bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Cyproheptadine Monotherapy in Hepatocellular Carcinoma With Bone Metastasis: A Case Report
Authors: Feng Yu-Min , Chen Tsung-Hsien , Berman Dara , Chou Chu-Kuang , Liao Kai-Sheng , Hsieh Ming-Chih , Chen Chi-Yi
Published: October 2021

Background

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. Particularly, cases of bone metastasis have poorer prognoses.

Case Presentation

A 62-year-old woman with suspected advanced HCC accompanied by bone metastasis with severe back pain and sciatica showed disease remission after cyproheptadine monotherapy. Initially, her serum alpha fetal protein (AFP) level was high, reaching up to 17697.62 ng/ml. A dose of 4 mg cyproheptadine, 3 times a day for 17 months was prescribed as the only treatment. Within 3 months, the serum AFP level gradually normalized down to 4.3 ng/ml. Both liver biopsy and bone biopsies were subsequently performed after 2 weeks of cyproheptadine. The results showed no malignancy. During the 34 months of follow-ups, the serum AFP remained normal in the range of 1.05 to 2.86 ng/ml. The patient has survived for 5 years without back pain and sciatica thus far.

Conclusions

This is the first report to investigate a successful clinical approach in cyproheptadine monotherapy for an advanced HCC patient with bone metastasis. We recommend cyproheptadine as a potential anti-HCC agent for the treatment of HCC with bone metastasis, but more related studies such as prospectively clinical trials, and ideally randomized trials are still needed.
Advances in the Resection and Reconstruction of Midfacial Tumors Through Computer Assisted Surgery
Authors: Wilkat Max , Kübler Norbert , Rana Majeed
Published: October 2021

Curatively intended oncologic surgery is based on a residual-free tumor excision. Since decades, the surgeon’s goal of R0-resection has led to radical resections in the anatomical region of the midface because of the three-dimensionally complex anatomy where aesthetically and functionally crucial structures are in close relation. In some cases, this implied aggressive overtreatment with loss of the eye globe. In contrast, undertreatment followed by repeated re-resections can also not be an option. Therefore, the evaluation of the true three-dimensional tumor extent and the intraoperative availability of this information seem critical for a precise, yet substance-sparing tumor removal. Computer assisted surgery (CAS) can provide the framework in this context. The present study evaluated the beneficial use of CAS in the treatment of midfacial tumors with special regard to tumor resection and reconstruction. Therefore, 60 patients diagnosed with a malignancy of the upper jaw has been treated, 31 with the use of CAS and 29 conventionally. Comparison of the two groups showed a higher rate of residual-free resections in cases of CAS application. Furthermore, we demonstrate the use of navigated specimen taking called tumor mapping. This procedure enables the transparent, yet precise documentation of three-dimensional tumor borders which paves the way to a more feasible interdisciplinary exchange leading e.g. to a much more focused radiation therapy. Moreover, we evaluated the possibilities of primary midface reconstructions seizing CAS, especially in cases of infiltrated orbital floors. These cases needed reduction of intra-orbital volume due to the tissue loss after resection which could be precisely achieved by CAS. These benefits of CAS in midface reconstruction found expression in positive changes in quality of life. The present work was able to demonstrate that the area of oncological surgery of the midface is a prime example of interface optimization based on the sensible use of computer assistance. The fact that the system makes the patient transparent for the surgeon and the procedure controllable facilitates a more precise and safer treatment oriented to a better outcome.
Recombinant Human Adenovirus-p53 Therapy for the Treatment of Cervical Cancer: A Meta-Analysis
Authors: Guo Yaru , Chen Jiuzhou , Zhang Xiwen , Fang Miao , Xu Mingna , Zhang Longzhen , Rao Enyu , Xin Yong
Published: October 2021

Objectives

To evaluate the clinical curative effects and toxicity of recombinant human adenovirus-p53 injection (rAd-p53) plus chemotherapy (CT), radiotherapy (RT), or concurrent chemoradiotherapy (CRT) for the treatment of cervical cancer.

Methods

We identified 14 eligible studies in the PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wangfangdate, CBM, and VIP databases from their inception to May 2021 and performed meta-analyses using RevMan version 5.3.

Results

This analysis included 14 studies involving 737 patients. The results of the meta-analysis results showed significantly improved complete remission (odds ratio [OR] = 2.54, 95% confidence interval [CI]: 1.74–3.70, p < 0.00001), partial remission (OR = 1.56, 95% CI: 1.14–2.14, p = 0.006), and object response (OR = 4.47, 95% CI: 3.02–6.60, p < 0.00001) rates in the rAd-p53 combination therapy group compared to those in the CT/RT/CRT group. The results of subgroup analyses of CT/RT/CRT were consistent with the overall results. Regarding the incidence of adverse reactions, only the occurrence rate of fever (OR = 18.21, 95% CI: 10.54–31.47, p < 0.00001) in the rAd-p53 combination group was higher than that in the CT/RT/CRT group. No other significant differences were observed in other adverse reactions.

Conclusion

RAd-p53 combined with CT/RT/CRT for the treatment of cervical cancer showed significant advantages in efficacy and safety compared to those in the CT/RT/CRT group. Therefore, rAd-p53 has great potential as an effective therapy for cervical cancer.

