bluuebunny/crossref_metadata_2025 huggingface dataset:
A Series of Genes for Predicting Responses to Anti-Tumor Necrosis Factor α Therapy in Crohn’s Disease
Authors: Nie Kai , Zhang Chao , Deng Minzi , Luo Weiwei , Ma Kejia , Xu Jiahao , Wu Xing , Yang Yuanyuan , Wang Xiaoyan
Published: April 2022

Background: Patients with Crohn’s disease (CD) experience severely reduced quality of life, particularly those who do not respond to conventional therapies. Antitumor necrosis factor (TNF)α is commonly used as first-line therapy; however, many patients remain unresponsive to this treatment, and the identification of response predictors could facilitate the improvement of therapeutic strategies.

Methods: We screened Gene Expression Omnibus (GEO) microarray cohorts with different anti-TNFα responses in patients with CD (discovery cohort) and explored the hub genes. The finding was confirmed in independent validation cohorts, and multiple algorithms and in vitro cellular models were performed to further validate the core predictor.

Results: We screened four discovery datasets. Differentially expressed genes between anti-TNFα responders and nonresponders were confirmed in each cohort. Gene ontology enrichment revealed that innate immunity was involved in the anti-TNFα response in patients with CD. Prediction analysis of microarrays provided the minimum misclassification of genes, and the constructed network containing the hub genes supported the core status of TLR2. Furthermore, GSEA also supports TLR2 as the core predictor. The top hub genes were then validated in the validation cohort (GSE159034; p < 0.05). Furthermore, ROC analyses demonstrated the significant predictive value of TLR2 (AUC: 0.829), TREM1 (AUC: 0.844), and CXCR1 (AUC: 0.841). Moreover, TLR2 expression in monocytes affected the immune–epithelial inflammatory response and epithelial barrier during lipopolysaccharide-induced inflammation (p < 0.05).

Conclusion: Bioinformatics and experimental research identified TLR2, TREM1, CXCR1, FPR1, and FPR2 as promising candidates for predicting the anti-TNFα response in patients with Crohn’s disease and especially TLR2 as a core predictor.
Effect of Crocin From Saffron (Crocus sativus L.) Supplementation on Oxidant/Antioxidant Markers, Exercise Capacity, and Pulmonary Function Tests in COPD Patients: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Ghobadi Hassan , Abdollahi Nasim , Madani Hanieh , Aslani Mohammad Reza
Published: April 2022

Background: Chronic obstructive pulmonary disease (COPD) is a progressive and chronic respiratory disorder characterized by reversible airflow limitation and lung parenchyma destruction. The main feature of COPD is inflammation and disturbance of the oxidant/antioxidant balance in the airways. The therapeutic use of herbal supplements with antioxidant and anti-inflammatory properties seems to be very useful in the medical management of patients with COPD.

Method: COPD patients were divided into placebo and intervention groups (each group n = 23) in a clinical trial study. The intervention group received crocin supplementation (30 mg/day for 12 weeks), and the control group received a placebo. Pre- and after the intervention, pulmonary function tests (PFTs), exercise capacity (using a 6-min walking distance test (6MWD)), and serum levels of total oxidant status (TOS), total antioxidant capacity (TAOC), and NF-kB were assessed using the ELISA test.

Results: Intervention with crocin for 12 weeks in COPD patients decreased serum levels of TOS and NF-κB as well as increased TAOC. In addition, the results of the 6MWD test reveal an improvement in patients’ exercise capacity.

Conclusion: Crocin supplementation appears to effectively establish oxidant/antioxidant balance and improve inflammatory conditions in patients with COPD.
Immunological Changes in Pregnancy and Prospects of Therapeutic Pla-Xosomes in Adverse Pregnancy Outcomes
Authors: Devvanshi Himadri , Kachhwaha Rohit , Manhswita Anima , Bhatnagar Shinjini , Kshetrapal Pallavi
Published: April 2022

Stringent balance of the immune system is a key regulatory factor in defining successful implantation, fetal development, and timely parturition. Interference in these primary regulatory mechanisms, either at adolescence or prenatal state led to adverse pregnancy outcomes. Fertility restoration with the help of injectable gonadotrophins/progesterone, ovulation-inducing drugs, immunomodulatory drugs (corticosteroids), and reproductive surgeries provides inadequate responses, which manifest its own side effects. The development of a potential diagnostic biomarker and an effectual treatment for adverse pregnancy outcomes is a prerequisite to maternal and child health. Parent cell originated bi-layered-intraluminal nano-vesicles (30–150 nm) also known as exosomes are detected in all types of bodily fluids like blood, saliva, breast milk, urine, etc. Exosomes being the most biological residual structures with the least cytotoxicity are loaded with cargo in the form of RNAs (miRNAs), proteins (cytokines), hormones (estrogen, progesterone, etc.), cDNAs, and metabolites making them chief molecules of cell-cell communication. Their keen involvement in the regulation of biological processes has portrayed them as the power shots of cues to understand the disease’s pathophysiology and progression. Recent studies have demonstrated the role of immunexosomes (immunomodulating exosomes) in maintaining unwavering immune homeostasis between the mother and developing fetus for a healthy pregnancy. Moreover, the concentration and size of the exosomes are extensively studied in adverse pregnancies like preeclampsia, gestational diabetes mellitus (GDM), and preterm premature rupture of membrane (pPROMs) as an early diagnostic marker, thus giving in-depth information about their pathophysiology. Exosomes have also been engineered physically as well as genetically to enhance their encapsulation efficiency and specificity in therapy for cancer and adverse pregnancies. Successful bench to bedside discoveries and interventions in cancer has motivated developmental biologists to investigate the role of immunexosomes and their active components. Our review summarizes the pre-clinical studies for the use of these power-shots as therapeutic agents. We envisage that these studies will pave the path for the use of immunexosomes in clinical settings for reproductive problems that arise due to immune perturbance in homeostasis either at adolescence or prenatal state.
Cold Exposure Induces Intestinal Barrier Damage and Endoplasmic Reticulum Stress in the Colon via the SIRT1/Nrf2 Signaling Pathway
Authors: Guo Jingru , Hu Huijie , Chen Zhuo , Xu Jing , Nie Junshu , Lu Jingjing , Ma Li , Ji Hong , Yuan Jianbin , Xu Bin
Published: April 2022

