bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Gut Microbiota Activates AhR Through the Tryptophan Metabolite Kyn to Mediate Renal Cell Carcinoma Metastasis
Authors: Dai Guoyu , Chen Xiang , He Yao 
Published: August 2021

Background: The incidence of renal cell carcinoma (RCC) is increasing year by year. It is difficult to have complete treatment so far. Studies have shown that tryptophan metabolite Kynurenine (Kyn) affects cell proliferation, migration, apoptosis, adhesion, and differentiation. Our aim is to explore whether Kyn activates aromatic hydrocarbon receptor (AhR) to mediate RCC metastasis.Methods: We collected RCC tissues and feces from RCC patients. 16S rRNA technology was performed to analyze the gut microbial composition of RCC patients. LC-MS/MS was used to analyze the gut microbial metabolites. The AhR was inhibited and treated with Kyn. Immunofluorescence was used to measure the degree of AhR activation. The migration and invasion ability of 786-O cells was tested by Transwell assay. Flow cytometry and cell cycle assay were utilized to observe the apoptosis and cycle of 786-O cells. CCK-8 assay was used to detect 786-O cells proliferation. qRT-PCR and Western blot were used to detect AhR and EMT-related genes expression level.Results: AhR expression was up-regulated in RCC tissues. RCC gut microbiota was disordered. The proportion of Kyn was increased in RCC. After being treated with Kyn, the migration, invasion, and proliferation ability of 786-O cells were decreased. Furthermore, the expression of EMT-related protein E-cadherin decreased, and the expression of N-cadherin and Vimentin increased. The proportion of 786-O cells in the S phase increased. The apoptosis rate of 786-O cells was inhibited.Conclusion: The tryptophan metabolite Kyn could activate AhR. Kyn could promote 786-O cells migration and invasion. Gut microbiota could activate AhR through its tryptophan metabolite Kyn to mediate RCC metastasis.
Prognostic Analysis of Gastric Signet Ring Cell Carcinoma and Hepatoid Adenocarcinoma of the Stomach: A Propensity Score-Matched Study
Authors: Yang Yu , Li Yuxuan , Du Xiaohui 
Published: August 2021

BackgroundHepatoid adenocarcinoma of the stomach (HAS) is a rare type of primary gastric cancer, and most previous studies have reported that HAS has a poor prognosis due to its aggressive biological behavior. The aim of this study was to compare the prognosis of HAS to that of gastric signet ring cell carcinoma (SRC).MethodsThis was a single-center, retrospective, observational cohort study (January 2010 to January 2016) of gastric cancer patients with pathological HAS and SRC. Overall survival was compared between HAS and SRC patients. We used univariate Cox regression, multivariate Cox regression, propensity score matching (PSM), inverse probability of treatment weighting, standardized mortality ratio weighting, standardized mortality ratio weighting, and overlap weighting to perform a prognostic analysis.ResultsA total of 725 (672 SRC and 53 HAS) patients were included. After nearest-neighbor 1:4 PSM, 200 SRC patients and 50 HAS patients were matched. Only in univariate Cox regression analysis with the cohort before PSM did HAS show a significantly worse prognosis than SRC [hazard ratio (HR), 1.66; 95% confidence interval (CI), 1.02–2.69, p = 0.040]. However, in the analysis of multivariate Cox regression with the cohort before PSM and series analysis based on the propensity score, all of the results indicated that there was no statistically significant difference in overall survival between HAS and SRC (all p &gt; 0.05). Furthermore, in the subgroup of proximal location (p = 0.027), T stage 4a &amp; 4b (p = 0.001), N stage 3a &amp; 3b (p = 0.022), with cancer nodules (p = 0.026), serum CEA higher than the normal value (p = 0.038), and serum CA199 higher than the normal value (p = 0.023), the prognosis of HAS was significantly worse than that of SRC.ConclusionBased on our study, there was no statistically significant difference in overall survival between HAS and gastric SRC patients. However, in patients with an advanced tumor stage, HAS may have a worse overall survival than SRC.
A Nano-Pharmaceutical Formula of Quercetin Protects from Cardiovascular Complications Associated with Metabolic Syndrome
Authors: Ahmed Osama A. A. , Hassan Noura A. , Azhar Ahmad S. , El-Mas Mahmoud M. , El-Bassossy Hany M. 
Published: August 2021

