bluuebunny/crossref_metadata_2025 huggingface dataset:
The Efficacy and Safety of Transarterial Chemoembolization Combined With Tyrosine Kinase Inhibitors Plus Camrelizumab for Unresectable Hepatocellular Carcinoma: a Two-center Retrospective Study
Authors: Sun Tao , Ren Yanqiao , Sun Bo , Chen Lei , Cao Yanyan , Zhang Weihua , Zhu Licheng , Liu Fengyong , Zhang Lijie , Zheng Chuansheng
Published: March 2022

Object: This study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs: sorafenib, lenvatinib, and apatinib) plus camrelizumab (TACE-TKIs-C) vs. TACE combined with TKIs (TACE-TKIs) for unresectable hepatocellular carcinoma.Methods: In this two-center retrospective study, patients with unresectable HCC treated with TACE-TKIs-C or TACE-TKIs were enrolled between January 1, 2018 to October 1, 2020. A total of 260 eligible patients received TACE-TKIs-C (N=70) or TACE-TKIs (N=190). The differences in overall survival (OS), progression free survival (PFS) and tumor response were compared between two groups. The risk factors affecting OS or PFS were analyzed.Results: The OS of TACE-TKIs-C was significantly longer than TACE-TKIs (P<0.0001). The median OS of TACE-TKIs-C was not reached and the OS of TACE-TKIs was 12 months ((95% CI, 11.0 to 13.0 months). The estimated rates of survival at 6 months and 12 months were 88.6±3.8% and 76.1±5.3%, respectively, in the TACE-TKIs-C group and 86.2±2.5% and 52.0±3.7% in the TACE-TKIs group. The median PFS of TACE-TKIs-C was significantly improved compared with TACE-TKIs (10.0 vs 6.0 months, P<0.0001). Multivariate analysis showed that ECOG performance, number of tumors, tumor size and treatment were independent factors of OS and treatment were independent predictive factors of PFS. Grade 3 or 4 hypertension occurred in 14.3% of patients in the TACE-TKIs-C group and other high-grade toxic effects were infrequent.Conclusion: In patients with unresectable HCC, TACE-TKIs-C may improve overall and progression-free survival outcomes over TACE-TKIs with manageable safety profile.
Novel pharmacokinetic model to estimate dopamine dynamics in humans using PET
Authors: Tomasi Dardo , Manza Peter , Logan Jean , Kojori Ehsan Shokri , Yonga Michele-Vera , Kroll Danielle , Feldman Dana , McPherson Katherine , Biesecker Catherine , Dennis Evan , Johnson Allison , Yuan Kai , Wang Wen-Tung , Butman John , Wang Gene-Jack , Volkow Nora
Published: March 2022

Dopamine facilitates cognition and is implicated in reward processing. Methylphenidate, a dopamine enhancing medication widely used to treat attention-deficit/hyperactivity disorder, has rewarding and addictive effects if injected. Since methylphenidate’s brain uptake is much faster when injected than when taken orally, we hypothesized that the amplitude and the speed of dopamine release in striatum would underly drug reward. To test this hypothesis we developed a non-invasive method to assess methylphenidate-related extracellular dopamine increases at 1-minute temporal resolution using positron emission tomography, which we validated in preclinical microdialysis data. Using a placebo-controlled double-blind within-subjects design, we show in 20 healthy controls that striatal dopamine increases induced by intravenous methylphenidate (0.25 mg/kg) were significantly faster than those induced by oral methylphenidate (60 mg) and that the time-to-peak of dopamine release was strongly associated with the intensity of self-reports of feeling “high”. With this novel approach we show for the first time in humans that stronger drug reward is associated with shorter dopamine time-to-peak after methylphenidate administration.
FUS aggregation following ischemic stroke favors brain astrocyte activation through inducing excessive autophagy
Authors: shusheng wu , Yin Yuye , Du Longfei
Published: March 2022

As is the case with neurodegenerative diseases, abnormal accumulation of aggregated proteins in neurons and glial are also known to implicate in the pathogenesis of ischemic stroke. However, the potential role of protein aggregates in brain ischemia remains largely unknown. Fused in Sarcoma (FUS) protein has a vital role in RNA metabolism and regulating cellular homeostasis. FUS pathology has been demonstrated in the formation of toxic aggregates and critically affecting cell viability in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but whether this also applies to neurological injury following cerebral ischemia is unclear. Herein, we demonstrated a critical role of aggregated FUS in astrocyte activation caused by cerebral ischemia and a possible underlying molecular mechanism. Cerebral ischemic injury significantly induced the formation of cytoplasmic FUS aggregates in reactive astrocytes, thereby aggravating neurofunctional damages and worsening stroke outcomes. Further analysis revealed that extranuclear aggregation of FUS in astrocytes was involved in the induction of excessive autophagy, which contributes to autophagic cell injury or death. In conclusion, our results reveal the important contribution of FUS aggregates in promoting astrocytes activation in stroke pathology independent of its transcriptional regulation activity. We thus propose that aggregation of FUS is an alternative pathomechanism of ischemic stroke and targeting FUS aggregates might be of unique therapeutic value in the development of future treatment strategies for ischemic stroke.
Bored at home? - A systematic review on the effect of environmental enrichment on the welfare of laboratory rats and mice
Authors: Mieske Paul , Hobbiesiefken Ute , Butzke Daniel , Rudeck Juliane , Lewejohann Lars , Diederich Kai
Published: March 2022