Ambient air temperature is a key factor affecting human health. Long-term exposure to a cold environment can cause various diseases, while the impact on the intestine, the organ which has the largest contact area with the external environment, cannot be ignored. In this study, we investigated the effect of chronic cold exposure on the colon and its preliminary mechanism of action. Mice were exposed to 4°C for 3 hours a day for 10 days. We found that cold exposure damaged the morphology and structure of the colon, destroyed the tight junctions of the colonic epithelial tissue, and promoted inflammation of the colon. At the same time, cold exposure also activated the unfolded protein response (UPR) in the colon and promoted apoptosis in intestinal epithelial cells. Chronic cold exposure induced oxidative stress in vivo, but also significantly enhanced the response of the Nrf2 pathway that promotes an anti-oxidant effect. Furthermore, we demonstrated that chronic cold exposure promoted p65 acetylation to aggravate the inflammatory response by inhibiting SIRT1. Similar results were observed following SIRT1 knock-down by shRNA in Caco-2 cells treated with Thapsigargin (Tg). Knock-down of SIRT1 promoted nuclear localization of Nrf2, and increased the level of Nrf2 acetylation. Taken together, our study indicates that cold exposure may aggravate endoplasmic reticulum stress and damage epithelial tight junctions in the colon by inhibiting SIRT1, which promotes nuclear localization of Nrf2 and induces an anti-oxidant response to maintain intestinal homeostasis. These findings suggest that SIRT1 is a potential target for regulating intestinal health under cold exposure conditions.
Road to Tokyo 2020 Olympic Games: Training Characteristics of a World Class Male Triathlete
Authors: Cejuela Roberto , Sellés-Pérez Sergio
Published: April 2022

There is a growing interest in the scientific literature for reporting top-class endurance athletes training programs. This case study reports on the training program of a world-class male triathlete preparing to compete in the Tokyo 2020 Olympic Games. A macrocycle of 43 weeks is presented. The triathlete performed 14.74 ± 3.01 h of weekly endurance training volume. Training intensity distribution (TID) was 81.93% ± 6.74%/7.16% ± 2.03%/10.91% ± 6.90% for zones 1 (low intensity, VT2) respectively. Pyramidal TID model is observed during the initial stages of the periodization and Polarized TID model is observed at the end of the macrocycle. The triathlete’s peak ⩒O2 was increased by 20% on cycling and by 14% on running. Peak power was increased by 3.13% on cycling test and peak speed by 9.71% on running test. Finally, the triathlete placed 12th in Olympic distance and 10th in Mixed Relay in Tokyo 2020 Olympic games.
Odor-Induced Vomiting Is Combinatorially Triggered by Palp Olfactory Receptor Neurons That Project to the Lobus Glomerulatus in Locust Brain
Authors: Sun Liyuan , Pan Xueqin , Li Hongwei , Zhang Xinyang , Zhao Xincheng , Zhang Liwei , Zhang Long
Published: April 2022

Although vomiting is commonly recognized as a protective reaction in response to toxic stimuli, the elaborate sensory processes and necessary molecular components are not fully clear, which is due to a lack of appropriate experimental animal models. Vomiting reflex to volatile chemicals renders locust one candidate for vomiting model. Here, we identified a panel of chemical cues that evoked evident vomiting in locust nymphs and demonstrated the selected combinatorial coding strategy that palps but not antennae olfactory receptor neurons (ORNs) employed. Specifically, knocking down individual palp odorant receptors (ORs) such as OR17, OR21, and OR22 attenuated the vomiting intensity evoked by E-2-hexenal and hexanal, while suppression of OR12 and OR22 augmented vomiting to E-2-hexenal and 2-hexanone, respectively. Furthermore, dual-RNAi treatment against OR17 or OR21 together with OR22 resulted in a much lower response intensity than that of individual OR suppression. Furthermore, OR12 was revealed in palp sensilla basiconica (pb) subtype 3 to tune the neuronal decaying activity to E-2-hexenal. Finally, anterograde labeling indicated that palp ORNs primarily projected into the lobus glomerulatus (LG), and the projection neurons (PNs) in the LG further projected into the accessary calyx (ACA). Together, the establishment of an olfaction-inducible vomiting model in locusts deepens the understanding of olfactory coding logics and provides an opportunity to clarify the neural basis underlying animal vomiting.
Insulin-Like ILP2 Regulates Trehalose Metabolism to Tolerate Hypoxia/Hypercapnia in Tribolium castaneum
Authors: Wang Yuan-Yuan , Zhang Xin-Yu , Mu Xue-Rui , Li Xian , Zhou Min , Song Yue-Hua , Xu Kang-Kang , Li Can
Published: April 2022