Metabolic syndrome (MetS) is closely associated with the development of cardiovascular diseases. We recently developed a nano-preparation of the flavonoid quercetin (QU) in a self-nanoemulsifying drug delivery system (SNEDDS). The latter comprised a mixture composed of pumpkin seed oil, D-α-Tocopherol polyethylene glycol 1,000 succinate and polyethylene glycol. The QU SNEDDS preparations exhibited a considerably higher bioavailability compared with the standard quercetin suspension. Here, we investigated whether the quercetin loaded SNEDDS could offer better protection compared with the standard formulation against cardiovascular complications of MetS in rats. MetS was induced by high fructose, high salt and high fat diet for 12 weeks while the nano-preparation or the standard suspension of quercetin was orally administered for the last 6 weeks. Compared to little effect for the standard quercetin suspension (MQ), the treatment of MetS rats with the quercetin loaded SNEDDS (MNQ) virtually abolished the depressant effect of MetS on contractility index (control, 114 ± 4; MetS, 92 ± 3; MQ, 100 ± 2; MNQ, 114 ± 6 1/s) and rate of rise in left ventricular pressure (dP/dtmax) (control, 8,171 ± 274; MetS, 6,664 ± 135; MQ, 6,776 ± 108; MNQ, 7,498 ± 303 mmHg/s). Likewise, the prolongation by MetS of electrocardiographic markers of arrhythmogenesis (QTc, JT, and Tpeak-to-Tend intervals) and concomitant rises in dicrotic notch pressure were preferentially reversed by quercetin nano-preparation. On the other hand, the rises in the isovolumic relaxation constant (Tau, denotes diastolic dysfunction), blood pressure, pulse pressure, and difference between systolic and dicrotic pressure (SDP difference) were equally improved by the two preparations of quercetin. Additionally, no differences were noted in the ability of the two quercetin preparations in abrogating the elevated oxidative (MDA) and inflammatory (TNFα) markers in cardiac tissues of MetS rats. Histopathological, microscopical signs of necrosis, inflammatory cell infiltration, and vascular congestion in MetS hearts were more markedly inhibited by the nano-preparation, compared with the standard preparation of quercetin. In conclusion, the quercetin loaded SNEDDS is evidently more advantageous than the standard preparation of the drug in alleviating functional and histopathological manifestations of cardiac damage incited by MetS.
Preclinical Characterization of a Novel Anti-Cancer PD-L1 Inhibitor RPH-120
Authors: Kulikov Andrey , Shipaeva Elena , Dmitrieva Anastasia , Batrak Vera , Shipunov Georgy , Guy Colin , Smith Jill , Zhang Ran , Zhang Michael , Duan Jeff , Chestukhin Anton , Barbashov Sergei , Samsonov Mikhail , Lavrovsky Yan 
Published: August 2021

RPH-120 is a novel fully human anti-PD-L1 IgG1 monoclonal antibody with specifically designed Asn300Ala mutation in Fc fragment. Surface plasmon resonance assay showed that affinity of the RPH-120 to the dimeric form of human PD-L1-Fc fusion protein was much higher than affinity to the monomeric His-tagged PD-L1. Further binding studies demonstrated that RPH-120 is able to bind to human and monkey but not mouse PD-L1. Tissue cross-reactivity study showed good comparability of human and Cynomolgus monkeys tissue staining. Bioactivity was assessed using mixed lymphocyte reaction assay. This study revealed that RPH-120 was able to activate T cells preventing PD1/PD-L1 interaction. Antitumor efficacy was analyzed in HCC-827 lung cancer xenografts in humanized CD34+ mice at three dosage levels: 20, 80, and 200 mg/kg. RPH-120 demonstrated significant tumor growth inhibition, and this inhibition was comparable to that of atezolizumab. In a single dose toxicity, toxicokinetic and dose range finding study performed in Cynomolgus monkeys, RPH-120 was administered via intravenous (IV) bolus or 60-min IV infusion, followed by 8-weeks recovery period. An acceptable toxicokinetic profile was demonstrated and administration at doses of up to 200 mg/kg was well tolerated by all animals. In conclusion, RPH-120 revealed promising in vitro and in vivo activity and safety. RPH-120 is a potent anti-PD-L1 drug candidate for cancer immunotherapy.
Self-Medication With Over-the-counter Medicines Among the Working Age Population in Metropolitan Areas of Thailand
Authors: Chautrakarn Sineenart , Khumros Waraporn , Phutrakool Phanupong 
Published: August 2021

