bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of the Physical, Technological and Physico-Chemical Characteristics of Hazelnuts
Authors: Mammadov D. , Alieva R.
Published: June 2021

In the article, to study the physical, technological and physico-chemical characteristics of hazelnuts, promising varieties of hazelnuts were selected: Ata-baba, Oilseed hazelnuts, Ganja hazelnuts, Ashraf, Kudryavchik and Lombard hazelnuts. Their main dimensions, mass, core yield, solid shell thickness, etc. are measured and recorded. Some technological characteristics of the selected hazelnut varieties were studied. In accordance with the procedure, round-shaped hazelnuts, large and small of this size, were checked in factories for processing products with a diameter of less than 13.2 mm, and oblong nuts were taken as small nuts. Hazelnuts of the Ata-baba, Oilseed and Ashraf varieties became more suitable for processing on the equipment of the processing enterprise. One of the important parameters is the kernel output. The core output must be at least 35%. This indicator is 55.7% in the Ata-baba variety, 58% in the Oilseed hazelnuts. The Ganja variety had 54%. The main reserve substances of hazelnuts are proteins and lipids. The content of lipids in the studied varieties was 60.4–72.5%, proteins 15.8–17.8%, carbohydrates 11.4–20.11%, core moisture 3.98–7.49%. According to the certification requirements, the drained cores should not exceed 4%. Set coefficients of external and internal friction of hazelnuts with shell and core without shell so that when the humidity increases from 12% to 21% for xar of the fetus increases with 0.622 to 0.649, for dax with 0.461 to 0.523 accordingly, when the humidity increases core from 4% to 9% for xar with 0.570 to 0.603, for dax increased the odds with 0.418 to 0.453. This suggests that an increase in moisture content increases the ratio of external and internal friction of hazelnuts with shell and core without the shell. It was found that the damage to the fruit depends more on the humidity. It is considered important to maintain the moisture content of the product served for the breakdown within 14%.
Deubiquitinating Enzymes Orchestrate the Cancer Stem Cell-Immunosuppressive Niche Dialogue: New Perspectives and Therapeutic Potential
Authors: Guo Jun-Nan , Xia Bai-Rong , Deng Shen-Hui , Yang Chang , Pi Ya-Nan , Cui Bin-Bin , Jin Wei-Lin
Published: June 2021

Cancer stem cells (CSCs) are sparks for igniting tumor recurrence and the instigators of low response to immunotherapy and drug resistance. As one of the important components of tumor microenvironment, the tumor associated immune microenvironment (TAIM) is driving force for the heterogeneity, plasticity and evolution of CSCs. CSCs create the inhibitory TAIM (ITAIM) mainly through four stemness-related signals (SRSs), including Notch-nuclear factor-κB axis, Hedgehog, Wnt and signal transducer and activator of transcription. Ubiquitination and deubiquitination in proteins related to the specific stemness of the CSCs have a profound impact on the regulation of ITAIM. In regulating the balance between ubiquitination and deubiquitination, it is crucial for deubiquitinating enzymes (DUBs) to cleave ubiquitin chains from substrates. Ubiquitin-specific peptidases (USPs) comprise the largest family of DUBs. Growing evidence suggests that they play novel functions in contribution of ITAIM, including regulating tumor immunogenicity, activating stem cell factors, upregulating the SRSs, stabilizing anti-inflammatory receptors, and regulating anti-inflammatory cytokines. These overactive or abnormal signaling may dampen antitumor immune responses. The inhibition of USPs could play a regulatory role in SRSs and reversing ITAIM, and also have great potential in improving immune killing ability against tumor cells, including CSCs. In this review, we focus on the USPs involved in CSCs signaling pathways and regulating ITAIM, which are promising therapeutic targets in antitumor therapy.
Oligo/Amenorrhea Is an Independent Risk Factor Associated With Low Ovarian Response
Authors: Hu Kai-Lun , Gan Kwanghann , Ying Yue , Zheng Junyan , Chen Ruixue , Xue Jinglei , Wu Yiqing , Liu Yifeng , Zhu Yimin , Xing Lanfeng , Zhang Dan
Published: June 2021

Capsule

Oligo/amenorrhea is an independent risk factor of low ovarian response but not high ovarian response, particularly in women with low AMH levels.

Objective

To investigate the association of menstrual cycle length (MCL) with anti-Müllerian hormone (AMH) and ovarian response.

Methods

This was a retrospective cohort study. A total of 7471 women who underwent ovarian stimulation and oocyte retrieval were enrolled. The main outcome was the number of oocytes retrieved.

Main Results

A total of 5734 patients were eligible for analysis. In women without polycystic ovary syndrome (PCOS), serum AMH levels and antral follicle count were significantly lower in women with short cycles and higher in women with oligo/amenorrhea than those with a normal menstrual cycle. In women with PCOS, compared to women with a normal menstrual cycle, women with short cycles and women with oligo/amenorrhea showed higher antral follicle count and higher serum AMH levels. Compared with the 0-25th range group of AMH levels, 75-100th percentile groups showed a significantly increased rate of oligo/amenorrhea in women with and without PCOS [adjusted odds ratio (OR) =1.9 (1.04, 3.46), 2.4 (1.70, 3.35)]. In women without PCOS, the low ovarian response was more common in women with short cycles and less common in women with oligo/amenorrhea compared to women with normal cycles [OR=3.0 (2.38, 3.78), 0.7 (0.55, 0.96), respectively]. When adjusted for AMH levels, both short cycles and oligo/amenorrhea were associated with an increased risk of low response [adjusted OR=1.3 (1.02, 1.75), 1.3 (0.93, 1.86), respectively]. In women without PCOS and with low AMH levels, the low ovarian response was more common in women with short cycles as well as in women with oligo/amenorrhea [OR=1.5 (1.08, 1.98), 1.7 (1.08, 2.69), adjusted OR=1.2 (0.86, 1.74), 2.2 (1.31, 3.82), respectively].