Systematic Review Registration

https://inplasy.com/inplasy-2021-5-0058/.
Choroidal Vascularity Index in CHM Carriers
Authors: Mucciolo Dario Pasquale , Giorgio Dario , Lippera Myrta , Passerini Ilaria , Pelo Elisabetta , Cipollini Francesca , Sodi Andrea , Virgili Gianni , Giansanti Fabrizio , Murro Vittoria
Published: October 2021

Purpose

To assess the choroidal structure using the Choroidal Vascularity Index (CVI) and analyse choroidal changes in choroideremia (CHM) carriers.

Material and Methods

Female CHM carriers, genetically characterized, and a control group were recruited at the Eye Clinic of Careggi Teaching Hospital, Florence. The patients underwent a complete ophthalmic evaluation and retinal imaging. In particular, the Stromal Area (SA), Luminal Area (LA), Total Choroidal Area (TCA), CVI, and Subfoveal Choroidal Thickness (SFCT) were calculated for each eye using Optical Coherence Tomography (OCT) examinations.

Results

Twelve eyes of 6 CHM carriers and 14 eyes of 7 age-matched controls were analysed. The mean SFCT was 270.9 ± 54.3μm in carriers and 281.4 ± 36.8μm in controls (p = 0.564); LA was 0.99 ± 0.25mm2 and 1.01 ± 0.13mm2 (p = 0.172); SA was 0.53 ± 0.09mm2 and 0.59 ± 0.07mm2 (p = 0.075), and TCA was 1.53 ± 0.34mm2 and 1.69 ± 0.19mm2 respectively (p = 0.146). Mean CVI measured 64.03 ± 3.98% in the CHM carriers and 65.25 ± 2.55% in the controls (p = 0.360).

Conclusions

The CVI and CVI-related parameters (SA, LA, and TCA) do not differ between CHM female carriers and controls. These findings reveal a preserved choroidal vasculature in eyes with RPE impairment and support the primary role of RPE in the pathogenesis of CHM disease.
Mechanistic Modeling of Placental Drug Transfer in Humans: How Do Differences in Maternal/Fetal Fraction of Unbound Drug and Placental Influx/Efflux Transfer Rates Affect Fetal Pharmacokinetics?
Authors: Liu Xiaomei I. , Green Dionna J. , van den Anker John N. , Rakhmanina Natella Y. , Ahmadzia Homa K. , Momper Jeremiah D. , Park Kyunghun , Burckart Gilbert J. , Dallmann André
Published: October 2021

Background: While physiologically based pharmacokinetic (PBPK) models generally predict pharmacokinetics in pregnant women successfully, the confidence in predicting fetal pharmacokinetics is limited because many parameters affecting placental drug transfer have not been mechanistically accounted for.

Objectives: The objectives of this study were to implement different maternal and fetal unbound drug fractions in a PBPK framework; to predict fetal pharmacokinetics of eight drugs in the third trimester; and to quantitatively investigate how alterations in various model parameters affect predicted fetal pharmacokinetics.

Methods: The ordinary differential equations of previously developed pregnancy PBPK models for eight drugs (acyclovir, cefuroxime, diazepam, dolutegravir, emtricitabine, metronidazole, ondansetron, and raltegravir) were amended to account for different unbound drug fractions in mother and fetus. Local sensitivity analyses were conducted for various parameters relevant to placental drug transfer, including influx/efflux transfer clearances across the apical and basolateral membrane of the trophoblasts.

Results: For the highly-protein bound drugs diazepam, dolutegravir and ondansetron, the lower fraction unbound in the fetus vs. mother affected predicted pharmacokinetics in the umbilical vein by ≥10%. Metronidazole displayed blood flow-limited distribution across the placenta. For all drugs, umbilical vein concentrations were highly sensitive to changes in the apical influx/efflux transfer clearance ratio. Additionally, transfer clearance across the basolateral membrane was a critical parameter for cefuroxime and ondansetron.

Conclusion: In healthy pregnancies, differential protein binding characteristics in mother and fetus give rise to minor differences in maternal-fetal drug exposure. Further studies are needed to differentiate passive and active transfer processes across the apical and basolateral trophoblast membrane.
The Influence of Hearing Impairment on Mental Age in Down Syndrome: Preliminary Results
Authors: Saksida Amanda , Brotto Davide , Pizzamiglio Giulia , Bianco Elena , Bressan Sara , Feresin Agnese , Bin Maura , Orzan Eva
Published: October 2021

The increased life expectancy for patients with Down Syndrome (DS) has elicited the need to improve their quality of life by enhancing functional outcomes and identifying the factors that contribute to their long-term cognitive decline. Although the majority of individuals with DS have issues with hearing impairment (HI) since early childhood, to our knowledge no study has investigated whether HI represents a potential modulator of cognitive decline over time. The present explorative cohort study, albeit very preliminary due to the limited cohort (17 children), highlights the significant relation of a significant HI not only with receptive language abilities, but also with mental age in young patients with DS. Additional studies are required to confirm the link between HI and mental age and to assess the impact of audiological treatment on the enhancement of functional outcomes and of cognitive decline in individuals with DS.
Big Data and Real-World Data based Cost-Effectiveness Studies and Decision-making Models: A Systematic Review and Analysis
Authors: Lu Z. Kevin , Xiong Xiaomo , Lee Taiying , Wu Jun , Yuan Jing , Jiang Bin
Published: October 2021

