bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the association between Th17 pathway gene polymorphisms and pulmonary tuberculosis
Authors: Li Hong-Miao , Wang Li-Jun , Huang Qian , Pan Hai-Feng , Zhang Tian-Ping
Published: November 2022

Th17 cells play a key role in immunity against Mycobacterium tuberculosis (MTB), and this study aimed to explore the association of Th17 pathway gene polymorphisms with pulmonary tuberculosis (PTB) susceptibility in a Chinese population. A total of 10 single nucleotide polymorphisms in Th17 pathway genes (IL-17A gene rs2275913, rs3748067, rs8193036, rs3819024, IL-17F gene rs7741835, rs763780, IL-21 gene rs907715, rs2055979, IL-23R gene rs11805303, and rs7518660) were genotyped in 456 PTB patients and 466 controls using SNPscan technique. The IL-23R rs11805303 CC genotype, C allele frequencies were significantly lower in PTB patients than in controls, and the rs11805303 variant was significantly associated with the reduced risk of PTB in a recessive model. There were no significant associations between IL-17A, IL-17F, and IL-21 gene variations and PTB risk. In IL-17A gene, rs2275913, rs3748067, and rs3819024 variants were associated with drug resistance in PTB patients. In IL-17F gene, rs7741835 variant affected drug resistance, and rs763780 variant was associated with hypoproteinemia in PTB patients. In addition, the lower frequencies of the TT genotype, T allele of rs2055979 were found in PTB patients with drug-induced liver injury. Haplotype analysis showed that IL-23R CG haplotype frequency was significantly lower in PTB patients than in controls, while the TG haplotype frequency was higher. In conclusion, IL-23R rs11805303 polymorphism may contribute to the genetic underpinnings of PTB in the Chinese population, and the IL-17A, IL-17F, and IL-21 genetic variations are associated with several clinical manifestations of PTB patients.
Assessing the sources and dynamics of organic matter in a high human impact bay in the northern Beibu Gulf: Insights from stable isotopes and optical properties
Authors: Lu Xuan , Lao Qibin , Chen Fajin , Zhou Xin , Chen Chunqing , Zhu Qingmei
Published: November 2022

Severe human activities in coastal areas have greatly impacted the sources and biogeochemical behaviors of organic matter (OM), including particulate OM (POM) and dissolved OM (DOM). However, few studies have incorporated the indices of POM and DOM to address this issue. Here, a dataset of the combination of stable isotopes of carbon and nitrogen in POM and the optical properties of DOM was presented in Xi Bay, a semi-enclosed bay with a highly developing industrial port in Beibu Gulf, South China, to reveal the origin, distribution, and fate of OM during the rainy season. In the upper bay, depleted δ13C suggested that particulate organic carbon (POC) mainly originated from terrestrial sources. However, the negative relationship between chromophoric DOM (CDOM) and particulate nitrogen (PN) suggested that bacterial-mediated decomposition of POM may be the primary source of CDOM. The negative correlation between humic-like fluorescent components (C1 and C2) and salinity suggested that those two components were mainly affected by terrestrial input. The significant correlation between the protein-like component (C3) and Chl a suggested that C3 was mainly derived from phytoplankton production in the upper bay. In the lower bay, the increase of δ13C values indicated an increased contribution of marine POC. The high levels of CDOM may be due to the decomposition of marine (fresh) POM. However, the low levels of C1 and C2 might be affected by dilution with seawater, and the increased levels of the protein-like C3 were due to enhanced primary production. In addition, the enhancement of δ15N values in both the upper and lower bays indicated serious nitrogen pollution in the bay. This study highlights that biological production fueled by excess nutrients is the dominant OM dynamic process in the bay with high human impact in Beibu Gulf.
Enhanced phycocyanin production of Arthrospira maxima by addition of mineral elements and polypeptides using response surface methodology
Authors: Yao Ting , Huang Jianke , Su Bocheng , Wei Liang , Zhang Ai-Hua , Zhang Dao-Feng , Zhou Yongsheng , Ma Guangyuan
Published: November 2022

Introduction

As a pigment protein, phycocyanin has been widely used in the fields of food, nutraceutical and biotechnology due to its excellent biological activities of antioxidant. So far, Arthrospira has been generally considered as a great species for phycocyanin production.

Methods

In this study, independent and interactive effect of three factors, NaCl, Bainengsi (BS) and Bainengtai (BT) on microalgae growth and phycocyanin production were explored by response surface methodology (RSM). Using Box-Behnken design (BBD) method, the well-fitting quadratic models were established based on experimental results.

Results

Moreover, the maximum phycocyanin concentration reached 704.66 mg L-1 at the optimal condition (185 mM NaCl, 200 mg L-1 BS, and 20 mg L-1 BT), while the maximum phycocyanin content of 19.03% was obtained at another optimal condition (136 mM NaCl, 200 mg L-1 BS, and 50 mg L-1 BT). Compared to control, the concentration and content of phycocyanin were increased by 22.98% and 16.73%, respectively.

Discussion

Overall, this study demonstrated that addition of exogenous substances (BS, BT) into culture medium optimized by RSM was an effective approach to increase phycocyanin production, which paved a potential way to realizing high efficient production of algal biomass and bioactive substances.
Expression patterns of hair-related keratins and epithelial keratins in onychopapilloma: The significance of clarifying the origin of onychopapilloma
Authors: Liu Mengxi , Li Fang , Wang Xiaoqing , Liu Zhenru , Wong Hoi Shiwn , Zhou Yuan , Wang Daguang
Published: November 2022

Background

Onychopapilloma is generally recognized as a benign tumor of the nail bed and distal matrix. However, the origin of onychopapilloma has not been explained yet.