Boredom is an emotional state that occurs when an individual has nothing to do, is not interested in the surrounding, and feels dreary and in a monotony. While this condition is usually defined for humans, it may very well describe the lives of many laboratory animals housed in small, barren cages. To make the cages less monotonous, environmental enrichment is often proposed. Although housing in a stimulating environment is still used predominantly as a luxury good and for treatment in preclinical research, enrichment is increasingly recognized as a way to improve animal welfare. To gain insight into how stimulating environment influences the welfare of laboratory rodents, we conducted a systematic review of studies that analyzed the effect of enriched environment on behavioral parameters of animal wellbeing. Remarkably, a considerable number of these parameters can be associated with symptoms of boredom. Our findings show that a stimulating living environment is essential for the development of natural behavior and animal welfare of laboratory rats and mice alike, regardless of age and sex. Conversely, confinement and under-stimulation in conventional housing systems has potentially detrimental effects on the mental and physical health of laboratory rodents. We show that boredom in experimental animals is measurable and does not have to be accepted as inevitable.
Reveal Postoperative Brain Glioma True Behavior by Real-Time Tracking of Tumor Gene Evolution Information
Authors: Bu Yage , Sheng Zhiyuan , Deng Kaiyuan , Wu Shuang , Xu Sensen , Guo Guangzhong , Zhang Ziyue , Liu Guanzheng , Yu Jinliang , Gao Yushuai , Yan Zhaoyue , Bu Chaojie , Gu Jianjun , Kong Lingfei , Liu Gang , Wang Meiyun , Li Tianxiao , Hernesniemi Juha , Zemmar Ajmal , Bu Xingyao
Published: March 2022

Background
At present, the in vivo gene evolution of human glioma after surgery is unknown. We need to understand the real-time in vivo gene evolution information of the tumor to dynamically reflect the real behavior of the tumor, so as to drive therapeutic decisions. TISF-ctDNA can provide real-time in vivo gene information after surgery, and then reveal postoperative glioma behavior more realistically.
Methods
This retrospective, Single center, sample collection, validation study conducted at Zheng Zhou University People's hospital from July 1st, 2016, to November 1st, 2021, assessed patients with glioma who were receiving surgical treatment and adjuvant radiotherapy and chemotherapy. The study including 69 patients, with radiological relapse identified in 44 patients forming the main cohort.
RESULTS
In the primary tumor, a total of 199 mutations were detected in 58 tumor tissue samples,12 patients (21%) with 1 mutation and 45 patients (79%) with multiple mutations,TP53 (44%) followed by IDH1(39%) and PTEN(25%), mean VAF from 2.1%-79.5%,with a median 40.5%.At or after a diagnosis of recurrence, A total of 613 gene mutations were found through TISF ctDNA sequencing, including TP53 (48%), NF1 (38%), PTEN (31%), mean VAF from 0.2%-34.14%, with a median 1.54%, and we also found Pseudo-progression and hypermutation associated with TMZ resistance. In the main cohort of 44 patients (mean age, 52 years) with a median follow-up of 190 days (20-1530 days), mean VAF of TISF ctDNA during follow-up was associated with relapse (hazard ratio, 4.058; 95% CI, 1.089 to 15.12; P = 0.0012). Similar outcomes were observed for tumor tissue (hazard ratio, 2.214; 95% CI, 1.003 to 4.887; P = 0.0165). Hypermutation was found in 3 patients in the cohort, and the in vivo evolution of hypermutation was tracked in 2 of these patients.
CONCLUSIONS
TISF ctDNA describes human glioma behavior, demonstrates the real tumor gene mutation landscape in vivo during treatment, providing prognostic and response data of clinical relevance.
Prevalence and quantification of thoracic pain (TP) through quantitative sensory testing (QST) in patients with chronic interstitial lung disease (cILD)
Authors: Scherer Manuela Juliana , Kampe Sandra , Fredebeul-Beverungen Jonas , Weinreich Gerhard , Costabel Ulrich , Bonella Francesco
Published: March 2022

BackgroundPrevalence and predisposing factors for the development of thoracic pain in patients with chronic interstitial lung disease are largely unknown. Underestimation and insufficient therapy of pain can lead to worsened ventilatory function. Quantitative sensory testing is an established tool for characterization of chronic pain and its neuropathic components. We investigated frequency and intensity of TP in cILD patients and the potential association with lung function and quality of life. MethodsWe prospectively investigated patients with chronic interstitial lung disease to analyze risk factors for the development of thoracic pain and quantify thoracic pain through quantitative sensory testing. In addition, we studied the relationship between pain sensitivity and lung function impairment. Results78 patients with chronic interstitial lung disease and 36 healthy controls were included. Thoracic pain occurred in 38 of 78 patients (49%), most frequently in 13 of 18 (72%) in pulmonary sarcoidosis. The occurrence was mostly spontaneous and not related to thoracic surgical interventions (76%). Patients with thoracic pain showed a significant impairment of mental well-being. A higher sensitivity to pinprick stimulation during QST can be observed in patients with thoracic pain. Steroid treatment was associated with lower sensitivity within thermal and pressure pain testing. We observed a significant correlation between total lung capacity and thermal or pressure pain sensitivity. ConclusionThis study was performed to investigate prevalence, risk factors and thoracic pain in patients with chronic interstitial lung disease. Thoracic pain mostly occurs spontaneous as a frequent symptom, and seems to be an underestimated symptom in patients with chronic interstitial lung disease, especially those with pulmonary sarcoidosis. Identifying thoracic pain at early stage may allow starting palliation of symptoms earlier.Clinical Trial RegistrationDeutsches Register Klinischer Studien (DRKS) https://www.drks.de/drks_web/ DRKS00022978
Offering women a choice in induction of labour: a prospective cohort study
Authors: DUPUIS Ninon , LOUSSERT Lola , de VRIES Pauline L. , PARANT Olivier , VAYSSIERE Christophe , GUERBY Paul
Published: March 2022

