bluuebunny/crossref_metadata_2025 huggingface dataset:
Salmonella Regulator STM0347 Mediates Flagellar Phase Variation via Hin Invertase
Authors: Wang Hongou , Tang Zhiheng , Xue Baoshuai , Lu Qinghui , Liu Xiaoyun , Zou Qinghua
Published: August 2022

Salmonella enterica is one of the most important food-borne pathogens, whose motility and virulence are highly related to flagella. Flagella alternatively express two kinds of surface antigen flagellin, FliC and FljB, in a phenomenon known as flagellar phase variation. The molecular mechanisms by which the switching orientation of the Hin-composed DNA segment mediates the expression of the fljBA promoter have been thoroughly illustrated. However, the precise regulators that control DNA strand exchange are barely understood. In this study, we found that a putative response regulator, STM0347, contributed to the phase variation of flagellin in S. Typhimurium. With quantitative proteomics and secretome profiling, a lack of STM0347 was confirmed to induce the transformation of flagellin from FliC to FljB. Real-time PCR and in vitro incubation of SMT0347 with the hin DNA segment suggested that STM0347 disturbed Hin-catalyzed DNA reversion via hin degradation, and the overexpression of Hin was sufficient to elicit flagellin variation. Subsequently, the Δstm0347 strain was outcompeted by its parental strain in HeLa cell invasion. Collectively, our results reveal the crucial role of STM0347 in Salmonella virulence and flagellar phase variation and highlight the complexity of the regulatory network of Hin-modulated flagellum phase variation in Salmonella.
Functional Characterization of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells
Authors: Fan Xuehui , Cyganek Lukas , Nitschke Katja , Uhlig Stefanie , Nuhn Philipp , Bieback Karen , Duerschmied Daniel , El-Battrawy Ibrahim , Zhou Xiaobo , Akin Ibrahim
Published: August 2022

Endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) provide a new opportunity for mechanistic research on vascular regeneration and drug screening. However, functions of hiPSC-ECs still need to be characterized. The objective of this study was to investigate electrophysiological and functional properties of hiPSC-ECs compared with primary human cardiac microvascular endothelial cells (HCMECs), mainly focusing on ion channels and membrane receptor signaling, as well as specific cell functions. HiPSC-ECs were derived from hiPS cells that were generated from human skin fibroblasts of three independent healthy donors. Phenotypic and functional comparison to HCMECs was performed by flow cytometry, immunofluorescence staining, quantitative reverse-transcription polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), tube formation, LDL uptake, exosome release assays and, importantly, patch clamp techniques. HiPSC-ECs were successfully generated from hiPS cells and were identified by endothelial markers. The mRNA levels of KCNN2, KCNN4, KCNMA1, TRPV2, and SLC8A1 in hiPSC-ECs were significantly higher than HCMECs. AT1 receptor mRNA level in hiPSC-ECs was higher than in HCMECs. AT2 receptor mRNA level was the highest among all receptors. Adrenoceptor ADRA2 expression in hiPSC-ECs was lower than in HCMECs, while ADRA1, ADRB1, ADRB2, and G-protein GNA11 and Gai expression were similar in both cell types. The expression level of muscarinic and dopamine receptors CHRM3, DRD2, DRD3, and DRD4 in hiPSC-ECs were significantly lower than in HCMECs. The functional characteristics of endothelial cells, such as tube formation and LDL uptake assay, were not statistically different between hiPSC-ECs and HCMECs. Phenylephrine similarly increased the release of the vasoconstrictor endothelin-1 (ET-1) in hiPSC-ECs and HCMECs. Acetylcholine also similarly increased nitric oxide generation in hiPSC-ECs and HCMECs. The resting potentials (RPs), ISK1–3, ISK4 and IK1 were similar in hiPSC-ECs and HCMECs. IBK was larger and IKATP was smaller in hiPSC-ECs. In addition, we also noted a higher expression level of exosomes marker CD81 in hiPSC-ECs and a higher expression of CD9 and CD63 in HCMECs. However, the numbers of exosomes extracted from both types of cells did not differ significantly. The study demonstrates that hiPSC-ECs are similar to native endothelial cells in ion channel function and membrane receptor-coupled signaling and physiological cell functions, although some differences exist. This information may be helpful for research using hiPSC-ECs.
Emodin Sensitizes Cervical Cancer Cells to Vinblastine by Inducing Apoptosis and Mitotic Death
Authors: Trybus Wojciech , Trybus Ewa , Król Teodora
Published: August 2022

In recent years, studies on the effects of combining novel plant compounds with cytostatics used in cancer therapy have received considerable attention. Since emodin sensitizes tumor cells to chemotherapeutics, we evaluated changes in cervical cancer cells after its combination with the antimitotic drug vinblastine. Cellular changes were demonstrated using optical, fluorescence, confocal and electron microscopy. Cell viability was assessed by MTT assay. The level of apoptosis, caspase 3/7, Bcl-2 protein, ROS, mitochondrial membrane depolarization, cell cycle and degree of DNA damage were analyzed by flow cytometry. The microscopic image showed indicators characteristic for emodin- and vinblastine-induced mitotic catastrophe, i.e., multinucleated cells, giant cells, cells with micronuclei, and abnormal mitotic figures. These compounds also increased blocking of cells in the G2/M phase, and the generated ROS induced swelling and mitochondrial damage. This translated into the growth of apoptotic cells with active caspase 3/7 and inactivation of Bcl-2 protein and active ATM kinase. Emodin potentiated the cytotoxic effect of vinblastine, increasing oxidative stress, mitotic catastrophe and apoptosis. Preliminary studies show that the combined action of both compounds, may constitute an interesting form of anticancer therapy.
The Nexus between Information Communication Technology and Human Rights in Southern Africa
Authors: Mlambo Courage
Published: August 2022