Objective

To clarify the origin of onychopapilloma, we detected the expression patterns of hair-related keratins and epithelial keratins, which are expressed specifically in the nail unit.

Materials and methods

The clinical and histopathologic features of 11 patients with onychopapilloma were analyzed, and the expression patterns of hair-related and epithelial keratins were detected.

Results

Histologically, all subjects showed acanthosis, papillomatosis and matrix metaplasia within the nail bed. Immunohistochemically, the expression pattern of keratins in our standard nail unit was consistent with previous reports. “Nail matrix-related keratins” HK31, HK34, HK85, and HK86 were only expressed in the nail matrix, and “Nail bed-related keratins” HK75 and K6/K16 were only expressed in the nail bed. However, in onychopapilloma, whether adjacent to the matrix or in the distal nail bed, all cases were positive for nail bed-related keratins and HK31 but negative for other nail matrix-related keratins.

Conclusion

Our study suggests that onychopapilloma may originate from the nail bed rather than the nail matrix. Furthermore, the expression of nail bed-related keratins and HK31 could be used as diagnostic markers of onychopapilloma.
Effects of intestinal microbiota on pharmacokinetics of cyclosporine a in rats
Authors: Zhou Jinping , Zhang Rui , Guo Pengpeng , Li Peixia , Huang Xixi , Wei Ye , Yang Chunxiao , Zhou Jiali , Yang Tingyu , Liu Yani , Shi Shaojun
Published: November 2022

Background

Intestinal microbiota has been confirmed to influencing the pharmacokinetic processes of a variety of oral drugs. However, the pharmacokinetic effects of the gut microbiota on cyclosporine A, a drug with a narrow therapeutic window, remain to be studied.

Method

Twenty-one rats were randomly divided into three groups: (a) control group (CON), (b) antibiotic treatment group (ABT) and (c) fecal microbe transplantation group (FMT). The ABT group was administrated with water containing multiple antibiotics to deplete microorganisms. FMT was with the same treatment, followed by oral administration of conventional rat fecal microorganisms for normalization.

Result

The bioavailability of CSA increased by 155.6% after intestinal microbes were consumed by antibiotics. After intestinal microbiota reconstruction by fecal transplantation, the increased bioavailability was significantly reduced and basically returned to the control group level. Changes in gut microbiota alter the protein expression of CYP3A1, UGT1A1 and P-gp in liver. The expressions of these three proteins in ABT group were significantly lower than those in CON and FMT groups. The relative abundance of Alloprevolleta and Oscillospiraceae UCG 005 was negatively correlated with CSA bioavailability while the relative abundance of Parasutterella and Eubacterium xylanophilum group was negatively correlated with CSA bioavailability.

Conclusion

Intestinal microbiota affects the pharmacokinetics of CSA by regulating the expression of CYP3A1, UGT1A1 and P-GP.
Therapeutic efficacy of n-Docosanol against velogenic Newcastle disease virus infection in domestic chickens
Authors: Orabi Ahmed , Hussein Ashraf , Saleh Ayman A. , Megahed Ayman M. , Metwally Mohamed , Moeini Hassan , Metwally Aya Sh.
Published: November 2022

Introduction

The control of Newcastle disease virus (NDV) infection depends solely on vaccination which in most cases is not sufficient to restrain the consequences of such a highly evolving viral disease. Finding out substances for preparing an efficient anti-ND drug would be of high value. n-Docosanol is a saturated fatty alcohol with an inhibitory effect against many enveloped viruses. In this study, we evaluated the therapeutic effect of n-docosanol on NDV infection and shedding in chickens.

Methods

Chickens infected with a highly virulent NDV were treated with low to high concentrations of n-docosanol (20, 40, and 60 mg/kg body weight) for 4-successive days, once they showed the disease symptoms. Survival and curative rates, virus load, histopathological scoring, and virus shedding were defined.

Results

Symptoms development was found to discontinue 24–72 hours post-treatment. Survival rate in the NDV-infected chickens raised 37.4–53.2% after the treatment. n-Docosanol treatment was also found to significantly reduce virus load in the digestive (26.2–33.9%), respiratory (38.3–63%), nervous (26.7–51.1%), and lymphatic (16.4–29.1%) tissues. Histopathological scoring of NDV lesions revealed prominent rescue effects on the histology of different tissues. Importantly, n-docosanol treatment significantly reduced virus shedding in oropharyngeal discharge and feces thereby allowing the restriction of NDV spread.

Conclusion

Our findings suggest n-docosanol as a promising remedy in the control strategy of Newcastle disease in the poultry industry.
The divergent effects of moderate climate warming on the gut microbiota and energetic state of cold-climate lizards from open and semi-closed microhabitats
Authors: Liu Wanli , Yang Jing , Meng Yu , Wu Danyang , Cui Luoxin , Li Teng , Sun Baojun , Liu Peng
Published: November 2022

Introduction

Understanding the physiological responses to warming temperatures is critical for evaluating the vulnerabilities of animals to climate warming. The physiological responses are increasingly affected by gut microbiota. However, the interactions between physiological responses and the gut microbiota of sympatric animals from various microhabitats in the face of climate change remain largely unknown.