Conclusion

AMH levels are significantly associated with increased risk of oligo/amenorrhea in women with and without PCOS. AMH is an indispensable confounder in the association between MCL and ovarian response in women without PCOS. Oligo/amenorrhea is an independent risk factor associated with a low ovarian response in women without PCOS, particularly those with low AMH levels.
Linking Fishing Behavior and Ecosystem Dynamics Using Social and Ecological Network Models
Authors: Luczkovich Joseph J. , Johnson Jeffrey C. , Deehr Rebecca A. , Hart Kevin J. , Clough Lisa , Griffith David C.
Published: June 2021

One goal of ecosystem-based management is studying an ecosystem and its people, the socio-ecological system, in a qualitative and quantitative modeling approach that can provide management agencies with possible outcomes of their actions using scenario forecasting. Ecosystem-based fisheries management strives to use the socio-ecological system approach, including direct and indirect impacts on multiple species including the behavioral responses of fishers after a regulatory change (a gillnet ban). Here, we link fisher behavioral networks with a mass-balanced food-web ECOPATH network model of an estuarine ecosystem and its commercial fisheries for an analysis of fishing impacts after a gillnet ban on multiple species using ECOSIM. We modeled fisher behavioral networks using reported catches of species from individual fishers along with the gear fished to create nodes in a gear/species affiliation network. Individual fishers with common gear/species use are indicative of common fishing behavior. When such fishers have high network centrality and are engaged in multiple gear/species fisheries, they can transition to other gear/species fisheries along “switching pathways” when facing a regulatory change. We used an index of joint gear participation to identify likely gear switching pathways, and we predicted changes in fishing effort after a gill net ban. We simulated the gill net ban in ECOSIM under two scenarios of fishing effort: Scenario 1, gill net fishing effort of 0%; Scenario 2, gill net fishing effort of 0% with increased effort in the alternative gear fisheries using the predicted switching pathways for the affiliation network. Scenario 1 predicted an increase in flounder (Paralichthys spp.) biomass over a decade. Under Scenario 2, fishers targeting flounders were predicted to switch from gill nets to pound nets. Scenario 2 predicted a 7% decline in flounder biomass over ten years, rather than an increase in flounders. The gillnet ban with increased effort due to switching is predicted to have the opposite effect on the conservation goal, which was to increase flounder stocks. Fishery management that incorporates a socio-ecological approach modeling both fisher behaviors and multi-species ecosystem responses can reveal single-species responses that are in the opposite direction of the anticipated management goals.
Altered Ex-Vivo Cytokine Responses in Children With Asymptomatic Plasmodium falciparum Infection in Burkina Faso: An Additional Argument to Treat Asymptomatic Malaria?
Authors: Post Annelies , Kaboré Berenger , Berendsen Mike , Diallo Salou , Traore Ousmane , Arts Rob J. W. , Netea Mihai G. , Joosten Leo A. B. , Tinto Halidou , Jacobs Jan , de Mast Quirijn , van der Ven André
Published: June 2021

Introduction

Patients with clinical malaria have an increased risk for bacterial bloodstream infections. We hypothesized that asymptomatic malaria parasitemia increases susceptibility for bacterial infections through an effect on the innate immune system. We measured circulating cytokine levels and ex-vivo cytokine production capacity in asymptomatic malaria and compared with controls.

Methods

Data were collected from asymptomatic participants <5 years old with and without positive malaria microscopy, as well as from hospitalized patients <5 years old with clinical malaria, bacteremia, or malaria/bacteremia co-infections in a malaria endemic region of Burkina Faso. Circulating cytokines (TNF-α, IFN-γ, IL-6, IL-10) were measured using multiplex assays. Whole blood from asymptomatic participants with and without positive malaria microscopy were ex-vivo stimulated with S. aureus, E. coli LPS and Salmonella Typhimurium; cytokine concentrations (TNF-α, IFN-γ, IL-1β, IL-6, IL-10) were measured on supernatants using ELISA.

Results

Included were children with clinical malaria (n=118), bacteremia (n=22), malaria and bacteremia co-infection (n=9), asymptomatic malaria (n=125), and asymptomatic controls (n=237). Children with either clinical or asymptomatic malaria had higher plasma cytokine concentrations than controls. Cytokine concentrations correlated positively with malaria parasite density with the strongest correlation for IL-10 in both asymptomatic (r=0.63) and clinical malaria (r=0.53). Patients with bacteremia had lower circulating IL-10, TNF-α and IFN-γ and higher IL-6 concentrations, compared to clinical malaria. Ex-vivo whole blood cytokine production to LPS and S. aureus was significantly lower in asymptomatic malaria compared to controls. Whole blood IFN-γ and IL-10 production in response to Salmonella was also lower in asymptomatic malaria.