Background:Big data and real-world data (RWD) have been increasingly used to measure the effectiveness and costs in cost-effectiveness analysis (CEA). However, the characteristics and methodologies of CEA based on big data and RWD remain unknown. The objectives of this study were to review the characteristics and methodologies of the CEA studies based on big data and RWD and to compare the characteristics and methodologies between the CEA studies with or without decision-analytic models.Methods:The literature search was conducted in Medline (Pubmed), Embase, Web of Science, and Cochrane Library (as of June 2020). Full CEA studies with an incremental analysis that used big data and RWD for both effectiveness and costs written in English were included. There were no restrictions regarding publication date.Results:70 studies on CEA using RWD (37 with decision-analytic models and 33 without) were included. The majority of the studies were published between 2011 and 2020, and the number of CEA based on RWD has been increasing over the years. Few CEA studies used big data. Pharmacological interventions were the most frequently studied intervention, and they were more frequently evaluated by the studies without decision-analytic models, while those with the model focused on treatment regimen. Compared to CEA studies using decision-analytic models, both effectiveness and costs of those using the model were more likely to be obtained from literature review. All the studies using decision-analytic models included sensitivity analyses, while four studies no using the model neither used sensitivity analysis nor controlled for confounders.Conclusion:The review shows that RWD has been increasingly applied in conducting the cost-effectiveness analysis. However, few CEA studies are based on big data. In future CEA studies using big data and RWD, it is encouraged to control confounders and to discount in long-term research when decision-analytic models are not used.
Experience of a Strategy Including CYP2C19 Preemptive Genotyping Followed by Therapeutic Drug Monitoring of Voriconazole in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation
Authors: García-García Irene , Dapía Irene , Montserrat Jaime , Martinez de Soto Lucía , Bueno David , Díaz Lucía , Queiruga Javier , Rodriguez Mariblanca Amelia , Guerra-García Pilar , Ramirez Elena , Frías Jesus , Pérez Martínez Antonio , Carcas-Sansuan Antonio J. , Borobia Alberto M.
Published: October 2021

Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in plasma concentrations, especially CYP2C19 genetic variability. In 2014, Hicks et al. presented data describing the correlation between VCZ plasma concentrations and CYP2C19 diplotypes in immunocompromised pediatric patients and utilized pharmacokinetic modeling to extrapolate a more suitable VCZ dose for each CYP2C19 diplotype. In 2017, in our hospital, a clinical protocol was developed for individualization of VCZ in immunocompromised patients based on preemptive genotyping of CYP2C19 and dosing proposed by Hicks et al., Clinical Pharmacogenetics Implementation Consortium (CPIC) clinical guidelines, and routine therapeutic drug monitoring (TDM). We made a retrospective review of a cohort of 28 immunocompromised pediatric patients receiving VCZ according to our protocol. CYP2C19 gene molecular analysis was preemptively performed using PharmArray®. Plasma trough concentrations were measured by immunoassay analysis until target concentrations (1–5.5 μg/ml) were reached. Sixteen patients (57.14%) achieved VCZ trough target concentrations in the first measure after the initial dose based on PGx. This figure is similar to estimations made by Hicks et al. in their simulation (60%). Subdividing by phenotype, our genotyping and TDM-combined strategy allow us to achieve target concentrations during treatment/prophylaxis in 90% of the CYP2C19 Normal Metabolizers (NM)/Intermediate Metabolizers (IM) and 100% of the Rapid Metabolizers (RM) and Ultrarapid Metabolizers (UM) of our cohort. We recommended modifications of the initial dose in 29% (n = 8) of the patients. In RM ≥12 years old, an increase of the initial dose resulted in 50% of these patients achieving target concentrations in the first measure after initial dose adjustment based only on PGx information. Our experience highlights the need to improve VCZ dose predictions in children and the potential of preemptive genotyping and TDM to this aim. We are conducting a multicenter, randomized clinical trial in patients with risk of aspergillosis in order to evaluate the effectiveness and efficiency of VCZ individualization: VORIGENIPHARM (EudraCT: 2019-000376-41).
Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage
Authors: Du Enming , Pu Guojuan , He Siyu , Qin Fangyuan , Wang Yange , Wang Gang , Song Zongming , Zhang Junjie , Tao Ye
Published: October 2021

Excessive UV-B exposure is well known to be a risk factor for corneal phototoxicity including direct DNA damage and disturbances in the antioxidant balance. Here, we showed a successful synthesis of a water-soluble and biocompatible small molecule DHPM 1 with dihydropyrimidinthione skeleton, which could effectively protect human corneal epithelial (HCE-2) cells from UV-B damage. In separate experiments, DHPM 1 absorbed UV-B rays and exhibited scavenging activity against intracellular ROS induced by UV-B radiation, thereby reducing the levels of DNA fragmentation. Additionally, UV-B exposure increased the expression of cleaved caspase-3, as well as the ratio of Bax/Bcl-2 at protein levels, while pretreatment with DHPM 1 significantly reversed these changes. To the best of our knowledge, this is the first report of a study based on dihydropyrimidinthione derivatives to develop a promising eye drops, which may well find extensive applications in UV-B caused corneal damage.
Measurement of Trust in Automation: A Narrative Review and Reference Guide
Authors: Kohn Spencer C. , de Visser Ewart J. , Wiese Eva , Lee Yi-Ching , Shaw Tyler H.
Published: October 2021