Methods

To evaluate the effects of warming temperatures on animals from different microhabitats, we compared locomotor performance, metabolic rate, growth, survival, and gut microbiota of two sympatric ectothermic species (Eremias argus and Takydromus amurensis) from open and semi-closed microhabitats under present and moderate warming climate conditions, respectively.

Results and discussion

We found that locomotor performance and growth rates of snout-vent length (SVL) were enhanced in both lizard species by warming climate. Interestingly, warming temperatures enhanced resting metabolic rates (RMR) in the open-habitat lizard, E. argus, but depressed them in the semi-closed habitat lizard, T. amurensis. Reversely, the metabolism-related gut microbiota was not affected by warming in E. argus, whereas it was significantly enhanced by warming in T. amurensis, indicating a plausible compensatory effect of the gut microbiota on the metabolic regulation of T. amurensis. Furthermore, warming likely improved immunity in both lizard species by significantly reducing pathogenic bacteria while increasing probiotics. This study found that high-latitude sympatric lizards from both open and semi-closed habitats were beneficial to warming temperatures by physiological modification and regulation of the gut microbiota and highlighted the importance of integrating the physiology and gut microbiota in evaluating the vulnerability of animals to climate warming.
Gut microbiome alterations in ICU patients with enteral nutrition-related diarrhea
Authors: Ni Weiwei , Jiao Xinwei , Zou Huihuang , Jing Mengjuan , Xia Ming , Zhu Shichao , Li Liming
Published: November 2022

Enteral Nutrition-related Diarrhea (END) is an extremely common complication in Intensive Care Unit (ICU) patients. However, it is currently unclear whether the patient’s gut microbiota is disturbed. Our study aimed to explore the characteristics of gut microbiota changes in END patients. We divided ICU patients into no-END group (n = 7) and END group (n = 7) according to whether they had END, then stool samples were collected separately. The V3-V4 region of stool bacterial 16S rRNA gene was amplified by PCR and sequenced on an Illumina MiSeq PE300 platform. Microbiome data obtained by quality control were analyzed, including microbial community composition, diversity and gene function prediction.The results showed that the dominant gut microbiota in ICU patients who were given total enteral nutrition were Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Verrucomicrobia. Bacterial richness and diversity in END patients were all significantly lower than those in no-END patients. In addition, END caused significant changes in bacterial composition. LEfSe found 34 biomarkers represented by Bacteroidetes and Subdoligranulum in the no-END group as well as 11 biomarkers represented by Enterococcus and Klebsiella in the END group. Finally, through PICRUST function prediction, we found that diarrhea led to abnormal changes in numerous KEGG pathways mainly related to immunity and metabolism. In short, ICU patients with END have severe gut dysbiosis, and our study provides a reliable experimental basis for the patient’s microbiota therapy.
Mechanism of curaxin-dependent nucleosome unfolding by FACT
Authors: Volokh Olesya I. , Sivkina Anastasia L. , Moiseenko Andrey V. , Popinako Anna V. , Karlova Maria G. , Valieva Maria E. , Kotova Elena Y. , Kirpichnikov Mikhail P. , Formosa Timothy , Studitsky Vasily M. , Sokolova Olga S.
Published: November 2022

Human FACT (FACT) is a multifunctional histone chaperone involved in transcription, replication and DNA repair. Curaxins are anticancer compounds that induce FACT-dependent nucleosome unfolding and trapping of FACT in the chromatin of cancer cells (c-trapping) through an unknown molecular mechanism. Here, we analyzed the effects of curaxin CBL0137 on nucleosome unfolding by FACT using spFRET and electron microscopy. By itself, FACT adopted multiple conformations, including a novel, compact, four-domain state in which the previously unresolved NTD of the SPT16 subunit of FACT was localized, apparently stabilizing a compact configuration. Multiple, primarily open conformations of FACT-nucleosome complexes were observed during curaxin-supported nucleosome unfolding. The obtained models of intermediates suggest “decision points” in the unfolding/folding pathway where FACT can either promote disassembly or assembly of nucleosomes, with the outcome possibly being influenced by additional factors. The data suggest novel mechanisms of nucleosome unfolding by FACT and c-trapping by curaxins.
Research trend of microbiota-gut-brain axis in Alzheimer’s disease based on CiteSpace (2012–2021): A bibliometrics analysis of 608 articles
Authors: Li Zi-Long , Ma Hao-Tian , Wang Meng , Qian Yi-Hua
Published: November 2022

Background

Recently, research on the microbiota-gut-brain axis (MGBA) has received increasing attention, and the number of studies related to Alzheimer’s disease (AD) has increased rapidly, but there is currently a lack of summary of MGBA in AD.

Objective

To capture research hotspots, grasp the context of disciplinary research, and explore future research development directions.

Methods

In the core dataset of Web of Science, documents are searched according to specific subject words. CiteSpace software is used to perform statistical analysis on measurement indicators such as the number of published papers, publishing countries, institutions, subject areas, authors, cocited journals, and keywords, and to visualize of a network of relevant content elements.

Results

The research of MGBA in AD has shown an upward trend year by year, and the cooperation between countries is relatively close, and mainly involves the intersection of neuroscience, pharmacy, and microbiology. This research focuses on the relationship between MGBA and AD symptoms. Keyword hotspots are closely related to new technologies. Alzheimer’s disease, anterior cingulate cortex, inflammatory degeneration, dysbiosis, and other research are the focus of this field.

