bluuebunny/crossref_metadata_2025 huggingface dataset:
Underreporting and Triggering Factors for Reporting ADRs of Two Ophthalmic Drugs: A Comparison between Spontaneous Reports and Active Pharmacovigilance Databases
Authors: Contreras-Salinas Homero , Baiza-Durán Leopoldo Martín , Bautista-Castro Manuel Alejandro , Alonso-Rodríguez Diego Rodrigo , Rodríguez-Herrera Lourdes Yolotzin
Published: November 2022

(1) Aims of the study: calculating the underreporting ratio for two different medications, a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (antiglaucoma) and a fixed combination of sodium hyaluronate 0.1% + chondroitin sulfate 0.18% (artificial tears) for characterizing the features influencing the reporting of adverse drug reactions (ADRs) in spontaneous reporting. (2) Methods: The underreporting ratio was calculated by comparing the adverse drug reactions reported in the spontaneous reporting database for every 10,000 defined daily doses marketed and the adverse drug reactions from an active surveillance study for every 10,000 defined daily doses used for different drugs (antiglaucoma and artificial tears). The factors related to the report in spontaneous reporting through statistical tests were also determined. (3) Results: The underreporting ratio of spontaneous reporting was 0.006029% for antiglaucoma and 0.003552% for artificial tears. Additionally, statistically significant differences were found for severity, unexpected adverse drug reactions, and incidence of adverse drug reactions in females when compared with spontaneous reporting and active surveillance. (4) Conclusions: The underreporting ratio of ADRs related to ophthalmic medications indicates worry since the cornerstone of pharmacovigilance focuses on spontaneous reporting. Additionally, since underreporting seems to b selective, the role of certain aspects, such as gender, seriousness, severity, and unexpected ADRs, must be considered in future research.
Advanced Endoscopy for Benign Esophageal Disease: A Review Focused on Non-Erosive Reflux Disease and Eosinophilic Esophagitis
Authors: Goda Kenichi , Abe Keiichiro , Kanamori Akira , Kondo Masayuki , Kojimahara Shunsuke , Kanazawa Mimari , Tanaka Takanao , Nagashima Kazunori , Suzuki Tsunehiro , Yamamiya Akira , Hoshi Koki , Tominaga Keiichi , Majima Yuichi , Iijima Makoto , Irisawa Atsushi
Published: November 2022

Advanced endoscopy (AVE) techniques include image-enhanced endoscopy methods, such as narrow-band imaging (NBI), and types of microscopic endoscopy, such as endocytoscopy. In the esophagus, AVE first showed diagnostic utility in the diagnosis of superficial esophageal cancer and was then applied to inflammatory disease. This review focuses on non-erosive reflux disease (NERD) and eosinophilic esophagitis (EoE), which sometimes show no abnormal findings on standard white light endoscopy alone. Studies have demonstrated that advanced endoscopy, including NBI magnification endoscopy and endocytoscopy, improved the diagnostic performance of white-light endoscopy alone for NERD and EoE. In this review, we explain why advanced endoscopy is needed for the diagnosis of these esophageal inflammatory diseases, summarize the study results, and discuss future perspectives.
Unintended Consequences of a Transition to Synchronous, Virtual Simulations for Interprofessional Learners
Authors: Champagne-Langabeer Tiffany , Neher Samuel E. , Cardenas-Turanzas Marylou , Swails Jennifer L.
Published: November 2022

The coronavirus pandemic shifted in-person environments to virtual environments. Little is known about the effectiveness of fully synchronous, virtual interprofessional education (IPE). This study aims to compare two IPE cases that occurred in-person pre-pandemic and virtual during-pandemic. Two cases are analyzed: a medical error care and a charity care case. Participants were students from various health science disciplines. Assessments were captured through The Interprofessional Collaborative Competency Attainment Survey (ICCAS). Effect sizes were calculated for the pre-and post-surveys and analyzed using Cohen’s d for independent samples. From the in-person collection period, a total of 479 students participated in the medical error simulation and 479 in the charity care simulation. During the virtual collection period, a total of 506 students participated in the medical error simulation and 507 participated in the charity care simulation. In the data for the virtual simulations, the medical error case study maintained a large effect size (0.81) while the charity care simulation had a lesser impact (0.64 effect size). Structural details of the patient cases may be a critical variable. Future research is needed to better understand how health science students can obtain more training to notice the subtle cues from patients assessed through telemedicine modalities.
Effectiveness of a Mobile Application for Postpartum Depression Self-Management: Evidence from a Randomised Controlled Trial in South Korea
Authors: Seo Ji-Min , Kim Su-Jeong , Na Hyunjoo , Kim Jin-Hee , Lee Hyejin
Published: November 2022

This study examined the effectiveness of the Happy Mother mobile app developed for self-management of postpartum depression, based on cognitive behavioural therapy. A randomized controlled trial, with a pre- and a post-test design, was conducted in South Korea. Effectiveness was analysed using repeated measures ANOVA and Wilcoxon Signed Rank Test. We confirmed that the experimental group performed significantly more health promoting behaviours than the control group (F = 5.15, p = 0.007). However, there was no significant difference in postpartum depression, knowledge of depression, maladaptive beliefs, social support, sleep quality, and stress-coping behaviours between the two groups. The experimental group’s mood score increased by 1.79 ± 2.51 points, resulting in significant differences before and after the intervention (Z = −2.81, p = 0.005). The quality of sleep score in the experimental group increased by 1.48 ± 1.70 points and was also significantly different after the intervention (Z = −3.23, p = 0.001). The activity practice rate of the experimental group significantly increased by 30.27 ± 29.27% after using the app (Z = −2.81, p = 0.005). We found the app to be effective in promoting mothers’ health behaviour and improving their depressive mood.
Behavioral Risk Factor and Primary Healthcare Utilization in South Africa
Authors: Megbowon Ebenezer Toyin , David Oladipo Olalekan , Makhalima Jabulile Lindiwe
Published: November 2022