With the rise of automated and autonomous agents, research examining Trust in Automation (TiA) has attracted considerable attention over the last few decades. Trust is a rich and complex construct which has sparked a multitude of measures and approaches to study and understand it. This comprehensive narrative review addresses known methods that have been used to capture TiA. We examined measurements deployed in existing empirical works, categorized those measures into self-report, behavioral, and physiological indices, and examined them within the context of an existing model of trust. The resulting work provides a reference guide for researchers, providing a list of available TiA measurement methods along with the model-derived constructs that they capture including judgments of trustworthiness, trust attitudes, and trusting behaviors. The article concludes with recommendations on how to improve the current state of TiA measurement.
Analysis of Psychological Trends and Policy Recommendations of Medical Staff in Northern China in the Latter Stages of the COVID-19 Pandemic
Authors: Yang Xueping , Miao Junxiao , Fan Weizhong , Wang Lili , Sun Shuning , Li Hongshi , Wang Na , Wang Xuesong , Lin Muhui , He Ru
Published: October 2021

Aim: Since the 2019 coronavirus disease (COVID-19) outbreak, medical staff have faced greater psychological stress and are prone to psychological problems such as anxiety and depression, as confirmed by several studies. This study further clarifies the psychological status of Chinese medical staff during the stable phase of the pandemic through a cross-sectional investigation in a large population sample in northern China.

Methods: Subjects: Clinical frontline medical staff from seven hospitals in Liaoning Province were recruited from November 2020 to February 2021.

Research Tools: The research tools used were the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Simplified Coping Style Questionnaire (SCSQ), and General Status Questionnaire.

Statistical Analysis: SPSS 22.0, ANOVA variance analysis, and multiple logistics regression were used for statistical analysis. P-values of <0.05 indicated significant statistical differences.

Results: A total of 3,144 medical staff completed the survey (599 men [19.1%] and 2,545 women [80.9%]; 1,020 doctors [32.4%] and 2,124 nurses [67.6%]). Among all subjects, the rates of anxiety and depression were 21.1% (663/3, 144) and 43.9% (1,381/3,144), respectively. Multiple logistic comparative analysis revealed that age (OR = 1.272, 95% CI = 1.036–1.561, P = 0.022), the need for psychological counseling (OR = 1.566, 95% CI = 1.339–1.830, P < 0.001), and the coexistence of depression (OR = 0.050, 95% CI = 0.038–0.066, P < 0.001) were significantly associated with anxiety. Coexisting anxiety was also associated with the occurrence of depression (OR = 0.050, 95% CI = 0.038–0.065, P < 0.001).

Conclusions: In the later stages of the pandemic in China, the occurrence rates of anxiety and depression among medical staff remain high. In addition to age, there is little correlation between anxiety or depression and general factors such as gender and profession. As a special group, medical staff show different psychological changes at various times during a stressful event. Concerning for the psychological needs of medical staff and different psychologically oriented policy implementation are needed.
Family Socioeconomic Status and Chinese Adolescents’ Academic Achievement in the Arts: The Mediating Role of Family Arts Resources and the Moderating Role of Family Arts Atmosphere
Authors: Yuan Wen , Guo Hui , Fung C. Victor , Chen Fumei , Liu Lisha , Xu Liangyuan , Li Yanfang
Published: October 2021

In the present study, we examined the association between family socioeconomic status (SES) and adolescents’ academic achievement in the arts and the mediating and moderating roles of family process factors, verified family investment model. Chinese adolescents (N= 8,723) in Grade 8 reported characteristics of family SES, family arts resources, and family arts atmosphere, and then completed a standardized test assessing academic achievement in music and visual art. The results showed that family SES significantly predicted adolescents’ level of academic achievement in the arts after controlling for adolescents’ gender and school location. The effect of family SES on adolescents’ academic achievement in the arts was partly mediated by family arts resources, constituting 20.51% of the total predicted effect. In addition, family arts atmosphere moderated the association between family SES and adolescents’ achievement in the arts. Specifically, family SES had a stronger relationship with academic achievement in the arts for adolescent with higher family arts atmosphere than for adolescent with poor family arts atmosphere. Findings in this study expands the field of influence of the family environments and enhance an understanding of the influence mechanisms of family environments on arts learning.
Identification of Plant Growth Promoting Bacteria Within Space Crop Production Systems
Authors: Handy David , Hummerick Mary E. , Dixit Anirudha R. , Ruby Anna Maria , Massa Gioia , Palmer Andrew
Published: October 2021

As we establish colonies beyond Earth, resupply missions will become increasingly difficult, logistically speaking, and less frequent. As a result, the on-site production of plants will be mission critical for both food production as well as complementing life support systems. Previous research on space crop production aboard the International Space Station (ISS) has determined that the spaceflight environment, though capable of supporting plant growth, is inherently stressful to plants. The combined stressors of this environment limits yield by inhibiting growth, as well as increasing susceptibility to infection by plant pathogens such as Fusarium spp. We propose that a consortium of space-viable, plant growth-promoting bacteria (PGPB) could assist in mitigating challenges to plant growth in a sustainable fashion. Here, we utilize biochemical and phenotypic assessments to identify potential PGPB derived from previously acquired isolates from the VEGGIE crop production system aboard the ISS. These assays confirmed the presence of bacteria capable of producing and/or interfering with plant hormones, facilitating plant uptake of high-value target nutrients for plants such as iron and phosphorus, and able to inhibit the growth of problematic fungal species. We discuss our findings with regards to their potential to support plant growth aboard spaceflight platforms as well as the Moon and Mars.
The Story of a Re-Operating Windmill
Authors: Bitay Enikő , Márton László , Talpas János
Published: October 2021

Research on the history of the development of grain milling structures is a priority topic of the Department of Technical Sciences of the Transylvanian Museum Association. Quite a few publications and study volumes contain the results of the research. The present dissertation presents another grinding structure, the windmill, its reconstruction, creating a connection between the theoretical foundations and the practical implementation. Although it was built as a museum and tourist object, it is also a significant work from the point of view of technical history.

