bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of Care and Data Quality in a National Registry of Black and White Patients with Merkel Cell Carcinoma
Authors: Rattani Abbas , Gaskins Jeremy , McKenzie Grant , Scharf Virginia Kate , Broman Kristy , Pisu Maria , Holder Ashley , Dunlap Neal , Schwartz David , Yusuf Mehran B.
Published: October 2022

Merkel Cell Carcinoma (MCC) is a rare cancer most commonly affecting White patients; less is known for Black patients. We aim to report presentation, treatment, and quality of registry data by race with a secondary endpoint of overall survival. We conducted a retrospective cohort analysis between 2006–2017 via the National Cancer Database of Black and White MCC patients with and without known staging information. Multivariable logistic, proportional odds logistic, and baseline category logistic regression models were used for our primary endpoint. Multivariable Cox regression was used to interrogate overall survival. Multiple imputation was used to mitigate missing data bias. 34,503 patients with MCC were included (2566 Black patients). Black patients were younger (median age 52 vs. 72, p < 0.0001), had higher rates of immunosuppression (28% vs. 14%, p = 0.0062), and were more likely to be diagnosed at a higher stage (proportional OR = 1.41, 95% CI 1.25–1.59). No differences were noted by race across receipt of definitive resection (DR), though Black patients did have longer time from diagnosis to DR. Black patients were less likely to receive adjuvant radiation. Black patients were more likely to have missing cancer stage (OR = 1.69, CI 1.52–1.88). Black patients had decreased adjusted risk of mortality (HR 0.73, 0.65–0.81). Given the importance of registry analyses for rare cancers, efforts are needed to ensure complete data coding. Paramount to ensuring equitable access to optimal care for all is the recognition that MCC can occur in Black patients.
Clinical Practice of Targeted Capture Sequencing to Identify Actionable Alterations in Cholangiocarcinoma
Authors: Ma Kai , Wang Youpeng , Zhang Yuanzheng , Sun Hongfa , Zhang Xuhui , Sun Chuandong , Zhang Bingyuan , Zhang Ying , Cheng Haoyue , Liu Ao , Wang Mengyao , Han Bing
Published: October 2022

The early diagnosis and treatment of cholangiocarcinoma (CCA) remain a challenge worldwide. Genetic testing promises to solve these problems. Due to the different mutation landscapes across populations and the paucity of sequencing data of Chinese patients with CCA, the existing mutation landscape is insufficient to reflect the mutation characteristics of Chinese patients. Thus, we retrospectively analyzed 72 Chinese patients with CCA who had received genetic testing of targeted capture sequencing. A total of 2152 somatic mutations were detected in 56 (77.78%) patients, of which, the frequently mutated driver genes were TP53 (27.78%), KMT2D (23.81%), KMT2C (20.63%), BCOR (18.06%), APC (15.28%), BAP1 (13.89%), ARID1A (12.50%), NF1 (12.50%), PIK3CA (12.50%), KRAS (11.11%), and LRP1B (11.11%). Most mutations were enriched in NRF2, TP53, and TGF-Beta oncogenic signaling pathways and cadherin repeat domains which were associated with intercellular adhesion. Based on cancer-related public databases and multiple protein function prediction algorithms, we identified 118 novel pathogenic or likely pathogenic somatic mutations and 77 actionable alterations. Molecular analysis of tumors from a precision oncology perspective can provide potential targets for early diagnosis and treatment of CCA and assist physicians in clinical decision making.
A Mac-2 Binding Protein Glycosylation Isomer-Based Risk Model Predicts Hepatocellular Carcinoma in HBV-Related Cirrhotic Patients on Antiviral Therapy
Authors: Chen Chien-Hung , Hu Tsung-Hui , Wang Jing-Houng , Lai Hsueh-Chou , Hung Chao-Hung , Lu Sheng-Nan , Peng Cheng-Yuan
Published: October 2022

Mac-2 binding protein glycosylation isomer (M2BPGi) has not been used in a risk score to predict hepatocellular carcinoma (HCC). We enrolled 1003 patients with chronic hepatitis B and cirrhosis receiving entecavir or tenofovir therapy for more than12 months to construct an HCC risk score. In the development cohort, Cox regression analysis identified male gender, age, platelet count, AFP and M2BPGi levels at 12 months of treatment as independent risk factors of HCC. We developed the HCC risk prediction model, the ASPAM-B score, based on age, sex, platelet count, AFP and M2BPGi levels at 12 months of treatment, with the total scores ranging from 0 to 11.5. This risk model accurately classified patients into low (0–3.5), medium (4–7), and high (>7) risk in the development and validation groups (p < 0.001). The areas under the receiver operating characteristic curve (AUROC) of 3-, 5- and 9-year risks of HCC were 0.742, 0.728 and 0.719, respectively, in the development cohort. All AUROC between the ASPAM-B and APA-B, PAGE-B, RWS-HCC and THRI scores at 3–9 years were significantly different. The M2BPGi-based risk model exhibited good discriminant function in predicting HCC in cirrhotic patients who received long-term antiviral treatment.
The Indicative Value of Serum Tumor Markers for Metastasis and Stage of Non-Small Cell Lung Cancer
Authors: Jiang Chunyang , Zhao Mengyao , Hou Shaohui , Hu Xiaoli , Huang Jinchao , Wang Hongci , Ren Changhao , Pan Xiaoying , Zhang Ti , Wu Shengnan , Zhang Shun , Sun Bingsheng
Published: October 2022

