significant pain scores before starting treatment. Both treatments reduce pain short-term in all cases. However, post-treatment pain values were significantly lower in dogs treated with CRet when compared to dogs treated with massage. The results show that capacitive-resistive electrical transfer has better short-term results and is beneficial in both younger and older dogs, making this technique attractive to veterinary teams working in canine sporting competitions.
Co-Expression of T- and B-Cell Markers in a Canine Intestinal Lymphoma: A Case Report
Authors: Valente Pâmela Cristina Lopes Gurgel , Peleteiro Maria Conceição , Carvalho Sandra , Leal Rodolfo Oliveira , Pomba Constança , Duarte António , Correia Jorge
Published: December 2022

An 8-year-old female neutered Labrador retriever was presented for a second opinion consultation due to vomiting and lethargy, having failed to respond to symptomatic therapy. Blood analysis revealed hyperbilirubinemia and hypoalbuminemia, associated with hypocobalaminemia. An abdominal ultrasound identified diffused bowel thickening and hypoechoic hepatomegaly. An ultrasound-guided liver fine-needle aspiration was performed for cytology and also for cell block immunocytochemistry. Gastric and duodenal biopsies were collected by gastroduodenoscopy. Liver cytology showed numerous lymphocytes, suggesting lymphoma at the hepatic infiltration stage, and immunocytochemistry in the cell block of the hepatic aspirate indicated co-expression of CD3 and CD20 in the lymphoid cells present. The histopathology of gastric and duodenal biopsies supported the hypothesis of gastrointestinal lymphoma due to heavy lymphoid infiltration of the gastric epithelium and intestinal mucosa, including the villi. Concurrent immunohistochemistry was performed using CD3, CD20, PAX5, and CD79αcy antibodies. Immunomarking was positive for CD3 and CD20, which overlapped populations of lymphoid cells, and was negative for all other antibodies. In the clonality test, lymphocyte co-expression of CD3 and CD20 was confirmed by monoclonal rearrangement of T-cell gamma receptors. The final diagnosis was type 2 enteropathy-associated T-cell lymphoma with hepatic infiltration. Co-expression was examined in conjunction with the PARR result in the presence of T-cell monoclonal rearrangement.
Deep Eutectic Solvent (DES) for In Situ Templating Carbon Material: Carbon Characterization and Application in Supercapacitors Containing Multivalent Ions
Authors: Zdolšek Nikola , Janković Bojan , Milović Miloš , Brković Snežana , Krstić Jugoslav , Perović Ivana , Vujković Milica
Published: December 2022

The development of carbon materials with desirable textures and new aqueous electrolytes is the key strategy to improve the performance of supercapacitors. Herein, a deep eutectic solvent (DES) was used for in situ templating of a carbon material. A carbon material was characterized (XRD, N2-physisorption, FTIR, SEM and EDS) and used as an electrode material for the first time in multivalent-based supercapacitors. In situ templating of carbon was performed using a novel DES, which serves as a precursor for carbon and for in situ generation of MgO. The generation of MgO and its roles in templating of carbon were discussed. Templating of carbon with MgO lead to an increase in surface area and a microporous texture. The obtained carbon was tested in multivalent-ion (Al3+ and Mg2+) electrolytes and compared with H2SO4. The charge-storage mechanism was investigated and elaborated. The highest specific capacitance was obtained for the Al(NO3)3 electrolyte, while the operating voltage follows the order: Mg(NO3)2 > Al(NO3)3 > H2SO4. Electrical double-layer capacitance (versus pseudocapacitance) was dominant in all investigated electrolytes. The larger operating voltage in multivalent electrolytes is a consequence of the lower fraction of free water, which suppresses hydrogen evolution (when compared with H2SO4). The GCD was experimentally performed on the Al(NO3)3 electrolyte, which showed good cyclic stability, with an energy density of 22.3 Wh kg−1 at 65 W kg−1.
Review on Battery Packing Design Strategies for Superior Thermal Management in Electric Vehicles
Authors: Widyantara Robby Dwianto , Zulaikah Siti , Juangsa Firman Bagja , Budiman Bentang Arief , Aziz Muhammad
Published: December 2022

In the last decades of electric vehicle (EV) development, battery thermal management has become one of the remaining issues that must be appropriately handled to ensure robust EV design. Starting from researching safer and more durable battery cells that can resist thermal exposure, battery packing design has also become important to avoid thermal events causing an explosion or at least to prevent fatal loss if the explosion occurs. An optimal battery packing design can maintain the battery cell temperature at the most favorable range, i.e., 25–40 °C, with a temperature difference in each battery cell of 5 °C at the maximum, which is considered the best working temperature. The design must also consider environmental temperature and humidity effects. Many design strategies have been reported, including novel battery pack constructions, a better selection of coolant materials, and a robust battery management system. However, those endeavors are faced with the main challenges in terms of design constraints that must be fulfilled, such as material and manufacturing costs, limited available battery space and weight, and low energy consumption requirements. This work reviewed and analyzed the recent progress and current state-of-the-art in designing battery packs for superior thermal management. The narration focused on significant findings that have solved the battery thermal management design problem as well as the remaining issues and opportunities to obtain more reliable and enduring batteries for EVs. Furthermore, some recommendations for future research topics supporting the advancement of battery thermal management design were also discussed.
Explore Big Data Analytics Applications and Opportunities: A Review
Authors: Al-Sai Zaher Ali , Husin Mohd Heikal , Syed-Mohamad Sharifah Mashita , Abdin Rasha Moh’d Sadeq , Damer Nour , Abualigah Laith , Gandomi Amir H.
Published: December 2022