(1) Background: An effective and efficient primary healthcare service is one of the reforms designed to achieve universal healthcare coverage. The success of the reform however depends on the ability to identify factors that could undermine through avoidable use, the effectiveness of various deployed scarce resources. The prevalence of unhealthy lifestyle risk factors that have been identified as a critical public health issue, which stimulate vulnerability and mortality through the development of non-communicable diseases, also have implications for government health spending through healthcare utilization. (2) Objective: This study aims to investigate the effect of behavioral risk factors on primary healthcare utilization in South Africa. (3) Methods: Using the NIDS wave 4 data set and a binary logistic estimation technique, the study is premised on a modified Anderson model of health service utilization. (4) Results: The binary logistic regression estimation results clearly show the intercepting effect of smoking in public primary healthcare utilization. Equally, the effect of these lifestyle behavior risk factors on public PHC is evident in urban communities. (5) Conclusion: This study suggests that there is a need to intensify awareness on the health effect of smoking; strengthen and broaden law that bans smoking; and introduce the screening of smoking patients for recurring counselling sessions and intervention at primary healthcare facilities in the country’s urban communities.
Neurologic Music Therapy in Geriatric Rehabilitation: A Systematic Review
Authors: Rusowicz Jagoda , Szczepańska-Gieracha Joanna , Kiper Paweł
Published: November 2022

(1) Introduction: Neurologic music therapy (NMT) is a non-pharmacological approach of interaction through the therapeutic use of music in motor, sensory and cognitive dysfunctions caused by damage or diseases of the nervous system. (2) Objective: This study aimed to critically appraise the available literature on the application of particular NMT techniques in the rehabilitation of geriatric disorders. (3) Methods: PubMed, ScienceDirect and EBSCOhost databases were searched. We considered randomized controlled trials (RCTs) from the last 12 years using at least one of the NMT techniques from the sensorimotor, speech/language and cognitive domains in the therapy of patients over 60 years old and with psychogeriatric disorders. (4) Results: Of the 255 articles, 8 met the inclusion criteria. All papers in the final phase concerned the use of rhythmic auditory stimulation (RAS) (sensorimotor technique) in the rehabilitation of both Parkinson’s disease (PD) patients (six studies) and stroke patients (SPs) (two studies). (5) Conclusion: All reports suggest that the RAS technique has a significant effect on the improvement of gait parameters and the balance of PD patients and SPs, as well as the risk of falls in PD patients.
Trends in Hospital Admissions for Mental, Behavioural and Neurodevelopmental Disorders in England and Wales between 1999 and 2019: An Ecological Study
Authors: Naser Abdallah Y. , Dahmash Eman Zmaily , Alqahtani Jaber S. , Alsairafi Zahra K. , Alsaleh Fatemah M. , Alwafi Hassan
Published: November 2022

Objectives: To investigate the trends in hospital admissions for mental, behavioural and neurodevelopmental disorders (MBNDs) in England and Wales. Methods: This is an ecological study using the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Hospital admission data was collected for the period between April 1999 and March 2019. Results: The most common type of hospital admission was for mental and behavioural disorders due to psychoactive substance use, which accounted for 26.6%. The admission rate among males increased by 8.1% [from 479.59 (95% CI 476.90–482.27) in 1999 to 518.30 (95% CI 515.71–520.90) in 2019 per 1000 persons; p < 0.001]. The admission rate among females increased by 0.3% [from 451.45 (95% CI 448.91–453.99) in 1999 to 452.77 (95% CI 450.37–455.17) in 2019 per 1000 persons; p = 0.547]. The 15–59 years’ age group accounted for 65.1% of the entire number of such hospital admissions, followed by the 75 years and above age group, with 19.0%. Conclusion: We observed an obvious variation in MBNDs influenced by age and gender. Observational studies are needed to identify other factors associated with increased hospital admission rates related to MBNDs, specifically among the young population (aged 15–59 years) and males.
Collaborating with the Community: Applying Non-Invasive Archaeological Methods in the Crypt and Churchyard of St Patrick’s Roman Catholic Church, Toxteth, Liverpool
Authors: Mytum Harold , Philpott Robert , Fairley Nielsson Anna , Burwood Eloise , Dark Naomi
Published: November 2022