Background and Objectives: Self-medication with over-the-counter (OTC) medicines is becoming an increasingly popular practice around the world. The global prevalence rate of self-medication ranges from 11.2% to 93.7%, depending on the target population and country. However, there is a lack of data on the prevalence and practices of self-medication among the working-age population, particularly in Thailand metropolitan areas. The current study describes the prevalence of self-medication practices, adverse drug reactions and severity, reasons for self-medication, and basic medication knowledge among people of working age in metropolitan areas in Thailand.Methods: We conducted an online cross-sectional study between December 2020 and January 2021. Descriptive statistics were used to analyze self-medication data. A chi-square test was used to assess the association between self-medication and sociodemographic characteristics.Results: This study found high prevalence of self-medication among the working-age population in metropolitan areas of Thailand (88.2%). The most commonly used drug groups were NSAIDs (34.8%) and antibiotics (30.2%). Minor illness and easy access to pharmacies were the most common reasons for self-medication. Almost half of the participants&amp;apos; illnesses (42.6%) for which they self-medicated were not always completely cured, necessitating treatment at a hospital or clinic. Although only a small number of participants (ranged from 0.6 to 6.6%) experienced adverse drug reactions as a result of self-medication, some had severe symptoms that disrupted their daily lives or required hospitalization. In terms of basic medication knowledge, we discovered that study participants misunderstood some antibiotic drug concepts.Conclusions: According to the study findings, it is recommended that more information about the risks of self-medication, drug adverse reactions, antibiotic stewardship, more supervision of the prohibition of over-the-counter drugs and selling practices, and adequate facilities for peoples access to medical services be provided at the policy level.
Rutin, A Natural Inhibitor of IGPD Protein, Partially Inhibits Biofilm Formation in Staphylococcus xylosus ATCC700404 in vitro and in vivo
Authors: Qu Qianwei , Cui Wenqiang , Xing Xiaoxu , Zou Rongfeng , Huang Xingyu , Wang Xiaozhen , Wu Tong , Bello-Onaghise God’spower , Yuan Shuguang , Li Yanhua 
Published: August 2021

Staphylococcus xylosus (S. xylosus) has become an emerging opportunistic pathogen due to its strong biofilm formation ability. Simultaneously, the biofilm of bacteria plays an important role in antibiotic resistance and chronic infection. Here, we confirmed that rutin can effectively inhibit biofilm formation in S. xylosus, of which the inhibition mechanism involves its ability to interact with imidazole glycerol phosphate dehydratase (IGPD), a key enzyme in the process of biofilm formation. We designed experiments to target IGPD and inhibited its activities against S. xylosus. Our results indicated that the activity of IGPD and the amount of histidine decreased significantly under the condition of 0.8 mg/ml rutin. Moreover, the expression of IGPD mRNA (hisB) and IGPD protein was significantly down-regulated. Meanwhile, the results from molecular dynamic simulation and Bio-layer interferometry (BLI) technique showed that rutin could bind to IGPD strongly. Additionally, in vivo studies demonstrated that rutin treatment reduced inflammation and protect mice from acute mastitis caused by S. xylosus. In summary, our findings provide new insights into the treatment of biofilm mediated persistent infections and chronic bacterial infections. It could be helpful to design next generation antibiotics to against resistant bacteria.
Association Between Daily Worry, Pathological Worry, and Fear of Progression in Patients With Cancer
Authors: Dinkel Andreas , Marten-Mittag Birgitt , Kremsreiter Katrin 
Published: August 2021