Conclusion

The study revealed that the research and development of MGBA in AD rapidly progressed, but no breakthrough has been made in the past decade, it still needs to be closely combined with multidisciplinary technology to grasp the frontier hotspots. Countries should further strengthen cooperation, improve the disciplinary system, and increase the proportion of empirical research in all research.
Exposure to soiled bedding reduces abnormal repetitive behaviors in mice
Authors: Müller Karin , Lengheimer Theresia , Kral-Pointner Julia B. , Wojta Johann , Yeghiazaryan Lusine , Krall Christoph , Palme Rupert , Kleindorfer Sonia , Plasenzotti Roberto , Pollak Daniela D. , Tillmann Katharina E.
Published: November 2022

Hygiene management protocols in laboratory mouse husbandries worldwide most commonly employ soiled bedding-exposed sentinel mice to monitor the occurrence of infections in mouse colonies. Using this approach, sentinel mice repeatedly receive a mixture of used bedding, supplied by a variety of cages of a defined hygienic unit for a period of several months. Hereby, microorganisms shed in the used bedding can infect the sentinel animals and can be detected in subsequent health monitoring procedures. However, murine excrements carry more than only microorganisms. Mouse feces and urine also contain a multitude of olfactory molecules, which the animals use to code information about social status and context. However, if and how the persistent and repeated experience with these odor cues affects the behavior of sentinel mice, has not yet been explored. To address this question, we conducted a longitudinal study for neurochemical output parameters related to an organism’s responsiveness to challenging conditions, and for the exploratory assessment of a panel of home cage behaviors in soiled bedding and control female C57BL/6J mice. We found that the number of mice showing abnormal repetitive behaviors, including barbering and bar mouthing, was lower in the soiled bedding group. While neutrophil/lymphocyte ratios and fecal corticosterone metabolites did not differ between groups, the within-group variance of the neutrophil/lymphocyte ratio was reduced in the soiled bedding group. These results show that the occurrence of abnormal repetitive behaviors is lower in sentinel than in control mice and suggest a beneficial effect of soiled bedding on the welfare of laboratory mice and on outcome variability.
Using inflammatory indexes and clinical parameters to predict radiation esophagitis in patients with small-cell lung cancer undergoing chemoradiotherapy
Authors: Qiu Jianjian , Ke Dongmei , Lin Hancui , Yu Yilin , Zheng Qunhao , Li Hui , Zheng Hongying , Liu Lingyun , Li Jiancheng
Published: November 2022

Objective

Radiation esophagitis (RE) is a common adverse effect in small cell lung cancer (SCLC) patients undergoing thoracic radiotherapy. We aim to develop a novel nomogram to predict the acute severe RE (grade≥2) receiving chemoradiation in SCLC patients.

Materials and methods

the risk factors were analyzed by logistic regression, and a nomogram was constructed based on multivariate analysis results. The clinical value of the model was evaluated using the area under the receiver operating curve (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA). The correlations of inflammation indexes were assessed using Spearman correlation analysis.

Results

Eighty-four of 187 patients (44.9%) developed grade ≥2 RE. Univariate analysis indicated that concurrent chemoradiotherapy (CCRT, p < 0.001), chemotherapy cycle (p = 0.097), system inflammation response index (SIRI, p = 0.048), prognostic-nutrition index (PNI, p = 0.073), platelets-lymphocyte radio (PLR, p = 0.026), platelets-albumin ratio (PAR, p = 0.029) were potential predictors of RE. In multivariate analysis, CCRT [p < 0.001; OR, 3.380; 95% CI, 1.767-6.465], SIRI (p = 0.047; OR, 0.436; 95% CI, 0.192-0.989), and PAR (p = 0.036; OR, 2.907; 95% CI, 1.071-7.891) were independent predictors of grade ≥2 RE. The AUC of nomogram was 0.702 (95% CI, 0.626-0.778), which was greater than each independent predictor (CCRT: 0.645; SIRI: 0.558; PAR: 0.559). Calibration curves showed high coherence between the predicted and actual observation RE, and DCA displayed satisfactory clinical utility.

Conclusion

In this study, CCRT, SIRI, and PAR were independent predictors for RE (grade ≥2) in patients with SCLC receiving chemoradiotherapy. We developed and validated a predictive model through these factors. The developed nomogram with superior prediction ability can be used as a quantitative model to predict RE.
Understanding the effects of opioids vs non-opioids in the treatment of neonatal abstinence syndrome, an in vitro model
Authors: Sithisarn Thitinart , Legan Sandra J. , Westgate Philip M. , Bada Henrietta S. , Wilson Melinda E.
Published: November 2022

