bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic Transsphenoidal Surgery with a Layered Peel Strategy for Cushing’s Disease Treatment: A Case Series
Authors: Shao Chuan , Wang Junwei , Wang Pan , Wu Nan
Published: April 2023

Patients with Cushing’s disease (CD) who underwent endoscopic transsphenoidal surgery (ETS) with a layered peel strategy at our center were retrospectively analyzed. Records on patients’ basic characteristics, preoperative and early postoperative evaluations, perioperative complications, and follow-up were collected. A total of 12 unselected, consecutive patients with CD were identified. Ten of the twelve patients were female. All tumors were confirmed by magnetic resonance imaging, with a maximum tumor diameter ranging from 5 mm to 11 mm. A lower rate of surgical complications was identified postoperatively, with no cases of carotid artery injury, epistaxis, hematoma, visual disturbance, or intracranial infection, but with one case of cerebrospinal fluid rhinorrhea. Ten patients experienced immediate remission, and two had delayed remission. No recurrence events were observed during a median follow-up of 51 months. In conclusion, our preliminary experience indicated that ETS with a layered peel strategy provided a perfect remission rate, low complication rate, and no recurrence in a case series of CD patients. Given the limited number of cases, future studies are warranted to confirm its effectiveness and safety.
Urban Microclimate, Outdoor Thermal Comfort, and Socio-Economic Mapping: A Case Study of Philadelphia, PA
Authors: Hashemi Farzad , Poerschke Ute , Iulo Lisa D. , Chi Guangqing
Published: April 2023

Urban areas are often warmer than rural areas due to the phenomenon known as the “urban heat island” (UHI) effect, which can cause discomfort for those engaging in outdoor activities and can have a disproportionate impact on low-income communities, people of color, and the elderly. The intensity of the UHI effect is influenced by a variety of factors, including urban morphology, which can vary from one area to another. To investigate the relationship between outdoor thermal comfort and urban morphology in different urban blocks with varying social vulnerability status, this study developed a geographic information system (GIS)-based workflow that combined the “local climate zone” (LCZ) classification system and an urban microclimate assessment tool called ENVI-met. To demonstrate the effectiveness of this methodology, the study selected two different urban blocks in Philadelphia, Pennsylvania–with high and low social vulnerability indices (SVI)–to compare their microclimate conditions in association with urban morphological characteristics such as green coverage area, sky view factor (SVF), albedo, and street height to width (H/W) ratio. The results of the study showed that there was a strong correlation between tree and grass coverage and outdoor air and mean radiant temperature during hot seasons and extremely hot days, which in turn affected simulated predicted mean vote (PMV). The effects of greenery were more significant in the block associated with a low SVI, where nearly 50% of the site was covered by trees and grass, compared to only 0.02% of the other block associated with a high SVI. Furthermore, the investigation discovered that reduced SVF, along with increased albedo and H/W ratio, had a beneficial impact on the microclimate at the pedestrian level within the two studied urban blocks. This study provided an effective and easy-to-implement method for tackling the inequity issue of outdoor thermal comfort and urban morphology at fine geographic scales.
A Review of Conceptual Design and Self Health Monitoring Program in a Vertical City: A Case of Burj Khalifa, U.A.E.
Authors: Yusuf Danjuma Abdu , Ahmed Abubakar , Sagir Abdullahi , Yusuf Abdulfatah Abdu , Yakubu Adamu , Zakari Abdullahi T. , Usman Abdullahi M. , Nashe Abdullahi S. , Hamma Abdulmalik Sule
Published: April 2023

Burj Khalifa, a notable landmark in a growing landscape of skyscrapers, along with other tall structures, has dramatically transformed the morphology of Dubai and elevated it to global prominence. This masterpiece was designed to attract international interest, as it diversifies the economy from an oil-based one towards one that is tourist-and servicebased. However, the foremost design input and major challenges of the super-tall building are associated with the increase in height, which put them at risk of wind- and earthquake-induced lateral loads and user satisfaction. Consequently, it was essential to study both the design and construction phases of the tallest towers in the context of the wind and earthquake impact. This study aims to revalidate the three structural design phases; conceptual, schematic, and detailed design of this vertical city to confirm that the requirements are achieved. The methodology is a theoretical and analytical elaboration of the case study that obtains and confirms the basic requirements through a review of the existing survey, drawings, literature, and archived documents. Finally, the study validates the presumed structural behaviour and the insitu determined response, which are outstanding. The study further unveils the development of the structural health monitoring programme that gives an instant and direct response to the real structural performance of the building from the commencement of the construction and throughout its lifespan.
Clinical Outcome of Low-Grade Myofibroblastic Sarcoma in Japan: A Multicenter Study from the Japanese Musculoskeletal Oncology Group
Authors: Kito Munehisa , Ae Keisuke , Okamoto Masanori , Endo Makoto , Ikuta Kunihiro , Takeuchi Akihiko , Yasuda Naohiro , Yasuda Taketoshi , Imura Yoshinori , Morii Takeshi , Kikuta Kazutaka , Kawamoto Teruya , Nezu Yutaka , Baba Ichiro , Ohshika Shusa , Uehara Takeshi , Ueda Takafumi , Takahashi Jun , Kawano Hirotaka
Published: April 2023