Background: Fear of progression (FoP), or fear of cancer recurrence (FCR), is characterized by worries or concerns about negative illness-related future events. Actually, to worry is a common cognitive process that, in its non-pathological form, belongs to daily life. However, worry can also become pathological appearing as a symptom of mental disorders. This study aimed at investigating the associations among daily worry, pathological worry, and FoP in patients with cancer.Methods: This is a cross-sectional study that includes 328 hospitalized patients with cancer. Patients filled out the FoP Questionnaire (FoP-Q), the Worry Domains Questionnaire (WDQ) for the assessment of daily worry, and the Penn State Worry Questionnaire (PSWQ) for the assessment of pathological worry. Depressive, anxiety, and somatic symptoms were measured with modules of the Patient Health Questionnaire [Patient Health Questionnaire-Depressive Symptoms (PHQ-2), Generalized Anxiety Disorder-2 (GAD-2), and Patient Health Questionnaire-Somatic Symptoms (PHQ-15)]. Furthermore, a structured clinical interview was conducted for the assessment of anxiety disorders. The hierarchical multiple linear regression analysis was used to identify factors independently associated with FoP.Results: Mean age of the participants was M = 58.5 years (SD = 12.8), and 64.6% were men. FoP and worry were significantly intercorrelated (r = 0.58–0.78). The level of FoP was most strongly associated with daily worry (β = 0.514, p &lt; 0.001), followed by pathological worry (β = 0.221, p &lt; 0.001). Further significant determinants were younger age and depressive and anxiety symptoms. Clinical variables were not independently associated with FoP. The final model explained 74% of the variance.Discussion: Fear of progression is strongly associated with daily worry and pathological worry. These results bring up the question of whether FoP is an expression of a general tendency to worry. Whether a general tendency to worry, in fact, represents an independent vulnerability factor for experiencing FCR/FoP needs to be investigated in a longitudinal research design.
The Predictive Role of Lymphocyte-to-Monocyte Ratio in Acute Kidney Injury in Acute Debakey Type I Aortic Dissection
Authors: Ma Xiaochun , Chen Shanghao , Yun Yan , Zhao Diming , Li Jinzhang , Wu Zezhong , Liu Yanwu , Shen Hechen , Ma Huibo , Wang Zhengjun , Zou Chengwei , Zhang Haizhou 
Published: August 2021

Background: The post-operative acute kidney injury (AKI) represents a common complication in the Acute Debakey Type I Aortic Dissection (ADTIAD) and predicts a poorer prognosis. The clinical evidence is scarce supporting the predictive value of the pre-operative lymphocyte-to-monocyte ratio (LMR) in post-operative AKI in ADTIAD.Methods: In this retrospective cohort study, 190 consecutive patients with ADTIAD enrolled for surgical treatment between January 1, 2013, and December 31, 2018. The diagnosis of AKI followed the Kidney Disease: Improving Global Outcomes guidelines (KDIGO). Pre-operative LMR and other possible risk factors were analyzed for their prognostic value in the post-operative AKI in ADTIAD.Results: The subjects were assigned to the low-LMR and high-LMR groups according to the median value of pre-operative LMR. For post-operative AKI, the incidence and the severity in the low-LMR group were statistically different from that of the high-LMR group. Besides, the lower LMR was statistically associated with the more extended ICU stay and intubation time and higher incidences of ischemic stroke and in-hospital mortality. Additionally, in the multivariable analysis, the pre-operative LMR was an independent predictor for post-operative AKI in ADTIAD. A predictive model for post-operative AKI in ADTIAD was established incorporating LMR.Conclusions: LMR is an independent prognostic indicator incorporated into the predictive model with other risk factors to predict the post-operative AKI in ADTIAD.
Effect of the Pyrolysis Process Applied to Waste Branches Biomass from Fruit Trees on the Calorific Value of the Biochar and Dust Explosivity
Authors: Saletnik Bogdan , Bajcar Marcin , Saletnik Aneta , Zaguła Grzegorz , Puchalski Czesław 
Published: August 2021