Purpose
To evaluate women’s choice in the method of labour induction between oral misoprostol, PGE2 pessary and the Foley catheter. To compare women’s satisfaction according to their choice and to identify factors associated with patient satisfaction.
Methods
We conducted a comparative, prospective cohort study of 520 women who chose their preferred method for labour induction, in a French tertiary hospital, from July 2019 to October 2020. Before and after the delivery, they were asked to argument their choice and to evaluate their satisfaction through the use of questionnaires. The primary outcome was global level of satisfaction.
Results
Of the 520 women included, 67,5% of women chose oral Misoprostol compared to 21% PGE2 pessary and 11.5% the Foley catheter. Regarding global satisfaction, we found no significant difference between the three groups: 78,4%, 68,8% and 71,2% (p = 0,091) for respectively oral misoprostol, PGE2 pessary and the Foley catheter. Factors that seem to improve women’s satisfaction were nulliparity (OR = 2.03, 95%CI [1.19–3.53]), delivery within 24 hours after the start of induction (OR = 3.46, 95%CI. [2.02–6.14]) and adequate information (OR = 4.21,95%CI [1.86–9.64]). Factors associated with lower satisfaction rates were postpartum hemorrhage (OR = 0.51, 95%CI [0.30–0.88]) and caesarean section (OR = 0.31, 95%CI [0.17–0.54]).
Conclusion
Women satisfaction rates were not different between the three methods, when chosen by the patients themselves. These finding should encourage caregivers to promote shared decision making when possible.
Increased Tim-3 and Gal-9 expression are related to poor prognosis in Oral Squamous Cell Carcinoma
Authors: Ahmed Sehrish , Shaikh Fouzia
Published: March 2022

Introduction: TIM3 is an inhibitory checkpoint marker that attenuates immune response when engaged with its ligand Gal9. Blockage of Tim3 reinvigorate immune response in various tumors and thus emerged as a potential candidate for cancer therapy. However, the biological basis of the Tim3/Gal9 axis in Oral Squamous Cell Carcinoma (OSCC) has remained unelucidated. To the best of our knowledge, this is the first research around the globe conducted on OSCC tissue samples to determine the expression of both Tim-3 and its ligand Gal-9 and evaluation of their prognostic values.Methods: To achieve this Immunohistochemistry was done in 126 OSCC tissue samples.Results: 65.9% Tim-3 expression on immune cells and 70.6% expression of Gal-9 on tumor cells was observed with mostly membranous and cytoplasmic staining. Increased Gal9 expression was associated with worse TNM staging, lymph-vascular invasion, lymph node metastasis, distant metastasis, and tobacco consumption habits (p=0.001, p=0.010, p=0.001, p=0.032, p=0.025 respectively). On the other hand, higher Tim3 expression was found in patients with worse TNM stages, tumor differentiation, and lymph-vascular invasion (p=<0.001, p=0.002, and p=0.021 respectively). Moreover, multivariate analysis shows that high Gal9 expression and high Tim3 expression were significantly associated with poor overall survival (p=0.015 and p=0.006 respectively). The combination of Tim3 and Gal9 expression was an independent prognostic predictor for patients with OSCC (HR: 2.79, 95% CI: 1.268-6.162).Conclusion: The results speculated that Tim3/Gal9 expression may be a potential, independent prognostic factor for OSCC patients. Tim3 and Gal9 may play a vital role in carcinogenesis.
Outcomes of Medical versus Surgical Management of Incomplete Abortion in Uganda. an Open Labeled Randomized Clinical Trial
Authors: Otieno Victor Tetty , Byonanuwe Simon , Bonet Ivan , Emillio Sanchez , Atuheire Collins
Published: March 2022

Background: Management decision on whether to use medical or surgical method in women diagnosed with incomplete abortion particularly in the first trimester has been a controversial topic in Uganda and the world in general with no local studies comparing effectiveness and secondary outcomes between the two approaches. This has posed a big challenge to the attending clinicians as regards making informed management options when encountered with such cases.Methods: A five months prospective open labeled randomized clinical trial involving 100 consecutively recruited participants was conducted from June 1st, 2018 to October 30th, 2018. Ethical clearance was obtained from KIUREC and UNCST. Data collection was achieved using an investigator administered questionnaire; in-depth face to face interviews as well as laboratory and ultrasound scan report forms. Baseline demographic and clinical characteristics were assessed using univariate analysis. Statistical difference was considered when p<0.05. Numerical variables were summarized using means, medians for non-normally distributed variables, and frequencies or proportions for categorical variables. All statistical analysis was carried out using IBM SPSS Statistics software version 23.0. Results: The effectiveness of surgical management was higher than that of medical management (RRR=11.7%; p=0.043). Majority in the medical arm reported mild pain (64% vs 4%; p<0.001) while most of those in surgical arm reported severe pain (78% vs 8%; p<0.001). Bleeding was prolonged in the medical arm method with majority of those in surgical arm reporting bleeding for less than six hours (94% vs 46%; p=0.0002). Although medical method had longer bleeding, it was associated with lesser symptoms of headache, dizziness, syncope and blood transfusion. 90% of those in medical arm and only 50% of those in surgical method would recommend the method assigned (p<0.001). Fever, chills and nausea were more common in medical method. Average hospital stay was longer in medical method (p=0.03). Only one participant in surgical arm developed infection while no patient had genitourinary trauma. There was no statistical significant difference between the satisfaction levels in the two arms. Conclusion: Surgical management is more effective than medical management. Although medical management has prolonged expulsion bleeding, prolonged hospital stay and increased fevers, chills and nausea that are self-limiting; it has reduced pain. Most patients are satisfied with and would recommend medical management.
New ITS rDNA barcodes clarify phylogenetic relationships and biogeography of aquatic hyphomycetes
Authors: Duarte Ricardo , Fernandes Isabel , Gulis Vladislav , Cássio Fernanda , Pascoal Cláudia
Published: March 2022