Objective: This study aimed to explore the roles of serum tumor markers for metastasis and stage of non-small cell lung cancer (NSCLC). Methods: This study recruited 3272 NSCLC patients admitted to the Tianjin Union Medical Center and the Tianjin Medical University Cancer Institute and Hospital. The predictive abilities of some serum tumor markers (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), total prostate-specific antigen (TPSA) and carbohydrate antigen 199 (CA199)) for NSCLC metastasis (intrapulmonary, lymphatic and distant metastasis) and clinical stage were analyzed. Results: Tumor markers exhibited different numerical and proportional distributions in NSCLC patients. Elevated CEA, CYFRA 21-1 and CA199 levels were indicative of tumor metastasis and stage. Increased CEA and CA199 provided an accurate prediction of intrapulmonary and distant metastasis with the area under the receiver operator characteristic curve (AUC) of 0.69 both (p < 0.001); Increased CEA, CYFRA 21-1 and CA199 provided an accurate prediction of lymphatic metastasis with the AUC of 0.62 (p < 0.001). Conclusion: Combined detection of serum tumor markers can indicate tumor metastasis and stage in NSCLC patients.
EGCG Prevents the Transcriptional Reprogramming of an Inflammatory and Immune-Suppressive Molecular Signature in Macrophage-like Differentiated Human HL60 Promyelocytic Leukemia Cells
Authors: Kassouri Celia , Rodriguez Torres Sahily , Gonzalez Suarez Narjara , Duhamel Stéphanie , Annabi Borhane
Published: October 2022

Background: The promyelocytic leukemia cell differentiation process enables recapitulation of the polarized M1 or M2 macrophage-like phenotype with inflammatory and immune-suppressive properties. While evidence supports the anti-inflammatory effect of dietary-derived epigallocatechin-3-gallate (EGCG), its impact on the onset of immune phenotype molecular signature remains unclear. Methods: Human HL60 promyelocytic cells grown in suspension were differentiated into CD11bHigh/CD14Low adherent macrophages with phorbol 12-myristate 13-acetate (PMA). Gelatin zymography was used to assess the levels of matrix metalloproteinase (MMP)-9, and total RNA was isolated for RNAseq and RT-qPCR assessment of differentially expressed gene levels involved in inflammation and immunity. Protein lysates were used to assess the phosphorylation status of signaling intermediates involved in macrophage-like cell differentiation. Results: Cell adhesion and induction of MMP-9 were indicative of HL60 cell differentiation into a macrophage-like phenotype. The extracellular signal-regulated kinase (ERK), glycogen synthase kinase (GSK)-3, p90 ribosomal S6 kinases (RSK), and cAMP-response-element-binding protein (CREB) were all phosphorylated, and EGCG reduced such phosphorylation status. Increases in inflammation and immunity genes included, among others, CCL22, CSF1, CSF2, IL1B, and TNF, which inductions were prevented by EGCG. This was corroborated by unbiased transcriptomic analysis which further highlighted the capacity of EGCG to downregulate the hematopoietic stem cell regulator CBFA2T3. Conclusion: EGCG inhibits inflammatory signaling crosstalk and prevents the onset of an immune phenotype in macrophage-like differentiated cells.
Analysis of Lenvatinib’s Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma
Authors: Amioka Kei , Kawaoka Tomokazu , Kinami Takahiro , Yamasaki Shintaro , Kosaka Masanari , Johira Yusuke , Yano Shigeki , Naruto Kensuke , Ando Yuwa , Fujii Yasutoshi , Uchikawa Shinsuke , Ono Atsushi , Yamauchi Masami , Imamura Michio , Kosaka Yumi , Ohya Kazuki , Mori Nami , Takaki Shintaro , Tsuji Keiji , Masaki Keiichi , Honda Yoji , Kouno Hirotaka , Kohno Hioshi , Morio Kei , Moriya Takashi , Naeshiro Noriaki , Nonaka Michihiro , Aisaka Yasuyuki , Azakami Takahiro , Hiramatsu Akira , Aikata Hiroshi , Oka Shiro
Published: October 2022

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin–bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.
Role of Radiation Therapy in Mortality among Adolescents and Young Adults with Lymphoma: Differences According to Cause of Death
Authors: Yin Xuejiao , You Liangshun , Hu Xuelian
Published: October 2022

Background: Despite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. Few long-term follow-up studies have examined the association between RT and outcomes. Methods: Lymphoma patients aged 15–39 years were identified in the Surveillance, Epidemiology and End Results (SEER) database from 1992 to 2016. Mortality was assessed by comparing those with and without RT using the Fine–Gray competing risk model. Standardized mortality ratios (SMRs) were used to assess the relative risk of death compared with the general U.S. population. Results: In total, 29,686 patients were included; 10,708 (36.07%) received RT. Cause-specific mortality was compared between patients with and without RT while considering other competing events, including death due to index cancer, second malignant neoplasms (SMNs), and noncancer causes. Patients with RT had a lower probability of death and crude 5-year cumulative incidence of death. Moreover, there were significantly lower SMRs in patients with RT than in patients without RT. Differences between the two groups were greatest for mortality due to hematological malignancies and infections. Additionally, in the RT cohort, the SMR for index-cancer-related death was highest in the first year after diagnosis and gradually decreased. Hematological malignancies and infections were the most common specific SMN and noncancer causes of death, respectively. Conclusions: RT did not increase mortality from index cancer, SMNs, or noncancer causes in AYA patients with lymphoid malignancies. The current analysis may serve as a reference for healthcare providers monitoring RT application for AYA lymphoid malignancy survivors.
Development of a Clinical–Biological Model to Assess Tumor Progression in Metastatic Pancreatic Cancer: Post Hoc Analysis of the PRODIGE4/ACCORD11 Trial
Authors: Egea Julie , Salleron Julia , Gourgou Sophie , Ayav Ahmet , Laurent Valérie , Juzyna Béata , Harlé Alexandre , Conroy Thierry , Lambert Aurélien
Published: October 2022