Big data applications and analytics are vital in proposing ultimate strategic decisions. The existing literature emphasizes that big data applications and analytics can empower those who apply Big Data Analytics during the COVID-19 pandemic. This paper reviews the existing literature specializing in big data applications pre and peri-COVID-19. A comparison between Pre and Peri of the pandemic for using Big Data applications is presented. The comparison is expanded to four highly recognized industry fields: Healthcare, Education, Transportation, and Banking. A discussion on the effectiveness of the four major types of data analytics across the mentioned industries is highlighted. Hence, this paper provides an illustrative description of the importance of big data applications in the era of COVID-19, as well as aligning the applications to their relevant big data analytics models. This review paper concludes that applying the ultimate big data applications and their associated data analytics models can harness the significant limitations faced by organizations during one of the most fateful pandemics worldwide. Future work will conduct a systematic literature review and a comparative analysis of the existing Big Data Systems and models. Moreover, future work will investigate the critical challenges of Big Data Analytics and applications during the COVID-19 pandemic.
Effect of Three Post-Harvest Methods at Different Altitudes on the Organoleptic Quality of C. canephora Coffee
Authors: Velásquez Sofía , Banchón Carlos , Chilán Willian , Guerrero-Casado José
Published: December 2022

C. canephora (syn. C. robusta) is distinctive due to its rising industrial value and pathogen resistance. Both altitude and post-harvest methods influence coffee cup quality; however, modest information is known about this coffee species. Therefore, the aim of this study was to determine the relationship between four different altitudes and post-harvest processes (dry, honey, and wet) to the improvement of the organoleptic quality of the C. canephora congolensis and conilon drink. For dry processing, congolensis and conilon showed the lowest scores in terms of fragrance/aroma, flavour, aftertaste, salt–acid, bitter–sweet, and body. Above 625 m, coffees from dry, honey, and wet processes increased scores in their sensory attributes, but there was no difference at such high altitudes when comparing post-harvest samples. Dry-processed coffee samples had total scores over 80 points at high altitudes. Conilon was perceived to have the best sensory attributes at high altitudes using honey processing. In general, the wet-processed congolensis and conilon samples had a tastier profile than dry-processed ones.
Vacuum and Electromagnetic Fields Treatment to Regenerate a Diffuse Mature Facial Scar Caused by Sulfuric Acid Assault
Authors: Veronese Sheila , Brunetti Bruno , Minichino Anna , Sbarbati Andrea
Published: December 2022

Acid attacks are on the rise, and they cause extensive and deep burns, especially on the face. The treatments used to improve the aesthetic, functional and social impact of non-acid scars do not always prove useful for acid scars. This article reports the case of a woman with an extended, mature, acid facial scar, caused by sulfuric acid assault, treated with a recent new procedure that combines the application of vacuum and electromagnetic fields. Before and after the treatment, the aesthetic appearance, and motor function of the face and neck were evaluated, as well as the level of hydration, the amount of sebum, the elasticity, and the pH of the skin. The improvements highlighted after the treatment of the aesthetic and functional characteristics of the face and neck, and of the physical parameters of the skin seemed to indicate that this particular treatment induces tissue regeneration, even in the nerve component. However, it is evident that the rehabilitation pathways of facial wounds and scars must be personalized, and must include continuous psychological support for the patient.
Functional Implications of Dynamic Structures of Intrinsically Disordered Proteins Revealed by High-Speed AFM Imaging
Authors: Ando Toshio
Published: December 2022

The unique functions of intrinsically disordered proteins (IDPs) depend on their dynamic protean structure that often eludes analysis. High-speed atomic force microscopy (HS-AFM) can conduct this difficult analysis by directly visualizing individual IDP molecules in dynamic motion at sub-molecular resolution. After brief descriptions of the microscopy technique, this review first shows that the intermittent tip–sample contact does not alter the dynamic structure of IDPs and then describes how the number of amino acids contained in a fully disordered region can be estimated from its HS-AFM images. Next, the functional relevance of a dumbbell-like structure that has often been observed on IDPs is discussed. Finally, the dynamic structural information of two measles virus IDPs acquired from their HS-AFM and NMR analyses is described together with its functional implications.
Exploring Potentials for Bioresource and Bioenergy Recovery from Vinasse, the “New” Protagonist in Brazilian Sugarcane Biorefineries
Authors: Fuess Lucas T. , Lens Piet N. L. , Garcia Marcelo L. , Zaiat Marcelo
Published: December 2022