The study sought to empirically test the contribution of information and communication technology (ICT) to the advancement of human rights, drawing on the fact that safeguarding human rights through the use of ICT is a field of increasing interest to academics and those working towards the advancement of human rights and development practitioners. The literature on ICT and human rights holds the view that ICT can play a significant role in the advancement of human rights. ICT has become an essential instrument for realising human rights, and ensuring its accessibility must be a primary concern for all governments. However, despite the increase in ICT usage, the southern African region has been marred by atrocities and human rights violations. Many southern African governments regularly impose restrictions on human rights defenders, journalists, and rights activists, often to suit political goals. The use of ICT has extensive effects on the human rights agenda and forms an important tool in its endeavours to gather, analyse, and spread information and advocate for fitting remedies in response to human rights infringements. It is against this background that this study sought to examine the contribution of ICT to the advancement of human rights. The study was quantitative in nature, using panel data to estimate its model. The findings reveal a weak positive relationship between ICT and the advancement of human rights. The study recommends that governments and civil society encourage the use of ICT functionality in ways that advance human rights.
Complex Causal Extraction of Fusion of Entity Location Sensing and Graph Attention Networks
Authors: Chen Yang , Wan Weibing , Hu Jimi , Wang Yuxuan , Huang Bo
Published: August 2022

At present, there is no uniform definition of annotation schemes for causal extraction, and existing methods are limited by the dependence of relations on long spans, which makes complex sentences such as multi-causal relations and nested causal relations difficult to extract. To solve these problems, a head-to-tail entity annotation method is proposed, which can express the complete semantics of complex causal relations and clearly describe the boundaries of entities. Based on this, a causal model, RPA-GCN (relation position and attention-graph convolutional networks), is constructed, incorporating GAT (graph attention network) and entity location perception. The attention layer is combined with a dependency tree to enhance the model’s ability to perceive relational features, and a bi-directional graph convolutional network is constructed to further capture the deep interaction information between entities and relationships. Finally, the classifier iteratively predicts the relationship of each word pair in the sentence and analyzes all causal pairs in the sentence by a scoring function. Experiments on SemEval 2010 task 8 and the Altlex dataset show that our proposed method has significant advantages in solving complex causal extraction compared to state-of-the-art methods.
The Central Dogma of Information
Authors: Cárdenas-García Jaime F.
Published: August 2022

Info-autopoiesis or the self-referenced, recursive, interactive process of information self-production that engages all living beings in their efforts to satisfy their physiological and/or relational needs relies on Bateson’s difference which makes a difference. Living beings, as active manipulators/observers of their environment, derive meaning from the sensorially detected motion of matter and/or energy in the Universe. The process of info-autopoiesis in humans is found to be triadic in nature and incorporates the simultaneity of a quantitative/objective perspective with a qualitative/subjective perspective. In this process of meaningful engagement with the environment, humans create and transform endogenous semantic information into countless expressions of exogeneous syntactic information, which is synonymous with ordered material structure and artificial creation. Other humans can interpret exogeneous syntactic information and uniquely transform it into semantic information that can take multifarious forms. This asymmetrical process is the basis to postulate the central dogma of information that states ‘info-autopoiesis results in endogenous semantic information that irreversibly becomes exogeneous syntactic information’. In other words, once the artificial, syntactic world, including machines, created by humans comes into being it can only be interpreted by others, i.e., it does not necessarily convey the same intended meaning to all. Additionally, these artificial creations only recognize, extract, create, transmit, preserve, store, and utilize syntactic information, unable to transform syntactic information into semantic information. In other words, our resourceful capacity for syntactic creation does not allow for creation of artificial beings with comparable capabilities as us for meaning making. It suggests that our dreams for sentient artificial general intelligence and superintelligence are misguided and parallel the central dogma of molecular biology which states that ‘once (sequential) information has passed into protein it cannot get out again’.
Spatial Analysis of Socio-Economic Vulnerability in COVID-19 Handling: Strategies for the Development of Smart Society and Smart Economy
Authors: Wahyuni Aisah Tri , Rachmawati Rini , Baiquni Muhammad
Published: August 2022

Sleman Regency has always had an increasing and highest rate of COVID-19 cases in the Special Region of Yogyakarta, Indonesia. One of the implementations of a smart city in some cities and regencies is an appropriate strategy in handling the COVID-19 pandemic. This study aims to analyze the level of socio-economic vulnerability during the COVID-19 pandemic, compile a village typology based on the level of vulnerability, and explore the strategies of smart society and smart economy in handling COVID-19. This study used a mixed method with a sequential explanatory design. The results show that the high level of socio-economic vulnerability can be found in urban areas, while the low and moderate ones dominate in rural areas or the northern region of Sleman Regency. The pattern of socio-economic vulnerability levels is clustered, resulting in eight village typologies. The COVID-19 handling through a smart society and smart economy does not spatially consider aspects of socio-economic vulnerability, but implicitly adjusts the needs and problems of the community. Strategies for managing socio-economic vulnerabilities during the COVID-19 pandemic in the implementation of smart society and smart economy are bringing services closer to the community, shifting services to digital, increasing application features, and increasing community capacity through training.
Characterization of Microbial Communities from the Alimentary Canal of Typhaea stercorea (L.) (Coleoptera: Mycetophagidae)
Authors: Eason Julius , Mason Linda
Published: August 2022