RNAi was used to downregulate the expression of insulin-like peptides (ILP2), with air-modulation, and high-concentration CO2 stress, in the larvae of Tribolium castaneum. We assessed the changes in carbohydrate-related content, trehalase activity, and the expression levels of trehalose pathway genes. And pupation, adult emergence, pupation rate, and mortality were assessed. There was a significant change in the expression of ILPs in T. castaneum, at a certain concentration of CO2. ILP2 RNAi did not alter the trehalose content significantly, however, the glycogen and glucose content increased significantly. High-concentration CO2 stress altered the trehalose content and reduced the glycogen and glucose content. The expression levels of TPS and TRE2 were up-regulated by hypoxia/hypercapnia and dsILP2 combination, with the increase of CO2 concentration, other trehalase genes begin to respond successively. ILP2 knockout raised the mortality and reduced the pupation rate and eclosion rate in CO2. Understanding the insulin pathway responses to hypoxic stress induced by a high concentration of CO2 would further elucidate the mechanisms underlying trehalose metabolism in insects.
Early Biomarkers of Altered Renal Function and Orthostatic Intolerance During 10-day Bedrest
Authors: Tamma Grazia , Di Mise Annarita , Ranieri Marianna , Centrone Mariangela , Venneri Maria , D’Agostino Mariagrazia , Ferrulli Angela , Šimunič Boštjan , Narici Marco , Pisot Rado , Valenti Giovanna
Published: April 2022

Exposure to actual or simulated microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion. We provided evidence that high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2)-mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration to reduce calcium saturation. To investigate early renal adaptation into simulated microgravity, we investigated the effects of 10 days of strict bedrest in 10 healthy volunteers. We report here that 10 days of inactivity are associated with a transient, significant decrease (day 5) in vasopressin (copeptin) paralleled by a decrease in AQP2 excretion, consistent with an increased central volume to the heart, resulting in reduced water reabsorption. Moreover, bedrest caused a significant increase in calciuria secondary to bone demineralization paralleled by a decrease in PTH. Urinary osteopontin, a glycoprotein exerting a protective effect on stone formation, was significantly reduced during bedrest. Moreover, a significant increase in adrenomedullin (day 5), a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity post-bedrest. We conclude that renal function is altered in simulated microgravity and is associated with an early increase in the risk of stone formation and reduced orthostatic capacity post-bedrest within a few days of inactivity.
Preserved Electroencephalogram Power and Global Synchronization Predict Better Neurological Outcome in Sudden Cardiac Arrest Survivors
Authors: Ho Li-Ting , Serafico Bess Ma. Fabinal , Hsu Ching-En , Chen Zhao-Wei , Lin Tse-Yu , Lin Chen , Lin Lian-Yu , Lo Men-Tzung , Chien Kuo-Liong
Published: April 2022

Quantitative EEG (qEEG) delineates complex brain activities. Global field synchronization (GFS) is one multichannel EEG analysis that measures global functional connectivity through quantification of synchronization between signals. We hypothesized that preservation of global functional connectivity of brain activity might be a surrogate marker for good outcome in sudden cardiac arrest (SCA) survivors. In addition, we examined the relation of phase coherence and GFS in a mathematical approach. We retrospectively collected EEG data of SCA survivors in one academic medical center. We included 75 comatose patients who were resuscitated following in-hospital or out-of-hospital nontraumatic cardiac arrest between 2013 and 2017 in the intensive care unit (ICU) of National Taiwan University Hospital (NTUH). Twelve patients (16%) were defined as good outcome (GO) (CPC 1–2). The mean age in the GO group was low (51.6 ± 15.7 vs. 68.1 ± 12.9, p < 0.001). We analyzed standard EEG power, computed EEG GFS, and assessed the cerebral performance category (CPC) score 3 months after discharge. The alpha band showed the highest discrimination ability (area under curve [AUC] = 0.78) to predict GO using power. The alpha band of GFS showed the highest AUC value (0.8) to predict GO in GFS. Furthermore, by combining EEG power + GFS, the alpha band showed the best prediction value (AUC 0.86) in predicting GO. The sensitivity of EEG power + GFS was 73%, specificity was 93%, PPV was 0.67%, and NPV was 0.94%. In conclusion, by combining GFS and EEG power analysis, the neurological outcome of the nontraumatic cardiac arrest survivor can be well-predicted. Furthermore, we proved from a mathematical point of view that although both amplitude and phase contribute to obtaining GFS, the interference in phase variation drastically changes the possibility of generating a good GFS score.
Between Multiple Identities and Values: Professionals’ Identity Conflicts in Ethically Charged Situations
Authors: Carminati Lara , Héliot YingFei Gao
Published: April 2022