Vinasse management in biorefineries bears a burden for sugarcane industries. Despite its high potassium-related fertilizer potential, a series of negative environmental impacts is expected to occur in long-term soil applications of vinasse through fertirrigation. Conversely, a high biodegradable organic content characterizes vinasse as a potential substrate for bioresource and bioenergy recovery from numerous (bio)technological perspectives. This review presents the alternative approaches proposed for sugarcane vinasse management in Brazil, with special attention dedicated to the role of anaerobic digestion as the core conversion step. The suitability of applying phase separation, i.e., the separation of fermentation from methanogenesis in sequential reactors, is discussed in detail. Laboratory and full-scale experiences were considered to discuss the energetic potential of sugarcane vinasse through biogas generation. With a national installed capacity of up to 1603 MW, energy from vinasse could replace half of the coal-derived electricity in Brazil. Meanwhile, investing in vinasse fermentation to obtain soluble organic metabolites could provide more than 10 g L−1 of (iso)butyrate. This is the first review addressing the potential use of sugarcane vinasse in anaerobic biorefineries that discusses applications far beyond conventional biogas production, and encourages the rational use of vinasse as a raw material for bioprocesses, either in short- or long-term scenarios.
Genetics of Cholesterol-Related Genes in Metabolic Syndrome: A Review of Current Evidence
Authors: Wong Sok Kuan , Ramli Fitri Fareez , Ali Adli , Ibrahim Nurul ‘Izzah
Published: December 2022

Metabolic syndrome (MetS) refers to a cluster of metabolic dysregulations, which include insulin resistance, obesity, atherogenic dyslipidemia and hypertension. The complex pathogenesis of MetS encompasses the interplay between environmental and genetic factors. Environmental factors such as excessive nutrients and sedentary lifestyle are modifiable and could be improved by lifestyle modification. However, genetic susceptibility to MetS, a non-modifiable factor, has attracted the attention of researchers, which could act as the basis for future diagnosis, prognosis, and therapy for MetS. Several cholesterol-related genes associated with each characteristic of MetS have been identified, such as apolipoprotein, lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and adiponectin. This review aims to summarize the genetic information of cholesterol-related genes in MetS, which may potentially serve as biomarkers for early prevention and management of MetS.
Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug
Authors: Schultz Christopher W. , Nevler Avinoam
Published: December 2022

Pyrvinium, a lipophilic cation belonging to the cyanine dye family, has been used in the clinic as a safe and effective anthelminthic for over 70 years. Its structure, similar to some polyaminopyrimidines and mitochondrial-targeting peptoids, has been linked with mitochondrial localization and targeting. Over the past two decades, increasing evidence has emerged showing pyrvinium to be a strong anti-cancer molecule in various human cancers in vitro and in vivo. This efficacy against cancers has been attributed to diverse mechanisms of action, with the weight of evidence supporting the inhibition of mitochondrial function, the WNT pathway, and cancer stem cell renewal. Despite the overwhelming evidence demonstrating the efficacy of pyrvinium for the treatment of human cancers, pyrvinium has not yet been repurposed for the treatment of cancers. This review provides an in-depth analysis of the history of pyrvinium as a therapeutic, the rationale and data supporting its use as an anticancer agent, and the challenges associated with repurposing pyrvinium as an anti-cancer agent.
Phonophoresis through Nonsteroidal Anti-Inflammatory Drugs for Knee Osteoarthritis Treatment: Systematic Review and Meta-Analysis
Authors: Martin-Vega Francisco Javier , Lucena-Anton David , Galán-Mercant Alejandro , Perez-Cabezas Veronica , Luque-Moreno Carlos , Vinolo-Gil Maria Jesus , Gonzalez-Medina Gloria
Published: December 2022

Knee osteoarthritis (OA) is the most common joint disease. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) by phonophoresis is a therapeutic alternative to relieve pain in inflammatory pathologies. The main aim was to analyze the efficacy of the application of NSAIDs by phonophoresis in knee OA. A systematic review and meta-analysis of controlled clinical trials were performed between January and March 2021 in the following databases: Web of Science, Scopus, PubMed, Cinahl, SciELO, and PEDro. The PEDro scale was used to evaluate the level of evidence of the selected studies. The RevMan 5.4 statistical software was used to obtain the meta-analysis. Eight studies were included, of which five were included in the meta-analysis, involving 195 participants. The NSAIDs used through phonophoresis were ibuprofen, piroxicam, diclofenac sodium, diclofenac diethylammonium, ketoprofen, and methyl salicylate. The overall result for pain showed not-conclusive results, but a trend toward significance was found in favor of the phonophoresis group compared to the control group (standardized mean difference (SMD) = −0.92; 95% confidence interval: −1.87–0.02). Favorable results were obtained for physical function (SMD = −1.34; 95% CI: −2.00–0.68). Based on the selected studies, the application of NSAIDs by phonophoresis is effective in relieving the symptoms of knee OA. Future long-term studies are recommended.
Recent Advances in Wearable Biosensors for Non-Invasive Detection of Human Lactate
Authors: Shen Yutong , Liu Chengkun , He Haijun , Zhang Mengdi , Wang Hao , Ji Keyu , Wei Liang , Mao Xue , Sun Runjun , Zhou Fenglei
Published: December 2022