The gut microbiomes of symbiotic insects typically mediate essential functions lacking in their hosts. Here, we describe the composition of microbes residing in the alimentary canal of the hairy fungus beetle, Typhaea stercorea (L.), at various life stages. This beetle is a post-harvest pest of stored grains that feeds on fungi and serves as a vector of mycotoxigenic fungi. It has been reported that the bacterial communities found in most insects’ alimentary canals contribute to nutrition, immune defenses, and protection from pathogens. Hence, bacterial symbionts may play a key role in the digestive system of T. stercorea. Using 16S rRNA amplicon sequencing, we examined the microbiota of T. stercorea. We found no difference in bacterial species richness between larvae and adults, but there were compositional differences across life stages (PERMANOVA:pseudo-F(8,2) = 8.22; p = 0.026). The three most abundant bacteria found in the alimentary canal of the larvae and adults included Pseudomonas (47.67% and 0.21%, respectively), an unspecified genus of the Enterobacteriaceae family (46.60 % and 90.97%, respectively), and Enterobacter (3.89% and 5.75%, respectively). Furthermore, Pseudomonas spp. are the predominant bacteria in the larval stage. Our data indicated that field-collected T. stercorea tended to have lower species richness than laboratory-reared beetles (Shannon: H = 5.72; p = 0.057). Furthermore, the microbial communities of laboratory-reared insects resembled one another, whereas field-collected adults exhibited variability (PERMANOVA:pseudo-F(10,3) = 4.41; p = 0.006). We provide evidence that the environment and physiology can shift the microbial composition in the alimentary canal of T. stercorea.
A Temperature-Dependent Model for Tritrophic Interactions Involving Tea Plants, Tea Green Leafhoppers and Natural Enemies
Authors: Qin Huaguang , Hong Wuxuan , Qi Zehua , Hu Yinghong , Shi Rui , Wang Shuyuan , Wang Yuxi , Zhou Jianping , Mu Dan , Fu Jianyu , Sun Tingzhe
Published: August 2022

The tea green leaf hopper, Empoasca onukii Matsuda, is a severe pest of tea plants. Volatile emissions from tea shoots infested by the tea green leafhopper may directly repel insect feeding or attract natural enemies. Many studies have been conducted on various aspects of the tritrophic relationship involving tea plants, tea green leafhoppers and natural enemies. However, mathematic models which could explain the dynamic mechanisms of this tritrophic interaction are still lacking. In the current work, we constructed a realistic and stochastic model with temperature-dependent features to characterize the tritrophic interactions in the tea agroecosystem. Model outputs showed that two leafhopper outbreaks occur in a year, with their features being consistent with field observations. Simulations showed that daily average effective accumulated temperature (EAT) might be an important metric for outbreak prediction. We also showed that application of slow-releasing semiochemicals, as either repellents or attractants, may be highly efficacious for pest biocontrol and can significantly increase tea yields. Furthermore, the start date of applying semiochemicals can be optimized to effectively increase tea yields. The current model qualitatively characterizes key features of the tritrophic interactions and provides critical insight into pest control in tea ecosystems.
Life Table Construction under Different Temperatures and Insecticide Susceptibility Analysis of Uroleucon formosanum (Hemiptera: Aphididae)
Authors: Jing Tian-Xing , Qi Chu-Chu , Jiao Ao , Liu Xiao-Qiang , Zhang Shuai , Su Hong-Hua , Yang Yi-Zhong
Published: August 2022

Uroleucon formosanum is an important aphid pest of lettuce, but basic information on its biology is scarce. In this study, effects of three constant temperatures (17, 21, and 25 °C, simulating the mean temperature range in greenhouses) on the development and fecundity of U. formosanum were analyzed by constructing a life table. U. formosanum could develop and reproduce under all three temperatures, but the survival rate, development, and fecundity of U. formosanum were affected by temperature. The intrinsic rate of increase was lowest at 17 °C (0.17) and it was significantly less than at 21 °C (0.20) and 25 °C (0.23). Furthermore, U. formosanum had the lowest finite rate of increase (1.19) and the largest mean generation time (20.21) at 17 °C. These results mean that U. formosanum is less adapted to the lower temperatures (17 °C) among these three set temperatures. To screen insecticides for control, susceptibility of U. formosanum to six insecticides including chlorpyrifos, abamectin, beta-cypermethrin, imidacloprid, nitenpyram, and thiamethoxam was evaluated. U. formosanum was relatively sensitive to all six test insecticides. Chlorpyrifos had the highest toxicity to U. formosanum (LC50 = 3.08 mg/L). These data may help to develop integrated management strategies for better population control of U. formosanum.
Modern Trends in Neutron Scattering Instrument Technologies
Authors: Ehlers Georg , Crow Morris L. , Diawara Yacouba , Gallmeier Franz X. , Geng Xiaosong , Granroth Garrett E. , Gregory Raymond D. , Islam Fahima F. , Knudson Robert O. , Li Fankang , Loyd Matthew S. , Vacaliuc Bogdan
Published: August 2022