The Felsőszentiván windmill is powered by a 14-meter-diameter windmill. The mill has a two-stage accelerator gear that increases the low, non-grinding speed of the wind turbine for the rotation typical of grindstone mills.

The upper stones of a pair of grindstones rest on a vertical axis, and by raising this the gap between the stones can be adjusted. This determines the particle size of the grind. The windmill consists of three functional parts: a windmill, an accelerator gear and a grain mill made up of a pair of grindstones.
Industry and Research: New Collaborative Perspectives in the Industry 4.0 Era
Authors: Forgó Zoltán , Bakos Levente
Published: October 2021

The paper presents some challenges of developing DIHs (Digital Innovation Hubs) based on the Industry 4.0 principles in Transylvania (Romania). DIHs have proven to be successful as knowledge transfer centers especially in information technologies, but they are still a novelty in the field of manufacturing technologies and industrial engineering in many regions. The paper presents conceptual possibilities of developing a manufacturing technology based DIH in Romania, based on cooperation among local organizations.
An Analysis of Manufacturing Precision of Involute Worms Using a Kinematical Model
Authors: Kelemen Csongor , Máté Márton
Published: October 2021

The manufacturing precision of involute worms constitutes a major requirement. On the one hand, the worm constitutes the input element of the worm drive; secondly, the involute helical surface is the basic surface of an involute worm-hob. This paper presents an analytic comparison between the involute surfaces obtained using theoretical equations, kinematic simulation of the cutting and the surface charged with errors. The surface error is considered the distance along the normal direction to the theoretical surface, measured between this and the surface charged with simulated manufacturing errors. The main sources of errors are considered the center-error of the edge plane, the edge profile error and deviation of the axial feed direction from the axis of the worm. The theoretical results allow us to conclude that the influence of the edge profile error is the largest. It is followed by the parallelism error between the feed direction and the axis of the worm, and finally, the center error of the tool edge.
Weight Gain after Interferon-Free Treatment of Chronic Hepatitis C—Results from the German Hepatitis C-Registry (DHC-R)
Authors: Schlevogt Bernhard , Boeker Klaus H. W. , Mauss Stefan , Klinker Hartwig , Heyne Renate , Link Ralph , Simon Karl-Georg , Sarrazin Christoph , Serfert Yvonne , Manns Michael P. , Wedemeyer Heiner
Published: October 2021

Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term weight change of patients receiving interferon-free antiviral treatment for chronic hepatitis C. The German Hepatitis C-registry (DHC-R) is a national multicenter real-world cohort. A total of 5111 patients were followed prospectively after DAA treatment for up to 3 years. Weight change compared to baseline was analyzed at end of treatment and at years 1, 2, and 3 after completion of antiviral therapy. Regression analysis was performed to identify baseline predictors for weight change. While there was no relevant mean weight change (−0.2 kg, SD 4.3 kg) at the end of antiviral treatment, weight started to increase during long-term follow-up reaching +1.7 kg (SD 8.0 kg, p < 0.001) compared to baseline at 3 years (follow-up year 3, FU3) after completion of antiviral therapy. 48%, 31%, and 22% of patients had a weight gain greater than 1, 3, and 5 kg at FU3, respectively. During follow-up, a body mass index (BMI) <30 proved to be the only consistent predictor for weight gain. DAA treatment is followed by a substantial weight gain (+3 kg or more) in one-third of the patients during long-term follow-up. Non-obese patients seemed to be most vulnerable to weight gain. The body compartment involved in weight gain as well as the mechanism of weight gain remain to be elucidated.
Anti-Quantum Lattice-Based Ring Signature Scheme and Applications in VANETs
Authors: Jiao Chunhong , Xiang Xinyin
Published: October 2021

Message authentication is crucial because it encourages participants to accept countermeasures and further transmit messages to legitimate users in a network while maintaining the legitimacy of the identity of network members. An unauthorized user cannot transmit false messages to a given network. Although traditional public key cryptography is suitable for message authentication, it is also easy to manage and generate keys, and, with the expansion of an entire network, the system needs a lot of computing power, which creates additional risks to network security. A more effective method, such as ring signature, can realize this function and guarantee more security. In this paper, we propose an anti-quantum ring signature scheme based on lattice, functionality analysis, and performance evaluation to demonstrate that this scheme supports unconditional anonymity and unforgeability. After efficiency analysis, our scheme proved more effective than the existing ring signature schemes in processing signature generation and verification. The proposed scheme was applied to VANETs that support strong security and unconditional anonymity to vehicles.
Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells
Authors: Mthembu Sinenhlanhla , Muller Christo , Dludla Phiwayinkosi , Madoroba Evelyn , Kappo Abidemi , Mazibuko-Mbeje Sithandiwe
Published: October 2021