Aquatic hyphomycetes are key microbial decomposers of allochthonous organic matter in freshwater ecosystems. Although their importance in carbon flow and food webs in streams is widely recognized, there are still gaps in our understanding of their phylogeny, molecular diversity and distribution patterns. Our study utilized the growing database of ITS rDNA barcodes of aquatic hyphomycetes (1252 sequences) and aimed to (i) produce new barcodes for some lesser-known taxa of aquatic hyphomycetes, (ii) clarify the phylogeny of aquatic hyphomycetes, including the placement of some taxa at the class or order level based on molecular data, and (iii) provide insights into biogeography of this group. This study increased the number of aquatic hyphomycetes with available ITS barcode from 120 species (out of ~ 300 species described) to 136 species. Phylogenetically, the 136 species of aquatic hyphomycetes were distributed between two phyla (Ascomycota and Basidiomycota), 6 classes and 10 orders of fungi. However, 36 species remain incertae sedis without attribution at the order level. The geographical distribution of species with available ITS sequences included 50 countries from 5 continents. North American and European countries showed the highest number of aquatic hyphomycete species with ITS barcodes, with 6 countries having more than 20 species: Portugal (34 species), United States of America (33 species), United Kingdom (29 species), Germany (28 species), France (22 species) and Czech Republic (21 species).
Heat-induced maternal effects shapes avian eggshell traits and embryo development and phenotype in high incubation temperatures
Authors: Hoffman Alexander , Dees Leslie , Wada Haruka
Published: March 2022

Populations without a sufficient rate of genetic adaptation may risk extinction in the face of rapid environmental change, however, phenotypic plasticity can facilitate their persistence. For example, mothers can prepare offspring for the thermal environment they will experience through maternal effects. In oviparous species, little is known about how variation in the timing and intensity of thermal stressors influences embryo phenotype. We demonstrate that when zebra finch mothers are exposed to a mild heat conditioning as juveniles, their embryos do not exhibit the increased water loss and shorter development times at high incubation temperatures shown by embryos from control mothers. Mothers exposed to the mild heat conditioning as juveniles and a high heat stressor as adults produced eggs with a higher density of shell pores, embryos with lower heart rates during development, and hatchlings with heavier pectoralis muscles when incubated at a high temperature. However, maternal heat exposure was only positively correlated with embryo survival at a control temperature, where embryos produced by mothers exposed to only the mild heat conditioning exhibited higher survival rates than all other groups. These results demonstrate that the thermal environment experienced by mothers can influence the physiology of their embryos and eggshell characteristics.
Corneal Densitometry in Bilateral Keratoconus Patients With Unilateral Corneal Vogt’s Striae: a Contralateral Eye Study
Authors: Wei Shengsheng , Li Jing , Li Yong , Zhang Yaohua , Cai Yan , Du Jing , Liu Jianguo , Wang Yan
Published: March 2022

Purpose: To investigate corneal densitometry and correlations with corneal morphological parameters in bilateral keratoconus (KCN) patients with unilateral Vogt’s striae. Methods: In total, 112 patients (224 eyes) were enrolled in this cross-sectional contralateral eye study. Corneal densitometry and morphological parameters were measured using Pentacam HR. Results: Corneal densitometry values of the anterior 0-2 mm and 2-6 mm, intermediate 0-2 mm and 2-6 mm, posterior 2-6 mm, and total cornea 2-6 mm were significantly higher in eyes with Vogt’s striae than in eyes without Vogt’s striae (P<0.05), while those of the anterior 6-10 mm, posterior 0-2 mm, and total cornea 6-10 mm were significantly lower in the former (P<0.05). Corneal densitometry values in the anterior 0-2 mm and total cornea 2-6 mm were positively correlated with K1, K2, Km, Kmax, anterior corneal elevation, and posterior corneal elevation (P<0.05) and negatively correlated with central corneal thickness and thinnest corneal thickness in eyes with Vogt’s striae (P<0.05). K2, Km, and Kmax were significantly correlated with densitometry values of the anterior 0-2 mm and intermediate 0-2 mm in eyes without Vogt’s striae (P<0.05). Densitometry values of the anterior and intermediate layers in the central cornea were higher in eyes with Vogt’s striae, while those of the anterior corneal stroma in the central region of the cornea were higher than those of the peripheral cornea in all eyes. Conclusions: Vogt’s striae mainly occur on the anterior and intermediate layers during the progression of KCN.
Endogenous melatonin concentration along with the expression of mitochondrial regulator genes is elevated by the serum shock process in the U87-MG cell line
Authors: Balkhi Shayan , Jazi Marie Saghaeian , Samaei Nader Mansour , Farahmandrad Mahtab
Published: March 2022