This retrospective multicenter study aimed to analyze the clinical features and prognosis of 24 patients diagnosed with LGMS between 2002 and 2019 in the Japanese sarcoma network. Twenty-two cases were surgically treated and two cases were treated with radical radiotherapy (RT). The pathological margin was R0 in 14 cases, R1 in 7 cases, and R2 in 1 case. The best overall response in the two patients who underwent radical RT was one complete response and one partial response. Local relapse occurred in 20.8% of patients. Local relapse-free survival (LRFS) was 91.3% at 2 years and 75.4% at 5 years. In univariate analysis, tumors of 5 cm or more were significantly more likely to cause local relapse (p < 0.01). In terms of the treatment of relapsed tumors, surgery was performed in two cases and radical RT was performed in three cases. None of the patients experienced a second local relapse. Disease-specific survival was 100% at 5 years. A wide excision aimed at the microscopically R0 margin is considered the standard treatment for LGMS. However, RT may be a viable option in unresectable cases or in cases where surgery is expected to cause significant functional impairment.
Review of Cardiovascular Risk of Androgen Deprivation Therapy and the Influence of Race in Men with Prostate Cancer
Authors: Fradin James , Kim Felix J. , Lu-Yao Grace L. , Storozynsky Eugene , Kelly William K.
Published: April 2023

Androgen deprivation therapy is the cornerstone of prostate cancer therapy. Recent studies have revealed an association between androgen deprivation therapy and cardiovascular adverse effects such as myocardial infarction and stroke. This review summarizes the available research on the cardiovascular risk of men using androgen deprivation therapy. We also discuss racial disparities surrounding both prostate cancer and cardiovascular disease, emphasizing the importance of biological/molecular and socioeconomic factors in assessing baseline risk in patients beginning androgen ablation. Based on the literature, we provide recommendations for monitoring patients who are at high risk for a cardiovascular adverse event while being treated on androgen deprivation therapy. This review aims to present the current research on androgen deprivation therapy and cardiovascular toxicity with an emphasis on racial disparities and provides a framework for clinicians to decrease the cardiovascular morbidity in men that are being treated with hormone therapy.
Myo-Inositol Reverses TGF-β1-Induced EMT in MCF-10A Non-Tumorigenic Breast Cells
Authors: Monti Noemi , Dinicola Simona , Querqui Alessandro , Fabrizi Gianmarco , Fedeli Valeria , Gesualdi Luisa , Catizone Angela , Unfer Vittorio , Bizzarri Mariano
Published: April 2023

Epithelial-Mesenchymal Transition (EMT), triggered by external and internal cues in several physiological and pathological conditions, elicits the transformation of epithelial cells into a mesenchymal-like phenotype. During EMT, epithelial cells lose cell-to-cell contact and acquire unusual motility/invasive capabilities. The associated architectural and functional changes destabilize the epithelial layer consistency, allowing cells to migrate and invade the surrounding tissues. EMT is a critical step in the progression of inflammation and cancer, often sustained by a main driving factor as the transforming growth factor-β1 (TGF-β1). Antagonizing EMT has recently gained momentum as an attractive issue in cancer treatment and metastasis prevention. Herein, we demonstrate the capability of myo-inositol (myo-Ins) to revert the EMT process induced by TGF-β1 on MCF-10A breast cells. Upon TGF-β1 addition, cells underwent a dramatic phenotypic transformation, as witnessed by structural (disappearance of the E-cadherin–β-catenin complexes and the emergence of a mesenchymal shape) and molecular modifications (increase in N-cadherin, Snai1, and vimentin), including the release of increased collagen and fibronectin. However, following myo-Ins, those changes were almost completely reverted. Inositol promotes the reconstitution of E-cadherin–β-catenin complexes, decreasing the expression of genes involved in EMT, while promoting the re-expression of epithelial genes (keratin-18 and E-cadherin). Noticeably, myo-Ins efficiently inhibits the invasiveness and migrating capability of TGF-β1 treated cells, also reducing the release of metalloproteinase (MMP-9) altogether with collagen synthesis, allowing for the re-establishment of appropriate cell-to-cell junctions, ultimately leading the cell layer back towards a more compact state. Inositol effects were nullified by previous treatment with an siRNA construct to inhibit CDH1 transcripts and, hence, E-cadherin synthesis. This finding suggests that the reconstitution of E-cadherin complexes is an irreplaceable step in the inositol-induced reversion of EMT. Overall, such a result advocates for the useful role of myo-Ins in cancer treatment.
P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer
Authors: Ledderose Stephan , Rodler Severin , Eismann Lennert , Ledderose Georg , Rudelius Martina , Junger Wolfgang G. , Ledderose Carola
Published: April 2023

Bladder cancer is amongst the most common causes of cancer death worldwide. Muscle-invasive bladder cancer (MIBC) bears a particularly poor prognosis. Overexpression of purinergic P2X receptors (P2XRs) has been associated with worse outcome in several malignant tumors. Here, we investigated the role of P2XRs in bladder cancer cell proliferation in vitro and the prognostic value of P2XR expression in MIBC patients. Cell culture experiments with T24, RT4, and non-transformed TRT-HU-1 cells revealed a link between high ATP concentrations in the cell culture supernatants of bladder cell lines and a higher grade of malignancy. Furthermore, proliferation of highly malignant T24 bladder cancer cells depended on autocrine signaling through P2X receptors. P2X1R, P2X4R, and P2X7R expression was immunohistochemically analyzed in tumor specimens from 173 patients with MIBC. High P2X1R expression was associated with pathological parameters of disease progression and reduced survival time. High combined expression of P2X1R and P2X7R increased the risk of distant metastasis and was an independent negative predictor of overall and tumor-specific survival in multivariate analyses. Our results suggest that P2X1R/P2X7R expression scores are powerful negative prognostic markers in MIBC patients and that P2XR-mediated pathways are potential targets for novel therapeutic strategies in bladder cancer.
The Role of Non-Peripancreatic Lymph Nodes in the Survival of Patients Suffering from Pancreatic Cancer of the Body and Tail: A Systematic Review and Meta-Analysis of High-Quality Studies
Authors: Granieri Stefano , Kersik Alessia , Bonomi Alessandro , Frassini Simone , Bernasconi Davide , Paleino Sissi , Germini Alessandro , Gjoni Elson , Cotsoglou Christian
Published: April 2023

