bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation of Bilayered Matrix Type of Transdermal Patches of a Classical Antihypertensive Drug: Assesment of Ex-vivo Permeation and in-vivo Pharmacokinetics
Authors: SUDDALA.SHIRISHA  , Sahoo Sunit Kumar , Seema Keerthana , Adluri Phanindra , Rao Yamsani Madhusudan 
Published: March 2023

Abstract
Objective
Felodipine (FD) is a calcium channel blocker used to treat hypertension and angina pectoris. Because of first-pass hepatic metabolism, it is less soluble, and its oral bioavailability is low (15%). To address the aforementioned drawbacks and maintain a consistent plasma concentration for optimal therapeutic efficacy, new methods, such as transdermal drug administration, must be developed. The goal of this study is to create bilayered transdermal films containing FD and test their efficacy using ex-vivo flux, and in-vivo pharmacokinetics studies.
Methods
Patches were made utilizing a solvent casting approach with both hydrophobic and hydrophilic polymers. The prepared films were thoroughly examined for ex-vivo permeation, and in-vivo pharmacokinetic tests on rabbits. The flux value for the formulation without the permeation enhancer (F4) was 14.585 g/cm2/h, but the flux increased in the formulation with the permeation enhancer lemongrass oil (F9) (1% v/v) was 30.4 g/cm2/h. In-vivo bioavailability findings in New Zealand white rabbits and blood samples were examined using HPLC and UV-visible spectrophotometer detector.
Results
When compared to FD with the transdermal patch system (F9) versus oral suspension administration, the bilayered transdermal films mean area under the curve values revealed an almost 1.2 times improvement in bioavailability (p < 0.05).
Conclusion
With a flux value of 30.4 g/cm2/h, the bilayered transdermal therapeutic system F9 containing lemongrass oil (1% v/v) as a permeation enhancer and a drug: polymer ratio (1:6) demonstrated good physicochemical and mechanical features. Formulation F9 may be deemed the best formulation for hypertension control based on above evaluation metrics.
Bcl-3 regulates T cell function through energy metabolism
Authors: Liu Hui , Zeng Lin , Pan Mengmeng , Huang Liwenhui , Li Hanying , Liu Mengxia , Niu Xinqing , Zhang Chenguang , Wang Hui 
Published: March 2023

Abstract
Background: Bcl-3 is a member of the IκB protein family and an essential nuclear factor NF-κB activity modulator. It is well established that Bcl-3 is critical for the normal development, survival and differentiation of adaptive immune cells, especially T cells. However, the regulation of immune cell function by Bcl-3 through metabolic pathways has rarely been studied.
Results: In this study, we explored the role of Bcl-3 on the metabolism and function of T cells through the mTOR pathway. We verified that the proliferation of Bcl-3-deficient Jurkat T cells was inhibited, but its activation was promoted, and Bcl-3 depletion regulated the cellular energy metabolism by reducing intracellular ATP and ROS production levels and mitochondrial membrane potential. Bcl-3 also regulates cellular energy metabolism in naive CD4+ T cells. In addition, the knockout of Bcl-3 altered the expression of mTOR, Akt, and Raptor, genes related to metabolism in Jurkat cells.
Conclusions: This finding indicates that Bcl-3 may mediate the energy metabolism of T cells through the mTOR pathway, thereby affecting their function. Overall, we provide novel insights into the regulatory role of Bcl-3 on T-cell energy metabolism for prevention and treatment strategies of immune diseases.
The effect of alcohol consumption on all-cause mortality in 70-year-olds in the context of other lifestyle risk factors: Results from the Gothenburg H70 Birth Cohort study
Authors: Ahlner Felicia , Erhag Hanna Falk , Johansson Lena , Samuelsson Jessica , Wetterberg Hanna , Fässberg Madeleine Mellqvist , Waern Margda , Skoog Ingmar 
Published: March 2023