This study explored identity conflict dynamics in interpersonal interactions in professionals facing ethically charged situations. Through semi-structured interviews (N = 47), we conducted a qualitative study among doctors and nurses working for the English National Healthcare Service and analyzed the data with grounded theory approaches. Our findings reveal that identity conflict is triggered by three micro processes, namely cognitive and emotional perspective taking, as well as identifying with the other. In these processes, identity conflict is signaled by emotions and recognized as a clash not only between identities and their values, but also within one identity and its multiple values. Behavioral and psychological outcomes of identity conflict involve seeking peer support, doing reflective practices and identity growth. This article contributes to identity literature by providing a multilevel approach of identity conflict dynamics able to account for both interpersonal and intrapsychic processes, deeply hold values and emotions, as well as crucial behavioral and psychological consequences.
Crystallization and physicochemical investigation of melevodopa hydrochloride, a commercially available antiparkinsonian active substance
Authors: Kiss Tamás , Katona Gábor , Ambrus Rita
Published: April 2022

In this work, the levodopa methyl ester was crystallized from different solvents and its physicochemical proper- ties were explored. This active pharmaceutical ingredient (API) is commercially available as an effervescent tablet in Italy. The crystallization methods were solvent evaporation from different solvents (water, ethanol, methanol) and crystalliza- tion by adding an antisolvent. These methods led to the same product which had the same different X­ray powder dif-fractogram that was different from the diffractogram of raw LDME. According to the hot­stage microscopy and differential scanning calorimetry (DSC), the melting point was remarkably decreased, however, above the melting point, the melt tended to recrystallize to the raw LDME which was shown by an exothermic peak on the DSC curve. This was verified by an additional test during which the API was heated to 145 °C, thereafter the diffractogram matched perfectly with theraw LDME. These results indicate the presumable formation of a new polymorph. During the crystallization, the LDME did not degrade according to the high-performance liquid chromatography. Besides the recrystallization kinetics of the amorphous form was also followed, the activation energy of recrystallization was 85.3 kJ/mol, the diffractogram of recrys- tallization was the same as in the case of the crystallized products.
Insulin for topical use in wound healing: opportunities and limitations
Authors: Benkő Beáta-Mária , Sebe István , Szabó Zoltán-István
Published: April 2022

Aims: The role of insulin in the regulation of energy metabolism, protein synthesis, proliferation, migration, secretion by keratinocytes, endothelial cells, and fibroblasts suggests that its presence is essential for wound healing (WH). The present study aims to explore the opportunities and limitations of topical insulin (TI) formulations. Methods: To obtain a complete picture of the challenges of the local insulin formulation a chronological review of previous publications in electronic databases was performed, applying data collection and selection criteria. Results: The opportunity of topically applied insulin has shown active interest over time. According to studies, regular insulin and isophane are suitable for local use, but currently there is no consensus on the appropriate concentration. Insulin can be incorporated into cutaneous liquid, semisolid, and solid dosage forms, either by itself, or by prior nano-or microencapsulation methods. The most important limiting factors to be evaluated are the stability of the peptide and the sterility of the obtained products. Conclusion: Examination of the balance of opportunities and limitations of TI formulations, it can be concluded that the range of  applicable technological methods is wide. A high-quality, safe, and efficacious form of TI would have great value from a socio-economic point of view.
Source Areas as a Key Factor Contributing to the Recovery Time of Controlled Feral Pigeon (Columba livia var. domestica) Colonies in Low-Density Urban Locations
Authors: Farfán Aguilar Miguel Ángel , Duarte Jesús , Díaz-Ruiz Francisco
Published: April 2022

Today, governments and administrations strive to minimise issues associated with Feral Pigeon (Columba livia var. domestica) colonies in urban areas. Scientific evidence has demonstrated that control measures are ineffective in the long term, and colonies recover rapidly. Most scientific research has occurred under high-density circumstances, primarily in large city centres. Moreover, very few studies have been conducted in residential zones or suburban areas where colony densities are lower, but where Feral Pigeons generate the same issues. In this study, we analysed the recovery time of Feral Pigeon colonies in 11 buildings in low-density urban areas where control campaigns were previously conducted to reduce their abundance. Recovery times were highly variable among the buildings (50–3072 days). Distance to the nearest uncontrolled colony of Feral Pigeons, i.e., a source area, was the primary factor that contributed to recovery time, which significantly increased with increasing distance to source colonies. Thus, buildings closest to the Pigeons’ source areas (<500 m) were recolonised more rapidly than were buildings that were >500 m away from source areas. Our findings highlight the relevance of identifying an effective management unit for the implementation of control programmes to reduce immigration rates and increase long-term effects.
BifA Triggers Phosphorylation of Ezrin to Benefit Streptococcus equi subsp. zooepidemicus Survival from Neutrophils Killing
Authors: Pan Fei , Peng Jie , Yu Dandan , Li Lianyue , Fan Hongjie , Ma Zhe
Published: April 2022