Lymph nodes (LNs)’ metastases have a well-known detrimental impact on the survival outcomes of patients suffering from pancreatic cancer of the body and tail. However, the extent of the lymphadenectomy for this tumor location is still debated. The aim of this study was to systematically review the current literature to explore the incidence and the prognostic impact of non-peripancreatic lymph nodes (PLNs) in patients suffering from pancreatic cancer of the body and tail. A systematic review was conducted according to PRISMA and MOOSE guidelines. The primary endpoint was to assess the impact of non-PLNs on overall survival (OS). As a secondary endpoint, the pooled frequencies of different non-PLN stations’ metastatic patterns according to tumor location were explored. Eight studies were included in data synthesis. An increased risk of death for patients with positive non-PLNs was detected (HR: 2.97; 95% CI: 1.81–4.91; p < 0.0001). Meta-analysis of proportions pointed out a 7.1% pooled proportion of nodal infiltration in stations 8–9. The pooled frequency for station 12 metastasis was 4.8%. LN stations 14–15 were involved in 11.4% of cases, whereas station 16 represented a site of metastasis in 11.5% of cases. Despite its potential beneficial effect on survival outcome, a systematic extended lymphadenectomy could not be recommended yet for patients suffering from PDAC of the body/tail.
Patient-Reported Mobility, Physical Activity, and Bicycle Use after Vulvar Carcinoma Surgery
Authors: van de Berg Nick J. , van Beurden Franciscus P. , Wendel-Vos G. C. Wanda , Duijvestijn Marjolein , van Beekhuizen Heleen J. , Maliepaard Marianne , van Doorn Helena C.
Published: April 2023

Patients treated for vulvar carcinoma may experience losses in mobility and physical activity. In this study, we assess the prevalence and severity of mobility problems using patient-reported outcomes of three questionnaires: EQ-5D-5L to estimate QoL and perceived health; SQUASH to estimate habitual physical activity; and a problem-specific questionnaire on bicycling. Patients treated for vulvar carcinoma between 2018 and 2021 were recruited, and 84 (62.7%) responded. The mean age was 68 ± 12 years (mean ± standard deviation). Self-reported QoL and perceived health were 0.832 ± 0.224 and 75.6 ± 20.0, respectively. Dutch physical activity guidelines were met by 34.2% of participants. Compared to baseline values, the times spent walking, bicycling, and participating in sports were all reduced. During bicycling, patients experienced moderate or severe pain in the skin of the vulva (24.5%), pain in the sit bones (23.2%), chafing (25.5%), or itching (8.9%). Overall, 40.3% experienced moderate or severe bicycling problems or could not bicycle, 34.9% felt that their vulva impeded bicycling, and 57.1% wished to make more or longer bicycling journeys. To conclude, vulvar carcinoma and its treatment reduce self-reported health, mobility, and physical activity. This motivates us to investigate ways to reduce discomfort during physical activities, and help women regain their mobility and self-reliance.
Differential Expression of miRNAs Contributes to Tumor Aggressiveness and Racial Disparity in African American Men with Prostate Cancer
Authors: Ottman Richard , Ganapathy Kavya , Lin Hui-Yi , Osterman Carlos Diaz , Dutil Julie , Matta Jaime , Ruiz-Deya Gilberto , Wang Liang , Yamoah Kosj , Berglund Anders , Chakrabarti Ratna , Park Jong Y.
Published: April 2023

Prostate cancer is the leading cancer in incidence and second leading cause of cancer mortality in US men. African American men have significantly higher incidence and mortality rates from prostate cancer than European American men. Previous studies reported that the disparity in prostate cancer survival or mortality can be explained by different biological backgrounds. microRNAs (miRNAs) regulate gene expression of their cognate mRNAs in many cancers. Therefore, miRNAs may be a potentially promising diagnostic tool. The role of miRNAs in prostate cancer aggressiveness and racial disparity has not been fully established. The goal of this study is to identify miRNAs associated with aggressiveness and racial disparity in prostate cancer. Here we report miRNAs that are associated with tumor status and aggressiveness in prostate cancer using a profiling approach. Further, downregulated miRNAs in African American tissues were confirmed by qRT-PCR. These miRNAs have also been shown to negatively regulate the expression of the androgen receptor in prostate cancer cells. This report provides a novel insight into understanding tumor aggressiveness and racial disparities of prostate cancer.
Characterization and Structural Insights of a Novel Arylsulfatase from Pseudoalteromonas atlantica T6c
Authors: Dong Panpan , Yang Wendi , Sun Lifang , Jing Dingding , Zhang Hong , Yang Jinbo , Wu Linjiao , Chen Leiqing , Wu Yunkun
Published: April 2023