Interpretation

In children with asymptomatic malaria, cytokine responses upon ex-vivo bacterial stimulation are downregulated. Further studies are needed to explore if the suggested impaired innate immune response to bacterial pathogens also translates into impaired control of pathogens such as Salmonella spp.
JAK/STAT-Dependent Chimeric Antigen Receptor (CAR) Expression: A Design Benefiting From a Dual AND/OR Gate Aiming to Increase Specificity, Reduce Tumor Escape and Affect Tumor Microenvironment
Authors: Khanali Javad , Azangou-Khyavy Mohammadreza , Boroomand-Saboor Melika , Ghasemi Mobina , Niknejad Hassan
Published: June 2021

Recent advances in cancer immunotherapy have attracted great interest due to the natural capacity of the immune system to fight cancer. This field has been revolutionized by the advent of chimeric antigen receptor (CAR) T cell therapy that is utilizing an antigen recognition domain to redirect patients’ T cells to selectively attack cancer cells. CAR T cells are designed with antigen-binding moieties fused to signaling and co-stimulatory intracellular domains. Despite significant success in hematologic malignancies, CAR T cells encounter many obstacles for treating solid tumors due to tumor heterogeneity, treatment-associated toxicities, and immunosuppressive tumor microenvironment. Although the current strategies for enhancing CAR T cell efficacy and specificity are promising, they have their own limitations, making it necessary to develop new genetic engineering strategies. In this article, we have proposed a novel logic gate for recognizing tumor-associated antigens by employing intracellular JAK/STAT signaling pathway to enhance CAR T Cells potency and specificity. Moreover, this new-generation CAR T cell is empowered to secrete bispecific T cell engagers (BiTEs) against cancer-associated fibroblasts (CAFs) to diminish tumor metastasis and angiogenesis and increase T cell infiltration.
PDCD1 Polymorphisms May Predict Response to Anti-PD-1 Blockade in Patients With Metastatic Melanoma
Authors: Parakh Sagun , Musafer Ashan , Paessler Sabrina , Witkowski Tom , Suen Connie S. N. Li Wai , Tutuka Candani S. A. , Carlino Matteo S. , Menzies Alexander M. , Scolyer Richard A. , Cebon Jonathan , Dobrovic Alexander , Long Georgina V. , Klein Oliver , Behren Andreas
Published: June 2021

A significant number of patients (pts) with metastatic melanoma do not respond to anti-programmed cell death 1 (PD1) therapies. Identifying predictive biomarkers therefore remains an urgent need. We retrospectively analyzed plasma DNA of pts with advanced melanoma treated with PD-1 antibodies, nivolumab or pembrolizumab, for five PD-1 genotype single nucleotide polymorphisms (SNPs): PD1.1 (rs36084323, G>A), PD1.3 (rs11568821, G>A), PD1.5 (rs2227981, C>T) PD1.6 (rs10204225, G>A) and PD1.9 (rs2227982, C>T). Clinico-pathological and treatment parameters were collected, and presence of SNPs correlated with response, progression free survival (PFS) and overall survival (OS). 115 patients were identified with a median follow up of 18.7 months (range 0.26 – 52.0 months). All were Caucasian; 27% BRAF V600 mutation positive. At PD-1 antibody commencement, 36% were treatment-naïve and 52% had prior ipilimumab. The overall response rate was 43%, 19% achieving a complete response. Overall median PFS was 11.0 months (95% CI 5.4 - 17.3) and median OS was 31.1 months (95% CI 23.2 - NA). Patients with the G/G genotype had more complete responses than with A/G genotype (16.5% vs. 2.6% respectively) and the G allele of PD1.3 rs11568821 was significantly associated with a longer median PFS than the AG allele, 14.1 vs. 7.0 months compared to the A allele (p=0.04; 95% CI 0.14 – 0.94). No significant association between the remaining SNPs and responses, PFS or OS were observed. Despite limitations in sample size, this is the first study to demonstrate an association of a germline PD-1 polymorphism and PFS in response to anti-PD-1 therapy in pts with metastatic melanoma. Extrinsic factors like host germline polymorphisms should be considered with tumor intrinsic factors as predictive biomarkers for immune checkpoint regulators.
Information-Driven Docking for TCR-pMHC Complex Prediction
Authors: Peacock Thomas , Chain Benny
Published: June 2021

T cell receptor (TCR) recognition of peptides presented by major histocompatibility complex (MHC) molecules is a fundamental process in the adaptive immune system. An understanding of this recognition process at the molecular level is crucial for TCR based therapeutics and vaccine design. The broad nature of TCR diversity and cross-reactivity presents a challenge for traditional structural resolution. Computational modelling of TCR-pMHC complexes offers an efficient alternative. This study compares the ability of four general-purpose docking platforms (ClusPro, LightDock, ZDOCK and HADDOCK) to make use of varying levels of binding interface information for accurate TCR-pMHC modelling. Each platform was tested on an expanded benchmark set of 44 TCR-pMHC docking cases. In general, HADDOCK is shown to be the best performer. Docking strategy guidance is provided to obtain the best models for each platform for future research. The TCR-pMHC docking cases used in this study can be downloaded from https://github.com/innate2adaptive/ExpandedBenchmark.
Comparative Genomics of Clostridium perfringens Reveals Patterns of Host-Associated Phylogenetic Clades and Virulence Factors
Authors: Geier Renae R. , Rehberger Thomas G. , Smith Alexandra H.
Published: June 2021