St. Patrick’s Roman Catholic Church and churchyard, Toxteth, Liverpool, UK, is the focus of community efforts to research and conserve the heritage asset, and archaeologists at the University of Liverpool were invited to contribute their expertise to co-produce new understandings of this locally significant place. Roman Catholic vault burial in Britain has not previously been archaeologically investigated, and the use of rock-cut burial pits, visible in the churchyard, appeared to be a response to the massive demand for urban burial during the nineteenth century. The project has combined local knowledge with surface survey and recording memorials in the churchyard, mapping the crypt and recording the interior of the four vaults at the western end of the crypt after they had been temporarily opened by the community volunteers. This enabled standard and photogrammetric recording, and PXRF analysis of the in-situ coffin fittings. No human remains were revealed. Interviews with volunteers and key stakeholders at the church provided the community’s voice, presented here. This project demonstrates how collaboration enables the skills and abilities of specialists, students and the local community to combine to create new knowledge and enhance public understanding of local heritage, with academically important and locally empowering results.
Rapid Detection of Moisture Content in the Processing of Longjing Tea by Micro-Near-Infrared Spectroscopy and a Portable Colorimeter Based on a Data Fusion Strategy
Authors: Zong Xuyan , Sheng Xufeng , Li Li , Zan Jiezhong , Jiang Yongwen , Zou Hanting , Shen Shuai , Yuan Haibo
Published: November 2022

Moisture content (MC) is an important indicator to monitor the quality of Longjing tea during processing; therefore, it becomes more critical to develop digital moisture content detection methods for processing. In this study, based on a micro-near infrared (NIR) spectrometer and portable colorimeter, we used Longjing tea under the full processing process as the research object, and used competitive adaptive reweighted sampling (CARS) and a principal component analysis (PCA) to extract characteristic bands of spectral data as well as the principal component reduction processing of the color difference and glossiness data, respectively, combined with sensor data fusion technology to establish a quantitative prediction model of the partial least squares (PLS) for the moisture content of Longjing tea. The PLS quantitative moisture content prediction model, based on middle-level data fusion, obtained the best prediction accuracy and model robustness, with the correlation coefficient of the prediction set (Rp) and the root mean square error of prediction (RMSEP) being 0.9823 and 0.0333, respectively, with a residual predictive deviation (RPD) of 6.5287. The results indicate that a data fusion of a micro NIR spectrometer and portable Colorimeter is feasible to establish a quantitative prediction model of the moisture content in Longjing tea processing, while multi-sensor data fusion can overcome the problem of a low prediction accuracy for the model established by single sensor data. More importantly, data fusion based on low-cost, fast, and portable detection sensors can provide new ideas and methods for real-time online detection in Longjing tea in actual production.
The Novelty Appraisal of the Feeling of Risk in Vehicles
Authors: Zhang Meng , Jipp Meike , Ihme Klas
Published: November 2022

Nowadays, vehicle assistance systems may assess the risks of the traffic situation with the help of advanced sensor technology and optimized algorithms. However, the passengers’ feelings of risk in the vehicle have been mostly neglected. According to the Component Process Model of emotions, during the feeling of risk, novelty is one of the relevant event appraisals leading to particular physiological and facial responses. In order to identify whether or not indicators for novelty appraisal may be used for detecting the feeling of risk of vehicle occupants, we investigated physiological responses and facial expressions of individuals experiencing the feeling of risk with different levels of novelty. This secondary analysis of an earlier simulator study revealed that pupil diameter amplitude, skin conductance level changes, and changes in and amplitude of activity in facial expressions (the inner and outer brow raiser, brow lowerer, upper lid raiser and lid tightener) were correlated with the reduction in the novelty, suggesting that they could indicate the novelty of the feeling of risk of vehicle occupants. Hence, this research provides evidence for the novelty appraisal of the feeling of risk. Furthermore, it informs research on affect-aware systems to identify and reduce the feeling of risk of vehicle occupants in order to help to keep trust in automated vehicles high.
Demands on Health Information and Clinical Practice Guidelines for Patients from the Perspective of Adults with Mental Illness and Family Members: A Qualitative Study with In-Depth Interviews
Authors: Schladitz Katja , Weitzel Elena C. , Löbner Margrit , Soltmann Bettina , Jessen Frank , Schmitt Jochen , Pfennig Andrea , Riedel-Heller Steffi G. , Gühne Uta
Published: November 2022

(1) Background: “Patient health information” promote health literacy. “Patient guidelines” as a sub group reflect the current evidence about illnesses and treatment options adapted to the needs of laypersons. Little is known about factors promoting and hindering their use by people affected by mental illness and their relatives. (2) Methods: Telephone interviews (N = 15; n = 4 adults affected by mental illness, n = 5 relatives, n = 6 both applicable) were conducted according to the Sørensen model of health literacy. Data were recorded, transcribed and content-analyzed following Mayring. (3) Results: Health information is used regularly by individuals affected by mental illness and their relatives, but “patient guidelines” are largely unknown. Yet, there is a great willingness to use them. Main barriers are a lack of statistical knowledge, the complexity of health-related topics and cognitive impairment sometimes accompanying mental illnesses. Target group-oriented adaptation as well as transparent and even-handed presentation of (dis-)advantages of treatment options can increase trust. (4) Conclusions: Health information and guidelines can help affected persons and relatives to make treatment decisions by conveying unbiased, up-to-date knowledge. Target group-specific adaptations should be made for psychiatric illnesses and features specific to mental illnesses compared to physical illnesses should be included. Clinical practice guidelines must be distributed more widely to increase their impact.
Spatiotemporal Evolution and Influential Factors of Rural Poverty in Poverty-Stricken Areas of Guizhou Province: Implications for Consolidating the Achievements of Poverty Alleviation
Authors: Li Guie , Jiao Yangyang , Li Jie , Yan Qingwu
Published: November 2022