According to the World Health Organization, glioblastoma, also known as the fourth grade in the development of astrocytoma, is a glial tumor limited to the central nervous system with a strong ability to invade the brain parenchyma. Melatonin can be generated outside of the pineal gland tissue, according to new research. Melatonin is produced by mitochondria independently but in concert with cell demands, and it plays an important function in cell cycle and metabolism regulation. As a result, we set out to investigate the association between cell metabolism and the serum shock-induced increase in endogenous melatonin, as well as the percentage of cell proliferation.Background: Melatonin can be produced in the mitochondria organelle of glioblastoma cells without the involvement of the pineal gland, according to new research. Regarding the physiological function of melatonin secreted by the pineal gland in the regulation of rhythmicity, the goal of this study was to see if the glioblastoma cell's melatonin production ability could be influenced using a typical serum shock technique established for cellular rhythm regulator.Material and methods: First, U87-MG glioblastoma cells were cultured in a DMEM medium containing 10% FBS and then cells were treated with a standard serum shock process (no FBS, 8h). The concentration of melatonin was measured using ELISA method in supernatant and cell extracts of Shock and control groups. The cell proliferation was measured by using BrdU staining and flow cytometry assessment. The gene expression levels of some mitochondria or circadian related genes including TFAM, BMAL1, PPARGC1A(PGC1-α), and DNM1L(DRP1) were measured, using qRT-PCR method.Results: In comparison to the control group, serum shock treated U87-MG glioblastoma cells had higher concentrations of cellular and released endogenous melatonin (two times). At the mRNA level, we discovered considerable upregulation of mitochondrial or circadian regulator genes (TFAM, BMAL1, PPARGC1A, and DNM1L); in the shock group compared to the control group (P <0.0002). Furthermore, although the percentage of proliferative cells (Brdu positive) was higher in the shock group, it was not statistically significant.Conclusion: The serum shock procedure has a significant impact on the U87-MG cell line's cellular activity. In terms of the study's findings, it's worth noting that an increase in endogenous melatonin concentration influences several signaling pathways within the U87-MG cell line, as seen by the increased expression of candidate genes.In light of the findings of this study, it's worth noting that further research into the role of endogenous melatonin and its effects on cancer cells is critical, and that comparing the results of normal and cancer cells can reveal the hotspots of the signaling pathways involved, which could facilitate in better understanding the biology of glioblastoma.
The Roles of Customer Perception of Innovativeness and Engagement on Loyalty through Value Co-creation Behaviors: The Case of Food-delivery Service
Authors: Paringan Adinda Toti , Novani Santi
Published: March 2022

The food delivery service that has gained popularity over the last few years should preserve its competitiveness by developing customer satisfaction and loyalty through customer value co-creation behaviors. However, there is still limited literature on understanding the antecedents and implications of customer value co-creation behavior in the service industry. The research aimed to evaluate the effect of customer perceptions of innovativeness and customer engagement on value co-creation behavior. Also, this study wants to reveal the relationship between value co-creation behavior on customer satisfaction and loyalty in food delivery services, using Service-Dominant (S-D) logic perspective. A survey of Indonesian GoFood customers was conducted through an online questionnaire. Then, 349 complete responses were empirically analyzed using the Partial Least Squares-Structural Equation Modeling (PLS-SEM) method. The findings reveal that customer engagement and perceived innovativeness affect customer value co-creation behavior. However, customer participation does not immediately increase customer loyalty. Instead, it must be accompanied by an increase in customer satisfaction. By investigating the antecedents and implications of value co-creation behavior among food delivery service users, the research provides practitioners with viable business strategies for maximizing customer loyalty by evaluating service innovation and the customers' behavior in co-creation value. Moreover, the research contributes to the theoretical development of customer value co-creation behaviors and the foodservice business.
INTERDISCIPLINARY EDUCATION THROUGH THE DEVELOPMENT OF A COST-EFFECTIVE PHOTOMETRIC pH METER SENSOR USING NATURAL PIGMENTS
Authors: Barboza Rodolfo , Vale Daniella , Gomes Thiago , Mesquita Thayná , Silva Carlos , Camargo Gabriela
Published: March 2022

There is a trend of development of analytical methodologies and technologies that allow in situ analysis, producing accurate information in real time, at low cost, using homemade experiments and devices to increase interest in scientific knowledge with a constructive approach in an interdisciplinary perspective in Chemistry Education. In this context, a photometric-chemometric method of analysis was developed to measure the pH of solutions using easily accessible and low-cost material based on the use of natural pigments found in red cabbage (Brassica oleracea L.). Calibrations and determinations were performed by RGB measurements of pigment coloration in solution at different pH values using the free app Photometrix, converted to HSV, YCbCr and YUV color spaces and processed by Partial Least Squares regression (PLS). The best PLS model found was HSV with mean central scale obtained pH measurements with RMSEP 0.98, R2 0.97 and bias close to zero. In addition, experimental data were statistically validated. Analyzes of predicted pH from three independents experiments revealed high recoveries (95-103%) and low relative standard deviations. Thus, the PhotoMetrix app was viable for colorimetric pH determinations using the low-cost photometric pH meter sensor and a smartphone, improving accessibility and applicability in Chemistry Education.
Synthesis of Eugenol-Fluorinated Triazole Derivatives and Evaluation of Their Fungicidal Activity
Authors: Lima Ângela , de Paula Wenderson , Leite Iris , Gazolla Poliana , de Abreu Lucas , Fonseca Victor , Romão Wanderson , Lacerda Jr. Valdemar , de Queiroz Vagner , Teixeira Róbson , Costa Adilson
Published: March 2022