Background: The follow-up of pancreatic cancer (PC) is based on computed tomography (CT) assessment; however, there is no consensus on the use of clinical and biological criteria in tumor progression. We aimed to establish a clinical–biological model to highlight the progression of metastatic PC during first-line treatment. Methods: The patients treated with first-line chemotherapy in the phase 2/3 PRODIGE4/ACCORD11 clinical trial were evaluated retrospectively. Clinical and biological markers were evaluated at the time of CT scans and during treatment to determine tumor progression. Results: In total, 196 patients were analyzed, with 355 available tumor assessments. The clinical and biological factors associated with tumor progression in multivariate analysis included gemcitabine, global health status ≤ 33 (OR = 3.38, 95%CI [1.15; 9.91], p = 0.028), quality of life score between 34 and 66 (OR = 2.65, 95%CI [1.06; 6.59], p = 0.037), carcinoembryonic antigen (CEA) ≥ 3 times the standard value without any increase in the CEA level from inclusion (OR = 2.22, 95%CI [1.01; 4.89], p = 0.048) and with an increase in the CEA level from inclusion (OR = 6.56, 95%CI [2.73; 15.78], p < 0.001), and an increase in the carbohydrate antigen 19-9 level from inclusion (OR = 2.59, 95%CI [1.25; 5.36], p = 0.016). Conclusions: The self-assessment of patients’ general health status alongside tumor markers is an interesting approach to the diagnosis of the tumor progression of metastatic pancreatic cancer patients during first-line treatment.
Stereotactic Body Radiotherapy for Renal Cell Carcinoma in Patients with Von Hippel–Lindau Disease—Results of a Prospective Trial
Authors: Kirste Simon , Rühle Alexander , Zschiedrich Stefan , Schultze-Seemann Wolfgang , Jilg Cordula A. , Neumann-Haefelin Elke , Lo Simon S. , Grosu Anca-Ligia , Kim Emily
Published: October 2022

Von Hippel–Lindau disease (VHL) is a hereditary disorder associated with malignant tumors including clear cell renal cell carcinoma (ccRCC). Partial nephrectomy is complicated by multilocular tumor occurrence and a high recurrence rate. The aim of this study was to evaluate the potential of stereotactic body radiotherapy (SBRT) as an alternative treatment approach in VHL patients with multiple ccRCC. Patients with VHL and a diagnosis of ccRCC were enrolled. SBRT was conducted using five fractions of 10 Gy or eight fractions of 7.5 Gy. The primary endpoint was local control (LC). Secondary endpoints included alteration of renal function and adverse events. Seven patients with a total of eight treated lesions were enrolled. Median age was 44 years. Five patients exhibited multiple bilateral kidney cysts in addition to ccRCC. Three patients underwent at least one partial nephrectomy in the past. After a median follow-up of 43 months, 2-year LC was 100%, while 2-year CSS, 2-year PFS and 2-year OS was 100%, 85.7% and 85.7%, respectively. SBRT was very well tolerated with no acute or chronic toxicities grade ≥ 2. Mean estimated glomerular filtration rate (eGFR) at baseline was 83.7 ± 13.0 mL/min/1.73 m2, which decreased to 76.6 ± 8.0 mL/min/1.73 m2 after 1 year. Although the sample size was small, SBRT resulted in an excellent LC rate and was very well tolerated with preservation of kidney function in patients with multiple renal lesions and cysts.
Chronotherapy: Circadian Rhythms and Their Influence in Cancer Therapy
Authors: Amiama-Roig Ana , Verdugo-Sivianes Eva M. , Carnero Amancio , Blanco José-Ramón
Published: October 2022

Living organisms present rhythmic fluctuations every 24 h in their behavior and metabolism to anticipate changes in the environment. These fluctuations are controlled by a very complex molecular mechanism, the circadian clock, that regulates the expression of multiple genes to ensure the right functioning of the body. An individual’s circadian system is altered during aging, and this is related to numerous age-associated pathologies and other alterations that could contribute to the development of cancer. Nowadays, there is an increasing interest in understanding how circadian rhythms could be used in the treatment of cancer. Chronotherapy aims to understand the impact that biological rhythms have on the response to a therapy to optimize its action, maximize health benefits and minimize possible adverse effects. Clinical trials so far have confirmed that optimal timing of treatment with chemo or immunotherapies could decrease drug toxicity and increase efficacy. Instead, chronoradiotherapy seems to minimize treatment-related symptoms rather than tumor progression or patient survival. In addition, potential therapeutic targets within the molecular clock have also been identified. Therefore, results of the application of chronotherapy in cancer therapy until now are challenging, feasible, and could be applied to clinical practice to improve cancer treatment without additional costs. However, different limitations and variables such as age, sex, or chronotypes, among others, should be overcome before chronotherapy can really be put into clinical practice.
Single-Atom Catalysts: Preparation and Applications in Environmental Catalysis
Authors: Yu Xiaohui , Deng Jiguang , Liu Yuxi , Jing Lin , Hou Zhiquan , Pei Wenbo , Dai Hongxing
Published: October 2022