Lactate, a crucial product of the anaerobic metabolism of carbohydrates in the human body, is of enormous significance in the diagnosis and treatment of diseases and scientific exercise management. The level of lactate in the bio-fluid is a crucial health indicator because it is related to diseases, such as hypoxia, metabolic disorders, renal failure, heart failure, and respiratory failure. For critically ill patients and those who need to regularly control lactate levels, it is vital to develop a non-invasive wearable sensor to detect lactate levels in matrices other than blood. Due to its high sensitivity, high selectivity, low detection limit, simplicity of use, and ability to identify target molecules in the presence of interfering chemicals, biosensing is a potential analytical approach for lactate detection that has received increasing attention. Various types of wearable lactate biosensors are reviewed in this paper, along with their preparation, key properties, and commonly used flexible substrate materials including polydimethylsiloxane (PDMS), polyethylene terephthalate (PET), paper, and textiles. Key performance indicators, including sensitivity, linear detection range, and detection limit, are also compared. The challenges for future development are also summarized, along with some recommendations for the future development of lactate biosensors.
P3b Amplitude and Latency in Tic Disorders: A Meta-Analysis
Authors: Yang Yue , Yang Hua , Deng Yao , Yu Tao , Luo Rong
Published: December 2022

P3b is an event-related potential (ERP) that may be abnormal in patients with tic disorders (TD), but evidence has been inconsistent. Given the possible association between P3b and TD and the need for biomarkers for TD, the primary objective of this meta-analysis was to characterize P3b in patients with TD in comparison to healthy controls (HCs). Methods: By searching PubMed, Embase, Web of Science, SCOPUS, Medline, and Google Scholar, we identified studies that compared P3b between TD patients and HCs. The amplitude and latency of P3b were then analyzed. Subgroup analyses were conducted to investigate the influence of different experimental factors on P3b indices. Result: Overall, 19 articles involving 388 cases and 414 controls were evaluated. There were no significant abnormalities in P3b amplitude and latency in TD patients. The P3b amplitude of the TD patients was significantly decreased during the oddball task, and the P3b amplitude of the adult TD patients was also significantly decreased. Conclusion: TD patients may have an abnormal P3b compared to HCs under specified conditions.
Effect of Sarcopenia on Survival and Health-Related Quality of Life in Patients with Hepatocellular Carcinoma after Hepatectomy
Authors: Hu Jiawei , Yang Jinhuan , Yu Haitao , Bo Zhiyuan , Chen Kaiwen , Wang Daojie , Xie Yitong , Wang Yi , Chen Gang
Published: December 2022

Background: Although sarcopenia has been reported as a negative prognostic factor in patients with hepatocellular carcinoma (HCC), the lack of studies with a prospective design utilizing comprehensive sarcopenia assessment with composite endpoints is an important gap in understanding the impact of sarcopenia in patients with HCC. The aim of this study was to investigate the relationship between sarcopenia and postoperative 1-year mortality and health-related quality of life (HRQOL) based on sarcopenia assessment. Methods: The study cohort, who received resection surgery for HCC between May 2020 and August 2021, was assessed for sarcopenia based on grip strength, the chair stand test, skeletal muscle mass, and gait speed. The primary outcome measures were 1-year mortality and HRQOL determined using the QLQ-C30 questionnaire. In addition, we collected hospital costs, postoperative hospital stays, complications, 30-day and 90-day mortality, and 90- and 180-day readmission rates. Univariate and multivariate linear regression analyses were conducted to examine factors associated with global health status. Results: A total of 153 eligible patients were included in the cohort. One-year mortality was higher in patients with sarcopenia than in those without sarcopenia (p = 0.043). There was a correlation between sarcopenia and the surgical approach to global health status (p = 0.025) and diarrhea (p = 0.003). Conclusions: Preoperative sarcopenia reduces postoperative survival and health-related quality of life in patients with HCC.
Lung Cancer Immunotherapy: Beyond Common Immune Checkpoints Inhibitors
Authors: Catalano Martina , Shabani Sonia , Venturini Jacopo , Ottanelli Carlotta , Voltolini Luca , Roviello Giandomenico
Published: December 2022