China has made remarkable reductions in absolute poverty. However, pressing questions remain of how to consolidate the existing achievements of poverty alleviation and prevent rural households from regressing back into poverty, especially in continuously poverty-stricken areas. This paper explores the spatiotemporal evolution of rural poverty and its influential factors under different poverty standards in three continuously poverty-stricken areas in Guizhou Province using 2003–2017 panel data and the spatiotemporal analysis method. The results show that decreasing poverty is an apparent spatial heterogeneity and there are area differences in the different research periods. The degrees of the average annual poverty reductions of all research counties were between 2.98–10.09%, 10.60–26.96%, and 11.46–43.19% in 2003–2007, 2008–2010, and 2011–2017, respectively; the poverty-stricken counties with high rates of poverty reduction are often adjacent to the nonpoverty-stricken counties. Influential factors vary in different areas over time, which is the result of the combination of leading influential factors (economy) and various influencing factors (natural location, social development, and education/labor) with regional characteristics. Although the effect of natural location on rural poverty in the research area is decreasing, its impact should not be ignored. Considering the complexity of poverty’s influential factors and the dependence on poverty alleviation policies, it’s essential for China to continue to strengthen its targeting of poverty in the continuously poverty-stricken areas, especially the counties in the inner areas. Devoting to building the coordination of regional development and ecological environment protection is an important way to achieve sustainable development goals with higher quality in the continuously poverty-stricken areas.
Immunosenescence in Aging-Related Vascular Dysfunction
Authors: Tylutka Anna , Morawin Barbara , Wawrzyniak-Gramacka Edyta , Wacka Eryk , Nowicka Wiktoria , Hiczkiewicz Jaroslaw , Zembron-Lacny Agnieszka
Published: November 2022

The immunosenescence-related disproportion in T lymphocytes may have important consequences for endothelial dysfunction, which is a key event in vascular aging. The study was designed to assess the prognostic values of the inflammatory-immune profile to better predict and prevent vascular diseases associated with old age. Eighty individuals aged 70.9 ± 5.3 years were allocated to a low- (LGI) or high-grade inflammation (HGI) group based on CRP (<3 or ≥3 mg/L) as a conventional risk marker of cardiovascular diseases. Significant changes in inflammatory and endothelium-specific variables IL-1β, IL-6, TNFα, oxLDL, H2O2, NO, 3-nitrotyrosine, and endothelial progenitor cells (OR 7.61, 95% CI 2.56–29.05, p < 0.0001), confirmed their interplay in vascular inflammation. The flow-cytometry analysis demonstrated a high disproportion in T lymphocytes CD4+ and CD8+ between LGI and HGI groups. CRP was <3 mg/mL for the CD4/CD8 ratio within the reference values ≥ 1 or ≤2.5, unlike for the CD4/CD8 ratio < 1 and >2.5. The odds ratios for the distribution of CD4+ (OR 5.98, 95% CI 0.001–0.008, p < 0.001), CD8+ (OR 0.23, 95% CI 0.08–0.59, p < 0.01), and CD8CD45RO+ T naïve cells (OR 0.27, 95% CI 0.097–0.695, p < 0.01) and CD4/CD8 (OR 5.69, 95% CI 2.07–17.32, p < 0.001) indicated a potential diagnostic value of T lymphocytes for clinical prognosis in aging-related vascular dysfunction.
Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential
Authors: Stradiotto Elisa , Allegrini Davide , Fossati Giovanni , Raimondi Raffaele , Sorrentino Tania , Tripepi Domenico , Barone Gianmaria , Inforzato Antonio , Romano Mario R.
Published: November 2022

Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF.
Fighting Non-Small Lung Cancer Cells Using Optimal Functionalization of Targeted Carbon Quantum Dots Derived from Natural Sources Might Provide Potential Therapeutic and Cancer Bio Image Strategies
Authors: El-brolsy Hanaa Mohammed Elsayed Mohammed , Hanafy Nemany A. N. , El-Kemary Maged A.
Published: November 2022

Non-small cell lung cancer (NSCLC) is an important sub-type of lung cancer associated with poor diagnosis and therapy. Innovative multi-functional systems are urgently needed to overcome the invasiveness of NSCLC. Carbon quantum dots (CQDs) derived from natural sources have received interest for their potential in medical bio-imaging due to their unique properties, which are characterized by their water solubility, biocompatibility, simple synthesis, and low cytotoxicity. In the current study, ethylene-diamine doped CQDs enhanced their cytotoxicity (98 ± 0.4%, 97 ± 0.38%, 95.8 ± 0.15%, 86 ± 0.15%, 12.5 ± 0.14%) compared to CQDs alone (99 ± 0.2%, 98 ± 1.7%, 96 ± 0.8%, 93 ± 0.38%, 91 ± 1.3%) at serial concentrations (0.1, 1, 10, 100, 1000 μg/mL). In order to increase their location in a specific tumor site, folic acid was used to raise their functional folate recognition. The apoptotic feature of A549 lung cells exposed to N-CQDs and FA-NCQDs was characterized by a light orange-red color under fluorescence microscopy. Additionally, much nuclear fragmentation and condensation were seen. Flow cytometry results showed that the percentage of cells in late apoptosis and necrosis increased significantly in treated cells to (19.7 ± 0.03%), (27.6 ± 0.06%) compared to untreated cells (4.6 ± 0.02%), (3.5 ± 0.02%), respectively. Additionally, cell cycle arrest showed a strong reduction in cell numbers in the S phase (14 ± 0.9%) compared to untreated cells (29 ± 0.5%). Caspase-3 levels were increased significantly in A549 exposed to N-CQDs (2.67 ± 0.2 ng/mL) and FA-NCQDs (3.43 ± 0.05 ng/mL) compared to untreated cells (0.34 ± 0.04 ng/mL). The functionalization of CQDs derived from natural sources has proven their potential application to fight off non-small lung cancer.
Gain of Function (GOF) Mutant p53 in Cancer—Current Therapeutic Approaches
Authors: Roszkowska Katarzyna A. , Piecuch Aleksandra , Sady Maria , Gajewski Zdzisław , Flis Sylwia
Published: November 2022