The current study investigated the physiological effects of flavonoids found in daily consumed rooibos tea, aspalathin, isoorientin, and orientin on improving processes involved in mitochondrial function in C2C12 myotubes. To achieve this, C2C12 myotubes were exposed to a mitochondrial channel blocker, antimycin A (6.25 µM), for 12 h to induce mitochondrial dysfunction. Thereafter, cells were treated with aspalathin, isoorientin, and orientin (10 µM) for 4 h, while metformin (1 µM) and insulin (1 µM) were used as comparators. Relevant bioassays and real-time PCR were conducted to assess the impact of treatment compounds on some markers of mitochondrial function. Our results showed that antimycin A induced alterations in the mitochondrial respiration process and mRNA levels of genes involved in energy production. In fact, aspalathin, isoorientin, and orientin reversed such effects leading to the reduced production of intracellular reactive oxygen species. These flavonoids further enhanced the expression of genes involved in mitochondrial function, such as Ucp 2, Complex 1/3, Sirt 1, Nrf 1, and Tfam. Overall, the current study showed that dietary flavonoids, aspalathin, isoorientin, and orientin, have the potential to be as effective as established pharmacological drugs such as metformin and insulin in protecting against mitochondrial dysfunction in a preclinical setting; however, such information should be confirmed in well-established in vivo disease models.
Microwave Irradiation: Alternative Heating Process for the Synthesis of Biologically Applicable Chromones, Quinolones, and Their Precursors
Authors: Albuquerque Hélio M. T. , Pinto Diana C. G. A. , Silva Artur M. S.
Published: October 2021

Microwave irradiation has become a popular heating technique in organic synthesis, mainly due to its short reaction times, solventless reactions, and, sometimes, higher yields. Additionally, microwave irradiation lowers energy consumption and, consequently, is ideal for optimization processes. Moreover, there is evidence that microwave irradiation can improve the regioselectivity and stereoselectivity aspects of vital importance in synthesizing bioactive compounds. These crucial features of microwave irradiation contribute to its inclusion in green chemistry procedures. Since 2003, the use of microwave-assisted organic synthesis has become common in our laboratory, making our group one of the first Portuguese research groups to implement this heating source in organic synthesis. Our achievements in the transformation of heterocyclic compounds, such as (E/Z)-3-styryl-4H-chromen-4-ones, (E)-3-(2-hydroxyphenyl)-4-styryl-1H-pyrazole, (E)-2-(4-arylbut-1-en-3-yn-1-yl)-4H-chromen-4-ones, or (E)-2-[2-(5-aryl-2-methyl-2H-1,2,3-triazol-4-yl)vinyl]-4H-chromen-4-ones, will be discussed in this review, highlighting the benefits of microwave irradiation use in organic synthesis.
Methoxy-Substituted γ-Oxa-ε-Lactones Derived from Flavanones—Comparison of Their Anti-Tumor Activity In Vitro
Authors: Pawlak Aleksandra , Henklewska Marta , Hernández-Suárez Beatriz , Siepka Monika , Gładkowski Witold , Wawrzeńczyk Czesław , Motykiewicz-Pers Karolina , Obmińska-Mrukowicz Bożena
Published: October 2021

Background: The study investigated four flavanone-derived γ-oxa-ε-lactones: a parent unsubstituted compound and its three derivatives with the methoxy group in positions 2′, 4′ and 8. Our objective was to find out if the introduction of the methoxy group into the aromatic ring affects in vitro anti-tumor potency of the investigated lactones. Methods: Cytotoxic and pro-apoptotic effects were assessed with cytometric tests with propidium iodide, annexin V, and Western blot techniques. We also investigated potential synergistic potency of the tested lactones and glucocorticoids in canine lymphoma/leukemia cell lines. Results: The tested flavanone-derived lactones showed anti-cancer activity in vitro. Depending on its location, the methoxy group either increased or decreased cytotoxicity of the derivatives as compared with the parent compound. The most potent lactone was the one with the methoxy group at position 4′ of the B ring (compound 3), and the weakest activity was observed when the group was located at C-8 in the A ring. A combination of the lactones with glucocorticoids confirmed their synergy in anti-tumor activity in vitro. Conclusions: Methoxy-substituted flavanone-derived lactones effectively kill canine lymphoma/leukemia cells in vitro and, thanks to their synergistic action with glucocorticoids, may potentially be applied in the treatment of hematopoietic cancers.
Synthesis and Anti-HIV Activity of a Novel Series of Isoquinoline-Based CXCR4 Antagonists
Authors: Shad Mastaneh , Claes Sandra , Goffin Eline , Van Loy Tom , Schols Dominique , De Jonghe Steven , Dehaen Wim
Published: October 2021

An expansion of the structure–activity relationship study of CXCR4 antagonists led to the synthesis of a series of isoquinolines, bearing a tetrahydroquinoline or a 3-methylpyridinyl moiety as head group. All compounds were investigated for CXCR4 affinity and antagonism in competition binding and calcium mobilization assays, respectively. In addition, the anti-HIV activity of all analogues was determined. All compounds showed excellent activity, with compound 24c being the most promising one, since it displayed consistently low nanomolar activity in the various assays.
Effects of Curcumin Analogues DMC and EF24 in Combination with the Cytokine TRAIL against Kidney Cancer
Authors: Ibáñez Gaspar Verónica , McCaul Jasmin , Cassidy Hilary , Slattery Craig , McMorrow Tara
Published: October 2021