Neonatal abstinence syndrome (NAS) refers to cadre of withdrawal manifestations in infants born to mothers who used illicit and licit substances during pregnancy. The increasing prevalence of NAS has been largely due to the maternal use of opioids during pregnancy. NAS contributes to increased morbidity and long-term disability in surviving infants. Clinically, oral opioid therapies for opioid exposure have been a standard treatment with morphine (MO) being the most commonly used medication. Recently, a non-opioid agent, clonidine (CD) has also been used with potentially favorable short- and long-term outcomes in infants. However, data regarding the cellular and molecular effects of these treatments on the developing brain is still lacking due to a lack of a reliable animal model that targets the neonatal brain. To address this gap in knowledge we determined the effects of MO or CD on the cell death of neonatal cortical explant cultures that were exposed to oxycodone (OXY) in utero. Sprague Dawley rats were randomized and implanted with programmable infusion pumps before mating to receive either the OXY (dose increasing from 1.21–1.90 mg/kg/day to a maximum dose of 2.86–3.49 mg/kg/day) or normal saline (NS) throughout pregnancy and until one week after delivery. Male and female rat pups were sacrificed on postnatal day 4, and the prefrontal cortex (PFC) and hippocampus (HC) were dissected and treated with MO (0.10–1.00 µM) or CD (1.20–120.00 µM) in culture media. After 5 days of treatment the explants were labeled with propidium iodide to detect cell death. Dead cells were analyzed and counted under fluorescence microscopy. In explants from the PFC, cell death was greater in those prenatally exposed to OXY and postnatally treated with MO (OXY/MO) (736.8 ± 76.5) compared to OXY/CD (620.9 ± 75.0; p = 0.005). In the HC explants, mean cell death counts were not significantly different between groups regardless of prenatal exposure or postnatal treatment (p = 0.19). The PFC is vital in controlling higher-order executive functions such as behavioral flexibility, learning and working memory. Therefore, our finding is consistent with executive function problems in children with prenatal opioid exposure.
Disparities in efficacy and safety of sodium-glucose cotransporter 2 inhibitor among patients with different extents of renal dysfunction: A systematic review and meta-analysis of randomized controlled trials
Authors: Hu Suiyuan , Lin Chu , Cai Xiaoling , Zhu Xingyun , Lv Fang , Yang Wenjia , Ji Linong
Published: November 2022

Background: The pleiotropic efficacy of SGLT2is in patients with different eGFR levels has not been well-understood. This systematic review and meta-analysis assessed the disparities in the efficacy and safety of SGLT2i treatment across stratified renal function.

Methods: We searched four databases from inception to December 2021. We included randomized controlled trials (RCTs) with reported baseline eGFR levels and absolute changes from baseline in at least one of the following outcomes: HbA1c, body weight, blood pressure, and eGFR. Continuous outcomes were evaluated as the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Categorical outcomes were evaluated as odds ratios (ORs) and accompanying 95% CIs.

Results: In total, 86 eligible RCTs were included. SGLT2is produces a substantial benefit in glycemic control, weight control, and blood pressure control even in patients with impaired renal function. HbA1c and weight reductions observed in SGLT2i users were generally parallel with the renal function levels, although there was an augmented weight reduction in severe renal dysfunction stratum [HbA1c: −0.49% (−0.58 to −0.39%) for normal renal function, −0.58% (−0.66 to −0.50%) for mild renal function impairment, −0.22% (−0.35 to −0.09%) for moderate renal function impairment, and −0.13% (−0.67 to 0.42%) for severe renal function impairment (p < 0.001 for subgroup differences); weight: −2.12 kg (−2.66 to −1.59 kg) for normal renal function, −2.06 kg (−2.31 to −1.82 kg) for mild renal function impairment; −1.23 kg (−1.59 to −0.86 kg) for moderate renal function impairment; −1.88 kg (−3.04 to −0.72 kg) for severe renal function impairment (p = 0.002 for subgroup differences)]. However, the blood pressure reduction observed in SGLT2i users was independent of renal function. When compared with the placebo, the occurrence of hypoglycemia was more frequent in patients with favorable renal function rather than in those with substantial renal dysfunction.

Conclusion: The HbA1c and body weight reductions observed in SGLT2i users were generally parallel with their baseline eGFR levels, while blood pressure reductions in SGLT2i users were independent of their baseline eGFR levels. Consistently, when compared with the placebo, hypoglycemia was more frequent in patients with favorable renal function, where the HbA1c reduction was profound.
HJ11 decoction restrains development of myocardial ischemia-reperfusion injury in rats by suppressing ACSL4-mediated ferroptosis
Authors: Zhang Fangyuan , Li Ziyun , Gao Ping , Zou Jiaxi , Cui Yuting , Qian Yi , Gu Renjun , Xu Weiming , Hu Jingqing
Published: November 2022

HJ11 is a novel traditional Chinese medicine developed from the appropriate addition and reduction of Si-Miao-Yong-An decoction, which has been commonly used to treat ischemia-reperfusion (I/R) injury in the clinical setting. However, the mechanism of action of HJ11 components remains unclear. Ferroptosis is a critical factor that promotes myocardial I/R injury, and the pathophysiological ferroptosis-mediated lipid peroxidation causes I/R injury. Therefore, this study explored whether HJ11 decoction ameliorates myocardial I/R injury by attenuating ACSL4-mediated ferroptosis. This study also explored the effect of ACSL4 expression on iron-dependent programmed cell death by preparing a rat model of myocardial I/R injury and oxygen glucose deprivation/reperfusion (OGD/R)–induced H9c2 cells. The results showed that HJ11 decoction improved cardiac function; attenuated I/R injury, apoptosis, oxidative stress, mitochondrial damage, and iron accumulation; and reduced infarct size in the myocardial I/R injury rat model. Additionally, HJ11 decoction suppressed the expression of ferroptosis-promoting proteins [Acyl-CoA synthetase long-chain family member 4 (ACSL4) and cyclooxygenase-2 (COX2)] but promoted the expression of ferroptosis-inhibiting proteins [ferritin heavy chain 1 (FTH1) and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4)] in the myocardial tissues of the I/R injury rat model. Similar results were found with the OGD/R-induced H9c2 cells. Interestingly, ACSL4 knockdown attenuated iron accumulation, oxidative stress, and ferroptosis in the OGD/R-treated H9c2 cells. However, ACSL4 overexpression counteracted the inhibitory effect of the HJ11 decoction on OGD/R-triggered oxidative stress and ferroptosis in H9c2 cells. These findings suggest that HJ11 decoction restrained the development of myocardial I/R injury by regulating ACSL4-mediated ferroptosis. Thus, HJ11 decoction may be an effective medication to treat myocardial I/R injury.
Economic impact of industry-sponsored clinical trials in inflammatory bowel diseases: Results from the national institute of gastroenterology “Saverio de Bellis”
Authors: Polignano Maurizio Gaetano , Pasculli Giuseppe , Trisolini Pietro , Di Lorenzo Michele Albino , Dalfino Giuseppe , Giannelli Gianluigi
Published: November 2022