Continuous development of personalized treatments is undoubtedly beneficial for oncogenic patients’ comfort and survival rate. Mutant TP53 is associated with a worse prognosis due to the occurrence of metastases, increased chemoresistance, and tumor growth. Currently, numerous compounds capable of p53 reactivation or the destabilization of mutant p53 are being investigated. Several of them, APR-246, COTI-2, SAHA, and PEITC, were approved for clinical trials. This review focuses on these novel therapeutic opportunities, their mechanisms of action, and their significance for potential medical application.
Role of SALL4 in HER2+ Breast Cancer Progression: Regulating PI3K/AKT Pathway
Authors: Pattanayak Birlipta , Lameirinhas Ana , Torres-Ruiz Sandra , Burgués Octavio , Rovira Ana , Martínez María Teresa , Tapia Marta , Zazo Sandra , Albanell Joan , Rojo Federico , Bermejo Begoña , Eroles Pilar
Published: November 2022

Treatment for the HER2+ breast cancer subtype is still unsatisfactory, despite breakthroughs in research. The discovery of various new molecular mechanisms of transcription factors may help to make treatment regimens more effective. The transcription factor SALL4 has been related to aggressiveness and resistance therapy in cancer. Its molecular mechanisms and involvement in various signaling pathways are unknown in the HER2+ breast cancer subtype. In this study, we have evaluated the implication of SALL4 in the HER2+ subtype through its expression in patients’ samples and gain and loss of function in HER2+ cell lines. We found higher SALL4 expression in breast cancer tissues compared to healthy tissue. Interestingly, high SALL4 expression was associated with disease relapse and poor patient survival. In HER2+ cell lines, transient overexpression of SALL4 modulates PI3K/AKT signaling through regulating PTEN expression and BCL2, which increases cell survival and proliferation while reducing the efficacy of trastuzumab. SALL4 has also been observed to regulate the epithelial–mesenchymal transition and stemness features. SALL4 overexpression significantly reduced the epithelial markers E-cadherin, while it increased the mesenchymal markers β-catenin, vimentin and fibronectin. Furthermore, it has been also observed an increased expression of MYC, an essential transcription factor for regulating epithelial-mesenchymal transition and/or cancer stem cells. Our study demonstrates, for the first time, the importance of SALL4 in the HER2+ subtype and partial regulation of trastuzumab sensitivity. It provides a viable molecular mechanism-driven therapeutic strategy for an important subset of HER2-overexpressing patients whose malignancies are mediated by SALL4 expression.
Soemmerring’s Rings Developed around IOLs, in Human Donor Eyes, Can Present Internal Transparent Areas
Authors: D’Antin Justin Christopher , Tresserra Francesc , Barraquer Rafael I. , Michael Ralph
Published: November 2022

Soemmerring’s rings consist of a ring of lens epithelial derived cells that grow along the periphery of an aphakic lens capsule, or around an intraocular lens. These rings when visualized frontally, appear opaque, however, in some cases the cells that compose these rings are organized in the same fashion as those in normal transparent adult lenses. Thus, our purpose was to test whether any part of the adult Soemmerring’s ring could be transparent and how this related to morphological factors. To study this, 16 Soemmerring’s rings were extracted from donor eye globes. After imaging, they were thickly sectioned sagittally in order to analyze the degrees of transparency of different areas. All samples were also histologically analyzed using alpha smooth muscle actin, Vimentin, wheat germ agglutinin and DAPI. Our results showed that many samples had some transparent areas, mostly towards the center of their cross-section. Of the factors that we analyzed, only lens fiber organization at the bow region and an increased area of mature lens fiber cells had a significant relation to the degree of transparency at the center. Thus, we can conclude that as Soemmerring’s rings mature, they can develop organized and transparent areas of lens cells.
Therapeutic Potential of Targeting the Oxytocinergic System
Authors: Romano Adele , Provensi Gustavo
Published: November 2022

The nine amino acid neuropeptide oxytocin (OXT, Cys–Tyr–Ile–Gln–Asn–Cys–Pro–Leu–Gly–NH2) is one of the most studied hormones of the body [...]
Proteomic Analysis Revealed Different Molecular Mechanisms of Response to PEG Stress in Drought-Sensitive and Drought-Resistant Sorghums
Authors: Li Yanni , Tan Binglan , Wang Daoping , Mu Yongying , Li Guiying , Zhang Zhiguo , Pan Yinghong , Zhu Li
Published: November 2022