Immunotherapy is an ever-expanding field in lung cancer treatment research. Over the past two decades, there has been significant progress in identifying immunotherapy targets and creating specific therapeutic agents, leading to a major paradigm shift in lung cancer treatment. However, despite the great success achieved with programmed death protein 1/ligand 1 (PD-1/PD-L1) monoclonal antibodies and with anti-PD-1/PD-L1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), only a minority of lung cancer patients respond to treatment, and of these many subsequently experience disease progression. In addition, immune-related adverse events sometimes can be life-threatening, especially when anti-CTLA-4 and anti-PD-1 are used in combination. All of this prompted researchers to identify novel immune checkpoints targets to overcome these limitations. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin (Ig) and Immunoreceptor Tyrosine-Based Inhibitory Motif (ITIM) domain (TIGIT), T cell immunoglobulin and mucin-domain containing-3 (TIM-3) are promising molecules now under investigation. This review aims to outline the current role of immunotherapy in lung cancer and to examine efficacy and future applications of the new immune regulating molecules.
Effectiveness of Nivolumab in Second-Line and Later in Patients with Advanced Non-Small Cell Lung Cancer in Real-Life Practice in France and Germany: Analysis of the ESME-AMLC and CRISP Cohorts
Authors: Chouaid Christos , Thomas Michael , Debieuvre Didier , Durand-Zaleski Isabelle , Zacharias Stefan , Bosquet Lise , Groth Annika , Fleitz Annette , Calleja Alan , Patel Sonya , Lacoin Laure , Daumont Melinda J. , Penrod John R. , Carroll Robert , Waldenberger Daniela , Cotté François-Emery , Audigier-Valette Clarisse , Griesinger Frank
Published: December 2022

This study reports characteristics and outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) receiving nivolumab in second-line or later (2L+) in France and Germany between 2015 and 2020. Patients with aNSCLC (stage IIIB–C/IV) receiving nivolumab in 2L+ were included from the retrospective Epidemiological Strategy and Medical Economics of Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015–2019) and Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients (CRISP, Germany; 2016–2020). Overall, 2262 ESME-AMLC and 522 CRISP patients were included. Median treatment duration (95% confidence intervals) was 2.8 months (2.5–3.2) in squamous and 2.5 months (2.3–2.8) in non-squamous/others patients in ESME-AMLC, and 2.3 months (1.4–3.1) and 2.3 months (2.0–2.8), respectively in CRISP. One-year and two-year overall survival (OS) were 47.2% and 26.7% in squamous and 50.8% and 32.8% in non-squamous/others patients in ESME-AMLC, and 43.1% and 20.9%, and 37.7% and 18.9%, respectively in CRISP. Poorer performance score and shorter time from start of previous line of therapy initiation were significantly associated with shorter treatment duration and OS. This study confirms, in real-world clinical databases, the efficacy of nivolumab previously observed in clinical trials.
Repurposing of Commercially Existing Molecular Target Therapies to Boost the Clinical Efficacy of Immune Checkpoint Blockade
Authors: Sinha Debottam , Moseley Philip , Lu Xuehan , Wright Quentin , Gabrielli Brian , Frazer Ian H. , Cruz Jazmina L. G.
Published: December 2022

Immune checkpoint blockade (ICB) is now standard of care for several metastatic epithelial cancers and prolongs life expectancy for a significant fraction of patients. A hostile tumor microenvironment (TME) induced by intrinsic oncogenic signaling induces an immunosuppressive niche that protects the tumor cells, limiting the durability and efficacy of ICB therapies. Addition of receptor tyrosine kinase inhibitors (RTKi) as potential modulators of an unfavorable local immune environment has resulted in moderate life expectancy improvement. Though the combination strategy of ICB and RTKi has shown significantly better results compared to individual treatment, the benefits and adverse events are additive whereas synergy of benefit would be preferable. There is therefore a need to investigate the potential of inhibitors other than RTKs to reduce malignant cell survival while enhancing anti-tumor immunity. In the last five years, preclinical studies have focused on using small molecule inhibitors targeting cell cycle and DNA damage regulators such as CDK4/6, CHK1 and poly ADP ribosyl polymerase (PARP) to selectively kill tumor cells and enhance cytotoxic immune responses. This review provides a comprehensive overview of the available drugs that attenuate immunosuppression and overcome hostile TME that could be used to boost FDA-approved ICB efficacy in the near future.
Prostacyclin Released by Cancer-Associated Fibroblasts Promotes Immunosuppressive and Pro-Metastatic Macrophage Polarization in the Ovarian Cancer Microenvironment
Authors: Sommerfeld Leah , Knuth Isabel , Finkernagel Florian , Pesek Jelena , Nockher Wolfgang A. , Jansen Julia M. , Wagner Uwe , Nist Andrea , Stiewe Thorsten , Müller-Brüsselbach Sabine , Müller Rolf , Reinartz Silke
Published: December 2022