Due to the expensive price and the low reserve of noble metals in nature, much attention has been paid to single-atom catalysts (SACs)—especially single-atom noble metal catalysts—owing to their maximum atomic utilization and dispersion. The emergence of SACs greatly decreases the amount of precious metals, improves the catalytic activity, and makes the catalytic process progressively economic and sustainable. However, the most remarkable challenge is the active sites and their stability against migration and aggregation under practical conditions. This review article summarizes the preparation strategies of SACs and their catalytic applications for the oxidation of methane, carbon monoxide, and volatile organic compounds (VOCs) and the reduction of nitrogen oxides. Furthermore, the perspectives and challenges of SACs in future research and practical applications are proposed. It is envisioned that the results summarized in this review will stimulate the interest of more researchers in developing SACs that are effective in catalyzing the reactions related to the environmental pollution control.
Development of Silicon Carbide-Supported Palladium Catalysts and Their Application as Semihydrogenation Catalysts for Alkynes under Batch- and Continuous-Flow Conditions
Authors: Yamada Tsuyoshi , Yamamoto Haruka , Kawai Kanon , Park Kwihwan , Aono Norihiko , Sajiki Hironao
Published: October 2022

Silicon carbide (SiC)-supported palladium (Pd) catalysts [3% Pd/SiC and a 3% Pd-diethylenetriamine (DETA)/SiC complex] for chemoselective hydrogenation under batch- and continuous-flow conditions were developed. The alkyne, alkene, azide, nitro, and benzyloxycarbonyl-protected aromatic amine (N-Cbz) functionalities were chemoselectively reduced in the presence of 3% Pd/SiC. By contrast, benzyl ether, alkyl N-Cbz, epoxide, aromatic chloride, aromatic ketone, and tert-butyldimethylsilyl ether were tolerant to the 3% Pd/SiC-catalyzed hydrogenation. The combined use of 3% Pd/SiC and DETA demonstrated excellent chemoselectivity toward the semihydrogenation of various mono- and disubstituted alkynes under batch- and continuous-flow conditions. Furthermore, compared with the separate use of 3% Pd/SiC and DETA, the newly developed 3% Pd(DETA)/SiC-packed in a cartridge showed higher chemoselectivity toward the continuous-flow semihydrogenation of alkyne over 24 h.
Dual Immune Regulatory Roles of Interleukin-33 in Pathological Conditions
Authors: Guo Han , Bossila Elhusseny A. , Ma Xinran , Zhao Chenxu , Zhao Yong
Published: October 2022

Interleukin-33 (IL-33), a member of the IL-1 cytokine family and a multifunctional cytokine, plays critical roles in maintaining host homeostasis and in pathological conditions, such as allergy, infectious diseases, and cancer, by acting on multiple types of immune cells and promoting type 1 and 2 immune responses. IL-33 is rapidly released by immune and non-immune cells upon stimulation by stress, acting as an “alarmin” by binding to its receptor, suppression of tumorigenicity 2 (ST2), to trigger downstream signaling pathways and activate inflammatory and immune responses. It has been recognized that IL-33 displays dual-functioning immune regulatory effects in many diseases and has both pro- and anti-tumorigenic effects, likely depending on its primary target cells, IL-33/sST2 expression levels, cellular context, and the cytokine microenvironment. Herein, we summarize our current understanding of the biological functions of IL-33 and its roles in the pathogenesis of various conditions, including inflammatory and autoimmune diseases, infections, cancers, and cases of organ transplantation. We emphasize the nature of context-dependent dual immune regulatory functions of IL-33 in many cells and diseases and review systemic studies to understand the distinct roles of IL-33 in different cells, which is essential to the development of more effective diagnoses and therapeutic approaches for IL-33-related diseases.
The Cytotoxicity and Genotoxicity of Bioactive Dental Materials
Authors: Kunert Marta , Rozpedek-Kaminska Wioletta , Galita Grzegorz , Sauro Salvatore , Bourgi Rim , Hardan Louis , Majsterek Ireneusz , Lukomska-Szymanska Monika
Published: October 2022