Drought is the major limiting factor that directly or indirectly inhibits the growth and reduces the productivity of sorghum (Sorghum bicolor (L.) Moench). As the main vegetative organ of sorghum, the response mechanism of the leaf to drought stress at the proteomic level has not been clarified. In the present study, nano-scale liquid chromatography mass spectrometry (nano-LC-MS/MS) technology was used to compare the changes in the protein expression profile of the leaves of drought-sensitive (S4 and S4-1) and drought-resistant (T33 and T14) sorghum varieties at the seedling stage under 25% PEG-6000 treatment for 24 h. A total of 3927 proteins were accurately quantitated and 46, 36, 35, and 102 differentially abundant proteins (DAPs) were obtained in the S4, S4-1, T14, and T33 varieties, respectively. Four proteins were randomly selected for parallel reaction monitoring (PRM) assays, and the results verified the reliability of the mass spectrometry (MS) results. The response mechanism of the drought-sensitive sorghum leaves to drought was attributed to the upregulation of proteins involved in the tyrosine metabolism pathway with defense functions. Drought-resistant sorghum leaves respond to drought by promoting the TCA cycle, enhancing sphingolipid biosynthesis, interfering with triterpenoid metabolite synthesis, and influencing aminoacyl-tRNA biosynthesis. The 17 screened important candidate proteins related to drought stress were verified by quantitative real-time PCR (qRT-PCR), the results of which were consistent with the results of the proteomic analysis. This study lays the foundation for revealing the drought-resistance mechanism of sorghum at the protein level. These findings will help us cultivate and improve new drought-resistant sorghum varieties.
Different Requirements of CBFB and RUNX2 in Skeletal Development among Calvaria, Limbs, Vertebrae and Ribs
Authors: Jiang Qing , Qin Xin , Nagano Kenichi , Komori Hisato , Matsuo Yuki , Taniuchi Ichiro , Ito Kosei , Komori Toshihisa
Published: November 2022

RUNX proteins, such as RUNX2, regulate the proliferation and differentiation of chondrocytes and osteoblasts. Haploinsufficiency of RUNX2 causes cleidocranial dysplasia, but a detailed analysis of Runx2+/− mice has not been reported. Furthermore, CBFB is required for the stability and DNA binding of RUNX family proteins. CBFB has two isoforms, and CBFB2 plays a major role in skeletal development. The calvaria, femurs, vertebrae and ribs in Cbfb2−/− mice were analyzed after birth, and compared with those in Runx2+/− mice. Calvarial development was impaired in Runx2+/− mice but mildly delayed in Cbfb2−/− mice. In femurs, the cortical bone but not trabecular bone was reduced in Cbfb2−/− mice, whereas both the trabecular and cortical bone were reduced in Runx2+/− mice. The trabecular bone in vertebrae increased in Cbfb2−/− mice but not in Runx2+/− mice. Rib development was impaired in Cbfb2−/− mice but not in Runx2+/− mice. These differences were likely caused by differences in the indispensability of CBFB and RUNX2, the balance of bone formation and resorption, or the number and maturation stage of osteoblasts. Thus, different amounts of CBFB and RUNX2 were required among the bone tissues for proper bone development and maintenance.
Comparison of EMT-Related and Multi-Drug Resistant Gene Expression, Extracellular Matrix Production, and Drug Sensitivity in NSCLC Spheroids Generated by Scaffold-Free and Scaffold-Based Methods
Authors: Qi Xiaoli , Prokhorova Alexandra V. , Mezentsev Alexander V. , Shen Ningfei , Trofimenko Alexander V. , Filkov Gleb I. , Sulimanov Rushan A. , Makarov Vladimir A. , Durymanov Mikhail O.
Published: November 2022

Multicellular 3D tumor models are becoming a powerful tool for testing of novel drug products and personalized anticancer therapy. Tumor spheroids, a commonly used 3D multicellular tumor model, more closely reproduce the tumor microenvironment than conventional 2D cell cultures. It should be noted that spheroids can be produced using different techniques, which can be subdivided into scaffold-free (SF) and scaffold-based (SB) methods. However, it remains unclear, to what extent spheroid properties depend on the method of their generation. In this study, we aimed to carry out a head-to-head comparison of drug sensitivity and molecular expression profile in SF and SB spheroids along with a monolayer (2D) cell culture. Here, we produced non-small cell lung cancer (NSCLC) spheroids based on human lung adenocarcinoma cell line A549. Drug sensitivity analysis of the tested cell cultures to five different chemotherapeutics resulted in IC50 (A549-SB) > IC50 (A549-SF) > IC50 (A549-2D) trend. It was found that SF and SB A549 spheroids displayed elevated expression levels of epithelial-to-mesenchymal transition (EMT) markers and proteins associated with drug resistance compared with the monolayer A549 cell culture. Enhanced drug resistance of A549-SB spheroids can be a result of larger diameters and elevated deposition of extracellular matrix (ECM) that impairs drug penetration into spheroids. Thus, the choice of the spheroid production method can influence the properties of the generated 3D cell culture and their drug resistance. This fact should be considered for correct interpretation of drug testing results.
Dietary-Fibre-Rich Fractions Isolated from Broccoli Stalks as a Potential Functional Ingredient with Phenolic Compounds and Glucosinolates
Authors: Núñez-Gómez Vanesa , González-Barrio Rocío , Baenas Nieves , Moreno Diego A. , Periago Mª Jesús
Published: November 2022