Clostridium perfringens is an opportunistic pathogenic bacterium that infects both animals and humans. Clostridium perfringens genomes encode a diverse array of toxins and virulence proteins, which continues to expand as more genomes are sequenced. In this study, the genomes of 44 C. perfringens strains isolated from intestinal sections of diseased cattle and from broiler chickens from diseased and healthy flocks were sequenced. These newly assembled genomes were compared to 141 publicly available C. perfringens genome assemblies, by aligning known toxin and virulence protein sequences in the assemblies using BLASTp. The genes for alpha toxin, collagenase, a sialidase (nanH), and alpha-clostripain were present in at least 99% of assemblies analyzed. In contrast, beta toxin, epsilon toxin, iota toxin, and binary enterotoxin of toxinotypes B, C, D, and E were present in less than 5% of assemblies analyzed. Additional sequence variants of beta2 toxin were detected, some of which were missing the leader or signal peptide sequences and therefore likely not secreted. Some pore-forming toxins involved in intestinal diseases were host-associated, the netB gene was only found in avian isolates, while netE, netF, and netG were only present in canine and equine isolates. Alveolysin was positively associated with canine and equine strains and only present in a single monophyletic clade. Strains from ruminant were not associated with known virulence factors and, except for the food poisoning associated clade, were present across the phylogenetic diversity identified to date for C. perfringens. Many C. perfringens strains associated with food poisoning lacked the genes for hyaluronidases and sialidases, important for attaching to and digesting complex carbohydrates found in animal tissues. Overall, the diversity of virulence factors in C. perfringens makes these species capable of causing disease in a wide variety of hosts and niches.
Deubiquitination of MITF-M Regulates Melanocytes Proliferation and Apoptosis
Authors: Hu Shuaishuai , Bai Shaocheng , Dai Yingying , Yang Naisu , Li Jiali , Zhang Xiyu , Wang Fan , Zhao Bohao , Bao Guolian , Chen Yang , Wu Xinsheng
Published: June 2021

Microphthalmia-associated transcription factor-M (MITF-M) is the key gene in the proliferation and differentiation of melanocytes, which undergoes an array of post-translation modifications. As shown in our previous study, deubiquitinase USP13 is directly involved in melanogenesis. However, it is still ambiguous that the effect of USP13-mediated MITF-M expression on melanocytes proliferation and apoptosis. Herein, we found that MITF-M overexpressing melanocytes showed high cell proliferation, reduced apoptosis, and increased melanin levels. Besides, melanin-related genes, TYR, DCT, GPNMB, and PMEL, were significantly up-regulated in MITF-M overexpressing melanocytes. Furthermore, Exogenous USP13 significantly upregulated the endogenous MITF-M protein level, downregulated USP13 significantly inhibited MITF-M protein levels, without altering MITF-M mRNA expression. In addition, USP13 upregulation mitigated the MITF-M degradation and significantly increased the half-life of MITF-M. Also, USP13 stabilized the exogenous MITF protein levels. In conclusion, the MITF-M level was regulated by USP13 deubiquitinase in melanocytes, affecting melanocytes proliferation and apoptosis. This study provides the theoretical basis for coat color transformation that could be useful in the development of the new breed in fur animals.
Cancer Treatment With the Ketogenic Diet: A Systematic Review and Meta-analysis of Animal Studies
Authors: Li Jing , Zhang Haiyan , Dai Zhu
Published: June 2021

Background: The ketogenic diet (KD) has been reported to play an important role in the development of cancer by an abundance of pre-clinical experiments; however, their conclusions have been controversial. We therefore aimed to perform a systematic review and meta-analysis of animal studies evaluating the effects of KD on cancer.

Methods: Relevant studies were collected by searching PubMed, Embase, and Web of Science. Outcome measures comprised tumor weight, tumor volume, and survival time. Meta-analysis was performed using the random-effect model according to heterogeneity.

Results: The search resulted in 1,254 references, of which 38 were included in the review and 17 included in the meta-analysis. Pooled results indicated that KD supplementation significantly prolonged survival time [standardized mean difference (SMD) = 1.76, 95% CI (0.58, 2.94), p = 0.003], and reduced tumor weight [SMD = −2.459, 95% CI (−4.188, −0.730), p = 0.027] and tumor volume [SMD = −0.759, 95% CI (−1.349, −0.168), p = 0.012]. Meta-regression and subgroup analysis results suggested that KD supplementation at a ratio of 4:1 was associated with remarkable prolongation of survival time in animals with limited tumor types.

Conclusion: In summary, the pre-clinical evidence pointed toward an overall anti-tumor effect of the KD in animals studies currently available with limited tumor types.
Role of Long Non-Coding RNAs in Conferring Resistance in Tumors of the Nervous System
Authors: Ghafouri-Fard Soudeh , Agabalazadeh Amin , Abak Atefe , Shoorei Hamed , Hassanzadeh Taheri Mohammad Mehdi , Taheri Mohammad , Sharifi Guive
Published: June 2021

Tumors of the nervous system can be originated from several locations. They mostly have high mortality and morbidity rate. The emergence of resistance to chemotherapeutic agents is a hurdle in the treatment of patients. Long non-coding RNAs (lncRNAs) have been shown to influence the response of glioblastoma/glioma and neuroblastoma to chemotherapeutic agents. MALAT1, NEAT1, and H19 are among lncRNAs that affect the response of glioma/glioblastoma to chemotherapy. As well as that, NORAD, SNHG7, and SNHG16 have been shown to be involved in conferring this phenotype in neuroblastoma. Prior identification of expression amounts of certain lncRNAs would help in the better design of therapeutic regimens. In the current manuscript, we summarize the impact of lncRNAs on chemoresistance in glioma/glioblastoma and neuroblastoma.
Rapunzel Syndrome—An Extremely Rare Cause of Digestive Symptoms in Children: A Case Report and a Review of the Literature
Authors: Marginean Cristina Oana , Melit Lorena Elena , Sasaran Maria Oana , Marginean Razvan , Derzsi Zoltan
Published: June 2021