The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action.
Effect of the Amount of Polysorbate 80 and Oregano Essential Oil on the Emulsion Stability and Characterization Properties of Sodium Alginate Microcapsules
Authors: Baranauskaite Juste , Ockun Mehmet Ali , Uner Burcu , Tas Cetin , Ivanauskas Liudas
Published: October 2021

Essential oils have a high volatility that leads to evaporation and loss of their pharmacological effect when exposed to the environment. The objectives of the present work were to prepare microcapsules with oregano essential oil by extrusion using sodium alginate as a shell material and non-ionic surfactant polysorbate 80 as an emulsifier to stabilize the emulsion. The present study was aimed to evaluate the physical parameters of microcapsules and to compare the influence of the amount of emulsifier and the essential oil-to-emulsifier ratio on the capsules’ physical parameters and encapsulation efficiency; to our knowledge, the existing research had not yet revealed whether unstable emulsion affects the encapsulation efficiency of oregano essential oil. This study showed that increasing the emulsifier amount in the formulation significantly influenced encapsulation efficiency and particle size. Moreover, increasing the emulsion stability positively influenced the encapsulation efficiency. The emulsion creaming index depended on the emulsifier amount in the formulation: the highest creaming index (%) was obtained with the highest amount of polysorbate 80. However, the essential oil-to-polysorbate 80 ratio and essential oil amount did not affect the hardness of the microcapsules (p > 0.05). In conclusion, the obtained results could be promising information for production of microcapsules. Despite the fact that microencapsulation of essential oils is a promising and extremely attractive application area for the pharmaceutical industry, further basic research needs to be carried out.
iTRAQ-BASED Proteomic Analysis of the Mechanism of Fructose on Improving Fengycin Biosynthesis in Bacillus Amyloliquefaciens
Authors: Lu Hedong , Li Ruili , Yang Panping , Luo Weibo , Chen Shunxian , Bilal Muhammad , Xu Hai , Gu Chengyuan , Liu Shuai , Zhao Yuping , Geng Chengxin , Zhao Li
Published: October 2021

Fengycin, as a lipopeptide produced by Bacillus subtilis, displays potent activity against filamentous fungi, including Aspergillus flavus and Soft-rot fungus, which exhibits a wide range of potential applications in food industries, agriculture, and medicine. To better clarify the regulatory mechanism of fructose on fengycin biosynthesis, the iTRAQ-based proteomic analysis was utilized to investigate the differentially expressed proteins of B. amyloliquefaciens fmb-60 cultivated in ML (without fructose) and MLF (with fructose) medium. The results indicated that a total of 811 proteins, including 248 proteins with differential expression levels (162 which were upregulated (fold > 2) and 86, which were downregulated (fold < 0.5) were detected, and most of the proteins are associated with cellular metabolism, biosynthesis, and biological regulation process. Moreover, the target genes’ relative expression was conducted using quantitative real-time PCR to validate the proteomic analysis results. Based on the results of proteome analysis, the supposed pathways of fructose enhancing fengycin biosynthesis in B. amyloliquefaciens fmb-60 can be summarized as improvement of the metabolic process, including cellular amino acid and amide, fatty acid biosynthesis, peptide and protein, nucleotide and nucleobase-containing compound, drug/toxin, cofactor, and vitamin; reinforcement of peptide/protein translation, modification, biological process, and response to a stimulus. In conclusion, this study represents a comprehensive and systematic investigation of the fructose mechanism on improving fengycin biosynthesis in B. amyloliquefaciens, which will provide a road map to facilitate the potential application of fengycin or its homolog in defending against filamentous fungi.
Characterisation and Classification of Foodborne Bacteria Using Reflectance FTIR Microscopic Imaging
Authors: Xu Jun-Li , Herrero-Langreo Ana , Lamba Sakshi , Ferone Mariateresa , Scannell Amalia G. M. , Caponigro Vicky , Gowen Aoife A.
Published: October 2021

This work investigates the application of reflectance Fourier transform infrared (FTIR) microscopic imaging for rapid, and non-invasive detection and classification between Bacillus subtilis and Escherichia coli cell suspensions dried onto metallic substrates (stainless steel (STS) and aluminium (Al) slides) in the optical density (OD) concentration range of 0.001 to 10. Results showed that reflectance FTIR of samples with OD lower than 0.1 did not present an acceptable spectral signal to enable classification. Two modelling strategies were devised to evaluate model performance, transferability and consistency among concentration levels. Modelling strategy 1 involves training the model with half of the sample set, consisting of all concentrations, and applying it to the remaining half. Using this approach, for the STS substrate, the best model was achieved using support vector machine (SVM) classification, providing an accuracy of 96% and Matthews correlation coefficient (MCC) of 0.93 for the independent test set. For the Al substrate, the best SVM model produced an accuracy and MCC of 91% and 0.82, respectively. Furthermore, the aforementioned best model built from one substrate was transferred to predict the bacterial samples deposited on the other substrate. Results revealed an acceptable predictive ability when transferring the STS model to samples on Al (accuracy = 82%). However, the Al model could not be adapted to bacterial samples deposited on STS (accuracy = 57%). For modelling strategy 2, models were developed using one concentration level and tested on the other concentrations for each substrate. Results proved that models built from samples with moderate (1 OD) concentration can be adapted to other concentrations with good model generalization. Prediction maps revealed the heterogeneous distribution of biomolecules due to the coffee ring effect. This work demonstrated the feasibility of applying FTIR to characterise spectroscopic fingerprints of dry bacterial cells on substrates of relevance for food processing.
Üvegszál-erősítésű kompozit fogtömések vizsgálata
Authors: Borhy Levente , Farkas Péter Zoltán , Volom András
Published: October 2021