Streptococcus equi subsp. zooepidemicus (SEZ) ATCC35246 can invade the brain and cause severe neutrophils infiltration in brain tissue. This microorganism can survive and reproduce to an extremely high CFU burden (108–109/organ) under stressful neutrophils infiltration circumstances. The aim of this research is to explore the mechanism of the SEZ hypervirulent strain with its specific bifA gene which avoids being eliminated by neutrophils in the brain. We isolated the primary mouse neutrophils to treat SEZ WT and bifA gene defective (ΔBif) strains. The ΔBif strain had a weakened function of defending against neutrophils killing in vitro. The interaction between BifA and ezrin proteins in neutrophils were identified by co-IP and immunoblot. In neutrophils, the BifA interacts with ezrin and triggers the phosphorylation of ezrin at its Thr567 site in a PKC-dependent manner, then the excessive elevation of phosphorylated-ezrin recruits Dbl and activates Rac1. Since the Rac1 is closely relevant to several critical cellular functions, its abnormal activation will lead to neutrophils dysfunction and benefit to SEZ survival from neutrophils killing. Our findings reveal a novel consequence of BifA and ERM family protein (for ezrin, radixin, moesin) interaction, which happens between BifA and ezrin in neutrophils and contributes to SEZ survival in the brain. BifA should be considered as a potential target for drug development to prevent SEZ infection.
Pre- and Postnatal Vitamin D Status and Allergy Outcomes in Early Childhood
Authors: Rueter Kristina , Siafarikas Aris , Palmer Debra J. , Prescott Susan L.
Published: April 2022

The dramatic increase in the prevalence of allergic disease in recent decades reflects environmental and behavioural changes that have altered patterns of early immune development. The very early onset of allergic diseases points to the specific vulnerability of the developing immune system to environmental changes and the development of primary intervention strategies is crucial to address this unparalleled burden. Vitamin D is known to have immunomodulatory functions. While allergic disease is multifactorial, associations with reduced sunlight exposure have led to the hypothesis that suboptimal vitamin D levels during critical early periods may be one possible explanation. Interventions to improve vitamin D status, especially in early life, may be the key to allergic disease prevention.
Front-Line Therapy for Metastatic Renal Cell Carcinoma: A Perspective on the Current Algorithm and Future Directions
Authors: Govindarajan Ameish , Castro Daniela V. , Zengin Zeynep B. , Salgia Sabrina K. , Patel Jalen , Pal Sumanta K.
Published: April 2022

Over the last decade, the treatment paradigm of metastatic renal cell carcinoma has rapidly evolved, with notable changes in the front-line setting. Combination therapies involving the use of either doublet therapy with immune checkpoint inhibitors or combination VEGFR-directed therapies with immune checkpoint inhibitors have significantly improved clinical outcomes, including prolonged overall survival and durable response to treatment. We aim to highlight the Food and Drug Administration-approved front-line therapy options, the navigation of treatment selection, and the future directions of metastatic renal cell carcinoma therapies.
Current and Developing Liquid Biopsy Techniques for Breast Cancer
Authors: Wu Hsing-Ju , Chu Pei-Yi
Published: April 2022

Breast cancer is the most commonly diagnosed cancer and leading cause of cancer mortality among woman worldwide. The techniques of diagnosis, prognosis, and therapy monitoring of breast cancer are critical. Current diagnostic techniques are mammography and tissue biopsy; however, they have limitations. With the development of novel techniques, such as personalized medicine and genetic profiling, liquid biopsy is emerging as the less invasive tool for diagnosing and monitoring breast cancer. Liquid biopsy is performed by sampling biofluids and extracting tumor components, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free mRNA (cfRNA) and microRNA (miRNA), proteins, and extracellular vehicles (EVs). In this review, we summarize and focus on the recent discoveries of tumor components and biomarkers applied in liquid biopsy and novel development of detection techniques, such as surface-enhanced Raman spectroscopy (SERS) and microfluidic devices.
Incidence and Risk Factors for Cerebrovascular-Specific Mortality in Patients with Colorectal Cancer: A Registry-Based Cohort Study Involving 563,298 Patients
Authors: Dai Zhi-Hui , Tang Ming , Chen Yun-Liang , Zhang Tao-Lan , Li Jing , Lv Guo-Hua , Yan Yi-Guo , Ouyang Zhi-Hua , Huang Wei , Zou Ming-Xiang
Published: April 2022

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive, and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from the Surveillance Epidemiology and End Results database, with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general U.S. population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563,298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among the competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during the study period. While age, surgery, other/unknown race and tumors located at the transverse colon positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, a more recent year (2001–2015) of diagnosis, a grade II or III CRC, rectal cancer, or multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM that may be helpful for risk stratification and the therapeutic optimization of cerebrovascular-specific diseases in CRC patients.
Gp130-Mediated STAT3 Activation Contributes to the Aggressiveness of Pancreatic Cancer through H19 Long Non-Coding RNA Expression
Authors: Sasaki Norihiko , Hirano Kazumi , Shichi Yuuki , Gomi Fujiya , Yoshimura Hisashi , Matsushita Akira , Toyoda Masashi , Ishiwata Toshiyuki
Published: April 2022