Introduction: The majority of the money spent on possible new medications’ clinical trials is accounted for by the innovative pharmaceutical sector, which also stimulates the economy of a nation. The objective of this study was to evaluate the impact of pharmaceutical industry-sponsored clinical trials (ISCTs) in inflammatory bowel diseases (IBDs) towards the national health service (NHS) in terms of avoided costs and leverage effect.

Methodology: The research was conducted at National Institute of Gastroenterology, “Saverio De Bellis”, Castellana Grotte (Apulia, Italy) collecting data from profit ISCTs of pharmaceutical products conducted over the time period 2018-2020 with focus on inflammatory bowel diseases. After the quantification of health services and drug costs from the latter studies, avoided costs and leverage effects were then estimated.

Results: The results on the avoided costs for healthcare facilities deriving from the conduct of clinical studies show that, in relation to the sample of five drug companies participating in our 2018-2020 analysis, out of a total of 235,102.46 €, identified as direct investment, 628,158.21 € of avoided costs for the NHS were measured, with an additional saving (leverage effect) for the NHS of 3.67 € for each € invested by the companies promoting clinical trials.

Conclusion: Conducting profit clinical trials has practical benefits and a favourable macroeconomic impact that, by completing its limited resources, helps to sustain one country NHS thanks to the avoided costs while also contributing to locational and industrial policy while guaranteeing novel therapeutics and health services for the patients enrolled.
Dermal open flow microperfusion for PK-based clinical bioequivalence studies of topical drug products
Authors: Birngruber Thomas , Tiffner Katrin I. , Mautner Selma I. , Sinner Frank M.
Published: November 2022

Topically applied drug products have experienced an extraordinary price increase in the United States, mostly due to a lack of generic products. Generic drug development is hindered by high costs and risks associated with clinical endpoint studies required to show bioequivalence (BE) of prospective generic products relative to their reference products. There is a continued need for cost- and time-efficient alternatives to clinical endpoint studies to determine BE of topically applied dermal drug products. Cutaneous PK-based BE studies present such an alternative and dOFM (dermal open flow microperfusion) has already been successfully used in several verifications studies to show an accurate and sensitive assessment of the rate and extent at which drugs become available in the skin. dOFM technology is discussed as well as the dOFM setup of clinical pilot and main studies to achieve BE assessment with a minimum number of participants and an outlook is given on the use of dOFM technology for other drug products.
Designing the content of religious education learning in creating sustainability among children with learning disabilities: A fuzzy delphi analysis
Authors: Zulkifli Hafizhah , Rashid Syar Meeze Mohd , Mohamed Suziyani , Toran Hasnah , Raus Norakyairee Mohd , Pisol Mohd Izzuddin Mohd , Suratman Muhamad Nasri
Published: November 2022

Teachers found it is hard to figure out what are the best approach and strategies shall be employed to create an effective learning activity that can benefit the children. Children with learning disabilities have distinctive learning difficulties, depending on each individual. Therefore, this requires modification and adaptation in the learning activities to make sure they can learn effectively. Teachers need to make adjustment to the instructions, learning materials, assessments, and activities to accommodate the children with learning disabilities. Therefore, the objective of this research is to develop the content of religious education for children with learning disabilities using fuzzy delphi. This research used method of design and developmental research approach which have three phases. In this research, the researchers focus on the second phase of fuzzy delphi. There were 20 panel experts involved in this research to rank the elements in developing religious education model. Findings showed that, all the elements such as learning style, rights of people with disabilities manners and universal design were above 70% that considered suitable and applicable. It is hoped that this model can assist and guide teachers in teaching religious education for children with learning disabilities.
Binge drinking indirectly predicts a negative emotional memory bias through coping motivations and depressive symptoms: The role of sex/gender
Authors: Johnstone Samantha , Courtenay Kesia , Girard Todd A.
Published: November 2022

Background

In this three-part study, we investigate whether the associations between binge and problematic drinking patterns with a negative emotional memory bias (NMB) are indirectly related through coping motivations and depressive symptoms. We also address potential sex differences in these relations.

Methods

Participants (N = 293) completed the Timeline Followback to assess binge drinking, the Alcohol Use Disorder Identification Test (AUDIT) to assess problematic alcohol use, the Drinking Motives Questionnaire-Revised to assess coping motivations, and the Depression, Anxiety, and Stress Scales-21 to assess depression. Participants were asked to identify whether 30 emotional sentences were self-referent or not in an incidental encoding task; 24 h later they were asked to recall as many sentences as possible and a negative memory bias score was calculated.