The Brassica oleracea industry generates large amounts of by-products to which value could be added because of the characteristics of their composition. The aim was to extract different fibre fractions from broccoli stalks to obtain potential new added-value ingredients. Using an ethanol and water extraction procedure, two fibre-rich fractions (total fibre fraction, TFB, and insoluble fibre fraction, IFB) were obtained. These fractions were analysed to determine the nutritional, (poly)phenols and glucosinolates composition and physicochemical properties, comparing the results with those of freeze-dried broccoli stalks (DBS). Although TFB showed a higher content of total dietary fibre, IFB had the same content of insoluble dietary fibre as TFB (54%), better hydration properties, higher content of glucosinolates (100 mg/100 g d.w.) and (poly)phenols (74.7 mg/100 g d.w.). The prebiotic effect was evaluated in IFB and compared with DBS by in vitro fermentation with human faecal slurries. After 48 h, the short-chain fatty acid (SCFA) production was higher with IFB than with DBS because of the greater presence of both uronic acids, the main component of pectin, and (poly)phenols. These results reveal that novel fibre-rich ingredients—with antioxidant, technological and physiological effects—could be obtained from broccoli stalks by using green extraction methods.
NH3 Sensor Based on ZIF-8/CNT Operating at Room Temperature with Immunity to Humidity
Authors: Yan Wenjun , Zhou Shiyu , Ling Min , Peng XinSheng , Zhou Houpan
Published: November 2022

Humidity effects on resistive gas sensors operating at room temperature remain a serious bottleneck. In this work, we introduce a resistive gas sensor based on a zeolitic imidazolate framework-8/carbon nanotube (ZIF-8/CNT) composite for the detection of ammonia gas at room temperature. The composite was prepared using a facile solution method. In this sensor, the basic mechanism was the charge transfer between ammonia molecules and CNTs; meanwhile, the ZIF-8 facilitated the adsorption of ammonia molecules as a preconcentrator, and prevented the adsorption of H2O molecules due to its hydrophobicity; CNTs were threaded through the ZIF-8 to form a great conductive network for charge transfer. The obtained sensor showed good ammonia sensing, especially at room temperature, with great selectivity and immunity to humidity under moderately humid conditions (45–70 % RH). However, the ammonia response was reduced at very high humidity (90% RH) due to the competitive adsorption of H2O molecules. This proved that the NH3 sensor based on ZIF-8/CNT could be suitable for practical applications under moderately humid conditions.
Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens
Authors: Mylonas Konstantinos S. , Sarantis Panagiotis , Kapelouzou Alkistis , Karamouzis Michalis V. , Kapetanakis Emmanouil I. , Kontzoglou Konstantinos , Iliopoulos Dimitrios C. , Nikiteas Nikolaos , Schizas Dimitrios
Published: November 2022

Aims: Inflammatory dysregulation of mechanosensitive developmental genes may be central to atherogenesis. In the present seven-week model, we utilized colchicine regimens to curtail aortic atherogenesis in New Zealand White rabbits. We also explored the effect of colchicine regimens on atheroprotective (Klotho, HOXA5, NOTCH1, and OCT4) and proatherogenic (HIF1a, SOX2, BMP4, and NANOG) genes. Methods: The control (n = 6) and group A (n = 6) received standard and cholesterol-enriched chow, respectively. Groups B (n = 8) and C (n = 8) were fed hypercholesterolemic diet and were treated with colchicine plus fenofibrate or N-acetylcysteine (NAC), respectively. Results: Group A developed significantly greater thoracic and abdominal aortic atherosclerosis compared to groups B (p < 0.001) and C (p < 0.001). Combining colchicine with NAC resulted in stronger atheroprotection both in the thoracic and the abdominal aorta. In group A thoracic aortas, Klotho was downregulated compared to controls (95% CI: 1.82–15.76). Both colchicine regimens upregulated Klotho back to baseline levels (p < 0.001). Colchicine/fenofibrate also significantly upregulated thoracic NOTCH1 compared to controls (95% CI: −8.09 to −0.48). Colchicine/NAC significantly reduced thoracic NANOG expression compared to hyperlipidemic diet alone (95% CI: 0.37–8.29). In the abdominal aorta, hypercholesterolemic diet resulted in significant downregulation of HOXA5 (95% CI: 0.03–2.74) which was reversed with colchicine/NAC back to baseline (95% CI: −1.19 to 1.51). Colchicine/fenofibrate downregulated HIF1a compared to baseline (95% CI: 0.83–6.44). No significant differences were noted in terms of BMP4, SOX2, and OCT4. Conclusions: Overall, the aortic expression pattern of mechanosensitive genes seems to be spatially influenced by a hyperlipidemic diet and can be modified using colchicine-based therapy.
Long-Term Outcomes in Severe Traumatic Brain Injury and Associated Factors: A Prospective Cohort Study
Authors: de Oliveira Daniel Vieira , Vieira Rita de Cássia Almeida , Pipek Leonardo Zumerkorn , de Sousa Regina Marcia Cardoso , de Souza Camila Pedroso Estevam , Santana-Santos Eduesley , Paiva Wellingson Silva
Published: November 2022