Signaling pathways involving signal transducer and activator of transcription 3 (STAT3) play key roles in the aggressiveness of pancreatic ductal adenocarcinoma (PDAC), including their tumorigenesis, invasion, and metastasis. Cancer stem cells (CSCs) have been correlated with PDAC aggressiveness, and activation of STAT3 is involved in the regulation of CSC properties. Here, we investigated the involvement of interleukin-6 (IL-6) or the leukemia inhibitory factor (LIF)/glycoprotein 130 (gp130)/STAT3 pathway and their role in pancreatic CSCs. In PDAC CSC-like cells formed by culturing on a low attachment plate, autocrine/paracrine IL-6 or LIF contributes to gp130/STAT3 pathway activation. Using a gp130 inhibitor, we determined that the gp130/STAT3 pathway contributes to the maintenance of stemness features, the expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), and the invasion of PDAC CSC-like cells. The gp130/STAT3 pathway also modulates the transforming growth factor (TGF)-β1/Smad pathway required for epithelial-mesenchymal transition induction through regulation of TGFβ-RII expression in PDAC CSC-like cells. Furthermore, chromatin immunoprecipitation assays revealed that p-STAT3 can access the active promoter region of H19 to influence this metastasis-related long non-coding RNA and contribute to its transcription in PDAC CSC-like cells. Therefore, the autocrine/paracrine IL-6 or LIF/gp130/STAT3 pathway in PDAC CSC-like cells may eventually facilitate invasion and metastasis, two hallmarks of malignancy. We propose that inhibition of the gp130/STAT3 pathway provides a promising strategy for targeting CSCs for the treatment of PDAC.
Signaling Pathways in Pregnancy
Authors: Tossetta Giovanni , Marzioni Daniela
Published: April 2022

We are pleased to present this Special Issue of Cells, entitled ‘Signaling Pathways in Pregnancy’ [...]
Thermal Metrics to Identify Canadian Coastal Environments
Authors: Gough William A.
Published: April 2022

A thermal metric developed using the day-to-day temperature variability framework that was previously applied to the east coast of China has been adapted for Canadian climate station data. The same metric, based on the variability of the minimum temperature of the day, was able to distinguish between coastal and inland stations, especially when the winter months of December, January and February, were removed from the analysis. While the threshold of the metric that distinguished between the two groups was different than that developed for the east coast of China, it was nonetheless unambiguous. The range of latitudes in the Canadian setting was sufficiently narrow that a latitude correction, as was performed for the China climate stations, was not required. A comparison with a more traditional measure of continentality suggests that the thermal variability measure performs better at identifying the coastal/continental nature of the climate station data. This work also suggests that a more nuanced treatment of winter months should be considered for all such measures in colder climates.
Research on the Corrosion Behaviors of Austenitic Steel in Molten Aluminum Alloy
Authors: Bai Zhixiong , Su Ning , Yang Hang , Wu Xiaochun
Published: April 2022

Die corrosion has been a concern during aluminum alloy die casting. The casting parameters play a significant role in causing corrosion, such as the temperature of the aluminum alloy melt and working time. In order to study the effect of temperature and working time on dynamic corrosion behaviors, SDHA steel was stirred in molten ADC12 aluminum alloy at 650–800 °C. The corrosion morphology and corrosion product were investigated through X-ray diffraction (XRD) and scanning electron microscope (SEM) observations. The results show that the matrix reacts with aluminum alloy to form an Al8Fe2Si phase at experimental temperatures. The growth activation energy of the Al8Fe2Si phase is 89 kJ/mol. The dynamic corrosion rate rises with increasing temperature and holding time. The most serious corrosion was found when the experimental temperature reached 800 °C, which is closely related to the peeling of matrix and the formation of Al8Fe2Si at the grain boundary. Besides, the vanadium carbides in the matrix act as barriers to hinder the diffusion of Al and Si atoms effectively.
Functional and Taxonomic Overlap in Shore Fish Assemblages in a Tropical Seascape
Authors: Kulbicki Michel , Wantiez Laurent , Thollot Pierre , Tham Gérard
Published: April 2022

The relationships between shore fish assemblages from habitats neighboring coral reefs have received little attention in the Indo-Pacific. The present study is based on the extensive sampling (539,000 fish; 898 taxa) of three fish assemblages: reefs, mangroves, and soft-bottoms in a large bay of New Caledonia. Species area curves indicate that sampling was nearly exhaustive in all three habitats (262 species in mangroves, 342 on soft-bottoms, 594 on reefs). Combinations of life-history traits were used as proxies of ecological functions. The species and functional overlaps were highest between soft-bottoms and mangroves and lowest between mangroves and reefs. These overlaps were lower than most recent studies in the Indo-Pacific, a result probably linked to the extent of the sampling in the present study. The life-history traits of species found exclusively in one habitat as opposed to several habitats were not a random selection within the species pool. Overlapping species were mostly large species that fed on nekton, large invertebrates, or plankton; exclusive species were mostly sedentary, solitary, and of small size, except for plankton-feeding species, which mostly had large home ranges and formed large schools. Herbivores were seldom found in several habitats. Functional redundancy was correlated to species richness, and was highest in reef fish assemblages. Functions common to several habitats had very seldom the same relative redundancy, implying that these functions had not the same importance for each assemblage. Functions exclusive to one habitat generally had low redundancy. These functional attributes and species overlap suggest that these three assemblages have a low level of interaction, despite the fact that they share extensive boundaries. These findings may have important applications in the management of shore fish assemblages.
Therapeutic Advances and Challenges in the Management of HER2-Positive Gastroesophageal Cancers
Authors: Chuang Jeremy , Klempner Samuel , Waters Kevin , Atkins Katelyn , Chao Joseph , Cho May , Hendifar Andrew , Gangi Alexandra , Burch Miguel , Mehta Pareen , Gong Jun
Published: April 2022