Abstract
Background The relationship between alcohol consumption and health is not fully understood. In this study, we examined the effect of alcohol as well as the combined effect of seven lifestyle factors on all-cause mortality in older adults (baseline age 70 years).
Methods Data was derived from the population-based Gothenburg H70 Birth Cohort study, including 1124 participants from the 2014-16 examination. Risk consumption was defined as >98 grams and hazardous drinking based on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire. Cox regression models were used to examine the individual effect of alcohol consumption, as well as the combined effect of seven lifestyle risk factors (high alcohol consumption, lifetime smoking, unhealthy Body Mass Index, insufficient physical activity, sedentary behavior, insufficient/prolonged sleep, unhealthy dietary pattern) on all-cause mortality.
Results During a mean follow-up of 7.7 years, 81 (7.2%) participants died. Neither risk consumption nor hazardous drinking were associated with elevated mortality, but hazardous drinking was associated with an increased risk of mortality in those with insufficient physical activity. Those with at least five lifestyle risk factors had an increased all-cause mortality compared to those fulfilling criteria for maximum one lifestyle risk factor, and high alcohol consumption contributed least to this risk, while physical activity and unhealthy dietary pattern had an independent effect on mortality.
Conclusions In this population study on 70-year-olds, neither risk consumption nor hazardous drinking were associated with 8-year all-cause mortality. Among seven life styles factors studied, risk or hazardous drinking of alcohol contributed least to mortality. It may be that high alcohol consumption is less important for mortality among older adults, especially in those with higher physical activity. However, it has to be emphasized that high alcohol consumption may have other adverse health effects among older adults.
Efficacy of hydroxyapatite-based skull base reconstruction for intraoperative high-flow cerebrospinal fluid leakage performed by less-experienced surgeons: a two-institution study
Authors: Hong Inseo , Kim Kyung Hwan , Seo Youngbeom , Choo Yoon-Hee , Lee Han-Joo , Kim Seon-Hwan 
Published: March 2023

Abstract
Cerebrospinal fluid (CSF) leakage after endoscopic skull base surgery remains a challenge despite multilayer reconstruction including nasoseptal flap (NSF) has become a standard technique. Injectable hydroxyapatite (HXA) has shown promising results to prevent CSF leakage. This study aimed to validate the efficacy of HXA-based skull base reconstruction performed by less-experienced neurosurgeons who had short-term clinical experiences as independent surgeons. Between March 2018 and November 2022, 41 patients who experienced intraoperative high-flow CSF leakage following endoscopic endonasal surgery at two independent tertiary institutions were enrolled. Skull base reconstruction was performed using conventional multilayer techniques combined with or without HXA. The primary outcome was postoperative CSF leakage. The surgical steps and nuances were described in detail. The most common pathology was craniopharyngioma. Injectable HXA was used in 22 patients (HXA group) and conventional techniques were performed in 19 patients (control group). The HXA group achieved a significantly lower incidence of postoperative CSF leakage than the control group (0% vs. 26.3%, p = 0.016). No HXA-related complications were observed. The use of injectable HXA in skull base reconstruction was highly effective and safe. This technique and its favorable results might be readily reproduced by less-experienced neurosurgeons.
Fine tuning expression levels of α-mannosidase II (MANII) and β-1,4-N-acetylglucosaminyl- transferase III (GNTIIII) in CHO cells for production of IgG1 antibody with tailored Fc-mediated effector functions
Authors: Nguyen Ngan T.B. , Leung Hau Wan , Pang Zach K. T. , Walsh Ian , Yang Yuansheng 
Published: March 2023

Abstract
Monoclonal antibodies (mAbs) eliminate cancer cells via various effector mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are determined by the structures of N-glycans on the Fc region of mAbs. Controlling the glycan structures on mAbs enables improving the therapeutic benefits of different effector functions. Traditional gene deletion or overexpression, which often result in only all-or-nothing changes, are not able to modulate the expression of multiple genes to defined ratios and levels. In this work, we developed a CHO cell engineering platform that allows precise modulation of multiple genes’ expression to custom design N-glycan profiles of mAbs for optimizing effector functions. A CHO targeted integration system with two independent landing pads was constructed, which allows expression of multiple genes at two pre-determined genomic sites. This platform was combined with internal ribosome entry site (IRES)-based polycistronic vectors to simultaneously fine-tuning the expression of α-mannosidase II (MANII) and chimeric β-1,4-N-acetylglucosaminyl-transferase III (cGNTIII) genes in CHO cells to produce mAbs carrying N-glycans with various levels of bisecting and non-fucosylated structures. These mAbs were confirmed to feature different degrees of ADCC and CDC, allowing mAbs with optimal effector functions to be identified. This platform was demonstrated as a powerful tool for producing antibody therapeutics with tailored effector functions via precise engineering of N-glycan profiles.
Sufficient Status of Vitamin D, Cobalamin and Folate in Healthy and Active German Home-Dwelling People Over 70 Years of Age
Authors: Kerlikowsky Felix , Schuchardt Jan Philipp , Hahn Andreas 
Published: March 2023