The promotion of biologically based treatment strategies in restorative dentistry is of paramount importance, as invasive treatments should be avoided to maintain the tooth’s vitality. This study aimed to assess the biocompatibility of commercially available bioactive materials that can be used for dental pulp capping. The study was performed with a monocyte/macrophage peripheral blood SC cell line (ATCC CRL-9855) on the following six specific bioactive materials: ProRoot MTA (Dentsply Sirona), MTA Angelus (Angelus), Biodentine (Septodont), TheraCal LC (Bisco), ACTIVA BioACTIVE (Pulpdent) and Predicta Bioactive Bulk (Parkell). The cytotoxicity of the investigated agents was measured using a resazurin-based cell viability assay, while the genotoxicity was evaluated using an alkaline comet assay. Additionally, flow cytometry (FC) apoptosis detection was conducted with a FITC (fluorescein isothiocyanate) Annexin V Apoptosis Detection Kit I. FC cell-cycle arrest assessment was carried out with propidium iodide staining. The results of this study showed no significant cytotoxicity and genotoxicity (p > 0.05) in ProRoot MTA, MTA Angelus, Biodentine, ACTIVA BioACTIVE and Predicta Bioactive. Conversely, TheraCal LC presented a significant decrease (p < 0.001). In conclusion, due to excellent biocompatibility and low cytotoxicity, MTA, Biodentine, ACTIVA BioACTIVE and Predicta Bioactive may be suitable for pulp capping treatments. On the other hand, due to the high cytotoxicity of TheraCal LC, its use should be avoided in vital pulp therapies.
Articular Cartilage Regeneration through Bioassembling Spherical Micro-Cartilage Building Blocks
Authors: Grottkau Brian E. , Hui Zhixin , Pang Yonggang
Published: October 2022

Articular cartilage lesions are prevalent and affect one out of seven American adults and many young patients. Cartilage is not capable of regeneration on its own. Existing therapeutic approaches for articular cartilage lesions have limitations. Cartilage tissue engineering is a promising approach for regenerating articular neocartilage. Bioassembly is an emerging technology that uses microtissues or micro-precursor tissues as building blocks to construct a macro-tissue. We summarize and highlight the application of bioassembly technology in regenerating articular cartilage. We discuss the advantages of bioassembly and present two types of building blocks: multiple cellular scaffold-free spheroids and cell-laden polymer or hydrogel microspheres. We present techniques for generating building blocks and bioassembly methods, including bioprinting and non-bioprinting techniques. Using a data set of 5069 articles from the last 28 years of literature, we analyzed seven categories of related research, and the year trends are presented. The limitations and future directions of this technology are also discussed.
Therapeutic Strategies for Restoring Perturbed Corneal Epithelial Homeostasis in Limbal Stem Cell Deficiency: Current Trends and Future Directions
Authors: Masood Faisal , Chang Jin-Hong , Akbar Anosh , Song Amy , Hu Wen-Yang , Azar Dimitri , Rosenblatt Mark
Published: October 2022

Limbal stem cells constitute an important cell population required for regeneration of the corneal epithelium. If insults to limbal stem cells or their niche are sufficiently severe, a disease known as limbal stem cell deficiency occurs. In the absence of functioning limbal stem cells, vision-compromising conjunctivalization of the corneal epithelium occurs, leading to opacification, inflammation, neovascularization, and chronic scarring. Limbal stem cell transplantation is the standard treatment for unilateral cases of limbal stem cell deficiency, but bilateral cases require the use of cultured non-limbal autologous stem cell or allogeneic limbal stem cell transplantation. Herein we review the current therapeutic utilization of limbal stem cells. We also describe several limbal stem cell markers that impact their phenotype and function and discuss the possibility of modulating limbal stem cells and other sources of stem cells to facilitate the development of novel therapeutic interventions. We finally consider several hurdles for widespread adoption of these proposed methodologies and discuss how they can be overcome to realize vision-restoring interventions.
Could Curdlan/Whey Protein Isolate/Hydroxyapatite Biomaterials Be Considered as Promising Bone Scaffolds?—Fabrication, Characterization, and Evaluation of Cytocompatibility towards Osteoblast Cells In Vitro
Authors: Klimek Katarzyna , Palka Krzysztof , Truszkiewicz Wieslaw , Douglas Timothy E. L. , Nurzynska Aleksandra , Ginalska Grazyna
Published: October 2022

The number of bone fractures and cracks requiring surgical interventions increases every year; hence, there is a huge need to develop new potential bone scaffolds for bone regeneration. The goal of this study was to gain knowledge about the basic properties of novel curdlan/whey protein isolate/hydroxyapatite biomaterials in the context of their use in bone tissue engineering. The purpose of this research was also to determine whether the concentration of whey protein isolate in scaffolds has an influence on their properties. Thus, two biomaterials differing in the concentration of whey protein isolate (i.e., 25 wt.% and 35 wt.%; hereafter called Cur_WPI25_HAp and Cur_WPI35_HAp, respectively) were fabricated and subjected to evaluation of porosity, mechanical properties, swelling ability, protein release capacity, enzymatic biodegradability, bioactivity, and cytocompatibility towards osteoblasts in vitro. It was found that both biomaterials fulfilled a number of requirements for bone scaffolds, as they demonstrated limited swelling and the ability to undergo controllable enzymatic biodegradation, to form apatite layers on their surfaces and to support the viability, growth, proliferation, and differentiation of osteoblasts. On the other hand, the biomaterials were characterized by low open porosity, which may hinder the penetration of cells though their structure. Moreover, they had low mechanical properties compared to natural bone, which limits their use to filling of bone defects in non-load bearing implantation areas, e.g., in the craniofacial area, but then they will be additionally supported by application of mechanically strong materials such as titanium plates. Thus, this preliminary in vitro research indicates that biomaterials composed of curdlan, whey protein isolate, and hydroxyapatite seem promising for bone tissue engineering applications, but their porosity and mechanical properties should be improved. This will be the subject of our further work.
Compartmentation of cGMP Signaling in Induced Pluripotent Stem Cell Derived Cardiomyocytes during Prolonged Culture
Authors: Faleeva Maria , Diakonov Ivan , Srivastava Prashant , Ramuz Masoud , Calamera Gaia , Andressen Kjetil , Bork Nadja , Tsansizi Lorenza , Cosson Marie-Victoire , Bernardo Andreia , Nikolaev Viacheslav , Gorelik Julia
Published: October 2022