Eugenol (C10H12O2, 4-allyl-2-methoxyphenol) is a phenolic natural product that has several biological activities and possibilities of applications. It is herein described the synthesis of eugenol-fluorinated triazole derivatives and evaluation of their fungicidal activity. The reaction of eugenol with epichlorohydrin resulted in the preparation of (±)-2-((4-allyl-2-methoxyphenoxy) methyl)oxirane (1) in 88% yield. The azidolysis of 1 with sodium azide gave the azido-alcohol (±)-1-(4-allyl-2-methoxyphenoxy)-3-azidopropan-2-ol (2) in 94% yield. The CuAAc reaction between compound 2 and different terminal alkynes afforded a series of eleven derivatives (3a‑3k) within 48-80% yield. All the synthesized compounds were characterized by infrared (IR) and nuclear magnetic resonance (1H and 13C) spectroscopies and high-resolution mass spectrometry. The in vitro inhibitory activity of the compounds on the mycelial growth of a strain of Colletotrichum sp., that causes anthracnose disease on papaya fruits, was evaluated. The best result was observed for compound 1-(4-allyl-2-methoxyphenoxy)-3-(4-(2-fluorophenyl)-1H-1,2,3-triazol-1-yl)propan-2-ol (3d) that showed a mean growth-inhibition zone of 5.10 mm in a well-diffusion assay, and may serve as a template for additional structural modifications, aiming for more potent fungicidal activity.
Ayurvedic hospital wastewater degradation using electrochemical treatment
Authors: Mahesh S. , Shivaprasad K. S. , Sanjana Mahesh
Published: March 2022

The goal of this research was to remove COD, oil and grease (O&G) and color from raw ayurvedic hospital wastewater (AHWW) using a novel electrochemical coagulation (ECC) process. Cell voltage was initially optimized using iron electrodes in bipolar mode for both raw AHWW and ayurvedic hospital therapy room wastewater (AH-TRWW) for a pre-optimized electrolysis time (ET) of 60 min. O&G, COD and color removals for AHWW at 8 V optimized cell voltage were 96, 61 and 96% respectively. Different electrode materials, copper, aluminum, graphite, were used to evaluate relative performances at 8 V. Iron electrodes showed maximum pollutant removal from raw AHWW. The sludge obtained after the ECC process showed good settling and filterability properties compared to graphite and aluminum electrodes. The low SVI value of 146 mL/g was obtained exercising absolute control on sludge volume. Solids flux values showed assurances of compact settling tank design with least spatial footprint. EDX analysis for ECC sludge of AHWW using iron showed gross elements 40.19% C, 48.63% O and 7.92% Fe redefining the fate of sludge. The XRD pattern of the ECC sludge showed an amorphous nature. Post-ECC filtration effluent showed clear water reclamation of 80–82%, proving the effectiveness of the novel ECC treatment process.
Suelo y cambio climático. Incluye estudio de casos
Authors: Aguirre Forero Sonia Esperanza , Piraneque Gambasica Nelson Virgilio , Mercado Fernández Teobaldis
Published: March 2022

Suelo y cambio climático es un enfoque sistémico resultado de investigaciones en el área de edafología, orientado a contribuir a la comprensión y apropiación del recurso como base del sistema ecológico. Este texto contiene experiencias contextualizadas que permiten repensar el uso del suelo y hacer aportes en la transformación de las relaciones socioculturales que sustentan los saberes, a fin de orientar un mejor manejo del recurso, prioridad indispensable para sostener la vida, lo que conlleva a repensar alternativas que limiten los efectos de la actividad antrópica. Se evidencian conceptos con visión histórica del recurso, así como sus enfoques y funciones, y las causas y consecuencias de su degradación. Luego, se destaca la importancia de la materia orgánica, la cobertura vegetal y las prácticas de conservación. Se añaden apuntes de la importancia del agua en los sistemas, la nutrición vegetal como eje básico de seguridad alimentaria y la jerarquía del suelo en el fenómeno de cambio climático. Por último, se presentan estudios de casos desarrollados por los autores en campo, en los que se resalta la importancia de la cobertura vegetal para la conservación del suelo y la captura de carbono en el trópico seco; se caracteriza el sector agropecuario del Magdalena y la importancia de la conservación del suelo para mitigar el cambio climático, y se finaliza detallando el rol del suelo en la regulación hídrica y térmica en microcuencas del departamento.
Wedelolactone, a Component from Eclipta prostrata (L.) L., Inhibits the Proliferation and Migration of Head and Neck Squamous Cancer Cells through the AhR Pathway
Authors: Liu Yanqiu , Zou Yi-xuan , Mu Zhen-qiang , Wang Jie , Tian Shuo , Li Yilin
Published: March 2022

Background:

Ecliptae prostrata (L.) L. has been widely used in East Asia with reported biological activities, including anti-cancer properties.

Objective:

We aimed to investigate the effect of ethyl acetate extract of Ecliptae prostrata (L.) L. (EAE) and its component wedelolactone on the proliferation and migration of head and neck squamous cancer cells.

Methods:

The proliferation of human SCC-4 and mouse CU110-1 tongue squamous carcinoma cells was assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method. Scratch wound assays were performed to assess cell migration rates. The levels of Ecadherin and vimentin were used as markers of the epithelial-to-mesenchymal transition (EMT). AhR, CYP1A1, and CYP1B1 levels were examined to uncover the mechanism of inhibition of cell migration by wedelolactone.