Rapunzel syndrome is an extremely rare condition seen in adolescents or young females with psychiatric disorders consisting of a gastric trichobezoar with an extension within the small bowel. The delays in diagnosis are common since in its early stages, it is usually asymptomatic. We report the case of a 13-year-old girl admitted in our clinic for abdominal pain, anorexia, and weight loss. The clinical exam pointed out diffuse alopecia, a palpable mass in the epigastric area, and abdominal tenderness at palpation, the patient weighing 32 kg. The laboratory tests showed anemia. The abdominal ultrasound showed a gastric intraluminal mass with a superior hyperechoic arc. The upper digestive endoscopy revealed a mass formed by hair, mucus, and food occupying the gastric cavity with the extension into the duodenum confirming the diagnosis of Rapunzel syndrome. The giant trichobezoar of 511 g, measuring 17 × 7 × 6.5 cm with a tail of approximately 3 cm, was successfully removed through laparotomy. Although rare, Rapunzel syndrome must never be forgotten as a differential diagnosis for digestive symptoms since its early detection hinders the occurrence of further complications.
Hydrogen Sulfide Attenuated Sepsis-Induced Myocardial Dysfunction Through TLR4 Pathway and Endoplasmic Reticulum Stress
Authors: Chen Yu-hong , Teng Xu , Hu Zhen-jie , Tian Dan-yang , Jin Sheng , Wu Yu-ming
Published: June 2021

Aims: We examined the change in endogenous hydrogen sulfide (H2S) production and its role in sepsis-induced myocardial dysfunction (SIMD).

Results: Significant elevations in plasma cardiac troponin I (cTnI), creatine kinase (CK), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were noted in SIMD patients, whereas left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and plasma H2S were significantly decreased relative to those in the controls. Plasma H2S was linearly related to LVEF and LVFS. Subsequently, an SIMD model was developed in mice by injecting lipopolysaccharide (LPS), and NaHS, an H2S donor, was used to elucidate the pathophysiological role of H2S. The mice showed decreased ventricular function and increased levels of TNF-α, IL-1β, cTnI, and CK after LPS injections. Toll-like receptor (TLR) 4 protein and endoplasmic reticulum stress (ERS) proteins were over expressed in the SIMD mice. All of the parameters above showed more noticeable variations in cystathionine γ-lyase knockout mice relative to those in wild type mice. The administration of NaHS could improve ventricular function and attenuate inflammation and ERS in the heart.

Conclusion: Overall, these findings indicated that endogenous H2S deficiency contributed to SIMD and exogenous H2S ameliorated sepsis-induced myocardial dysfunction by suppressing inflammation and ERS via inhibition of the TLR4 pathway.
Examining the Moderating Effects of Work Unit Size and Task Analyzability in the Relation Between Leader’s Communication Style and Leader-Member Exchange
Authors: Brown Ofelia , Paz-Aparicio Carmen
Published: June 2021

There is a consensus regarding the impact of the leader’s communication on the relationship with their followers and on the achievement of organizational outcomes. This study seeks to contribute to clarifying the impact that contextual factors have on the leader’s communication in order to know how leaders should adjust their communication style, depending on the job characteristics, to build high quality relationships with their followers. Therefore, the current research examines the moderating role of two context factors in the effectiveness of leaders’ communication in generating the leader-member relationship. Through a moderation analysis on a sample of 149 white-collar workers, this research study analyzes how work unit size and task analyzability interact regarding six dimensions of leader communication style in relation to LMX. Results suggest that the work unit size moderates the relationship between two dimensions of leader’s communication style (preciseness and verbal aggressiveness) and LMX. Specifically, the positive effect of preciseness on LMX smooths as the work unit size increases. The negative effect of verbal aggressiveness on LMX becomes more intense as work unit size increases. Furthermore, task analyzability moderates the positive relationship between emotionality and LMX for low levels of task analyzability. As a result, this study contributes by deepening on why leaders’ communicative behaviors can have favorable/unfavorable results in specific contexts and on how a leader can modulate his/her communication style according to the context, in order to improve the LMX. Implications are discussed.
Sleep Quality in Medical Staffs During the Outbreak of Coronavirus Disease 2019 in China: A Web-Based Cross-Sectional Study
Authors: Jiang Furong , Xiao Yi , Dong Huixi , Liu Siyu , Guo Feng , Gong Zhicheng , Xiao Shuiyuan , Shen Minxue , Zhou Qiuhong , Li Jianling
Published: June 2021

Background: The aim of this study was to describe the sleep quality and its influencing factors among medical workers of different working statuses and staff types during the coronavirus disease 2019 (COVID-19) epidemic.

Methods: Through an online questionnaire survey, all medical staffs in Xiangya Hospital were invited to complete sections on general information, the Self-Rating Scale of Sleep (SRSS), the Depression, Anxiety and Stress Scale (DASS-21), the Social Support Rating Scale (SSRS), and the Simplified Coping Style Questionnaire (CSQ).