Arylsulfatases exhibit great potential in industry for desulfation applications, but less is known about the metallo-β-lactamase (MBL) fold arylsulfatases. To learn more about them, an MBL fold arylsulfatase from Pseudoalteromonas atlantica T6c (PaAst) was identified and characterized, and its structure was elaborated in this study. PaAst was sequence analyzed, heterologously expressed in E. coli, purified by Ni2+-NTA resin affinity chromatography and size-exclusion chromatography, functionally studied by p-nitrophenyl sulfate (pNPS), and crystallized for structure determination. The MBL fold arylsulfatase was identified by sequence analysis and confirmed by enzymatic assay on pNPS with Km 1.00 mM and Vmax 60.80 U/mg at 50 °C and pH 7.5. Furthermore, its crystals were obtained in 0.2 M sodium thiocyamate, 20% PEG3350, and its structure was determined at 2.0 Å that formed a dimer with MBL fold. Our work highlighted the MBL fold arylsulfatases from structural insights and could be the theoretical foundation for investigations into their catalytic mechanism.
ZnO-ZnFe2O4 Catalyst for Hydrogen Production from Methanol Steam Reforming
Authors: Hsu Bing-Zhen , Yu Chung-Lun , Sakthinathan Subramanian , Chiu Te-Wei , Yu Bing-Sheng , Lin Chia-Cheng , Fan Liangdong , Lee Yi-Hsuan
Published: April 2023

In this study, ZnFe2O4 and ZnO-ZnFe2O4 catalysts were prepared using the glycine–nitrate process (GNP). The prepared ZnFe2O4 and ZnO-ZnFe2O4 catalyst powders were characterized using a scanning electron microscope, transmission electron microscope, XRD diffraction studies, and selected area diffraction pattern studies. In addition, the specific surface area was measured using a Brunauer–Emmett–Teller specific surface area analysis. The hydrogen reduction in different temperature ranges was analyzed using the H2 temperature-programmed reduction technique. The specific surface area of the ZnFe2O4 was 5.66 m2/g, and the specific surface area of the ZnO-ZnFe2O4 was 8.20 m2/g at a G/N ratio of 1.5 and at a G/N ratio of 1.7, respectively. The specific surface area of the ZnFe2O4 was 6.03 m2/g, and the specific surface area of the ZnO-ZnFe2O4 was 11.67 m2/g. The ZnFe2O4 and ZnO-ZnFe2O4 were found to have the best catalytic effect at 500 °C. In particular, the highest H2 generation rate of the ZnO-ZnFe2O4 (GN = 1.7) at 500 °C was 7745 mL STP min−1 g-cat−1. Moreover, the ZnO-ZnFe2 O4 catalyst demonstrated good H2 selectivity and stability during the process of steam reforming methanol. Therefore, the ZnO-ZnFe2O4 catalyst powder exhibited high catalytic activity due to the good dispersibility of the ZnO, which increased the specific surface area of the catalyst. In the future, the catalyst can be applied to the steam reforming of methanol for industrial purposes.
Early Visibility of Cellular Aggregates and Changes in Central Corneal Thickness as Predictors of Successful Corneal Endothelial Cell Injection Therapy
Authors: Wong Evan N. , Foo Valencia H. X. , Peh Gary S. L. , Htoon Hla M. , Ang Heng-Pei , Tan Belinda Y. L. , Ong Hon-Shing , Mehta Jodhbir S.
Published: April 2023

(1) Background: Cell injection therapy is an emerging treatment for bullous keratopathy (BK). Anterior segment optical coherence tomography (AS-OCT) imaging allows the high-resolution assessment of the anterior chamber. Our study aimed to investigate the predictive value of the visibility of cellular aggregates for corneal deturgescence in an animal model of bullous keratopathy. (2) Methods: Cell injections of corneal endothelial cells were performed in 45 eyes in a rabbit model of BK. AS-OCT imaging and central corneal thickness (CCT) measurement were performed at baseline and on day 1, day 4, day 7 and day 14 following cell injection. A logistic regression was modelled to predict successful corneal deturgescence and its failure with cell aggregate visibility and CCT. Receiver-operating characteristic (ROC) curves were plotted, and areas under the curve (AUC) calculated for each time point in these models. (3) Results: Cellular aggregates were identified on days 1, 4, 7 and 14 in 86.7%, 39.5%, 20.0% and 4.4% of eyes, respectively. The positive predictive value of cellular aggregate visibility for successful corneal deturgescence was 71.8%, 64.7%, 66.7% and 100.0% at each time point, respectively. Using logistic regression modelling, the visibility of cellular aggregates on day 1 appeared to increase the likelihood of successful corneal deturgescence, but this did not reach statistical significance. An increase in pachymetry, however, resulted in a small but statistically significant decreased likelihood of success, with an odds ratio of 0.996 for days 1 (95% CI 0.993–1.000), 2 (95% CI 0.993–0.999) and 14 (95% CI 0.994–0.998) and an odds ratio of 0.994 (95% CI 0.991–0.998) for day 7. The ROC curves were plotted, and the AUC values were 0.72 (95% CI 0.55–0.89), 0.80 (95% CI 0. 62–0.98), 0.86 (95% CI 0.71–1.00) and 0.90 (95% CI 0.80–0.99) for days 1, 4, 7 and 14, respectively. (4) Conclusions: Logistic regression modelling of cell aggregate visibility and CCT was predictive of successful corneal endothelial cell injection therapy.
Down Syndrome Altered Cell Composition in Blood, Brain, and Buccal Swab Samples Profiled by DNA-Methylation-Based Cell-Type Deconvolution
Authors: Zhang Ze , Stolrow Hannah G. , Christensen Brock C. , Salas Lucas A.
Published: April 2023