Gastroesophageal cancer is one of the most common cancers in the world, with a high rate of mortality. While there has been significant progress over the past decade, particularly with the addition of anti-HER2 therapies to platinum-based chemotherapy agents in the advanced setting, the prognosis remains poor and the treatment options for this disease entity remain limited. In this review, we discuss the current therapeutic landscape for HER2-positive gastroesphageal cancer and the seminal clinical trials that have shaped our approach to this disease entity. In addition, we highlight some of the challenges to the understanding and management of this disease, specifically discussing the breadth of molecular diversity and intratumoral heterogeneity of HER2 expression that impact the clinical efficacy and prognosis. Furthermore, we discuss the potential role of next-generation sequencing (NGS) and circulating-tumor DNA (ctDNA) as complementary tools to immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH) to guiding clinical decision making. Finally, we highlight promising clinical trials of new treatment regimens that will likely reshape the therapeutic approach to this disease entity.
Algorithmic Modelling of Financial Conditions for Macro Predictive Purposes: Pilot Application to USA Data
Authors: Qin Duo , van Huellen Sophie , Wang Qing Chao , Moraitis Thanos
Published: April 2022

Aggregate financial conditions indices (FCIs) are constructed to fulfil two aims: (i) The FCIs should resemble non-model-based composite indices in that their composition is adequately invariant for concatenation during regular updates; (ii) the concatenated FCIs should outperform financial variables conventionally used as leading indicators in macro models. Both aims are shown to be attainable once an algorithmic modelling route is adopted to combine leading indicator modelling with the principles of partial least-squares (PLS) modelling, supervised dimensionality reduction, and backward dynamic selection. Pilot results using US data confirm the traditional wisdom that financial imbalances are more likely to induce macro impacts than routine market volatilities. They also shed light on why the popular route of principal-component based factor analysis is ill-suited for the two aims.
Executive Turnover and Founder CEO Experience: Effect on New Ventures’ R&D Investment
Authors: Cho Hyejin , Lee Pyoungsoo , Shin Choong Ho
Published: April 2022

As the direction and strategies of new ventures depend on the top management team (TMT)’s stability and continuous efforts, we investigate the relationship between executive turnover and research and development (R&D) investment investment. Furthermore, we assess the moderating role of the founder chief executive officer (CEO)’s prior experiences to show that founders’ experiential knowledge mitigates the adverse side effects of executives’ departure. Our empirical analysis utilizes a large pool of firm-level survey datasets comprising 1897 Korean founder-led ventures. The empirical results show that executive turnover reduces R&D intensity, suggesting that new ventures’ longer-term investments may be affected by the instability of the management team. We also show that the negative effects of executive turnover weaken when the founder CEO has a longer prior work experience, prior business group experience, and founding experience. Our findings show that the founder CEO’s entrepreneurship based on valuable prior experiential knowledge mitigates the negative impact of organizational instability. While the TMT factor is essential for a new venture’s survival, our findings show that the manner in which leaders act should also be considered separately.
Biodegradation of Methylene Blue Using a Novel Lignin Peroxidase Enzyme Producing Bacteria, Named Bacillus sp. React3, as a Promising Candidate for Dye-Contaminated Wastewater Treatment
Authors: Pham Van Hong Thi , Kim Jaisoo , Chang Soonwoong , Chung Woojin
Published: April 2022

The emission of methylene blue (MB) from common industries causes risks to human health by making clean drinking water unavailable and hampering environmental safety. A biological approach offering a more cost-efficient and sustainable alternative solution has been studied and demonstrated to be significantly effective for the removal of MB using promising microbial isolates. Therefore, this study targeted bacterial candidates, namely Bacillus sp. React3, isolated from soil with the potential to decolorize MB. The phenogenic identification of strain React3 was performed by 16S rRNA sequencing, showing a similarity of 98.86% to Bacillus velezensis CR-502T. The ability of this bacterial strain to decolorize MB was proven through both the lignin peroxidase efficiency and accumulation in the biomass of the living cells. MB removal was determined by the reduction in the maximum absorption at a wavelength of 665 nm, which was observed to be up to 99.5% after 48 h of incubation. The optimal conditions for the MB degradation of strain React3 were pH 7, 35 °C, static, 4% inoculum, and 1000 mg/L of MB, with tryptone as a carbon source and yeast extract as a nitrogen source.
Screening of Estrogenic-Disrupting Compounds in Dairy Products Based on the Estrogen Receptor Cocktail
Authors: Li Xiaoqi , Du Shuyuan , Tian Fangyuan , Wang Minglu , Wang Ying , Zhang Hongyan , Zang Liguo
Published: April 2022