Metastasis of high-grade ovarian carcinoma (HGSC) is orchestrated by soluble mediators of the tumor microenvironment. Here, we have used transcriptomic profiling to identify lipid-mediated signaling pathways encompassing 41 ligand-synthesizing enzymes and 23 cognate receptors in tumor, immune and stroma cells from HGSC metastases and ascites. Due to its strong association with a poor clinical outcome, prostacyclin (PGI2) synthase (PTGIS) is of particular interest in this signaling network. PTGIS is highly expressed by cancer-associated fibroblasts (CAF), concomitant with elevated PGI2 synthesis, whereas tumor-associated macrophages (TAM) exhibit the highest expression of its surface receptor (PTGIR). PTGIR activation by PGI2 agonists triggered cAMP accumulation and induced a mixed-polarization macrophage phenotype with altered inflammatory gene expression, including CXCL10 and IL12A repression, as well as reduced phagocytic capability. Co-culture experiments provided further evidence for the interaction of CAF with macrophages via PGI2, as the effect of PGI2 agonists on phagocytosis was mitigated by cyclooxygenase inhibitors. Furthermore, conditioned medium from PGI2-agonist-treated TAM promoted tumor adhesion to mesothelial cells and migration in a PTGIR-dependent manner, and PTGIR activation induced the expression of metastasis-associated and pro-angiogenic genes. Taken together, our study identifies a PGI2/PTGIR-driven crosstalk between CAF, TAM and tumor cells, promoting immune suppression and a pro-metastatic environment.
Pathogenic Variant Spectrum in Breast Cancer Risk Genes in Finnish Patients
Authors: Nurmi Anna K. , Suvanto Maija , Dennis Joe , Aittomäki Kristiina , Blomqvist Carl , Nevanlinna Heli
Published: December 2022

Recurrent pathogenic variants have been detected in several breast and ovarian cancer (BC/OC) risk genes in the Finnish population. We conducted a gene-panel sequencing and copy number variant (CNV) analysis to define a more comprehensive spectrum of pathogenic variants in BRCA1, BRCA2, PALB2, CHEK2, ATM, BARD1, RAD51C, RAD51D, BRIP1, and FANCM genes in Finnish BC patients. The combined frequency of pathogenic variants in the BRCA1/2 genes was 1.8% in 1356 unselected patients, whereas variants in the other genes were detected altogether in 8.3% of 1356 unselected patients and in 12.9% of 699 familial patients. CNVs were detected in 0.3% of both 1137 unselected and 612 familial patients. A few variants covered most of the pathogenic burden in the studied genes. Of the BRCA1/2 carriers, 70.8% had 1 of 10 recurrent variants. In the other genes combined, 92.1% of the carrier patients had at least 1 of 11 recurrent variants. In particular, PALB2 c.1592delT and CHEK2 c.1100delC accounted for 88.9% and 82.9%, respectively, of the pathogenic variation in each gene. Our results highlight the importance of founder variants in the BC risk genes in the Finnish population and could be used in the designing of population screening for the risk variants.
Correction: Ponzo et al. Nucleolin Therapeutic Targeting Decreases Pancreatic Cancer Immunosuppression. Cancers 2022, 14, 4265
Authors: Ponzo Matteo , Debesset Anais , Cossutta Mélissande , Chalabi-Dchar Mounira , Houppe Claire , Pilon Caroline , Nicolas-Boluda Alba , Meunier Sylvain , Raineri Fabio , Thiolat Allan , Nicolle Rémy , Maione Federica , Brundu Serena , Cojocaru Carina Florina , Bouvet Philippe , Bousquet Corinne , Gazeau Florence , Tournigand Christophe , Courty José , Giraudo Enrico , Cohen José L. , Cascone Ilaria
Published: December 2022

In the original publication [...]
Antagonistic Functions of Androgen Receptor and NF-κB in Prostate Cancer—Experimental and Computational Analyses
Authors: Basílio José , Hochreiter Bernhard , Hoesel Bastian , Sheshori Emira , Mussbacher Marion , Hanel Rudolf , Schmid Johannes A.
Published: December 2022