The article discusses the findings related to the calorific value as well as the explosion and combustion parameters of dust from the raw biomass of fruit trees, i.e., apple, cherry, and pear branches, and from biochars produced using this type of biomass during pyrolysis processes conducted under various conditions. The plant biomass was thermally processed at 400, 450, or 500 °C for a duration of 5, 10, or 15 min. The study aimed to identify the calorific value of the biomass obtained from waste produced in orchards and to estimate the explosion hazard during the processing of such materials and during the storage of the resulting solid fuels. Tests were conducted to assess the total contents of carbon, ash, nitrogen, hydrogen, and volatile substances as well as the calorific value. The findings show a significant effect of the thermal transformation of fruit tree branches on the calorific value of the biochars that were produced. It was found that the mean calorific value of all of the biochars was increased by 62.24% compared to the non-processed biomass. More specifically, the mean calorific values of the biochars produced from apple, cherry, and pear branches amounted to 27.90, 28.75, and 26.84 MJ kg−1, respectively. The maximum explosion pressure Pmax measured for the dust from the biomass and for the biochars was in the range 7.56–7.8 and 7.95–11.72 bar, respectively. The maximum rate of pressure rose over time (dp/dt)max in the case of the dust from the biomass, which was in the range of 274.77–284.97 bar s−1, and the dust from biochar amounted to 282.05–353.41 bar s−1. The explosion index Kst max measured for non-processed biomass and biochars was found to range from 74.46 to 77.23 and from 76.447 to 95.77 bar s−1, respectively. It was also shown that a change in the temperature and duration of the pyrolysis process affected the quality of the biochars that were obtained. The findings show that pyrolysis, as a method of plant biomass processing, positively affects the calorific value of the products and does not lead to an increased risk of explosion during the treatment and storage of such materials. It is necessary, however, to continue research on biomass processing in order to develop practices that adequately ensure safety during the production of novel fuels.
Pemenuhan Gizi Berdasarkan AKG Bagi Anak di Lembaga Pemasyarakatan Mengenai Hak Mendapatkan Makanan yang Layak
Authors: Setiawati Mutiah , Mitro Subroto  
Published: August 2021

Nutritional Adequacy Rate (RDA) is the level of consumption of various essential nutrients with a value content that is used to meet the nutritional needs of an average healthy person living in a country. The AKG determination in Indonesia is based on the provisions regarding body weight for each gender, age and periodic physical activity according to the population survey. Where nutrition is a factor in child development. Children in prison have the right to obtain nutrition in accordance with the nutritional adequacy standard of 2,240 kcal / day. This has been regulated in Permenkumham No. 40 of 2017 concerning Food Administration for Prisoners, Children and Prisoners. The fulfillment of nutritional value is based on the use of food ingredients for 10 days / child. This juridical normative research focuses on literature study with three legal materials, namely primary legal materials using regulations regarding AKG standards, secondary legal materials with journals, books, research results, and documents and tertiary legal materials in the form of legal dictionaries, encyclopedias. The results showed that prisons have provided children's rights in the form of fulfillment of proper food, but it is still necessary to provide nutritional needs based on differences in children's nutritional status in order to obtain balanced nutrition according to the AKG standards that have been set so that they do not experience errors due to excess nutrition (overnutrition) and malnutrition (undernutrition).
Abstrak
Angka Kecukupan Gizi (AKG) merupakan tingkatan konsumsi berbagai zat gizi esensial dengan kandungan nilai yang digunakan sebagai pemenuhan kebutuhan gizi rata-rata orang sehat yang hidup disuatu negara. Penetapan AKG di Indonesia berdasarkan pada ketentuan mengenai berat badan untuk setiap gender, umur dan aktifitas fisik secara berkala sesuai dengan survei penduduk. Dimana gizi menjadi faktor dalam tumbuh kembang anak. Anak di dalam lapas berhak memperoleh gizi sesuai dengan standar kecukupan gizi sebesar 2.240 kkal/hari. Hal ini telah diatur dalam Permenkumham No 40 Tahun 2017 tentang Penyelenggaraan Makanan bagi Tahanan, Anak dan Narapidana. Pemenuhan nilai gizi didasarkan pada penggunaan bahan makanan untuk 10 hari/anak. Penelitian ini bersifat yuridis normatif yang memfokuskan pada studi kepustakaan dengan tiga bahan hukum yaitu bahan hukum primer menggunakan peraturan-peraturan mengenai standar AKG, bahan hukum sekunder dengan jurnal, buku, hasil penelitian, dan dokumen serta bahan hukum tersier berupa kamus hukum, ensiklopedia. Hasil penelitian menunjukkan bahwa lapas sudah memberikan hak anak berupa pemenuhan makanan yang layak, namun masih perlunya pemberian kebutuhan gizi berdasarkan perbedaan status gizi anak yang agar diperoleh gizi yang seimbang sesuai dengan standar AKG yang telah ditetapkan sehingga tidak mengalami kesalahan akibat kelebihan gizi (overnutrition) dan kekurangan gizi (undernutrition).