Results: A total of 4,245 respondents completed the survey. Among them, 38.7% had sleep disturbance. After matching, the SRSS scores in the staffs who were assigned to the intensive care unit (ICU) of Union Hospital in Wuhan and working in the epidemic area of Xiangya Hospital were not significantly different (P > 0.05); the SRSS scores in the battlefront staffs were significantly higher than (P < 0.05) those who were not treating patients infected with COVID-19. The SRSS scores of nurses were significantly higher than those of doctors and hospital administrators (P < 0.01). Anxiety, depression, and coping style were associated with sleep disturbance.

Conclusion: The sleep quality of the medical staffs has been impaired during the epidemic period, especially among nurses, doctors, and administrators who are working on the front line. Medical institutions should strengthen psychological services and coping strategies for medical staffs.
Quality of Life and Mental Health in Kidney Transplant Recipients During the COVID-19 Pandemic
Authors: De Pasquale Concetta , Pistorio Maria Luisa , Veroux Pierfrancesco , Gioco Rossella , Giaquinta Alessia , Privitera Francesca , Veroux Massimiliano
Published: June 2021

Introduction: The COVID-19 pandemic has led to an increase in mental distress such as phobic anxieties, depressive reactions, hypochondriac concerns, and insomnia. Among the causes are risk of infection and prolonged isolation. This study aimed to analyze psychopathological variables and dysfunctional lifestyles related to adequate therapeutic compliance in kidney transplant recipients.

Methods: Eighty-nine kidney transplant recipients were evaluated using an online protocol including a questionnaire concerning habits, lifestyle and psychophysical well-being in the COVID-19 period, the Middlesex Hospital Questionnaire (MHQ) and the SF-36 Health Survey to evaluate the perception of their physical and emotional health.

Results: Of these recipients, 28.6% reported changes in their emotional state. Sleep quality deteriorated for 16.1%. Anxiety (M = 5.57, r = 0.33; p < 0.05) and phobia (M = 6.28, r = 0.26; p < 0.05) correlated with concerns related to physical health. There was no negative impact on relational and socialization aspects, which were likely well compensated by the use of remote technologies such as video phone calls, Zoom meetings and use of computers (r = 0.99; r = 0.80; p < 0.05).

Conclusions: It would be interesting to maintain this remote visit and interview mode to monitor, on a clinical and psychological level, kidney transplant recipients in subsequent follow-ups (12–18 months), to check for any psychopathological disorders and/or changes in their resilience capacity in the Coronavirus emergency.
Running Scared? A Critical Analysis of LGBTQ+ Inclusion Policy in Schools
Authors: Glazzard Jonathan , Stones Samuel
Published: June 2021

This article provides an overview of the UK government policy in relation to relationships and sex education in schools. It focuses on the latest statutory guidance which requires primary and secondary schools in England to teach pupils about different types of relationships, including same-sex relationships. We outline the current policy frameworks and present a rationale for why Lesbian, Gay, Bisexual, Trans and Queer (LGBTQ+) identities and relationships should be present in the curriculum. We critically interrogate the government response and we present a framework to support the implementation of a whole school approach to LGBTQ+ inclusion. We draw on Meyer's model of minority stress to explore risks to children and young people if they are not provided with an LGBTQ+ curriculum.
Monte Carlo Analysis: An Application to Aircraft Design and Crash
Authors: Soydemir Emre , Petratos Panagiotis
Published: June 2021

The current study investigates the application of statistical methods to flight, which have been used in science over time to understand complex physical and mathematical systems by using randomly generated numbers as input into those systems to generate a range of solutions and, specifically, how mathematics is used to examine airplane design and crash frequency. In order to make very accurate predictions, one also requires an appropriate mathematical model. Using randomly selected numbers, the Monte Carlo statistical method is able to make very accurate predictions. With the Monte Carlo statistical method, by using significantly larger numbers of trials, the likelihood of the solutions can be determined very accurately. Currently, Monte Carlo methods are widely used and play a key part in various fields of science. Monte Carlo methods have vast uses in trials with limited observations that cannot be replicated many times. This paper adds new findings to the knowledge base on causes of crashes by airplane design. First, mathematical methods are used in this paper to investigate what the most likely casualty number and range are in the five years after the first flight based on 5000 simulations. Second, an investigation is performed to determine if certain casualty numbers are outliers of certain airplane designs based on the number of casualties reported using Monte Carlo analysis.
Myeloma Bone Disease: A Comprehensive Review
Authors: Mukkamalla Shiva Kumar Reddy , Malipeddi Dhatri
Published: June 2021

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells in the bone marrow microenvironment, characterized by overproduction of heavy- and light-chain monoclonal proteins (M-protein). These proteins are mainly found in the serum and/or urine. Reduction in normal gammaglobulins (immunoparesis) leads to an increased risk of infection. The primary site of origin is the bone marrow for nearly all patients affected by MM with disseminated marrow involvement in most cases. MM is known to involve bones and result in myeloma bone disease. Osteolytic lesions are seen in 80% of patients with MM which are complicated frequently by skeletal-related events (SRE) such as hypercalcemia, bone pain, pathological fractures, vertebral collapse, and spinal cord compression. These deteriorate the patient’s quality of life and affect the overall survival of the patient. The underlying pathogenesis of myeloma bone disease involves uncoupling of the bone remodeling processes. Interaction of myeloma cells with the bone marrow microenvironment promotes the release of many biochemical markers including osteoclast activating factors and osteoblast inhibitory factors. Elevated levels of osteoclast activating factors such as RANK/RANKL/OPG, MIP-1-α., TNF-α, IL-3, IL-6, and IL-11 increase bone resorption by osteoclast stimulation, differentiation, and maturation, whereas osteoblast inhibitory factors such as the Wnt/DKK1 pathway, secreted frizzle related protein–2, and runt-related transcription factor 2 inhibit osteoblast differentiation and formation leading to decreased bone formation. These biochemical factors also help in development and utilization of appropriate anti-myeloma treatments in myeloma patients. This review article summarizes the pathophysiology and the recent developments of abnormal bone remodeling in MM, while reviewing various approved and potential treatments for myeloma bone disease.
The Media’s Influence on the Government: A Case Study of Venezuela’s Media Agenda Setting with a Non-Free Press and Its Repercussions
Authors: Fredricks Susan M. , Phillips Joshua D.
Published: June 2021