Prostate cancer is very frequent and is, in many countries, the third-leading cause of cancer related death in men. While early diagnosis and treatment by surgical removal is often curative, metastasizing prostate cancer has a very bad prognosis. Based on the androgen-dependence of prostate epithelial cells, the standard treatment is blockade of the androgen receptor (AR). However, nearly all patients suffer from a tumor relapse as the metastasizing cells become AR-independent. In our study we show a counter-regulatory link between AR and NF-κB both in human cells and in mouse models of prostate cancer, implying that inhibition of AR signaling results in induction of NF-κB-dependent inflammatory pathways, which may even foster the survival of metastasizing cells. This could be shown by reporter gene assays, DNA-binding measurements, and immune-fluorescence microscopy, and furthermore by a whole set of computational methods using a variety of datasets. Interestingly, loss of PTEN, a frequent genetic alteration in prostate cancer, also causes an upregulation of NF-κB and inflammatory activity. Finally, we present a mathematical model of a dynamic network between AR, NF-κB/IκB, PI3K/PTEN, and the oncogene c-Myc, which indicates that AR blockade may upregulate c-Myc together with NF-κB, and that combined anti-AR/anti-NF-κB and anti-PI3K treatment might be beneficial.
A Targeted Epigenetic Clock for the Prediction of Biological Age
Authors: Gensous Noémie , Sala Claudia , Pirazzini Chiara , Ravaioli Francesco , Milazzo Maddalena , Kwiatkowska Katarzyna Malgorzata , Marasco Elena , De Fanti Sara , Giuliani Cristina , Pellegrini Camilla , Santoro Aurelia , Capri Miriam , Salvioli Stefano , Monti Daniela , Castellani Gastone , Franceschi Claudio , Bacalini Maria Giulia , Garagnani Paolo
Published: December 2022

Epigenetic clocks were initially developed to track chronological age, but accumulating evidence indicates that they can also predict biological age. They are usually based on the analysis of DNA methylation by genome-wide methods, but targeted approaches, based on the assessment of a small number of CpG sites, are advisable in several settings. In this study, we developed a targeted epigenetic clock purposely optimized for the measurement of biological age. The clock includes six genomic regions mapping in ELOVL2, NHLRC1, AIM2, EDARADD, SIRT7 and TFAP2E genes, selected from a re-analysis of existing microarray data, whose DNA methylation is measured by EpiTYPER assay. In healthy subjects (n = 278), epigenetic age calculated using the targeted clock was highly correlated with chronological age (Spearman correlation = 0.89). Most importantly, and in agreement with previous results from genome-wide clocks, epigenetic age was significantly higher and lower than expected in models of increased (persons with Down syndrome, n = 62) and decreased (centenarians, n = 106; centenarians’ offspring, n = 143; nutritional intervention in elderly, n = 233) biological age, respectively. These results support the potential of our targeted epigenetic clock as a new marker of biological age and open its evaluation in large cohorts to further promote the assessment of biological age in healthcare practice.
A Novel Framework for Inner-Outer Sustainability Assessment
Authors: Cooper Kira J. , Gibson Robert B.
Published: December 2022

Calls for systemic transformations have become prevalent throughout sustainability discourse. Increasingly, these calls point towards consciousness expanding practices and interventions, such as mindfulness, to support the development of individual understandings, skills, and capacities that are conducive to more sustainable ways of being and doing. The growing interest in leveraging inner capacities, including mindsets, worldviews, values, and beliefs for sustainability transformations emerges from concerns that conventional approaches are failing to align social and ecological systems towards long-term viability. Interest in these consciousness-driven transformations is spreading, particularly in governments and prominent organisations. Tempering this enthusiasm are concerns that untethered from moral and ethical guidelines as well as caring understanding of local and global prospects for lasting wellbeing, mindfulness programs, workshops, and interventions for inner transformation can inadvertently strengthen unsustainable systems and deepen inequities. Accordingly, this paper presents an exploratory assessment framework to increase understandings of how events focused on interventions for inner transformation align with broad sustainability requirements. Findings from application of the framework should help to elucidate how these offerings can disrupt normative ways of thinking and doing, and in turn, positively influence multi-scalar transformations. Furthermore, use of the assessment process to plan and/or evaluate inner development offerings is anticipated to help strengthen progress towards sustainability and reduce adverse trade-offs that might undermine positive systemic transformations.
Pithecellobium dulce Leaf-Derived Carbon Dots for 4-Nitrophenol and Cr(VI) Detection
Authors: Torres Landa Simei Darinel , Kaur Inderbir , Agarwal Vivechana
Published: December 2022

Luminescent carbon dots (CDs) synthesized from Pithecellobium dulce (P. Dulce) leaves, in a simple, single-step carbonization procedure, were used as optical nanosensors. TEM revealed the crystalline nature of the CDs with the average dimension of 20 nm with a quantum yield of 24%. In addition to carbon, the X-ray photoelectron spectroscopy shows the presence of oxygen and nitrogen. The FTIR spectra and Zeta potential were used for additional characterization of the nanoprobes. Among the contaminants and heavy metals, the proposed nanoprobes were found to be selective towards 4-nitrophenol (4-NP) and Cr(VI), respectively. The emission response of CDs towards 4-NP solution not only reveals the high sensitivity of the CDs (Limit of detection (LOD) of 14 nM) but also demonstrates a color change (light to dark yellow) that is attributed to spontaneous deprotonation detectable with the naked eye. The selectivity of CDs towards Cr(VI) (LOD 0.9 nM) was also tested in the presence of other metals. The quenching mechanism has been attributed to the inner filter effect for both analytes. The observed low detection limits in river and tap water opens up the possible applicability of the proposed nanoprobes as optical sensors in environmental pollution monitoring.
Green Nanocomposite for the Adsorption of Toxic Dyes Removal from Colored Waters
Authors: Akbar Ishaa , Hanif Muhammad Asif , Rashid Umer , Bhatti Ijaz Ahmad , Khan Rais Ahmad , Kazerooni Elham Ahmed
Published: December 2022