The residue of estrogenic-disrupting compounds (EDCs) that are secreted by cows, added as drugs, and present in the feed may exist in dairy products. A gold nanoparticles (AuNPs)-estrogen receptor (ER) cocktail colorimetric assay equipped with ER cocktail solid phase extraction (SPE) was established to screen EDCs. Nine EDCs with high, moderate, and low estrogenic activity were selected to be the representative targets. The recognition range of the colorimetric assay combined with the ER cocktail SPE was wider than that of a single ERα or ERβ. The lowest detection limit of the established assay was about 10−9 mg·mL−1. The detection limits of estrone, bisphenol A, and bisphenol B were about one order of magnitude lower than the method based on a single ER. The recoveries of the spiked nine EDCs were between 80.0% and 110.0%, and daidzein was identified in the dairy product. The developed method has potential application prospects in food safety and environmental monitoring.
Polyphenols Recovery from Thymus serpyllum Industrial Waste Using Microwave-Assisted Extraction–Comparative RSM and ANN Approach for Process Optimization
Authors: Mrkonjić Živan , Rakić Dušan , Takači Aleksandar , Kaplan Muammer , Teslić Nemanja , Zeković Zoran , Lazarević Ivana , Pavlić Branimir
Published: April 2022

The aim of this study was to valorize Thymus serpyllum L. herbal dust, the particular fraction distinguished as industrial waste from filter-tea production. This work demonstrated comparable analysis considering model fitting, influence analysis and optimization of microwave-assisted extraction (MAE) of bioactive compounds from the aforementioned herbal dust using face-centered central composite experimental design within the response surface methodology (RSM), as well as artificial neural networks (ANN). In order to increase yield and amount of compounds of interest and minimize solvent, time and energy consumption, the ethanol concentration (45, 60 and 75%), extraction time (5, 12.5 and 20 min), liquid–solid ratio (10, 20 and 30 mL/g) and irradiation power (400, 600 and 800 W) were used as independent variables. Total extraction yield (Y), total phenols yield (TP), as well as antioxidant activity parameters obtained by DPPH and ABTS assays, were selected as responses. It could be concluded that the MAE technique is an efficient approach for the extraction of biologically active compounds from T. serpyllum herbal dust, which represents a high-value source of natural antioxidants with great potential for further use in various forms within different branches of industry.
Effect of Pulsed Light on Quality of Shelled Walnuts
Authors: Gómez-López Vicente Manuel , Noguera-Artiaga Luis , Figueroa-Morales Fernando , Girón Francisco , Carbonell-Barrachina Ángel Antonio , Gabaldón José Antonio , Pérez-López Antonio Jose
Published: April 2022

Shelled walnuts are considered a microbiologically low-risk food but have been linked to some outbreaks, and a treatment aiming to decrease this risk is desirable. Pulsed light (PL) may be an alternative, providing it does not seriously impair their quality. This work assessed the impact of PL on some quality attributes of walnuts. To do this, measurements of rancidity, volatiles, total phenols, antioxidant activity, and descriptive sensory analysis were carried out on untreated and PL (43 J/cm2)-treated kernels. PL had no statistically significant (p > 0.05) effects on TBARS, peroxide value, total phenols, and antioxidant activity but significantly increased the concentration of volatiles related to green/herbaceous odors and decreased compounds related to fruity and citrus odors. The descriptors nut overall, walnut odor and flavor, and aftertaste were given statistically significantly (p < 0.05) higher scores, while descriptors woody odor and sweet received lower scores; 16 other traits such as all those related to color, texture, and rancidity were unaffected. No significant (p > 0.05) effects on total phenols and antioxidant activity in general were observed during the course of PL treatment. It can be concluded that PL technology may be used in shelled walnuts with only mild effects on their quality; a storage study must be carried out in order to determine the effect of PL treatment on its shelf-life.
An Autopsy Case of Posterior Pharyngeal Abscesses Caused by Periodontal Bacteria
Authors: Bandou Risa , Ichioka Hiroaki , Kawamoto Masataka , Ikegaya Hiroshi
Published: April 2022

A woman in her seventies living alone was found dead on the floor of her living room. A blue-green swelling was found from her right cheek to her anterior neck and an autopsy was performed. The autopsy revealed subcutaneous abscesses from the right cheek to the anterior neck, posterior pharyngeal abscesses, mediastinal abscesses, pleuritis, and pericarditis. The cause of death was diagnosed as sepsis due to a retropharyngeal abscess caused by extensive severe periodontitis. The presence of a dentist at the autopsy allowed for a rapid diagnosis of periodontal disease, which was the cause of the posterior pharyngeal abscesses and septic shock. Therefore, the participation of a dentist in a forensic autopsy is important not only for personal identification but also for the rapid diagnosis of the cause of death.
The Distributed Kolkata Paise Restaurant Game
Authors: Kastampolidou Kalliopi , Papalitsas Christos , Andronikos Theodore
Published: April 2022

The Kolkata Paise Restaurant Problem is a challenging game in which n agents decide where to have lunch during their break. The game is not trivial because there are exactly n restaurants, and each restaurant can accommodate only one agent. We study this problem from a new angle and propose a novel strategy that results in greater utilization. Adopting a spatially distributed approach where the restaurants are uniformly distributed in the entire city area makes it possible for every agent to visit multiple restaurants. For each agent, the situation resembles that of the iconic traveling salesman, who must compute an optimal route through n cities. We rigorously prove probabilistic formulas that confirm the advantages of this policy and the increase in utilization. The derived equations generalize formulas that were previously known in the literature, which can be seen as special cases of our results.