Down syndrome (DS) is a genetic disorder caused by an extra copy of chromosome 21 that presents developmental dysfunction and intellectual disability. To better understand the cellular changes associated with DS, we investigated the cell composition in blood, brain, and buccal swab samples from DS patients and controls using DNA methylation-based cell-type deconvolution. We used genome-scale DNA methylation data from Illumina HumanMethylation450k and HumanMethylationEPIC arrays to profile cell composition and trace fetal lineage cells in blood samples (DS N = 46; control N = 1469), brain samples from various regions (DS N = 71; control N = 101), and buccal swab samples (DS N = 10; control N = 10). In early development, the number of cells from the fetal lineage in the blood is drastically lower in DS patients (Δ = 17.5%), indicating an epigenetically dysregulated maturation process for DS patients. Across sample types, we observed significant alterations in relative cell-type proportions for DS subjects compared with the controls. Cell-type proportion alterations were present in samples from early development and adulthood. Our findings provide insight into DS cellular biology and suggest potential cellular interventional targets for DS.
Xanthine Dehydrogenase Is a Modulator of Dopaminergic Neurodegeneration in Response to Bacterial Metabolite Exposure in C. elegans
Authors: Thies Jennifer L. , Willicott Karolina , Craig Maici L. , Greene Madeline R. , DuGay Cassandra N. , Caldwell Guy A. , Caldwell Kim A.
Published: April 2023

Oxidative stress is a contributing factor to Parkinson’s disease (PD). Considering the prevalence of sporadic PD, environmental exposures are postulated to increase reactive oxygen species and either incite or exacerbate neurodegeneration. We previously determined that exposure to the common soil bacterium, Streptomyces venezuelae (S. ven), enhanced oxidative stress and mitochondrial dysfunction in Caenorhabditis elegans, leading to dopaminergic (DA) neurodegeneration. Here, S. ven metabolite exposure in C. elegans was followed by RNA-Seq analysis. Half of the differentially identified genes (DEGs) were associated with the transcription factor DAF-16 (FOXO), which is a key node in regulating stress response. Our DEGs were enriched for Phase I (CYP) and Phase II (UGT) detoxification genes and non-CYP Phase I enzymes associated with oxidative metabolism, including the downregulated xanthine dehydrogenase gene, xdh-1. The XDH-1 enzyme exhibits reversible interconversion to xanthine oxidase (XO) in response to calcium. S. ven metabolite exposure enhanced XO activity in C. elegans. The chelation of calcium diminishes the conversion of XDH-1 to XO and results in neuroprotection from S. ven exposure, whereas CaCl2 supplementation enhanced neurodegeneration. These results suggest a defense mechanism that delimits the pool of XDH-1 available for interconversion to XO, and associated ROS production, in response to metabolite exposure.
Molecular and Clinical Advances in Understanding Early Embryo Development
Authors: Van Winkle Lon J.
Published: April 2023

The articles in this Special Issue address a wide variety of topics concerning molecular and clinical advances in understanding early embryo development [...]
Can Epigenetics Predict Drug Efficiency in Mental Disorders?
Authors: Ben David Gil , Amir Yam , Salalha Randa , Sharvit Lital , Richter-Levin Gal , Atzmon Gil
Published: April 2023

Psychiatric disorders affect millions of individuals and their families worldwide, and the costs to society are substantial and are expected to rise due to a lack of effective treatments. Personalized medicine—customized treatment tailored to the individual—offers a solution. Although most mental diseases are influenced by genetic and environmental factors, finding genetic biomarkers that predict treatment efficacy has been challenging. This review highlights the potential of epigenetics as a tool for predicting treatment efficacy and personalizing medicine for psychiatric disorders. We examine previous studies that have attempted to predict treatment efficacy through epigenetics, provide an experimental model, and note the potential challenges at each stage. While the field is still in its infancy, epigenetics holds promise as a predictive tool by examining individual patients’ epigenetic profiles in conjunction with other indicators. However, further research is needed, including additional studies, replication, validation, and application beyond clinical settings.
Correlation of Electrophysiological and Fluorescence-Based Measurements of Modulator Efficacy in Nasal Epithelial Cultures Derived from People with Cystic Fibrosis
Authors: Gunawardena Tarini N. A. , Bozóky Zoltán , Bartlett Claire , Ouyang Hong , Eckford Paul D. W. , Moraes Theo J. , Ratjen Felix , Gonska Tanja , Bear Christine E.
Published: April 2023

It has been suggested that in vitro studies of the rescue effect of CFTR modulator drugs in nasal epithelial cultures derived from people with cystic fibrosis have the potential to predict clinical responses to the same drugs. Hence, there is an interest in evaluating different methods for measuring in vitro modulator responses in patient-derived nasal cultures. Commonly, the functional response to CFTR modulator combinations in these cultures is assessed by bioelectric measurements, using the Ussing chamber. While this method is highly informative, it is time-consuming. A fluorescence-based, multi-transwell method for assaying regulated apical chloride conductance (Fl-ACC) promises to provide a complementary approach to theratyping in patient-derived nasal cultures. In the present work, we compared Ussing chamber measurements and fluorescence-based measurements of CFTR-mediated apical conductance in matching, fully differentiated nasal cultures derived from CF patients, homozygous for F508del (n = 31) or W1282X (n = 3), or heterozygous for Class III mutations G551D or G178R (n = 5). These cultures were obtained through a bioresource called the Cystic Fibrosis Canada-Sick Kids Program in Individual CF Therapy (CFIT). We found that the Fl-ACC method was effective in detecting positive responses to interventions for all genotypes. There was a correlation between patient-specific drug responses measured in cultures harbouring F508del, as measured using the Ussing chamber technique and the fluorescence-based assay (Fl-ACC). Finally, the fluorescence-based assay has the potential for greater sensitivity for detecting responses to pharmacological rescue strategies targeting W1282X.
CircADAMTS16 Inhibits Differentiation and Promotes Proliferation of Bovine Adipocytes by Targeting miR-10167-3p
Authors: Hu Chunli , Feng Xue , Ma Yanfen , Wei Dawei , Zhang Lingkai , Wang Shuzhe , Ma Yun
Published: April 2023