Abstract
Background: Ageing is characterised by physiological changes that can affect the nutrient availability and requirements. In particular, the status of vitamin D, cobalamin and folate has often been found to be critical in older people living in residential care. However, there is a lack of studies investigating the status of these nutrients in healthy and active home-dwelling elderly people.
Methods: The aim of this cross-sectional study was to assess the status of vitamin D based on serum concentrations of 25-hydroxycholecalciferol [25-(OH)D], cobalamin based on serum concentrations of holotranscobalamin (holoTC) and folate based on red blood cell (RBC) folate in unsupplemented, healthy and active German home-dwelling subjects ≥70 years of age (n=134, mean±SD: 75.8±4.5 years). Dietary intake was assessed by 3-day food recalls. The study was conducted between March and November of 2021 (during the COVID-19 pandemic).
Results: The mean 25-(OH)D concentration was unexpectedly high at 85.1±26.0 nmol/L, while the majority of women (63%) and men (84%) had 25-(OH)D concentrations ≥75 nmol/L. Less than 10% of men and women had 25-(OH)D concentrations <50 nmol/L. The mean holoTC concentration was 88.9±33.7 pmol/L. Women had significantly higher holoTC concentrations (94.8±34.6 pmol/L) than men (73.6±25.6 pmol/L), despite lower consumption of meat, eggs and meat products. Only 8% of the women were cobalamin deficient (<50 pmol/L holoTC) compared to 22% of the men. The mean RBC folate concentration was 831±244 nmol/L, while the prevalence of folate deficiency was 10%. Linear regression analysis showed that age (range: 70 to 100 years) was not associated with the nutrient status.
Conclusion: Our findings suggest that healthy, independently living older people with high levels of education, physical activity, and health awareness are not necessarily at higher risk of vitamin D, folate and cobalamin deficiency. However, it should be noted that about 10 % of the study collective were deficit in these vitamins. Further studies are needed to verify these findings and to identify lifestyle and dietary patterns that can predict adequate nutrient status for healthy ageing.
Trial registration: This study is officially recorded in the German Clinical Trials Register (DRKS00021302).
Patients with postprandial distress syndrome have problems with their interoceptive process limited to the gastric region: a case control study
Authors: Yoshida Kohei , Abe Tetsuya , Kanbara Kenji , Ueda Kento , Kouchi Yukie Saka , Hasuo Hideaki 
Published: March 2023

Abstract
Background

Visceral hypersensitivity in functional dyspepsia can be localized or widespread, and there is no simple method of assessment. Measuring interoceptive accuracy at different sites provides an assessment of perceptual hypersensitivity to specific ecological phenomena. The purpose of this study was to characterize visceral hypersensitivity by comparing gastric sensory and cardiac perceptual tests in patients with postprandial distress syndrome and in healthy volunteers.

Methods

Sixteen patients with postprandial distress syndrome (age = 47.5 ± 17.4, all female) and 16 healthy volunteers (age = 43.3 ± 16.1, all female) participated in the study after a six-hour fast. Each participant answered questionnaires about physical and mental quality of life, depression and anxiety, tendency of alexithymia, and somatosensory amplification. After completing the questionnaire, the participants took the heartbeat tracking task and the five-minute water load test. We performed statistical analysis using the Mann–Whitney U test and Spearman’s rank correlation coefficient.

Results

Subjects with postprandial distress syndrome had a lower drinking capacity than healthy volunteers (postprandial distress syndrome = 360.9 ± 170.0 mL, healthy volunteers = 644.1 ± 297 mL, P = .009), but there was no significant difference in the heartbeat perception score (postprandial distress syndrome = 0.599 ± 0.175, healthy volunteers = 0.623 ± 0.181, P = .647). There was a negative correlation (r = − .509, P < .05) between drinking capacity and the heartbeat perception score in healthy volunteers, but no correlation in postprandial distress syndrome (r = − .156, P = .564). Heartbeat perception score did not correlate with psychological measures.