This article reviews some current trends that can be observed in the development of neutron scattering instrument technologies. While the number of neutron scattering facilities worldwide and the number of beam days they offer are largely stable, their scientific impact is increasing through improving instrumental capabilities, new and more versatile instruments, and more efficient data collection protocols. Neutron beams are becoming smaller but more intense, and instruments are being designed to utilize more ‘useful’ neutrons in unit time. This article picks and discusses a few recent developments in the areas of integrated source and instrument design, use of computational tools, new detectors, and experiment automation.
Impact and Value of Hospital Antibiotic Stewardship: Retrospective Pre-COVID-19-Pandemic Analysis
Authors: Costantino Maria , Conti Valeria , Corbi Graziamaria , Iannelli Alessandra Anna , Marongiu Francesco , Torsiello Martina , Della Vecchia Antonio , Sellitto Carmine , Genovese Armando , Moccia Giuseppina , Filippelli Amelia , De Caro Francesco
Published: August 2022

Aim: “Antimicrobial stewardship” (AMS) is defined as a healthcare-system-wide approach to promoting and monitoring the judicious use of antimicrobials to preserve their future effectiveness. Therefore, we structured an observational study to monitor the hospital trend of antibiotic consumption and related expenditure before the COVID-19 pandemic and to evaluate how much AMS could affect this trend. Methods: The research covered the antibiotic prescriptions at the University Hospital (U.H.) “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy, comparing data on the therapies prescribed from 1 January to 31 December 2017 (27,384 patients) with those collected during the same period in 2019 (27,047 patients). Results: Unlike national data, our results highlighted a decreasing trend in the consumption of antibiotics that did not concern only carbapenems and fluoroquinolones, but also the third-generation cephalosporins. Noteworthily, there was also a reduction in 2019 compared with 2017 in the consumption of colistin, an antibiotic towards which an increase in bacterial resistance in animals has been found nationally. In agreement with the national data, our research confirms a trend of an increase (+3.7%) in the total antibiotic consumption corresponding to more than 26% and 29% reductions in the total and therapy per-day costs, respectively. Conclusions: The results show a positive impact of the AMS at the University Hospital “San Giovanni di Dio e Ruggi d’Aragona”.
Paracrine IGF-1 Activates SOD2 Expression and Regulates ROS/p53 Axis in the Treatment of Cardiac Damage in D-Galactose-Induced Aging Rats after Receiving Mesenchymal Stem Cells
Authors: Hu Wei-Syun , Liao Wei-Yu , Chang Chin-Hsien , Chen Tung-Sheng
Published: August 2022

Aging is one of the causative agents associated with heart failure. Cell-based therapies show potential in the treatment of cardiac aging due to the characteristics of stem cells, including differentiation and the paracrine effect. This study aimed to investigate in detail the mechanism related to biomolecules released from mesenchymal stem cells in the treatment of cardiac aging. In vitro and in vivo models were designed to explore the above hypothesis. Experimental results from the in vitro model indicated that the elevation of oxidative stress, the expression of aging marker p53, and the suppression of antioxidant marker SOD2 could be found in D-galactose-stressed H9c2 cardiomyoblasts. The co-culture of D-galactose-stressed H9c2 with mesenchymal stem cells significantly improved the above pathological signaling. An animal model revealed that the change in cardiac structure, the accumulation of fibrotic collagen, and the activation of the above pathological signaling could be observed in heart tissues of D-galactose-stressed rats. After the rats had received mesenchymal stem cells, all the pathological conditions were significantly improved in D-galactose-stressed hearts. Further evidence indicated that the release of the survival marker IGF-1 was detected in a stem-cell-conditioned medium. Significant increases in cell viability and the expression of SOD2, as well as a reduction in oxidative stress and the suppression of p53, were found in D-galactose-stressed H9c2 cells cultured with a stem-cell-conditioned medium, whereas the depletion of IGF-1 in stem-cell-conditioned medium diminished the antiaging effect on H9c2 cells. In conclusion, the paracrine release of IGF-1 from mesenchymal stem cells increases the expression of antioxidant marker SOD2, and the expression of SOD2 reduces oxidative stress as well as suppresses p53, leading to a reduction in cardiac senescence in D-galactose-stressed rats.
Protective Effects of BNT162b2 Vaccination on Aerobic Capacity Following Mild to Moderate SARS-CoV-2 Infection: A Cross-Sectional Study Israel
Authors: Blumberg Yair , Edelstein Michael , Abu Jabal Kamal , Golan Ron , Tuvia Neta , Perets Yuval , Saad Musa , Levinas Tatyana , Saleem Dabbah , Israeli Zeev , Alaa Abu Raya , Elbaz Greener Gabby , Amital Anat , Halabi Majdi
Published: August 2022