Objective: The presence of focal lesion (FL) after a severe traumatic brain injury is an important factor in determining morbidity and mortality. Despite this relevance, few studies show the pattern of recovery of patients with severe traumatic brain injury (TBI) with FL within one year. The objective of this study was to identify the pattern of recovery, independence to perform activities of daily living (ADL), and factors associated with mortality and unfavorable outcome at six and twelve months after severe TBI with FL. Methodology: This is a prospective cohort, with data collected at admission, hospital discharge, three, six, and twelve months after TBI. RESULTS: The study included 131 adults with a mean age of 34.08 years. At twelve months, 39% of the participants died, 80% were functionally independent by the Glasgow Outcome Scale Extended, 79% by the Disability Rating Scale, 79% were independent for performing ADLs by the Katz Index, and 53.9% by the Lawton Scale. Report of alcohol intake, sedation time, length of stay in intensive care (ICU LOS), Glasgow Coma Scale, trauma severity indices, hyperglycemia, blood glucose, and infection were associated with death. At six and twelve months, tachypnea, age, ICU LOS, trauma severity indices, respiratory rate, multiple radiographic injuries, and cardiac rate were associated with dependence. Conclusions: Patients have satisfactory functional recovery up to twelve months after trauma, with an accentuated improvement in the first three months. Clinical and sociodemographic variables were associated with post-trauma outcomes. Almost all victims of severe TBI with focal lesions evolved to death or independence.
Proactive versus Rank-Down Topical Corticosteroid Therapy for Maintenance of Remission in Pediatric Atopic Dermatitis: A Randomized, Open-Label, Active-Controlled, Parallel-Group Study (Anticipate Study)
Authors: Kamiya Koji , Saeki Hidehisa , Tokura Yoshiki , Yoshihara Shigemi , Sugai Junichi , Ohtsuki Mamitaro
Published: November 2022

Topical corticosteroids are used as first-line treatment for atopic dermatitis (AD). Regarding the maintenance of remission achieved by topical corticosteroids, no previous studies have compared proactive therapy with rank-down therapy. We compared their efficacy and safety in Japanese children with moderate to severe AD. Patients who had achieved remission with a very strong topical corticosteroid were randomized to 4-week maintenance treatment with either intermittent use of the same drug (proactive therapy) or daily use of a strong topical corticosteroid for 1 week followed by daily use of a medium-potency topical corticosteroid for 3 weeks (rank-down therapy); 49 patients were randomized (proactive therapy, n = 24; rank-down therapy, n = 25). During maintenance treatment, the relapse rate was 8.33% in the proactive therapy group and 20.0% in the rank-down therapy group (p = 0.0859). The mean (±standard deviation) itching score on a numerical rating scale in the rank-down therapy group increased significantly from 2.5 ± 1.9 to 3.6 ± 2.6 (p = 0.0438). Adverse events occurred in 2 patients receiving proactive therapy and 3 patients receiving rank-down therapy. Proactive therapy appears to be as safe as rank-down therapy and may be more effective for itch in pediatric AD in remission.
On Cubic Spudcan Deep Penetration in Dense Sand Overlying Non-Uniform Clay
Authors: Zhao Jun , Zhang Yang , Liu Luyu
Published: November 2022

Installing spudcans for jack-up rigs in a layered seabed with an interbedded strong-over-soft layer is challenging in the offshore industry due to possible punch-through failure. The methods currently used to predict punch-through failure mainly focus on generic spudcans, usually ignoring the geometric features of the spudcan. The aim of this study is to determine whether the punch-through potential of a generic spudcan is applicable to a cubic spudcan of a BH12# jack-up rig installed in dense sand overlying non-uniform clay. We conducted a series of large deformation finite element (LDFE) analyses on dense sand overlying non-uniform clay using a generic spudcan and a cubic spudcan. The thickness of the sand layer was also varied to cover a range of practical interest. The special cubic spudcan was found to be less likely to induce punch-through failure on sand-over-clay sediments compared with the corresponding generic spudcan. Herein, we propose a method to predict the degree of post-peak bearing reduction, which is a key measure of the severity of punch-through failure.
Pulmonary Cryptococcosis
Authors: Howard-Jones Annaleise R. , Sparks Rebecca , Pham David , Halliday Catriona , Beardsley Justin , Chen Sharon C.-A.
Published: November 2022

Pulmonary cryptococcosis describes an invasive lung mycosis caused by Cryptococcus neoformans or Cryptococcus gattii complex. It is often a high-consequence disease in both immunocompromised and immunocompetent populations, and may be misdiagnosed as pulmonary malignancy, leading to a delay in therapy. Epidemiology follows that of cryptococcal meningoencephalitis, with C. gattii infection more common in certain geographic regions. Diagnostic tools include histopathology, microscopy and culture, and the detection of cryptococcal polysaccharide antigen or Cryptococcus-derived nucleic acids. All patients with lung cryptococcosis should have a lumbar puncture and cerebral imaging to exclude central nervous system disease. Radiology is key, both as an adjunct to laboratory testing and as the initial means of detection in asymptomatic patients or those with non-specific symptoms. Pulmonary cryptococcomas (single or multiple) may also be associated with disseminated disease and/or cryptococcal meningitis, requiring prolonged treatment regimens. Optimal management for severe disease requires extended induction (amphotericin B and flucytosine) and consolidation therapy (fluconazole) with close clinical monitoring. Susceptibility testing is of value for epidemiology and in regions where relatively high minimum inhibitory concentrations to azoles (particularly fluconazole) have been noted. Novel diagnostic tools and therapeutic agents promise to improve the detection and treatment of cryptococcosis, particularly in low-income settings where the disease burden is high.