Results:

We found that EAE and wedelolactone decreased the proliferation of human SCC-4 cells and mouse CU110-1 cells at doses of EAE at > 25 μg/ml and wedelolactone at > 6.25 μg/ml. Similarly, both EAE and wedelolactone produced inhibitory effects against migration, but the effective doses that significantly inhibited migration were lower than those affecting proliferation. Wedelolactone below 12.5 μg/ml inhibited the epithelial-to-mesenchymal transition (EMT) with increased expression of E-cadherin and decreased expression of vimentin in SCC-4 and CU110-1 cells. Further analysis showed wedelolactone inhibited the expression of AhR and its downstream target molecules CYP1A1 and CYP1B1 in both squamous carcinoma cells at the same doses inhibiting cell migration. The addition of benzo (a)pyrene [B(a)P], an agonist of AhR, stimulated migration, especially in the CU110-1 cells with reported cancer stem cell-like characteristics. Instructively, B(a)P reversed the inhibitory effects of wedelolactone on AhR expression and cell migration, suggesting that wedelolactone antagonizes cell migration through the AhR pathway. Moreover, the higher activity of EAE and wedelolactone against the migration of cancer stem-like CU110-1 cells relative to SCC-4 cells suggests selective activity against cancer stem cells.

Conclusion:

Our study identifies wedelolactone as a major active component of Ecliptae prostrata (L.) L. with promising anti-cancer properties against head and neck squamous cancer cells.
Key Advances in MIP-based Sensors Applied for Cancer and Cardiovascular
Biomarkers Detection
Authors: Lamaoui Abderrahman , Amine Aziz
Published: March 2022

Cancer and cardiovascular diseases have become one of the leading causes of death worldwide. Therefore, early detection of these diseases and rapid intervention by medical staff remain a great challenge for clinicians and healthcare providers worldwide. Cancer and cardiovascular disease biomarkers are promising tools for early diagnosis of the disease before it becomes incurable at an advanced stage. They also contribute to monitoring the progress of therapy and surgical treatment. Indeed, sensors have shown great importance for the detection of cancer and cardiovascular biomarkers. Sensors usually require a recognition element for the selective detection of targets. Molecularly imprinted polymer (MIP), as an artificial antibody, has been proposed as an alternative recognition element in sensing fields to overcome the main drawbacks of natural antibodies. With the high need for sensors providing results in a short time and making easier the early diagnosis of these diseases, MIP-based sensors are attracting considerable interest recently, which will undoubtedly be increased in the future due to the sustainability trend. The key aim of this review is to emphasize the recent applications of sensors based on MIP for the detection of cancer and cardiovascular biomarkers and to highlight the key advances related to MIP-based sensors. Furthermore, several key future trends about the applications of MIP-based sensors for the detection of cardiovascular and cancer biomarkers are presented.
Targeting Janus Kinase (JAK) for Fighting Diseases: The Research of
JAK Inhibitor Drugs
Authors: Zhao Min-Yan , Zhang Wen , Rao Guo-Wu
Published: March 2022

Janus Kinase (JAK), a nonreceptor protein tyrosine kinase, has emerged as an
excellent target through research and development since its discovery in the 1990s. As
novel small-molecule targeted drugs, JAK inhibitor drugs have been successfully used in
the treatment of rheumatoid arthritis (RA), myelofibrosis (MF), and ulcerative colitis
(UC). With the gradual development of JAK targets in the market, JAK inhibitors have
also received considerable feedback in the treatment of autoimmune diseases, such as
atopic dermatitis (AD), Crohn's disease (CD), and graft-versus-host disease (GVHD).
This article reviews the research progress of JAK inhibitor drugs, focusing on the existing
JAK inhibitors in the market and some JAK inhibitors in clinical trials currently. In addition,
the synthesis of various types of JAK inhibitors and the effects of different drug
structures on drug inhibition and selectivity are summarized.
Screening of Phytoconstituents from Traditional Plants against SARSCoV-
2 using Molecular Docking Approach
Authors: Saini Deepika , Madan Kumud , Chauhan Shilpi
Published: March 2022

Background:

The emergence of COVID-19 as a fatal viral disease encourages researchers to
develop effective and efficient therapeutic agents. The intervention of in silico studies has led to revolutionary
changes in the conventional method of testing the bioactivity of plant constituents.

Objective:

The current study deals with the investigation of some traditional immunomodulators of plant
origin to combat this ailment.

Materials and Methods:

A total of 151 phytomolecules of 12 immunomodulatory plants were evaluated
for their inhibitory action against the main protease (PDB ID: 7D1M) and NSP15 endoribonuclease (PDB
ID: 6WLC) by structure-based virtual screening. In addition, the promising molecules with ligand efficiency
of more than -0.3(kcal/mol)/heavy atoms were further predicted for pharmacokinetic properties
and druggability using the SwissADME web server, and their toxicity was also evaluated using Protox-II.

Result:

Myricetin-3-O-arabinofuranoside of cranberry plant was found to be the most potential candidate
against both enzymes: main protease (–14.2 kcal/mol) and NSP15 endoribonuclease (–12.2 kcal/mol).