Conclusions

Compared with healthy volunteers, only the five-minute water load test values were reduced in patients with postprandial distress syndrome, and no difference was observed in the heartbeat tracking task. The cross-organ perceptual relationships observed in healthy volunteers were not present in patients with postprandial distress syndrome. Combining the five-minute water load test and heartbeat tracking task revealed visceral hypersensitivity confined to the stomach in patients with postprandial stress syndrome, suggesting that the problem may be limited to sensory processing in the stomach. Performing sensory examinations at two different sites may be useful in clarifying whether visceral hypersensitivity is localized.
Trial registration: UMIN000057586. Registered11 March 2023（retrospectively registered）.
The Influence of War and Global Economy on Article Publication (Bibliometric Analysis using Biblioshiny-R)
Authors: Buyamin Buyamin , Rahayu Budi , Suradi Suradi , Herawaty Istiana , Suryadi Suryadi , Syaifullah Dian Hafit , Kurniawati Ardhian , Syahr Zulfia Hanum Alfi 
Published: March 2023

Abstract
This descriptive qualitative research uses Bibliometric Analysis by utilizing the Biblioshiny-R tool. This research is to determine the influence of an author, document, affiliation, source, and country in article publication with war and global economy themes. The source of the analysis data with the theme of war and global economy comes from the Scopus database without any restrictions. Weiss MA is the most influential author, at the same time Liu Y has the highest h index. The University of California is the most influential affiliate, and at the same time, the Cambridge Journal of Economics has the highest h index. The economy is the most influential keyword in the publication, at the same time, the war keyword also appears the most. Gössling S, 2020, J Sustainable Tour and USA are the most influential documents and country publications. Until now, no bibliometric research has been found that discusses the Scopus database on war and the global economy. What is new from this research is the use of Biblioshiny-R in the Scopus database analysis on war and the global economy which has never been done before. It is hoped that in the future more scientists, students, lecturers, and researchers will be interested in researching the effects of war on the global economy, especially wars that use nuclear and chemical weapons. As a result, the Government can develop policies to anticipate/avoid wars using nuclear weapons and chemical weapons.
Improving user satisfaction by analysing users’ subjective cognitive types in smart home systems
Authors: Zhang Na , Wang Shuyi , Li Hesen 
Published: March 2023

Abstract
This research aims to identify the types of users' subjective preferences in smart home systems and build respective strategies to improve user satisfaction. Forty-one Q samples were collected and screened using the entropy weight method, and Q sorting on 30 P samples was performed. Three types of user preference cognition of smart home systems and their characteristics are obtained and analysed. The results showed that the smart home system design strategy comprised 5 design features and 15 design contents. This provides implications for research and development of the smart home system from the user's subjective preferences and needs.
Association between uveitis onset and economic development in mainland China
Authors: Tan Handan , Feng Xiaojie , Yang Peizeng 
Published: March 2023

Abstract
Background
Economic prosperity has fostered numerous changes that may translate into better or worse outcomes across all domains of health. This study aims to explore the associations of economic development with uveitis onset in mainland China.
Methods
We used Poisson regression with generalized estimated equations to quantify the associations of per capita gross domestic product (GDP) with uveitis onset in 31 provinces of mainland China from 2006 to 2017. We further estimated the effects mediated by economic growth on the temperature-uveitis and PM2.5-uveitis associations established in our previous studies.
Results
A total of 12,721 uveitis patients from 31 provinces of mainland China were studied. Overall, every 10,000 Chinese yuan ($ 1491.278, 2006–2017) increase in per capita GDP, with no weighted value or weighted by population, corresponded to a 1.84% (95% confidence interval, 2.49%~1.12%) and a 1.42% (95% confidence interval, 0.37 ~ 2.84%) decrease in the risk ratio (RR) of uveitis onsets, respectively. Stratified analysis showed this negative association between per capita GDP and uveitis onset, only existed in male patients (P < .001), individuals aged 20–50 years (P < 0 .05), non-infectious uveitis, uveitis with systemic disease, and Bechet’s disease (all P < 0 .05). Moreover, the increased per capita GDP, if above the national level, could reinforce both temperature-uveitis and PM2.5-uveitis association (both P < 0.001).
Conclusions
The findings suggest that economic development is negatively associated with uveitis onset. However, it may facilitate the uveitis onset mediated by both increased temperature and PM2.5 exposure if the per capita GDP is above national level.
Targeting Nano-regulator based on Metal-Organic Frameworks for Enhanced Immunotherapy of Bone Metastatic Prostate Cancer
Authors: Huang Shu , Yuan Jun , Xie Yong , Qing Kai , Shi Zeya , Chen Guanyu , Gao Jie , Tan Haoxiang , Zhou Wenhu 
Published: March 2023