Results

Across all three studies, we found significant bivariate relations between AUDIT scores, coping, depression, and an NMB, particularly for sentences participants deemed self-referent. In two undergraduate samples, there were significant indirect effects through coping motivations and depressive symptoms between binge drinking and an NMB in females as well as between AUDIT scores and an NMB in females only. In the community sample, there was only an indirect effect through coping motives, but this was observed in both females and males.

Conclusion

These findings support a relation between binge drinking as well as problematic alcohol use and a self-referent NMB in the context of coping motivations for alcohol use and depressive symptoms. Moreover, the pattern of findings suggests this model primarily holds for females, yet may also apply to males at higher levels of problematic alcohol use.
Financial hardship and mental health among cancer survivors during the COVID-19 pandemic: An analysis of the US COVID-19 Household Impact Survey
Authors: Islam Jessica Y. , Turner Kea , Saeb Huda , Powell Margaux , Dean Lorraine T. , Camacho-Rivera Marlene
Published: November 2022

Purpose

Our objective was to (1) identify associated characteristics of financial hardship (FH), and (2) evaluate associations of FH with mental health symptoms among cancer survivors during the COVID-19 pandemic.

Methods

Using data from the nationally representative COVID-19 Impact Survey, we defined cancer survivors as those with a self-reported diagnosis of cancer (n = 854,7.6%). We defined FH using the following question: “Based on your current financial situation, how would you pay for an unexpected $400 expense?” Multivariable Poisson regression was used to estimate adjusted prevalence ratios (aPR) with 95% confidence intervals (95%CI) to identify associated characteristics of FH and associations of FH with mental health symptoms among cancer survivors overall and by age (18–59 years/60+ years).

Results

Forty-one percent of cancer survivors reported FH, with 58% in 18–59 and 33% in 60+ year old respondents. Compared to cancer survivors aged 60+ years, those aged 30–44 (aPR:1.74,95% CI:1.35–2.24), and 45–59 years (aPR:1.60,95% CI:1.27–1.99) were more likely to report FH. Compared to non–Hispanic(NH)–White cancer survivors, NH–Black cancer survivors had a 56% higher prevalence of FH (aPR:1.56; 95% CI: 1.23–1.97). Among 60+ years aged cancer survivors, NH–Black (aPR:1.80; 95% CI: 1.32–2.45) and NH–Asian cancer survivors (aPR:10.70,95% CI:5.6–20.7) were more likely to experience FH compared to their NH–White counterparts. FH was associated with feeling anxious (aPR:1.51,95% CI:1.11–2.05), depressed (aPR:1.66,95% CI:1.25–2.22), and hopeless (aPR:1.84,95% CI:1.38–2.44).

Conclusion

Minoritized communities, younger adults, and cancer survivors with low socioeconomic status had a higher burden of FH, which was associated with feelings of anxiety, depression, and hopelessness.
Impacts of humic-based products on the microbial community structure and functions toward sustainable agriculture
Authors: Lumactud Rhea Amor , Gorim Linda Yuya , Thilakarathna Malinda S.
Published: November 2022

Humic-based products (HPs) are carbon-rich organic amendments in the forms of extracted humic substances from manure, compost, and raw and extracted forms of lignites, coals and peats. HPs are widely used in agriculture and have beneficial effects on plants. While the agronomic benefits of HPs have been widely reported, information on their impact on the soil microbial community composition and functions is lacking, despite claims made by companies of humic substances as biostimulants. In this review, we explored published research on microbial responses with HPs application in an agronomic context. Although research data are sparse, current results suggest indirect impacts of HPs on microbial community composition and activities. HPs application changes the physico-chemical properties of the soil and influence root exudation, which in turn impact the microbial structure and function of the soil and rhizosphere. Application of HPs to the soil as biostimulants seemed to favor plant/soil beneficial bacterial community composition. HPs impacts on microbial activities that influence soil biogeochemical functioning remain unclear; existing data are also inconsistent and contradictory. The structural properties of HPs caused inconsistencies in their reported impacts on soil properties and plants. The sources of HPs and forms (whether extracted or raw), soil type, geographic location, crop species, and management strategies, among others, affect microbial communities affecting HPs efficacy as biostimulants. A more holistic approach to research encompassing multiple influential factors and leveraging the next-generation sequencing technology is needed to unravel the impacts of HPs on the soil microbiome. Addressing these knowledge gaps facilitates sustainable and efficient use of HPs as organic agricultural amendments reducing the use of chemical fertilizers.
A Methodology to Design Quantized Deep Neural Networks for Automatic Modulation Recognition
Authors: Góez David , Soto Paola , Latré Steven , Gaviria Natalia , Camelo Miguel
Published: November 2022