A free and open press (unincumbered by political pressures) is necessary to hold government officials accountable. When governments become entangled in the business of licensing and regulating news outlets, news outlets succumb to the pressures of only publishing stories favorable to the current regime. The temptation to publish negative stories could result in losing one’s publishing license. This scenario has been playing out in Venezuela for the past two decades and has led to a media culture of misinformation, confusion, and propaganda. This paper first analyzes the Venezuelan view on the influential forces on its government through the International Social Survey Programme (ISSP). Second, it explores how the Venezuelan government vanquished the free press by affecting the Venezuelan citizens’ attitudes towards the press. Finally, it reviews how the internet and social media are creating new avenues for publishing uncensored and unregulated information in an effort to challenge current government restrictions.
Development of a Derivatization Reagent with a 2-Nitrophenylsulfonyl Moiety for UHPLC-HRMS/MS and Its Application to Detect Amino Acids Including Taurine
Authors: Uekusa Shusuke , Onozato Mayu , Sakamoto Tatsuya , Umino Maho , Ichiba Hideaki , Okoshi Kenji , Fukushima Takeshi
Published: June 2021

Taurine (Tau) has some important ameliorating effects on human health and is present in bivalve. For the selective analysis of Tau with other amino acids, we designed a derivatization reagent, 2,5-dioxopyrrolidin-1-yl(4-(((2-nitrophenyl)sulfonyl)oxy)-6-(3-oxomorpholino)quinoline-2-carbonyl)pyrrolidine-3-carboxylate (Ns-MOK-β-Pro-OSu). After derivatization with Ns-MOK-β-Pro-OSu, amino acids with Tau in Japanese littleneck clams were determined through ultra-high-performance-liquid chromatography with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) using an octadecyl silica column. We could detect 18 amino acids within 10 min. Tau, valine, glutamine, glutamic acid, and arginine in the clams were determined in the negative ion mode using the characteristic fragment ion, C6H4N1O5S, which corresponded to the 2-nitrobenzenesulfonylate moiety. The fragment ion, C6H4N1O5S, was recognized as a common feature regardless of the amino acid to be derivatized, and it was convenient for detecting amino acid derivatives with high selectivity and sensitivity. Therefore, highly selective quantification using UHPLC-HRMS/MS was possible using Ns-MOK-β-Pro-OSu.
Preparation and Electrical Properties of Polyacrylonitrile Based Porous Carbon by Different Activation Methods
Authors: Wang Xiaoqiang , Tan Yifan , Sun Meijiao , Yu Binbin , Yang Junhe , Xue Yuhua , Yang Guangzhi
Published: June 2021

Polyacrylonitrile (PAN)-based porous carbon was prepared by different methods of activation with PAN polymer microsphere as precursor. The morphology, structure and electrical properties for supercapacitor of the porous carbon were investigated. It was found that the morphology of PAN nanospheres tended to be destroyed in the process of one-step activation (activation and carbonization were carried out simultaneously, and could only be retained when the amount of activating agent KOH was small). While the spherical morphology could be well reserved during the two-step activation method (carbonization and activation sequentially). The specific surface area and pore volume increased first and then decreased, with the increase in activation holding time for both one-step and two-step activation methods. The specific surface area reached the maximum value with 2430 m2 g−1 for the one-step activation method and 2830 m2 g−1 for the two-step activation method. Additionally, their mass-specific capacitances were 178.8 F g−1 and 160.2 F g−1, respectively, under the current density of 1 A g−1. After 2000 cycles, the specific capacitance retentions were 92.9% and 91.3%.
The Protection of Lactic Acid Bacteria Fermented-Mango Peel against Neuronal Damage Induced by Amyloid-Beta
Authors: Lee Bao-Hong , Hsu Wei-Hsuan , Hou Chih-Yao , Chien Hao-Yuan , Wu She-Ching
Published: June 2021

Mango peels are usually discarded as waste; however, they contain phytochemicals and could provide functional properties to food and promote human health. This study aimed to determine the optimal lactic acid bacteria for fermentation of mango peel and evaluate the effect of mango peel on neuronal protection in Neuron-2A cells against amyloid beta (Aβ) treatment (50 μM). Mango peel can be fermented by different lactic acid bacteria species. Lactobacillus acidophilus (BCRC14079)-fermented mango peel produced the highest concentration of lactic acid bacteria (exceeding 108 CFU/mL). Mango peel and fermented mango peel extracts upregulated brain-derived neurotrophic factor (BDNF) expression for 1.74-fold in Neuron-2A cells. Furthermore, mango peel fermented products attenuated oxidative stress in Aβ-treated neural cells by 27%. Extracts of L. acidophilus (BCRC14079)-fermented mango peel treatment decreased Aβ accumulation and attenuated the increase of subG1 caused by Aβ induction in Neuron-2A cells. In conclusion, L. acidophilus (BCRC14079)-fermented mango peel acts as a novel neuronal protective product by inhibiting oxidative stress and increasing BDNF expression in neural cells.
Development of a Fast and Robust UHPLC Method for Apixaban In-Process Control Analysis
Authors: Kormány Róbert , Rácz Norbert , Fekete Szabolcs , Horváth Krisztián
Published: June 2021