The discharge of dyes from textile industries led to a broad range of toxicological and environmental effects, posing severe health issues for humans and animals worldwide. These dyes are highly stable and, if not adequately treated, remain in the environment for extended periods. Adsorption, the most efficient and cost-effective method, offers unique advantages for using natural adsorbents, such as marble waste composites, for dye removal. The easy availability of marble waste, its low cost, its eco-friendly nature, its ease of operation, its simplicity of design, its flexibility, and its great affinity for dyes make it a suitable option for dye removal. Golden marble waste nanocomposites are prepared for dye removal. The results from the studies suggested that treated golden marble composite materials exhibit better adsorption efficiency (224.8, 299.5, and 369.2 mg/g) for adsorptive removal of dyes than untreated golden marble composite materials (114.4 mg/g). This research also used isothermic and kinetic models to evaluate the effects of numerous parameters, for example, the initial dye concentration, pH, time, temperature, and adsorbent dose. The highest removal of 369.9 mg/g was achieved during the present study for blue dye at an optimized pH of 7 and a temperature of 30 °C. It was observed that golden marble waste composites gave better R2 (0.99) values for second-order kinetics in the kinetic model. Results obtained from comparing Langmuir, Freundlich, Temkin, Dubinin, and Herkin Jura isotherms showed that the R2 values of the Langmuir isotherm for Foron red (0.97), the Temkin isotherm for Foron blue (0.98), and the Freundlich isotherm for Foron black dye (0.97) fit on adsorption for both treated and untreated composites. Characterization techniques, such as scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), are also discussed for the structural determination of golden marble waste composites.
Mechanical and Morphological Properties of Cellulosic Fabrics Treated with Microencapsulated Essential Oils
Authors: Indrie Liliana , Affandi Nor Dalila Nor , Díaz-García Pablo , Haji Aminoddin , Ilies Dorina Camelia , Zlatev Zlatin , Taghiyari Hamid R. , Grama Vasile , Farima Daniela
Published: December 2022

This study focused on the mechanical and morphological properties of lignocellulosic heritage textiles (cotton and hemp) made using eco-friendly salvia and thyme microencapsulated essential oils, characterized by low toxicity for humans and the environment. A morphological evaluation of the tested fabrics was performed using scanning electron microscopy. The ATR–FTIR spectra of the untreated and treated fabric samples were tested using Perkin Elmer, Spectrum 3. A tensile test of the samples was conducted based on the ISO 13934-1 using a MESDAN-Lab tensile strength tester. According to the analysis, the salvia improved the tensile strength of the fabric by 20% and 39% in the warp and weft directions, respectively. The data for the untreated cotton, untreated hemp, and fabrics treated with salvia and thyme were processed using the kernel PCA method. From the principal component analysis it was found that the textile fabrics treated with salvia coalesced close to the untreated ones. This shows that treatment with essential oils from the indicated plant does not significantly affect the tensile properties of textile fabrics. The thymol-treated textile fabrics were significantly distant from those of the control sample. In cotton textile fabrics, thymol treatment was found to have a significant effect on their tensile properties. In hemp fabrics, two types of thymol and salvia treatments were found to have a very significant effect on the tensile strength performance of the textile fabrics. The results obtained can be used in museums, universities, and ethnographic studies that own or maintain collections of heritage textiles.
Nitrogen-Doped Graphene Sheets as Efficient Nanofillers at Ultra-Low Content for Reinforcing Mechanical and Wear-Resistant Properties of Acrylic Polyurethane Coatings
Authors: Xu Hui , Liu Danlian , Liang Lizhe , Tian Zhiqun , Shen Peikang
Published: December 2022

The enhancement of the mechanical and wear-resistant properties of polymer coatings plays a vital role for their application in hostile serving environments, and nanofiller is effective for this purpose. Herein, we systematically investigate a new nanofiller, nitrogen-doped graphene sheets (NGSs), which possess a multilayer sheet-like morphology and share a good compatibility with water. After the incorporation of NGS into a waterborne polyurethane (WPU), the mechanical and wear-resistant properties of NGS/WPU composite coatings significantly improve, and wear resistance behaves best at an ultra-low content, reaching up to 0.005 wt% (50 ppm). Furthermore, Young’s modulus is elevated by 52.67% and tensile strength is appreciably boosted by 58.87%. Simultaneously, an apparent reduction of weight loss of 78.74% is observed in the abrasion testing, and the ductility of NGS/WPU composite films is reduced by 48.38%. These make it possible that an ultra-low content of nanofiller efficiently reinforces polymer-based composites, with low cost in the wear-resistance related field.