Patients previously infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may experience post-acute adverse health outcomes, known as long COVID. The most reported symptoms are fatigue, headache and attention/concentration issues, dyspnea and myalgia. In addition, reduced aerobic capacity has been demonstrated in both mild and moderate COVID-19 patients. It is unknown whether COVID-19 vaccination mitigates against reduced aerobic capacity. Our aim was to compare the aerobic capacity of vaccinated and unvaccinated individuals previously infected with SARS-CoV-2. Methods: Individuals aged 18 to 65 years with laboratory-confirmed mild to moderate COVID-19 disease were invited to Ziv Medical Centre, Israel, three months after SARS-CoV-2 infection. We compared individuals unvaccinated at the time of infection to those vaccinated in terms of aerobic capacity, measured using symptom-limited cardiopulmonary exercise test (CPET). Results: We recruited 28 unvaccinated and 22 vaccinated patients. There were no differences in baseline demographic and pulmonary function testing (PFT) parameters. Compared with unvaccinated individuals, those vaccinated had higher V’O2/kg at peak exercise and at the anaerobic threshold. The V’O2/kg peak in the unvaccinated group was 83% of predicted vs. 100% in the vaccinated (p < 0.002). At the anaerobic threshold (AT), vaccinated individuals had a higher V’O2/kg than those unvaccinated. Conclusions: Vaccinated individuals had significantly better exercise performance. Compared with vaccinated individuals, a higher proportion of those unvaccinated performed substantially worse than expected on CPET. These results suggest that vaccination at the time of infection is associated with better aerobic capacity following SARS-CoV-2 infection.
Cortical and Subcortical Alterations and Clinical Correlates after Traumatic Brain Injury
Authors: Xue Qiang , Wang Linbo , Zhao Yuanyu , Tong Wusong , Wang Jiancun , Li Gaoyi , Cheng Wei , Gao Liang , Dong Yan
Published: August 2022

Background: Traumatic brain injury (TBI) often results in persistent cognitive impairment and psychiatric symptoms, while lesion location and severity are not consistent with its clinical complaints. Previous studies found cognitive deficits and psychiatric disorders following TBI are considered to be associated with prefrontal and medial temporal lobe lesions, however, the location and extent of contusions often cannot fully explain the patient′s impairments. Thus, we try to find the structural changes of gray matter (GM) and white matter (WM), clarify their correlation with psychiatric symptoms and memory following TBI, and determine the brain regions that primary correlate with clinical measurements. Methods: Overall, 32 TBI individuals and 23 healthy controls were recruited in the study. Cognitive impairment and psychiatric symptoms were examined by Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS), and Wechsler Memory Scale-Chinese Revision (WMS-CR). All MRI data were scanned using a Siemens Prisma 3.0 Tesla MRI system. T1 MRI data and diffusion tensor imaging (DTI) data were processed to analyze GM volume and WM microstructure separately. Results: In the present study, TBI patients underwent widespread decrease of GM volume in both cortical and subcortical regions. Among these regions, four brain areas including the left inferior temporal gyrus and medial temporal lobe, supplementary motor area, thalamus, and anterior cingulate cortex (ACC) were highly implicated in the post-traumatic cognitive impairment and psychiatric complaints. TBI patients also underwent changes of WM microstructure, involving decreased fractional anisotropy (FA) value in widespread WM tracts and increased mean diffusivity (MD) value in the forceps minor. The changes of WM microstructure were significantly correlated with the decrease of GM volume. Conclusions: TBI causes widespread cortical and subcortical alterations including a reduction in GM volume and change in WM microstructure related to clinical manifestation. Lesions in temporal lobe may lead to more serious cognitive and emotional dysfunction, which should attract our high clinical attention.
Safety of Biological Therapies in Elderly Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis
Authors: Hahn Gustavo Drügg , Golovics Petra Anna , Wetwittayakhlang Panu , Santa Maria Dirlene Melo , Britto Usiara , Wild Gary Edward , Afif Waqqas , Bitton Alain , Bessissow Talat , Lakatos Peter Laszlo
Published: August 2022

Background and Aim: Newer biologics appeared safer in landmark clinical trials, but their safety is understudied in vulnerable populations. The aim of the present study was to perform a systematic review and meta-analysis to assess the safety of available biologicals in the elderly IBD population. Methods: We systematically searched PubMed/Medline and conference proceedings between 1 April 1969 and 1 June 2021 to identify eligible studies that examined the safety of biologics in elderly patients with IBD. Of the 2885 articles and 12 congress abstracts identified, 12 peer reviewed papers and 3 abstracts were included after independent evaluation by two reviewers. The identified studies collected safety data on anti-TNF, vedolizumab (VDZ) and ustekinumab (UST). Results: Rates of AE and infections were not different among the biologics (AE mean rate: 11.3 (CI 95% 9.9–12.7)/100 pts-years; p = 0.11, infection mean rate: 9.5 (CI 95% 8.4–10.6)/100 pts-years; p = 0.56) in elderly IBD patients on anti-TNF, VDZ or UST. Infusion/injection reaction rates were more common on anti-TNFs (mean rate: 2.51 (CI 95% 1.7–3.4/100 pts-years; p = 0.02). and malignancy rates were higher on VDZ/UST (mean rate: 2.14 (CI 95% 1.6–2.8)/100 pts-years; p = 0.01). Conclusions: Rates of AEs and infections were not different among biologicals. Infusion/injection reactions were more common on anti-TNFs. Current data are insufficient to suggest the sequencing of biologicals in elderly patients based on safety.
Effect of Sarcopenia on Mortality in Type 2 Diabetes: A Long-Term Follow-Up Propensity Score-Matched Diabetes Cohort Study
Authors: Lin Jui-An , Hou Jin-De , Wu Szu-Yuan
Published: August 2022