Circular RNAs (CircRNAs) are covalently closed-loop non-coding RNA (ncRNA) molecules present in eukaryotes. Numerous studies have demonstrated that circRNAs are important regulators of bovine fat deposition, but their precise mechanisms remain unclear. Previous transcriptome sequencing studies have indicated that circADAMTS16, a circRNA derived from the a disintegrin-like metalloproteinases with the thrombospondin motif 16 (ADAMTS16) gene, is high expressed in bovine adipose tissue. This gives a hint that the circRNA may be involved in the process of bovine lipid metabolism. In this study, the targeting relationship between circADAMTS16 and miR-10167-3p was verified using a dual-luciferase reporter assay. Then, the functions of circADAMTS16 and miR-10167-3p in bovine adipocytes were explored through gain-of-function and lose-of-function. The mRNA expression levels of genes were detected by real-time quantitative PCR (qPCR), and lipid droplet formation was phenotypically evaluated by Oil Red O staining. Cell proliferation and apoptosis were detected using CCK-8, EdU, and flow cytometry. We demonstrated that circADAMTS16 targeted binding to miR-10167-3p. The up-regulation of circADAMTS16 inhibited the differentiation of bovine preadipocytes, and the overexpression of miR-10167-3p promoted the differentiation of bovine preadipocytes. Meanwhile, CCK-8 and EdU results indicated that circADAMTS16 promoted adipocyte proliferation. Subsequently, flow cytometry analysis showed that circADAMTS16 promoted cell transition from G0/G1 phase to S phase, and inhibited cell apoptosis. However, up-regulation of miR-10167-3p inhibited cell proliferation and promoted apoptosis. Briefly, circADAMTS16 inhibited the differentiation and promotes the proliferation of bovine adipocytes by targeting miR-10167-3p during bovine fat deposition, which provides new insights into the mechanism of circRNAs regulation of beef quality.
Tertiary Lymphoid Structures (TLSs) and Stromal Blood Vessels Have Significant and Heterogeneous Impact on Recurrence, Lymphovascular and Perineural Invasion amongst Breast Cancer Molecular Subtypes
Authors: Barb Alina Cristina , Pasca Fenesan Mihaela , Pirtea Marilena , Margan Madalin Marius , Tomescu Larisa , Melnic Eugen , Cimpean Anca Maria
Published: April 2023

Background: Tertiary lymphoid structures (TLSs) mediate local antitumor immunity, and interest in them significantly increased since cancer immunotherapy was implemented. We examined TLS− tumor stromal blood vessel interplay for each breast cancer (BC) molecular subtype related to recurrence, lymphovascular invasion (LVI), and perineural invasion (PnI). Methods: TLSs were quantified on hematoxylin and eosin stain specimens followed by CD34/smooth muscle actin (SMA) double immunostaining for stromal blood vessel maturation assessment. Statistical analysis linked microscopy to recurrence, LVI, and PnI. Results: TLS negative (TLS−) subgroups in each BC molecular subtype (except to Luminal A) have higher LVI, PnI, and recurrence. A significant rise in LVI and PnI were observed for the HER2+/TLS− subgroup (p < 0.001). The triple negative breast cancer (TNBC)/TLS− subgroup had the highest recurrence and invasion risk which was also significantly related to tumor grade. PnI but not LVI significantly influenced recurrence in the TNBC/TLS+ subgroup (p < 0.001). TLS−stromal blood vessel interrelation was different amongst BC molecular subtypes. Conclusion: BC invasion and recurrence are strongly influenced by TLS presence and stromal blood vessels, especially for HER2 and TNBC BC molecular subtypes.
Electrochemical Sweat Sensors
Authors: Bilbao Emanuel , Garate Octavio , Rodríguez Campos Theo , Roberti Mariano , Mass Mijal , Lozano Alex , Longinotti Gloria , Monsalve Leandro , Ybarra Gabriel
Published: April 2023

Sweat analysis by means of minimally invasive wearable sensors is considered a potentially disruptive method for assessing clinical parameters, with exciting applications in early medical diagnostics and high-performance sports. Electrochemical sensors and biosensors are especially attractive because of the possibility of the electronic integration of wearable devices. In this article, we review several aspects regarding the potentialities and present limitations of electrochemical sweat (bio)sensors, including: the main target analytes and their relationships with clinical conditions; most usual electrochemical techniques of transduction used according to the nature of the target analytes; issues connected to the collection of representative sweat samples; aspects regarding the associated, miniaturized electronic instrumentation used for signal processing and communication; and signal processing by machine learning.
Sensitive and Reversible Ammonia Gas Sensor Based on Single-Walled Carbon Nanotubes
Authors: Machín Abniel , Cotto María , Duconge José , Morant Carmen , Petrescu Florian I. , Márquez Francisco
Published: April 2023