In-process control (IPC) is an important task during chemical syntheses in pharmaceutical industry. Despite the fact that each chemical reaction is unique, the most common analytical technique used for IPC analysis is high performance liquid chromatography (HPLC). Today, the so-called “Quality by Design” (QbD) principle is often being applied rather than “Trial and Error” approach for HPLC method development. The QbD approach requires only for a very few experimental measurements to find the appropriate stationary phase and optimal chromatographic conditions such as the composition of mobile phase, gradient steepness or time (tG), temperature (T), and mobile phase pH. In this study, the applicability of a multifactorial liquid chromatographic optimization software was studied in an extended knowledge space. Using state-of-the-art ultra-high performance liquid chromatography (UHPLC), the analysis time can significantly be shortened. By using UHPLC, it is possible to analyse the composition of the reaction mixture within few minutes. In this work, a mixture of route of synthesis of apixaban was analysed on short narrow bore column (50 × 2.1 mm, packed with sub-2 µm particles) resulting in short analysis time. The aim of the study was to cover a relatively narrow range of method parameters (tG, T, pH) in order to find a robust working point (zone). The results of the virtual (modeled) robustness testing were systematically compared to experimental measurements and Design of Experiments (DoE) based predictions.
Asperflaloids A and B from Aspergillus flavipes DZ-3, an Endophytic Fungus of Eucommia ulmoides Oliver
Authors: Liu Wan , Liu Yu , Yang Fan , Han Shouye , Zhang Jia , Yang Hui , Cheng Zhongbin , Li Qin
Published: June 2021

The fungus strain DZ-3 was isolated from twigs of the well-known medicinal plant Eucommia ulmoides Oliver and identified as Aspergillus flavipes. Two new alkaloids, named asperflaloids A and B (1 and 2), together with 10 known compounds (3–12) were obtained from the EtOAc extract of the strain. Interestingly, the alkaloids 1–4 with different frameworks are characterized by the presence of the same anthranilic acid residue. The structures were established by detailed analyses of the spectroscopic data. The absolute configuration of asperflaloids A and B was resolved by quantum chemistry calculation. All compounds were screened for their inhibitions against α-glucosidase and the antioxidant capacities. The results were that compound 3 had an IC50 value of 750.8 μM toward α-glucosidase, and the phenol compounds 7 and 8 exhibited potent antioxidant capacities with IC50 values 14.4 and 27.1 μM respectively.
Mechanistic Actions between Garcinia atroviridis Essential Oil and 2 Deoxy-d-glucose in Cultured PANC-1 Human Pancreatic Cancer Cells
Authors: Nik Mohamed Kamal Nik Nur Syazni , Abdul Aziz Fatin Athirah , Tan Wen-Nee , Fauzi Agustine Nengsih , Lim Vuanghao
Published: June 2021

Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.
Antiepileptic Drug Tiagabine Does Not Directly Target Key Cardiac Ion Channels Kv11.1, Nav1.5 and Cav1.2
Authors: Kowalska Magdalena , Fijałkowski Łukasz , Kubacka Monika , Sałat Kinga , Grześk Grzegorz , Nowaczyk Jacek , Nowaczyk Alicja
Published: June 2021

Tiagabine is an antiepileptic drug used for the treatment of partial seizures in humans. Recently, this drug has been found useful in several non-epileptic conditions, including anxiety, chronic pain and sleep disorders. Since tachycardia—an impairment of cardiac rhythm due to cardiac ion channel dysfunction—is one of the most commonly reported non-neurological adverse effects of this drug, in the present paper we have undertaken pharmacological and numerical studies to assess a potential cardiovascular risk associated with the use of tiagabine. A chemical interaction of tiagabine with a model of human voltage-gated ion channels (VGICs) is described using the molecular docking method. The obtained in silico results imply that the adverse effects reported so far in the clinical cardiological of tiagabine could not be directly attributed to its interactions with VGICs. This is also confirmed by the results from the isolated organ studies (i.e., calcium entry blocking properties test) and in vivo (electrocardiogram study) assays of the present research. It was found that tachycardia and other tiagabine-induced cardiac complications are not due to a direct effect of this drug on ventricular depolarization and repolarization.
Parvaxanthines D–F and Asponguanosines C and D, Racemic Natural Hybrids from the Insect Cyclopelta parva
Authors: Chen Heng , Yan Yong-Ming , Wang Dai-Wei , Cheng Yong-Xian
Published: June 2021

Five new compounds including three pairs of enantiomeric xanthine analogues, parvaxanthines D–F (1–3), two new guanosine derivatives, asponguanosines C and D (6 and 7), along with two known adenine derivatives were isolated from the insect Cyclopelta parva. Racemic 1–3 were further separated by chiral HPLC. Their absolute configurations were assigned by spectroscopic and computational methods. It is interesting that all of these isolates are natural product hybrids. Antiviral, immunosuppressive, antitumor and anti-inflammatory properties of all the isolates were evaluated.