Purpose: The effect of sarcopenia on the survival of patients with type 2 diabetes remains unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare the patients with diabetes with or without sarcopenia. Patients and Methods: We included patients with type 2 diabetes and categorized them into two groups according to whether they had sarcopenia and compared their survival; patients in the groups were matched at a ratio of 1:2. Results: The matching process yielded a final cohort of 201,698 patients (132,805 and 68,893 in the sarcopenia and nonsarcopenia diabetes groups, respectively) who were eligible for further analysis. According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of all-cause death for the sarcopenia diabetes group compared with the control group: 1.35 (1.33–1.38; p < 0.001). The aHRs (95% CIs) of all-cause death for those aged 41–50, 51–60, and >60 years (compared with those aged ≤40 years) were 1.53 (1.48–1.60), 2.61 (2.52–2.72), and 6.21 (5.99–6.45), respectively. The aHR (95% CI) of all-cause death for the male patients compared with the female patients was 1.56 (1.54–1.60). The aHRs (95% CIs) of all-cause death for those with adapted Diabetes Complications Severity Index (aDCSI) scores of 1, 2, 3, 4, and ≥5 (compared with an aDCSI score of 0) were 1.01 (1.00–1.14), 1.38 (1.35–1.42), 1.58 (1.54–1.63), and 2.23 (2.14–2.33), respectively. Conclusion: Patients with type 2 diabetes and sarcopenia had higher mortality than did those without sarcopenia.
Assessment of Anxiety, Depression, Work-Related Stress, and Burnout in Health Care Workers (HCWs) Affected by COVID-19: Results of a Case–Control Study in Italy
Authors: La Torre Giuseppe , Barletta Vanessa India , Marte Mattia , Paludetti Francesca , Faticoni Augusto , Barone Lavinia Camilla , Rocchi Ilaria , Picchioni Filippo , Previte Carlo Maria , Serruto Pasquale , Deriu Gloria , Ajassa Camilla , Campagna Roberta , Antonelli Guido , Matroianni Claudio Maria
Published: August 2022

This study aims to investigate whether HCWs infected with COVID-19 may experience potential psychological consequences and a higher incidence of depression, anxiety, work-related stress, and burnout compared to non-infected HCWs. A case–control study with 774 participants was conducted comparing COVID-19-infected HCWs (cases) and non-infected HCWs (controls) from the Occupational Medicine Unit at the Teaching Hospital Policlinico Umberto I, who were administered the same questionnaire including Hospital Anxiety and Depression Scale, Copenhagen Burnout Inventory and Karasek’s Job Content Questionnaire. No differences in the levels of burnout and decision latitude were found between the two groups. Cases showed higher level of anxiety and job demand compared to controls. In contrast, levels of depression in the case group were significantly lower compared to the control group. The results are indicating the need for workplace health promotion activities based on stress and burnout management and prevention. Multiple organizational and work-related interventions can lower the impact of mental health-related issues in the COVID-19 pandemics, including the improvement of workplace infrastructures, as well as the adoption of correct and shared anti-contagion measures, which must include regular personal protective equipment supply, and the adoption of training programs that deal with mental health-related issues.
Evolving Devices and Material in Transcatheter Aortic Valve Replacement: What to Use and for Whom
Authors: Chiarito Mauro , Spirito Alessandro , Nicolas Johny , Selberg Alexandra , Stefanini Giulio , Colombo Antonio , Reimers Bernhard , Kini Annapoorna , Sharma Samin K. , Dangas George D. , Mehran Roxana
Published: August 2022

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic stenosis, providing a viable alternative to surgical aortic valve replacement (SAVR) for patients deemed to be at prohibitive surgical risk, but also for selected patients at intermediate or low surgical risk. Nonetheless, there still exist uncertainties regarding the optimal management of patients undergoing TAVR. The selection of the optimal bioprosthetic valve for each patient represents one of the most challenging dilemmas for clinicians, given the large number of currently available devices. Limited follow-up data from landmark clinical trials comparing TAVR with SAVR, coupled with the typically elderly and frail population of patients undergoing TAVR, has led to inconclusive data on valve durability. Recommendations about the use of one device over another in given each patient’s clinical and procedural characteristics are largely based on expert consensus. This review aims to evaluate the available evidence on the performance of different devices in the presence of specific clinical and anatomic features, with a focus on patient, procedural, and device features that have demonstrated a relevant impact on the risk of poor hemodynamic valve performance and adverse clinical events.
Bing-Neel Syndrome, a Rare Presentation of Waldenström Macroglobulinemia—A Multicenter Report by the Polish Lymphoma Research Group
Authors: Drozd-Sokołowska Joanna , Waszczuk-Gajda Anna , Witkowska Magdalena , Sienkiewicz Elżbieta , Kopińska Anna , Kołkowska-Leśniak Agnieszka , Barankiewicz Joanna , Długosz-Danecka Monika , Smolewski Piotr , Helbig Grzegorz , Lech-Marańda Ewa , Jurczak Wojciech , Biecek Przemysław , Giebel Sebastian , Wiktor-Jędrzejczak Wiesław , Basak Grzegorz
Published: August 2022

Bing-Neel syndrome (BNS) is a rare presentation of Waldenström macroglobulinemia (WM). BNS is a consequence of the central nervous system (CNS) involvement by lymphoplasmacytic lymphoma (LPL) and, rarely, the peripheral nervous system. The data on BNS are extremely scarce. Therefore, we performed a multicenter retrospective analysis of BNS patients diagnosed and treated in centers aligned with the Polish Lymphoma Research Group. The analysis covers the years 2014–2021. Eleven patients were included, 55% females and the median age at BNS diagnosis was 61 years. The median time from WM to BNS was 3.5 years; 27% of patients did have a diagnosis of WM and BNS made simultaneously or within 30 days from each other. Isolated parenchymal involvement was the least frequent (20%). Patients were treated with different regimens, mostly able to cross the blood-brain barrier, including 18% treated with ibrutinib first line. The cumulative objective response to treatment was 73%. With the median follow-up of 20 months (95% CI, 2–32), the 36-month estimates were: overall survival (OS) 47%, progression-free survival (PFS) 33%, and cumulative incidence of BNS-associated death 41%. The performance status according to ECOG was significant for PFS (HR = 7.79) and the hemoglobin concentration below 11 g/dL was correlated with PFS. To conclude, BNS is a very rare manifestation of WM. It is associated with a poor outcome with most patients succumbing to BNS.
Provider Perspectives on Sleep Apnea from Appalachia: A Mixed Methods Study
Authors: Stansbury Robert , Rudisill Toni , Salyer Rachel , Kirk Brenna , De Fazio Caterina , Baus Adam , Aryal Shubekchha , Strollo Patrick J. , Sharma Sunil , Feinberg Judith
Published: August 2022

