bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface bio-interactions stand at the base of the short-term nano CuO-induced cell oxidative stress: insights for a safe(r)-by-design approach
Authors: Mantecca Paride , Moschini Elisa , Colombo Graziano , Chirico Giuseppe , Capitani Giancarlo , Dalle-Donne Isabella
Published: April 2022

Background:It is well known that copper oxide nanoparticles (CuO NPs) are heavily toxic on in vitro systems. In human alveolar epithelial cells, the mechanism of toxicity is mostly related to oxidative insults, coming from intracellularly dissolved copper ions, finally leading to apoptotic or autophagic cell death.Our hypothesis is based on possible early oxidative events coming from specific NP surface reactivity able to undermine the cell integrity and to drive cell to death, independently from lysosomal-enhanced Trojan horse mechanism. Two types of CuO NPs, with different oxidative potential, were selected and tested on A549 cells for 1h and 3h at 10, 25, 50 and 100 mg/mL. Cells were then analyzed for viability and oxidative change of the proteome. Oxidative by-products were localized by immunocytochemistry and cell-NP interactions characterized by confocal and electron microscopy techniques.Results:CuO NPs induced oxidative changes soon after 1 h exposure as revealed by the increase in protein carbonylation and reduced-protein-thiol oxidation. In parallel, cell viability significantly decreased, as shown by MTT assay. Such effects were higher for CuO NPs with more crystalline defects and with higher ROS production than for fully crystalline NPs. At these exposure times, although NPs efficiently interacted with cell surface and were taken up by small endocytic vesicles, no ion dissolution is visible inside endo-lysosomal compartment and no effects were produced by extracellularly dissolved copper ions.Conclusions:A specific NP surface-dependent oxidative cell injury was demonstrated. More detailed studies are required to understand which targets precociously react to CuO NPs, but these results introduce new paradigms for the toxicity of the metal-based NPs, beyond the Trojan horse-related mechanism, and opens-up new opportunities to investigate the interactions and effects at the bio-interface for designing safer as well as more effective CuO-based biocides.
Clinical and therapeutic patterns of lower extremity amputation (LEA) in a tertiary hospital in Togo: a retrospective study
Authors: KOUEVI-KOKO Têtê Edem , Amouzou Komla Sena , Sogan Ananivi , Apeti Sodjehoun , Dakey Yao Eme Lumière , Abalo Anani
Published: April 2022

Background
We analysed the clinical and therapeutic profile of the patients who underwent a surgical lower extremity amputation (LEA) in Togo.
Methods
Retrospective study based on clinical files of the adult patients who underwent a LEA at a single centre (Sylvanus Olympio Teaching Hospital, SOTH) from 1st January 2010 to 31st December 2020. We analysed files with 95% of the studied parameters and excluded those with less than 5%. Data were analysed by CDC Epi Info Version 7 and Microsoft Office Excel 2013 software.
Results
We included 245 cases. The mean age was 59.62 years (15.22SD) (range 15 to 90 years), the sex ratio, 1.99. The medical history of diabetes mellitus was found in 143/222 (64.41%). Gangrene was diagnosed in 212/245 (86.53%) patients; crush syndrome in 23/245 (9.39%); bone tumour in 5/245 (2.04%); osteomyelitis in 2/245 (0.82%); chronic ulcer in 2/245 (0.82%); necrosis fasciitis in 1/245 (0.40%). A Doppler-ultrasound of the lower limbs was performed in 91/245 (37.14%) cases. The anatomical site of LEA found in 241/245 (98.37%) files was leg in 133/241 (55.19%), knee in 14/241 (5.81%), thigh in 83/241 (34.44%), and foot in 11/241 (4.56%) patients. The mean delay from the indication of amputation to surgery retrieved in 239/245 (97.55%) files was 6.75 (1–78) days (11.59 SD). The immediate postoperative complications have been reported in 242/245 (98.78%) files, and no complication in 234/242 (96.69%). There were early complications in 56/238 (23.53%) patients. The mortality rate after LEA was 17/238 (7.14%). The mean duration of hospitalization marked in 241/245 (98.37%) files was 36.30 (1-278) days (36.20SD).
Conclusion
Most patients admitted to SOTH (Lomé, Togo) who underwent LEA had diabetes mellitus at the late presentation, which led to challenging complications. This result entails essential information campaigns to prevent diabetes mellitus and cardiovascular diseases.
The Pattern of Cardiovascular Disease Risks among Working People (18-64 years) via a Nationwide Household-based Survey in Malaysia
Authors: Awaluddin S Maria , Lim Kuang Kuay , Shawaluddin Nor Syaqilah , Lah Tuan Amin Tuan , Robat Rosnawati Muhamad , Mahjom Maznieda , Yussof Muhammad Fadhli Mohd
Published: April 2022