The therapeutic benefit of stimulating the cGMP pathway as a form of treatment to combat heart failure, as well as other fibrotic pathologies, has become well established. However, the development and signal compartmentation of this crucial pathway has so far been overlooked. We studied how the three main cGMP pathways, namely, nitric oxide (NO)-cGMP, natriuretic peptide (NP)-cGMP, and β3-adrenoreceptor (AR)-cGMP, mature over time in culture during cardiomyocyte differentiation from human pluripotent stem cells (hPSC-CMs). After introducing a cGMP sensor for Förster Resonance Energy Transfer (FRET) microscopy, we used selective phosphodiesterase (PDE) inhibition to reveal cGMP signal compartmentation in hPSC-CMs at various times of culture. Methyl-β-cyclodextrin was employed to remove cholesterol and thus to destroy caveolae in these cells, where physical cGMP signaling compartmentalization is known to occur in adult cardiomyocytes. We identified PDE3 as regulator of both the NO-cGMP and NP-cGMP pathway in the early stages of culture. At the late stage, the role of the NO-cGMP pathway diminished, and it was predominantly regulated by PDE1, PDE2, and PDE5. The NP-cGMP pathway shows unrestricted locally and unregulated cGMP signaling. Lastly, we observed that maturation of the β3-AR-cGMP pathway in prolonged cultures of hPSC-CMs depends on the accumulation of caveolae. Overall, this study highlighted the importance of structural development for the necessary compartmentation of the cGMP pathway in maturing hPSC-CMs.
“Sharpening Your Mind, Strengthening Your Body” Parental Perceptions on the Use of Strength and Conditioning in Children and Youth
Authors: Duncan Michael Joseph , Martins Ricardo Manuel Gonçalves , Eyre Emma Lisa Jane
Published: October 2022

Although strength and conditioning is beneficial and safe for children to engage in there remain myths and misconceptions form parents regarding its use which prevent its widespread take up. This study explored parents’ attitudes and beliefs about strength and conditioning in their children. Thirty-one parents (21 dads, 10 mums) took part in one of four focus groups exploring the topic. Thematic analysis was used resulting in themes and sub themes centred on: Beliefs; Determinants; Coach Education; Coach Communication; and Relationship to the Game. There were also smaller aspects of the focus groups which touched upon autonomy as a concept related to implementation of strength and conditioning specifically. Overall, parents of children who play grassroots sport hold generally positive perceptions on use of strength and conditioning with their children, considering it beneficial for both physical and mental development. Key factors relating to successful implementation of strength and conditioning for children focus on having a qualified coach in that particular area (rather than a generic sports coach), effective communication between coach and parents, and coach and children in terms of the benefits of engaging with strength and conditioning.
The Moderating Role of Maternal Education and Employment on Child Health in Pakistan
Authors: Asif Muhammad Farhan , Ali Shafaqat , Ali Majid , Abid Ghulam , Lassi Zohra S.
Published: October 2022

Background: Pakistan has challenges in fulfilling its universal responsibilities of providing better health facilities to everyone. The Sustainable Development Goals (SDGs) aim to reduce maternal and infant mortality rates. Despite declines in mother and child death, the total mortality ratio has marginally increased. However, neonatal death has not decreased significantly. Family planning is important for controlling population growth and improving child as well as maternal health. Pakistan’s government has unceasingly tried to enhance the provision of contraceptive facilities, but still, an unmet need for family planning (UMNFP) exists in our country. Women are said to have UMNFP if they want to limit or space childbearing, but they are not using contraception methods for any reason. The study aimed to explore the effect of the UMNFP and to investigate the moderating role of a mother’s education and employment status on a child’s health. Methods: We analyzed the data of 2,244 women in this study. To investigate the study objectives, we utilized the secondary dataset of the Pakistan Demographic and Health Survey (PDHS) 2017–18 (publicly available on the website of the National Institute of Population Studies) and applied binary logistic regression using SPSS 24. Results: Results suggest a positive effect of a woman’s age (25 to 39 years), maternal education (higher), father’s education (higher), family’s wealth status (richest), mass media exposure, and adequate birth spacing (at least for 33 months) on a child’s health. On the other hand, there is an indirect association between maternal employment, unmet need for family planning, and a child’s health. The moderating role of maternal education and employment on the relationship between household wealth status and a child’s health is positive. Conclusions: We conclude that the strong predictors of child health are UMNFP, maternal education, and employment. The link between the met need for family planning and the child’s health is positive. The moderating effect of maternal education and household wealth status on a child’s health is progressive. Similarly, the interaction effect of a mother’s employment and household wealth status on a child’s health is positive. Finally, we concluded that the link between the health of the child and household wealth status is much more diverse and positive when the mother is highly educated and currently employed.
The Joint Effect of Perceived Psychosocial Stress and Phthalate Exposure on Hormonal Concentrations during the Early Stage of Pregnancy: A Cross-Sectional Study
Authors: Hlisníková Henrieta , Nagyová Miroslava , Kolena Branislav , Mlynček Miloš , Trnovec Tomáš , Petrovičová Ida
Published: October 2022