West Virginia (WV) has the highest rates of obesity and cardiopulmonary disease in the United States (U.S.). Recent work has identified a significant care gap in WV for obstructive sleep apnea (OSA). This OSA care gap likely has significant health implications for the region given the high rates of obesity and cardiopulmonary disease. The purpose of this mix methods study was to identify barriers that contribute to the rural OSA care disparity previously identified in WV. Methods: This study used mixed methods to evaluate the barriers and facilitators to management of OSA at Federally Qualified Health Centers serving communities in southern WV. Focus groups were conducted at federally qualified health centers with providers serving Appalachian communities. Participants also completed the validated Obstructive Sleep Apnea Knowledge and Attitudes (OSAKA) questionnaire to gain insight into provider knowledge and beliefs regarding OSA. EMR analysis using diagnostic codes was completed at the sites to assess OSA prevalence rates. The same individual served as the interviewer in all focus group sessions to minimize interviewer variability/bias. Our team checked to ensure that the professional transcriptions were correct and matched the audio via spot checks. Results: Themes identified from the focus groups fell into three broad categories: (1) barriers to OSA care delivery, (2) facilitators to OSA care delivery, and (3) community-based care needs to optimize management of OSA in the targeted rural areas. Questionnaire data demonstrated rural providers feel OSA is an important condition to identify but lack confidence to identify and treat OSA. Evaluation of the electronic medical record demonstrates an even larger OSA care gap in these rural communities than previously described. Conclusion: This study found a lack of provider confidence in the ability to diagnose and treat OSA effectively and identified specific themes that limit OSA care in the communities studied. Training directed toward the identified knowledge gaps and on new technologies would likely give rural primary care providers the confidence to take a more active role in OSA diagnosis and management. An integrated model of care that incorporates primary care providers, specialists and effective use of modern technologies will be essential to address the identified OSA care disparities in rural WV and similar communities across the U.S. Community engaged research such as the current study will be essential to the creation of feasible, practical, relevant and culturally competent care pathways for providers serving rural communities with OSA and other respiratory disease to achieve health equity.
Hyaluronic Acid and Galacto-Xyloglucan Eyedrop Efficacy in Young-Adult Oral Contraceptive Users of Childbearing Age
Authors: Sánchez-González José-María , De-Hita-Cantalejo Concepción , Sánchez-González María Carmen
Published: August 2022

To assess the efficacy of 0.4% hyaluronic acid and 0.2% galacto-xyloglucan for the subjective symptoms of dry eye disease and tear film invasive and noninvasive signs in 34 young-adult oral contraceptive users of childbearing age, a prospective, longitudinal, single-blind, clinical study was performed in a population of childbearing-age oral-contraceptive consumers. Subjective dry eye disease questionnaires, and invasive and noninvasive tear film assessments were reported before and after six weeks of hyaluronic acid with galacto-xyloglucan (HA-GX) treatment versus hyaluronic acid alone (HA). HA-GX treatment resulted in a greater decrease in the ocular surface disease index (17.01 ± 11.36 score points, p < 0.01) than the HA variation (11.61 ± 11.18 score points, p < 0.01). The standard patient evaluation of eye dryness also decreased more in the HA-GX group (4.06 ± 5.50 score points, p < 0.01) than in the HA alone group (0.70 ± 3.16, p = 0.21). Regarding noninvasive break-up time (NIBUT), the HA-GX group’s first NIBUT achieved an increase of 1.75 ± 1.16 s, p < 0.01, while the HA-alone group increased by only 0.54 ± 1.01 s, p < 0.01. The HA-GX group’s mean NIBUT reported an increase of 3.72 ± 5.69 s, p < 0.01; however, the HA-alone group achieved 2.19 ± 5.26 s, p = 0.05. Hyaluronic acid in combination with galacto-xyloglucan significantly decreased subjective dry eye disease symptoms and increased first and mean NIBUT compared to hyaluronic acid alone. Galacto-xyloglucan added efficacy in young-adult childbearing-age oral contraceptive users.
Updates in Management of SARS-CoV-2 Infection
Authors: Flisiak Robert , Zarębska-Michaluk Dorota , Flisiak-Jackiewicz Marta , Rzymski Piotr
Published: August 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide since the beginning of 2020 [...]
Anti-Inflammatory and Mineralization Effects of an ASP/PLGA-ASP/ACP/PLLA-PLGA Composite Membrane as a Dental Pulp Capping Agent
Authors: Yan Wenjuan , Yang Fenghe , Liu Zhongning , Wen Quan , Gao Yike , Niu Xufeng , Zhao Yuming
Published: August 2022