The present study reports on the fabrication and performance of ammonia sensors based on single-walled carbon nanotubes (SWCNTs) coated with gold nanoparticles (AuNPs). The AuNPs were incorporated onto the SWCNTs using two different methods: sputtering and chemical deposition. The sensors were exposed to controlled concentrations of ammonia at two temperatures, namely, 25 °C and 140 °C, and their response was monitored through successive cycles of ammonia exposure (0.5 ppm and 1.0 ppm) and nitrogen purging. The results demonstrate that the sputtering-based deposition of the AuNPs on SWCNTs led to the best sensor performance, characterized by a rapid increase in resistance values (tresp = 12 s) upon exposure to ammonia and an efficient recovery at 140 °C (trec = 52 s). By contrast, the sensor with chemically impregnated AuNPs exhibited a slower response time (tresp = 25 s) and the same recovery time (trec = 52 s). Additionally, a novel device was developed that combined MoS2-AuNPs (sputtering)-SWCNTs. This sensor was obtained by impregnating nanosheets of MoS2 onto AuNPs (sputtering)-SWCNTs showing improved sensor performance compared to the devices with only AuNPs. In this case, the sensor exhibited a better behavior with a faster recovery of resistance values, even at room temperature. Overall, the study provides valuable insights into the fabrication and optimization of SWCNT-based ammonia sensors for various applications, particularly in detecting and quantifying small amounts of ammonia (concentrations below 1 ppm).
Cognitive and Interpersonal Factors in Adolescent Inpatients with Anorexia Nervosa: A Network Analysis
Authors: Delaquis Chantal P. , Godart Nathalie T. ,   EVHAN Group, Fatséas Melina , Berthoz Sylvie
Published: April 2023

The cognitive-interpersonal model of anorexia nervosa (AN) posits that cognitive and interpersonal traits contribute to the development and maintenance of AN. We investigated cognitive and interpersonal factors put forward by the model in a sample of 145 adolescent inpatients with AN using network analysis. Our main outcomes included core eating disorder symptoms, cognitive style, socio-affective factors, and mood symptoms. We estimated a cross-sectional network using graphical LASSO. Core and bridge symptoms were identified using strength centrality. Goldbricker was used to reduce topological overlap. The node with the highest strength centrality was Concern over Mistakes, followed by Eating Preoccupation, Social Fear, and Overvaluation of Weight and Shape. The nodes with the highest bridge strength were Concern over Mistakes, Doubt about Actions, Overvaluation of Weight and Shape, and Depression. Notably, both performance on a cognitive flexibility task and BMI were not connected to any other nodes and were subsequently removed from the final network. We provide partial support for the cognitive-interpersonal model while also supporting certain premises put forward by the transdiagnostic cognitive-behavioral model. The high centrality of Concern over Mistakes and Social Fear supports the theory that both cognitive and interpersonal difficulties contribute to AN, particularly in adolescence.
Sex Differences in Patterns of Childhood Traumatic Experiences in Chinese Rural-To-Urban Migrant Children
Authors: Liang Yiming , Wu Ruiyao , Huang Qi , Liu Zhengkui
Published: April 2023

Background: Children and adolescents are likely to be exposed to various types of childhood traumatic experiences (CTEs) with gender-specific patterns. Rural-to-urban migrant children have been demonstrated a greater risk of CTE exposure than local children. However, no study has investigated sex differences in the patterns of CTEs and predictive factors among Chinese children. Methods: A large-scale questionnaire survey of rural-to-urban migrant children (N = 16,140) was conducted among primary and junior high schools in Beijing. Childhood trauma history, including interpersonal violence, vicarious trauma, accidents and injuries was measured. Demographic variables and social support were also examined. Latent class analysis (LCA) was utilized to examine patterns of childhood trauma, and logistic regression was used to examine predictors. Results: Four classes of CTEs were found among both boys and girls, labeled low trauma exposure, vicarious trauma exposure, domestic violence exposure, and multiple trauma exposure. The possibility of various CTEs in the four CTE patterns was higher among boys than girls. Sex differences also manifested in predictors of childhood trauma patterns. Conclusions: Our findings shed light on sex differences in CTE patterns and predictive factors in Chinese rural-to-urban migrant children, suggesting that trauma history should be considered along with sex, and sex-specific prevention and treatment programs should be developed.
Mouse CCL9 Chemokine Acts as Tumor Suppressor in a Murine Model of Colon Cancer
Authors: Łazarczyk Marzena , Kurzejamska Ewa , Mickael Michel-Edwar , Poznański Piotr , Skiba Dominik , Sacharczuk Mariusz , Gaciong Zbigniew , Religa Piotr
Published: April 2023

Colorectal cancer is the third most frequently diagnosed cancer in the world. Despite extensive studies and apparent progress in modern strategies for disease control, the treatment options are still not sufficient and effective, mostly due to frequently encountered resistance to immunotherapy of colon cancer patients in common clinical practice. In our study, we aimed to uncover the CCL9 chemokine action employing the murine model of colon cancer to seek new, potential molecular targets that could be promising in the development of colon cancer therapy. Mouse CT26.CL25 colon cancer cell line was used for introducing lentivirus-mediated CCL9 overexpression. The blank control cell line contained an empty vector, while the cell line marked as CCL9+ carried the CCL9-overexpressing vector. Next, cancer cells with empty vector (control) or CCL9-overexpressing cells were injected subcutaneously, and the growing tumors were measured within 2 weeks. Surprisingly, CCL9 contributed to a decline in tumor growth in vivo but had no effect on CT26.CL25 cell proliferation or migration in vitro. Microarray analysis of the collected tumor tissues revealed upregulation of the immune system-related genes in the CCL9 group. Obtained results suggest that CCL9 reveals its anti-proliferative functions by interplay with host immune cells and mediators that were absent in the isolated, in vitro system. Under specific study conditions, we determined unknown features of the murine CCL9 that have so far bee reported to be predominantly pro-oncogenic.
Structural Optimized Design of a Powder Mixer for Multi-Material Directed Energy Deposition Based on CFD-DPM
Authors: Gao Guochao , Zhang Xiaowei , Xu Meng , Han Yibo , Ao Jingxuan , Cai Yaozeng , Wang Jinzhe
Published: April 2023