Phthalates alter the hormonal balance in humans during pregnancy, potentially affecting embryonic and fetal development. We studied the joint effect of exposure to phthalates, quantified by urinary phthalate metabolite concentration, and perceived psychological stress on the concentration of hormones in pregnant women (n = 90) from the Nitra region, Slovakia, up to the 15th week of pregnancy. We used high-performance liquid chromatography, tandem mass spectrometry (HPLC-MS/MS), and electro-chemiluminescence immunoassay to determine urinary concentrations of phthalates and serum concentrations of hormones, respectively. We used Cohen perceived stress scale (PSS) to evaluate the human perception of stressful situations. Our results showed that mono(carboxy-methyl-heptyl) phthalate (cx-MiNP) and a molar sum of di-iso-nonyl phthalate metabolites (ΣDiNP) were negatively associated with luteinizing hormone (LH) (p ≤ 0.05). Mono(hydroxy-methyl-octyl) phthalate (OH-MiNP) and the molar sum of high-molecular-weight phthalate metabolites (ΣHMWP) were positively associated with estradiol (p ≤ 0.05). PSS score was not significantly associated with hormonal concentrations. When the interaction effects of PSS score and monoethyl phthalate (MEP), cx-MiNP, ΣDiNP, and ΣHMWP on LH were analyzed, the associations were positive (p ≤ 0.05). Our cross-sectional study highlights that joint psychosocial stress and xenobiotic-induced stress caused by phthalates are associated with modulated concentrations of reproductive hormones in pregnant women.
Recent Report on the Hydrothermal Growth of LiFePO4 as a Cathode Material
Authors: Vernardou Dimitra
Published: October 2022

Various growth processes have been utilized for the development of lithium iron phosphate including microwave treatment, spray thermal decomposition, sol-gel and the hydrothermal route. However, microwave treatment, spray process and sol-gel suffer from high costs and difficulties in controlling growth parameters. In this review paper, recent synthetic strategies, including the raw materials utilized for the hydrothermal growth of lithium iron phosphate, their effect on the basic characteristics and, as a consequence, the electrochemical performance of cathodes, are reported. The advantages of the hydrothermal process, including high material stability, eco-friendliness, low production costs and material abundance, are explained along with the respective processing parameters, which can be easily tuned to modify lithium iron phosphate characteristics such as structure, morphology and particle size. Specifically, we focus on strategies that were applied in the last three years to improve the performance and electrochemical stability of the cathode utilizing carbon-based materials, N-doped graphene oxide and multi-wall carbon nanotubes (MWCNTs), along with the addition of metallic nanoparticles such as silver. Finally, future perspectives on the hydrothermal process are discussed including the simultaneous growth of powders and solid-state electrodes (i.e., growth of lithium iron phosphate on a rigid substrate) and the improvement in morphology and orientation for its establishment and standardization for the growth of energy storage materials.
Biomaterials in Orthopedic Devices: Current Issues and Future Perspectives
Authors: Filip Nina , Radu Iulian , Veliceasa Bogdan , Filip Cristiana , Pertea Mihaela , Clim Andreea , Pinzariu Alin Constantin , Drochioi Ilie Cristian , Hilitanu Remus Lucian , Serban Ionela Lacramioara
Published: October 2022

In orthopedics, bone fixation imposes the use of implants in almost all cases. Over time, the materials used for the implant have evolved from inert materials to those that mimic the morphology of the bone. Therefore, bioabsorbable, biocompatible, and bioactive materials have emerged. Our study aimed to review the main types of implant materials used in orthopedics and present their advantages and drawbacks. We have searched for the pros and cons of the various types of material in the literature from over the last twenty years. The studied data show that consecrated metal alloys, still widely used, can be successfully replaced by new types of polymers. The data from the literature show that, by manipulating their composition, the polymeric compounds can simulate the structure of the different layers of human bone, while preserving its mechanical characteristics. In addition, manipulation of the polymer composition can provide the initiation of desired cellular responses. Among the implanting materials, polyurethane is distinguished as the most versatile polymeric material for use both as orthopedic implants and as material for biomechanical testing of various bone reduction and fixation techniques.
Adsorption Capacity of Plastic Foils Suitable for Barrier Resuscitation
Authors: Holczmann Philipp , Lederer Wolfgang , Isser Markus , Klinger Andreas , Jürschik Simone , Wiesenhofer Helmut , Mayhew Chris A. , Ruzsanyi Veronika
Published: October 2022

Chest compressions and ventilation attempts can generate aerosols during resuscitation. It is important to determine whether different materials suitable for the blanketing of cardiac arrest patients can diminish exposure to aerosols. In this study, three volatile organic compounds, ethanol, acetone, and isoprene, commonly found in human breath in moistened air, acted as substitutes for aerosols. Here, we present information on the adsorption of these volatiles to three blanketing materials: polyvinyl chloride, polyethylene, and aluminum coated polyethylene terephthalate. After exposure to the surfaces of these materials the test volatiles were quantified by the proton transfer reaction-time of flight-mass spectrometry. There was a trend towards a potentially higher reduction for acetone (p = 0.071) and isoprene (p = 0.050) on polyethylene, compared to polyvinyl chloride and aluminum coated polyethylene terephthalate during the rise interval. Adsorption capacity did not differ between the foils and was between 67% and 70%. From our studies, we propose that the aluminum-coated polyethylene terephthalate surface of space blankets prove adequate to diminish exposure to volatiles in moistened air, and hence to aerosols.
Numerical Study on Particle Behavior and Deposition Accuracy in Cold Spray Additive Manufacturing
Authors: Garmeh Saeed , Jadidi Mehdi
Published: October 2022