Abstract
Bone metastasis is the main cause of death in patients with prostate cancer (PCa), but there lacks effective treatment method. Immunotherapy shows new hopes for bone metastatic PCa patients, while the efficacy is still unsatisfactory and limited by the unique immunosuppressive microenvironment in metastatic bone site. Here, we developed a bone-targeted nano delivery system as a nano-regulator to enhance the immunotherapy of bone metastatic PCa. The nanosystem was assembled via coordination between phytic acid (PA) and Fe3+ to form nano-sized metal-organic-framework (MOF), through which mitoxantrone (MTO) was encapsulated. At cellular level, the nanosystem showed selective cytotoxicity towards RM-1 PCa cells over immune cells, and could induce tumor cells immunogenic cell death (ICD) to improve the immunogenicity of the tumor. Moreover, the nanosystem was able to induce ubiquitination of TGFβ receptor (TβR) on immune cells to promote its degradation, thus serving as a nano-regulator to block the functions of TGF-β, an abundant cytokine that has a systematically immunosuppressive effect in the tumor microenvironment. Upon intravenous injection, the nanoparticle showed pro-longed blood circulation and targeting accumulation into bone metastatic site, and imposed robust anti-tumor effect in combination with αCTLA-4. In addition, bone destruction was significantly alleviated after treatment to reduce the skeletal-related events. Overall, this work provides a biocompatible nanomedicine to restore immune sensitivity of bone metastatic tumor for enhanced immunotherapy by blocking TGF-β signaling pathway.
Prediction of malaria outcomes using patients’ demographical, environmental and clinical features
Authors: Ojurongbe taiwo Adetola , Afolabi Habeeb Abiodun , Akinde S.B , Bashiru kehinde Adekunle , Sule Waidi Folorunso , Ojurongbe Olusola , Adegoke Nurudeen Adedayo 
Published: March 2023

Abstract
Background: The current malaria diagnosis methods, which rely on microscopy and Histidine Rich Protein2 (HRP2) based RDT, have drawbacks that necessitate the development of improved and complementary malaria diagnostic methods to overcome some or all the limitations. Consequently, automated detection and classification of malaria can provide patients with a faster and more accurate diagnosis. This study, therefore, used a machine learning model to predict the occurrence of malaria based on socio-demographicbehaviour, environment, and clinical features.
Methods:Data from 200 Nigerian patients were used to develop predictive models using nested cross-validation and sequential backward features selection (SBFS), with 80% of the dataset randomly selected for training and optimisation and the remaining 20% for testing the models.
Results: Among the three machine learningmodels examined, penalised logistic regression model had the best area under the receiver operating characteristic (ROC) curve performance for the training set (84%; 95% confidence interval (CI) =75–93%) and test set (83%; 95% CI =63–100%). The model included age, BMI, body temperature, bushes in surroundings, body weight, dizziness, fever, headache, mosquito repellant, muscle pain, sex, sore throat, stagnant water in the home, and vomiting. An increased odd of patients having malaria was associated with high body weight (adjusted odd ratio (AOR) = 4.50, 95% CI =2.27-8.01, p-value <0.0001). Even though the association between the odds of having malaria and body temperature was insignificant, patients who had body temperature had higher odds of having malaria than those who did not have body temperature (AOR = 1.40, CI =0.99-1.91, p-value = 0.068). Also, patients who had bushes in the surroundings (AOR = 2.60, 95% CI =1.30-4.66, p-value = 0.006) or experienced fever (AOR = 2.10, CI =0.88–4.24, p-value = 0.099), headache (AOR = 2.07; CI =0.95–3.95, p-value = 0.068), muscle pain (AOR =1.49; CI =0.66–3.39, p-value = 0.333) and vomiting (AOR = 2.32; CI =0.85–6.82, p-value = 0.097) were more likely to experience malaria compared to those without bushes in the surrounding or those who did not experience fever, headache, muscle pain and vomiting. In contrast, decreased odds of malaria were associated with age (AOR = 0.62, 95% CI= 0.41-0.90, p-value = 0.012) or BMI (AOR = 0.47, 95% CI= 0.26-0.80, p-value =0.006).
Conclusion:Newly developed routinely collected baseline socio-demographical, environmental, and clinical features topredict malaria types and may serve as a valuable tool for clinical decision making.