Dental pulp is essential for the development and long-term preservation of teeth. Dental trauma and caries often lead to pulp inflammation. Vital pulp therapy using dental pulp-capping materials is an approach to preserving the vitality of injured dental pulp. Most pulp-capping materials used in clinics have good biocompatibility to promote mineralization, but their anti-inflammatory effect is weak. Therefore, the failure rate will increase when dental pulp inflammation is severe. The present study developed an amorphous calcium phosphate/poly (L-lactic acid)-poly (lactic-co-glycolic acid) membrane compounded with aspirin (hereafter known as ASP/PLGA-ASP/ACP/PLLA-PLGA). The composite membrane, used as a pulp-capping material, effectively achieved the rapid release of high concentrations of the anti-inflammatory drug aspirin during the early stages as well as the long-term release of low concentrations of aspirin and calcium/phosphorus ions during the later stages, which could repair inflamed dental pulp and promote mineralization. Meanwhile, the composite membrane promoted the proliferation of inflamed dental pulp stem cells, downregulated the expression of inflammatory markers, upregulated the expression of mineralization-related markers, and induced the formation of stronger reparative dentin in the rat pulpitis model. These findings indicate that this material may be suitable for use as a pulp-capping material in clinical applications.
PLGA Nanoparticles Uptake in Stem Cells from Human Exfoliated Deciduous Teeth and Oral Keratinocyte Stem Cells
Authors: Tizu Maria , Mărunțelu Ion , Cristea Bogdan Mihai , Nistor Claudiu , Ishkitiev Nikolay , Mihaylova Zornitsa , Tsikandelova Rozaliya , Miteva Marina , Caruntu Ana , Sabliov Cristina , Calenic Bogdan , Constantinescu Ileana
Published: August 2022

Polymeric nanoparticles have been introduced as a delivery vehicle for active compounds in a broad range of medical applications due to their biocompatibility, stability, controlled release of active compounds, and reduced toxicity. The oral route is the most used approach for delivery of biologics to the body. The homeostasis and function of oral cavity tissues are dependent on the activity of stem cells. The present work focuses, for the first time, on the interaction between two types of polymeric nanoparticles, poly (lactic-co-glycolic acid) or PLGA and PLGA/chitosan, and two stem cell populations, oral keratinocyte stem cells (OKSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). The main results show that statistical significance was observed in OKSCs uptake when compared with normal keratinocytes and transit amplifying cells after 24 h of incubation with 5 and 10 µg/mL PLGA/chitosan. The CD117+ SHED subpopulation incorporated more PLGA/chitosan nanoparticles than nonseparated SHED. The uptake for PLGA/chitosan particles was better than for PLGA particles with longer incubation times, yielding better results in both cell types. The present results demonstrate that nanoparticle uptake depends on stem cell type, incubation time, particle concentration, and surface properties.
Binocular-Vision-Based Obstacle Avoidance Design and Experiments Verification for Underwater Quadrocopter Vehicle
Authors: Zhang Meiyan , Cai Wenyu , Xie Qinan , Xu Shenyang
Published: August 2022

As we know, for autonomous robots working in a complex underwater region, obstacle avoidance design will play an important role in underwater tasks. In this paper, a binocular-vision-based underwater obstacle avoidance mechanism is discussed and verified with our self-made Underwater Quadrocopter Vehicle. The proposed Underwater Quadrocopter Vehicle (UQV for short), like a quadrocopter drone working underwater, is a new kind of Autonomous Underwater Vehicle (AUV), which is equipped with four propellers along the vertical direction of the robotic body to adjust its body posture and two propellers arranged at the sides of the robotic body to provide propulsive and turning force. Moreover, an underwater binocular-vision-based obstacle positioning method is studied to measure an underwater spherical obstacle’s radius and its distance from the UQV. Due to its perfect ability of full-freedom underwater actions, the proposed UQV has obvious advantages such as a zero turning radius compared with existing torpedo-shaped AUVs. Therefore, one semicircle-curve-based obstacle avoidance path is planned on the basis of an obstacle’s coordinates. Practical pool experiments show that the proposed binocular vision can locate an underwater obstacle accurately, and the designed UQV has the ability to effectively avoid multiple obstacles along the predefined trajectory.
Individualized Management of Patients with Coronary Artery Disease
Authors: Bil Jacek
Published: August 2022

We can characterize personalized medicine as a compilation of diagnostic and screening modalities to better manage individual patients, their diseases, or their predisposition toward various disorders [...]
Digital Twins in Healthcare: Is It the Beginning of a New Era of Evidence-Based Medicine? A Critical Review
Authors: Armeni Patrizio , Polat Irem , De Rossi Leonardo Maria , Diaferia Lorenzo , Meregalli Severino , Gatti Anna
Published: August 2022

Digital Twins (DTs) are used in many different industries (e.g., manufacturing, construction, automotive, and aerospace), and there is an initial trend of applications in healthcare, mainly focusing on precision medicine. If their potential is fully unfolded, DTs will facilitate the as-yet-unrealized potential of connected care and alter the way lifestyle, health, wellness, and chronic disease will be managed in the future. To date, however, due to technical, regulatory and ethical roadblocks, there is no consensus as to what extent DTs in healthcare can introduce revolutionary applications in the next decade. In this review, we present the current applications of DTs covering multiple areas of healthcare (precision medicine, clinical trial design, and hospital operations) to identify the opportunities and the barriers that foster or hinder their larger and faster diffusion. Finally, we discuss the current findings, opportunities and barriers, and provide recommendations to facilitate the continuous development of DTs application in healthcare.