Cold Spray additive manufacturing (CSAM) is an emerging technique to fabricate freestanding objects by depositing solid-state layers of materials. Thanks to its remarkable deposition rate and maneuverability, it can be tailored to manufacturing intricate geometries in aerospace industries. In comparison to other additive manufacturing techniques, it is the processing speed, solid-state deposition, and the cost that make CSAM unique. In this study, CSAM process was modeled for a system comprised of a high-pressure cold spray gun with axial powder injection. To represent the flow structure around the already built objects and the deposited layers of CSAM, three walls with different profiles are placed on a flat substrate. In this work, the gas-particle behaviors are studied at the vicinity of these non-axisymmetric objects that can be generalized to more complex geometries and the applications of CSAM. The model is 3D and aluminum and copper powders were used for the feedstock. The particles’ conditions upon impact, such as particles’ footprint and normal impact velocities are studied. The numerical results show that the deviation of particles which is caused by the supersonic flow inside the nozzle and the shock waves outside the nozzle defines the accuracy of the deposition. Furthermore, the results manifest the particle’s material and size have a significant influence on the acquired velocities and trajectories of the particles, and consequently on the resolution of the process. It is found that the profile of the deposited layers has some effects on the gas flow near the substrate which plays a role in the dispersion of fine particles.
Regulating Monolayer Aligned Silver Nanowire Coatings for Energy-Saving Windows
Authors: Yu Zhongrui , Ma Huirong , Shao Yuqiu , Yu Xiaole , Chen Jingjing , Dong Chenlong , Mao Zhiyong , Wang Dajian
Published: October 2022

Low-emissivity (low-e) glass has garnered considerable attention for implementation in energy-saving windows, which can effectively decrease the energy consumption of buildings. However, the traditional vacuum-coating technology of low-e films greatly enhances the cost of energy-saving windows, and the influence of the vacuum-coating parameters on the optical characteristics of low-e films necessitates a complex optimization process. Herein, we prepared Ag NWs with controllable diameters using the polyol method, and the alignment of the Ag NW film coating on glass substrates was regulated by the shear force of the liquid flow generated through magnetic stirring. After optimization, the low-εMIR windows based on aligned Ag NW (60 nm) coatings showed an optical transmittance of 84.4% and a low εMIR of 0.3, which were superior to those of commercial low-εMIR glass (T: 65.6%; εMIR: 0.4). The simplicity and low cost of aligned Ag NW coatings for low-e glass open up a new avenue for reducing energy consumption in existing windows.
Advances on Cr and Ni Electrodeposition for Industrial Applications—A Review
Authors: Okonkwo Bright O. , Jeong Chaewon , Jang Changheui
Published: October 2022

Electrodeposition of chromium (Cr) and nickel (Ni) and their alloys have been subjects of interest for a long time. Owing to their special features such as high corrosion resistance, good wear resistance, lustrous nature etc., Cr and Ni electrodeposit continue to be the subject of investigation and further development, and improvements in their qualities and application remain one of the aims. This paper reviews the advances made so far in Cr and Ni electrodeposited coatings, with special emphasis on showing the potential of the process for achieving high-quality coatings. Furthermore, this review focuses on the mechanisms involved in Cr and Ni electrodepositions, with the aim of understanding the basis and manipulating the processes to produce coatings with excellent features and high-end usage. The issues encountered in the electrodeposition processes and products, as well as proffered solutions via research and development, were also addressed. Finally, long-term prospects and applications of these coatings were discussed to provide powerful and complementary toolkits for engineering applications while enabling future advances in critical aspects identified.
Effect of Nanodiamond Content in the Plating Solution on the Corrosion Resistance of Nickel–Nanodiamond Composite Coatings Prepared on Annealed 45 Carbon Steel
Authors: Wang Dongai , Li Feihui , Liu Meihua , Zhang Wengang , Yu Xiaohan , Da Wei
Published: October 2022

A nickel-nanodiamond composite coating was prepared on the surface of annealed 45 carbon steel by double-pulse electrodeposition. The effect of nanodiamond particle content on the surface morphology, grain size and wear and corrosion resistance of the composite coating were investigated. According to the analysis of the test results of X-ray diffractometry and scanning electron microscopy, it was found that the cathodic polarization of the electrodeposition process was enhanced after the addition of nanodiamond particles to the Watts nickel plating solution. The positively charged nanodiamond particles on the surface facilitate the reduction reaction at the cathode. Nanodiamond particles provide crystalline growth sites for the non-spontaneous nucleation of nickel atoms. As the addition of nanodiamond particles increases, the diffusely distributed nanodiamond particles are able to attract more nickel ions to deposit nuclei, and its fine crystallization effect increases, resulting in improved wear resistance and corrosion resistance of the composite plating. Among the results, the polarization potential was the smallest when the nanodiamond content in the plating solution was 10 g/L. The surface of the prepared nickel-nanodiamond composite coating was relatively flat and smooth, with good density and a uniform grain size distribution, and the content of element C on the surface of the composite coating was the largest, reaching 1.99%.