Next-generation communication systems will face new challenges related to efficiently managing the available resources, such as the radio spectrum. DL is one of the optimization approaches to address and solve these challenges. However, there is a gap between research and industry. Most AI models that solve communication problems cannot be implemented in current communication devices due to their high computational capacity requirements. New approaches seek to reduce the size of DL models through quantization techniques, changing the traditional method of operations from a 32 (or 64) floating-point representation to a fixed point (usually small) one. However, there is no analytical method to determine the level of quantification that can be used to obtain the best trade-off between the reduction of computational costs and an acceptable accuracy in a specific problem. In this work, we propose an analysis methodology to determine the degree of quantization in a DNN model to solve the problem of AMR in a radio system. We use the Brevitas framework to build and analyze different quantized variants of the DL architecture VGG10 adapted to the AMR problem. The evaluation of the computational cost is performed with the FINN framework of Xilinx Research Labs to obtain the computational inference cost. The proposed design methodology allows us to obtain the combination of quantization bits per layer that provides an optimal trade-off between the model performance (i.e., accuracy) and the model complexity (i.e., size) according to a set of weights associated with each optimization objective. For example, using the proposed methodology, we found a model architecture that reduced 75.8% of the model size compared to the non-quantized baseline model, with a performance degradation of only 0.06%.
RCS Prediction Using Prony Method in High-Frequency Band for Military Aircraft Models
Authors: Ahn Sungbae , Koh Jinhwan
Published: November 2022

Obtaining Radar Cross Section (RCS) data, one of the essential parameters for aircraft design, generally takes a lot of time and cost. Measurement time and accuracy of measurement results may be affected depending on the RCS measurement method and environment. When it comes to the RCS measurement method, the direct approach, which measures RCS on a real item, is more accurate than the indirect approach, which is implemented through simulation. However, in consideration of balancing accuracy, time and cost, the indirect approach is more generally used due to its efficiency. In this paper, in order to find an optimized method for more improved prediction results of indirect approach in the high-frequency band, three prediction methods are proposed: the Prony method, the Matrix pencil method (MPM) and the Rational Function method. It is confirmed that the RCS prediction result utilizing the Prony method in the high-frequency band has the minimum error in the case of Prony and MPM Methods, which have not been utilized for RCS prediction in the high-frequency band, and the Rational function method with currently applicable cases are employed. The prediction methods are, respectively, applied to a model based on three military aircraft models such as Jet Plane, F-117 and Transport Plane, and its simulation is performed under identical conditions. The original data and the extrapolated data obtained from the methods are compared at a certain angle for each model, and the errors between the extrapolated data are also compared in order to verify the efficacy of the prediction methods.
Detecting Emotions behind the Screen
Authors: Alkaabi Najla , Zaki Nazar , Ismail Heba , Khan Manzoor
Published: November 2022

Students’ emotional health is a major contributor to educational success. Hence, to support students’ success in online learning platforms, we contribute with the development of an analysis of the emotional orientations and triggers in their text messages. Such analysis could be automated and used for early detection of the emotional status of students. In our approach, we relied on transfer learning to train the model, using the pre-trained Bidirectional Encoder Representations from Transformers model (BERT). The model classified messages as positive, negative, or neutral. The transfer learning model was then used to classify a larger unlabeled dataset and fine-grained emotions in the negative messages only, using NRC lexicon. In our analysis to the results, we focused in discovering the dominant negative emotions expressed and the most common words students used to express them. We believe this can be an important clue or first line of detection that may assist mental health practitioners to develop targeted programs for students, especially with the massive shift to online education due to the COVID-19 pandemic. We compared our model to a state-of-the-art ML-based model and found our model outperformed the other by achieving a 91% accuracy compared to an 86%. To the best of our knowledge, this is the first study to focus on a mental health analysis of students in online educational platforms other than massive open online courses (MOOCs).
Yeast Products Mediated Ruminal Subenvironmental Microbiota, and Abnormal Metabolites and Digestive Enzymes Regulated Rumen Fermentation Function in Sheep
Authors: Su Manchun , Wang Huihui , Shi Huibin , Li Qiao , Zhang Yong , Li Taotao , Ma Youji
Published: November 2022

Yeast products (YP) are commonly used as rumen regulators, but their mechanisms of action are still unclear. Based on our previous studies, we questioned whether yeast products would have an impact on rumen solid-associated (SA) and liquid-associated (LA) microorganisms and alter rumen fermentation patterns. Thirty 3-month-old male sheep weighing 19.27 ± 0.45 kg were selected and randomized into three groups for 60 days: (1) basal diet group (CON group), (2) basal diet add 20 g YP per day (low YP, LYP group) and (3) basal diet add 40 g YP per day (high YP, HYP group). The results demonstrated that the addition of YP increased rumen cellulase activity, butyrate and total volatile fatty acid (TVFA) concentrations (p < 0.05), while it decreased rumen amylase activity and abnormal metabolites, such as lactate, lipopolysaccharides (LPS) and histamine (HIS) (p < 0.05). Metagenomic analysis of rumen microorganisms in three groups revealed that YP mainly influenced the microbial profiles of the SA system. YP increased the relative abundance of R. flavefaciens and decreased methanogens in the SA system (p < 0.05). With the addition of YP, the abundance of only a few lactate-producing bacteria increased in the SA system, including Streptococcus and Lactobacillus (p < 0.05). However, almost all lactate-utilizing bacteria increased in the LA system, including Megasphaera, Selenomonas, Fusobacterium and Veillonella (p < 0.05). In addition, YP increased the abundance of certain GHs family members, including GH43 and GH98 (p < 0.05), but decreased the abundance of some KEGG metabolic pathways involved in starch and sucrose metabolism, biosynthesis of antibiotics and purine metabolism, among others. In conclusion, the addition of YP to high-concentrate diets can change the abundance of major functional microbiota in the rumen, especially in the solid fraction, which in turn affects rumen fermentation patterns and improves rumen digestibility.