A fogászatban ma már mindennapos eljárásnak számít a fogak kompozit töméssel való ellátása. Ez a legtöbb esetben egyszerű és foganyagkímélő (minimálinvazív) beavatkozás, azonban a mély üregek tömése kihívást jelent. Kutatásunk során háromféle töméstípust vizsgáltunk: közvetlenül a fogban polimerizált kompozit tömést, közvetett módon az üregbe ragasztott (ún. semi-direct) tömést, illetve polietilén rosttal erősített kompozit tömést. Vizsgálataink során pásztázó elektronmikroszkóp segítségével figyeltük meg a fogtömés és a betömött üreg falai között keletkező réseket, illetve a résképződés mértékét, ezekből következtetve az egyes töméstípusok minőségére és várható tartósságára.
EFEKTIFITAS PENYULUHAN KESEHATAN TERHADAP PENCEGAHAN STUNTING DI KLINIK MARIANA
Authors: Siregar Patimah Sari , Nurhayati Eva Latifah , Silalahi Kristina L
Published: October 2021

Stunting is a chronic nutritional problem in toddlers characterized by a shorter height compared to other children of their age. Children who suffer from Stunting will be more susceptible to disease and as adults are at risk for degenerative diseases. Health counseling is held to increase the knowledge, awareness, willingness, and ability of mothers to continue to provide good nutrition during pregnancy. Knowledge of feeding is from pregnancy to prevent Stunting. Research that focuses on intention, motivation, and knowledge is not sufficient to help mothers overcome obstacles during pregnancy. Besides getting counseling, mothers overcome obstacles during pregnancy. In addition to getting maternal counseling, it requires support, education, and information that is consistent, realistic, and evidence-based to successfully improve nutrition during pregnancy. The goal is to find out the effectiveness of health education on Stunting prevention at the Mariana Clinic. The research will be conducted using a Quasi-Experiment design (quasi-experimental), with the target that pregnant women are given counseling. The methods of data collection are using questionnaires, interviews, and observations. The data analysis method used the dependent t-test, namely the Wilcoxon test. In the paired group, the same subjects were examined before and after the intervention (before and after design) of the questionnaire as a research instrument. The test used is the Wilcoxon test. The results study based on the Wilcoxon test, it was found that the p-value (<0.05) statistically showed that there was the effectiveness of health education on the prevention of Stunting in pregnant women at the Mariana clinic (p-value = 0.002).
PERBANDINGAN UJI EFEKTIVITAS EKSTRAK BENGKUANG (PACHYRIZUS AROSUS) DAN DAUN SIRIH HIJAU (PIPER BETLE L.) TERHADAP BAKTERI PROPIONIBACTERIUM ACNES
Authors: Lister I Nyoman Ehrich
Published: October 2021

Propionibacterium acnes is a gram-positive bacteria and consists of the Propionibacteriaceae family. Propionibacterium acnes is a bacteria that causes acne or acne vulgaris, a disease that is quite disturbing and gets the attention that occurs in adolescents and young adults. This research aimed to compare and determine the effectiveness of the extract of yam (Pachyrizus arosus) and green betel leaf (Piper betle L.) in inhibiting the growth of Propionibacterium acnes bacteria. The research variables were concentrations of yam extract (Pachyrizus arosus) 5%, 10%, 15%, 20% and green betel leaf (Piper betle L.) 1,5%, 3%, 5%, 7,5%. The results showed that there was an inhibiting zone against the growth of Propionibacterium acnes bacteria.
PENGARUH MUSIK INSTRUMENTAL TERHADAP KUALITAS HIDUP PADA PASIEN GAGAL GINJAL KRONIK YANG MENJALANI HEMODIALISA
Authors: Nababan Tiarnida
Published: October 2021

Chronic renal failure or late-stage renal disease is a progressive and irreversible disorder of renal function (the body fails in maintaining metabolism and balance of fluids and electrolytes), thereby causing uremia (retention of urea and other nitrogen waste in the blood). Treatment of kidney failure disease can be done by pharmacological and non-pharmacological means. Non-pharmacological treatment can be in the form of the provision of instrumental music. This study aims to find out the influence of instrumental music on quality of life in chronic kidney failure patients undergoing hemodialysis at the Royal Prima Hospital Medan. This type of research is pre-experimental research with a one-group pre-post-test design with the provision of instrumental music for 20 minutes. The population is 66 people and sampled as many as 20 people with accidental sampling techniques. The analysis used in using Wilcoxon test. Based on the calculation of the Wilcoxon signed-rank test, obtained Z= - 3,938 with (p=0.000) < 0.05, so it can be concluded that there is an instrumental music influence on the quality of life in chronic renal failure patients undergoing hemodialysis at Royal Prima Medan Hospital in 2018. It is recommended that instrumental music can be applied as an alternative therapy to improve the quality of life.