Conclusion:

The promising outcomes of the current study may be implemented in future drug development
against coronavirus. The findings also help in the development of lead candidates of plant origin
with a better ADMET profile in the future.
Evaluation and Prediction of End of Second-wave and Starting of Thirdwave
Covid-19 Cases in India
Authors: Veer Karan , Sharma Sachin
Published: March 2022

Background:

The second wave of coronavirus has appeared to be an extensive uphill of the number of daily new confirmed cases, recovered cases, and deaths than the first wave in India and the whole world. In India, the second wave of COVID-19 is much dangerous than the first wave that hit on 14th April 2020. The maximum number of new cases was 406901 recorded on May 7, 5.3 times more than the first wave peak. Many researchers worldwide are using machine learning prediction models to forecast the upcoming trends of this pandemic.

Method:

This study used an Autoregressive Integrated Moving Average (ARIMA) model to pre-dict the daily new confirmed cases, daily new deaths, and daily new recoveries between and after the second wave of COVID-19 in India. The dataset was collected from March 14, 2020- July 7, 2021, using the ARIMA model to predict corona cases for the next 60 days.

Results:

In the context of the current scenario in India, the second wave will score low new cases in mid-August 2021, and the third wave will hit the country in the middle of September 2021.

Conclusion:

The ARIMA model was chosen based on AIC (Akaike Information Criterion) values and acquired the maximum accuracy of 95%.
A Case of Chronic HCV Infection Reactivation in a Psoriasis Patient
Treated with Guselkumab
Authors: Ruggiero Angelo , Megna Matteo , Fabbrocini Gabriella , Gallo Lucia , Patrì Angela
Published: March 2022

Introduction:

Psoriasis is a chronic inflammatory skin disease requiring long-term
treatment. However, there are approximately 71 million individuals with chronic HCV infection
worldwide. In psoriatic patients affected by chronic HCV infection, conventional systemic drugs
may be frequently contraindicated, while data on biologics use are limited.

Case presentation:

The case of a 48-year-old Caucasian man suffering from a severe form of
plaque psoriasis and affected by a chronic-HCV-infection treated with guselkumab has been reported.
Despite a huge improvement of the skin lesions (PASI reduced from 18 to 2), guselkumab
was discontinued due to an HCV-infection reactivation after 3 months of treatment.

Conclusion:

To the best of our knowledge, this is the first case report of the use of guselkumab in
an HCV psoriatic patient. Further studies are needed to evaluate the safety of guselkumab in chronic
HCV patients.
Analytical Transient Thermal Model for Predicting Cooldown
Temperature in a Subsea Pipe-in-Pipe Flowline System
Authors: Shukla Keshawa
Published: March 2022

Background:

For the reliable operation of deep-water production systems transporting
hydrocarbons, the critical flow assurance problems to manage are wax and hydrate
formation and their deposition due to the heat transfer between the production system and
surroundings. Wax and hydrate deposition can restrict the flow with significant production
loss.

Method:

The adequate thermal insulation of such systems can allow the retention of thermal
energy in the production system to ensure that the fluid cooldown temperature remains
above the wax and hydrate formation temperatures. This may provide sufficient time for
taking the preventive measures during an emergency shut-in operation. The purpose of this
paper is to predict the cooldown temperature of a subsea Pipe-in-Pipe flowline system
transporting crude oil from the reservoir to the host facility using a recently developed transient
thermal model. The model incorporates the energy redistribution inside the system
through the internal temperature gradient and allows to determine the requirement of thermal
insulation of the Pipe-in-Pipe system to retain sufficient heat before the fluid temperature
falls below the hydrate and wax temperatures.

Result:

The model results are compared with an industry accepted commercial simulator
results to illustrate the accuracy of the model for emergency shut-in operations.

Conclusion:

With limited pipeline configurations and fluid properties, the model can successfully
predict the requirements of thermal insulation and cooldown temperature efficiently
and economically.
Development and Validation of Stability Indicating RP-HPLC Method for
Simultaneous Determination of Doxycycline and Rifampicin in Polymeric
Nanoparticles
Authors: Dawre Shilpa
Published: March 2022

Background:

The combination of doxycycline (DOXY) and rifampicin (RIF) is recom-mended as a treatment therapy for brucellosis by the World Health Organization.

Objective:

The aim of the current study was to develop and validate the stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method for the analysis of a combina-tion of doxycycline & rifampicin.

Methods:

The RP-HPLC method was developed and validated to estimate the doxycycline and ri-fampicin combination as per ICH guidelines. The drug combination solution was exposed to differ-ent stress conditions: acidic, basic, photo-oxidation, and oxidation.

Results:

The method was found linear in the range of 2 -10μg/mL for both the drugs with a reten-tion time of 3.5 min for doxycycline and 6.5 min for rifampicin at lambda maximum of 350 nm. The RP-HPLC method was precise and accurate with %RSD < 2%. The intra-day and inter-day precisions were calculated and found within the acceptable range of 5%. Both drugs demonstrated good stability in the mobile phase after 6 hours. The LOD and LOQ of doxycycline and rifampicin were 100 ng/mL & 200ng/mL and 150ng/mL & 500ng/mL, respectively. The forced degradation of the combination of drug solutions was performed. The degraded drug peaks were well-resolved from the peaks of drugs. The percentage encapsulation efficiency of doxycycline and rifampicin in the nanoparticle system was assessed by utilizing the validated RP-HPLC method and found >60% (DOXY) and >70% (RIF).

Conclusion:

The developed RP-HPLC method of DOXY-RIF combination was rapid, accurate, precise, and stability-indicating. The method can be appropriately applied todetecte drugs in the na-noparticulate system.