Directed energy deposition (DED) offers an unprecedentedly convenient and efficient additive manufacturing approach to novel alloy designs such as high entropy alloys. As a critical component of the novel DED system, a powder mixer to stably and uniformly mix different powders plays an important role in the DED process. In this paper, the computational fluid dynamics-discrete phase model (CFD-DPM) method was used to simulate the characteristics of the gas-solid coupled fluid inside the powder mixer. The influence of the structural details of the powder mixer on the motion characteristics of the gas-solid coupled fluid was investigated by numerical simulation. Based on the numerical simulation results, the range of parameters of critical structure such as the inlet angle, the diameter and height mixing chamber, and the height of the bottom was determined. The difference in powder mixing uniformity among different powder mixers was qualitatively analyzed through powder mixing experiments. The BSE-EDS results of mixed powder samples show that the mixer with reasonable structural parameters has better mixing uniformity. In summary, this work provides a powerful reference for the rapid optimization design of the powder mixer structure.
Laser Processing of Liquid Crystal Droplets with Diverse Internal Structures
Authors: Guo Jin-Kun , Ling Jinzhong , Yuan Ying , Chang Fengjiao , Wang Xiaorui , Song Jang-Kun
Published: April 2023

To control the spatial placement and organize micro/nanodroplets (NDs) has fundamental importance both in science and engineering. Cholesteric liquid crystal (CLC) droplets with topological diversity can offer many self-assembly modalities to arrange guest NDs in their spherical confinement; however, limited progress has been achieved due to difficulties of loading NDs into stabilized host droplets. Here, a laser injection technique is introduced, through which a controlled number of NDs were injected from a pre-selected location onto the surface of the host droplet. The sequentially injected NDs spontaneously drifted toward areas with topological defects and self-assembled along its geometry or local director field into a predefined shape. Within CLC droplets with different topological structures, guest NDs self-assembled near areas with defect points as twisting radial chains and quill-like assembly structures, and along defect lines as discrete beads and helical threads, respectively. The injection speed of the NDs, controlled by laser power, was found to play a key role in the assembly geometry of NDs as well as the internal structure of the CLC droplet processed. This study expands our abilities to precisely organize NDs in a spherical confinement and such droplet-based microsystems have potential applications for sensors, photonic devices, pharmaceuticals, and biotechnology.
Growth Mechanism of Eutectic Si in Super-Gravity Solidified Al-Si Alloy during Annealing
Authors: Lu Yuehui , Wu Chuandong , Wu Hao , Wang Jiamin , Su Yin , Gan Zhanghua , Liu Jing
Published: April 2023

Herein, we report that the influence of annealing time on the microstructure and mechanical properties of Al-14.5Si alloys solidified under a super-gravity field. The results indicate that the coarsening of metastable eutectic Si and formation of precipitated Si could be observed at the early stage of annealing. A slight increase in yield strength and tensile strength could be observed in the sample annealed for 0.25 h, which can be ascribed to the formation of precipitated Si with limited size during the early stage of annealing. The intensified diffusion of Si atoms during annealing led to the coarsening and coalescence of the eutectic Si, as well as the coarsening of precipitated Si with further extension of the annealing time.
Deep-Blue Organic Light-Emitting Diodes Employed Traditional Hole Transporting Material as Emitter for 31-Inch 4K Flexible Display
Authors: Xue Yan , Nie Qiong , Hou Xin , Wang Baolei , Chen Yanbo , Zhang Yu , Xiang Lijuan
Published: April 2023

High-efficiency deep-blue organic light-emitting diodes (OLEDs) play a crucial role in realizing ultra-high-definition (UHD) flat-panel displays and reducing power consumption. Generally, most reported OLEDs with a Commission Internationale de L’Eclairage (CIE) y coordinate < 0.06 are achieved by traditional fluorescent deep-blue emitters. However, it is challenging to obtain deep-blue fluorescent OLEDs with a high external quantum efficiency (EQE) (reaching the theoretical limit of 5%). In this work, we have successfully employed a hole-transporting material for an emitter, which can increase the efficiency in deep-blue OLEDs. The device employed with the proposed hole-transporting material exhibits deep-blue emission peaks at 427.0 nm with CIE coordinates of (0.155, 0.051), a turn-on voltage (Von) of 4.5 V, and an EQE of 4.5%. The performance of the OLED can be improved by 5.0% by optimizing the device structure. Finally, the flexible display when using the OLED devices exhibited a high image quality.
Determination of the Relationship between Proportional and Non-Proportional Fatigue Damage in Magnesium Alloy AZ31 BF
Authors: Anes Vitor , Bumba Francisco , Reis Luís , Freitas Manuel
Published: April 2023

In this work, the magnesium alloy AZ31BF subjected to proportional and non-proportional loads has been studied. For this purpose, a series of experimental multiaxial fatigue tests were carried out according to the ASTM E466 protocol. The main objective was to determine the relationship between the multiaxial fatigue strength of this alloy under these two different types of loading. The results showed that the AZ31BF magnesium alloy has different fatigue strengths depending on the loading type. Based on these results, it was found that the ratio between proportional and non-proportional damage in AZ31BF magnesium alloy varies depending on the number of loading cycles. To represent this variation, parameter Y was used to modulate the non-proportional damage of AZ31BF. In this way, two Y functions were considered, one for the normal stress component and the other for the shear stress component. The results obtained for the non-proportional parameter Y are of particular interest since the multiaxial fatigue models do not distinguish between these two types of loading when evaluating fatigue life. In this sense, the results of this study can be used in these models to overcome this limitation.