Background: Cardiovascular diseases (CVDs) are prevalent globally and are increasing tremendously. This article aimed to determine the prevalence and prevalence odds ratio of seven CVD risks among working people (18-64 years) in Malaysia.Methods: A cross-sectional study among a nationally representative sample in Malaysia was conducted using a validated questionnaire. Clinical procedures were performed by registered nurses to measure glucose, cholesterol, body mass index and blood pressure. The prevalence and prevalence odds ratio were calculated via complex sample data analysis of IBM SPSS Statistics version 25.Results: The overall prevalence of CVD risks among working people was 14.1%, 17.3%, 24.5%, 28.8%, 31.7%, 45.9% and 94.2% for diabetes, obesity, hypertension, physical inactivity, tobacco smoking, hypercholesterolemia and inadequate fruit and vegetable (FV) intake, respectively. This study found that older age was associated with the odds of having the most CVD risks. Males were associated with higher odds of having hypertension and tobacco smoking, whereas females were more likely to have hypercholesterolemia, obesity, and physical inactivity. Those who worked as manager & senior officials, clerical workers and services & sales workers were physically inactive, while workers from the lower educational level were more likely to smoke tobacco. Workers in the public sector were more likely to have a higher prevalence of diabetes, hypertension, hypercholesterolemia, smoking and obesity than workers in the private sector.Conclusions: This study highlighted that working people have significant CVD risks and a regular medical screening should be conducted at workplace settings.
Estimating and Validating the Structure of Feeding Behavior Networks
Authors: Zhang Hao , Li Xinrui , Lu Zhou , Zhang Haiyue , Yang Zhe , Wang Yue , Zhang Yuhai , Jiang Xun , Shang Lei
Published: April 2022

Purpose Network analysis has been widely used in psychometrics over the past decade, yet it is unknown that whether this methodology could be applied in the field of child health assessment such as caregivers’ feeding behavior and child eating behavior. Our study leveraged network psychometrics method to estimating and examining the network structure of Chinese Preschoolers’ Caregivers’ Feeding Behavior Scale (CPCFBS), and compared the applicability of network methods in the feeding behavior scale.Methods The CPCFBS was applied in a sample of 768 preschoolers’ caregivers. Network structure was estimated with Gaussian Graphical Model. Dimensionality was detected using Exploratory Graph Analysis (EGA). The network structural consistency was tested using EGA bootstrap. The network structure was compared with the original structure using model fit indices and reliability. ResultsA seven-dimensional EGA network was explored after rearranging four items and deleting one item with unstable structural consistency. The absolute fit and relative fit of EGA structure were better than the original structure. The EGA structure had nearly same values of the reliability with the original structure. Conclusion Our study presented a novel perspective for feeding behavior analytical strategies and demonstrated that network analysis was applicable and superior in exploring the structure of feeding behavior scales.Level of evidence Level V, cross-sectional descriptive study.
Tailor the Deacetylation for High Yield Preparation of Carboxyl β-Chitin Nanofibers from Squid Pen by TEMPO Oxidation
Authors: Liu Daying , Huang Shasha , Wu Hao , Zhang Jianming
Published: April 2022

2,2,6,6-tetramethylpiperidine-1-oxyl-radical (TEMPO) oxidized is a classical method to obtain carboxyl chitin nanomaterials, but when the traditional TEMPO/NaBr/NaClO (TBN) oxidation system was oxidizing β-chitin, it was only suitable for β-chitin with a degree of deacetylation (DD) of 1%. Herein, the high yield carboxyl β-chitin nanofibers (CO-ChNFs) were successfully prepared from squid pen β-chitin with partially deacetylated (DD: 5–30%) using the TEMPO/NaClO/NaClO2 (TNN) oxidation system. The results show that the DD of purified β-chitin has a great impact on the yield of CO-ChNFs, and the yield is as high as 98% when the DD of β-chitin was 11%. XRD results showed that β-chitin undergoes slight of β-α transformation after TNN TEMPO oxidation, and the 010 crystal planes are arranged more closely. AFM characterization suggests that thus prepared CO-ChNFs have a diameter of 2–6 nm and a length in the micrometer range. The proposed preparation method breaks through the previous limitation of TEMPO oxidation in the application of β-chitin, and will facilitate the in-depth research and application of carboxyl β-chitin nanofibers.
Phytosomal curcumin elicits potent protective responses in post-surgical adhesion band formation by decreasing inflammation and fibrosis
Authors: Askarnia-Faal Mohammad-Mostafa , Sayyed-Hosseinian Sayyed-Hadi , Nazari Seyedeh Elnaz , Asgharzadeh Fereshteh , Ghasemi Haniyeh , Avan Amir , Eskandari Moein , Alaei Maryam , Naimi Hamideh , Soleimani Atena , Alalikhan Abbas , Mohammadzadeh Reza , Hassanian Seyed Mahdi , Khazei Majid
Published: April 2022

Background
In this study we investigated the therapeutic potential of the phytosomal form of pharmacologically active component of Curcuma longa, curcumin, in attenuating Post-operative adhesion bands (PSAB) formation in both peritoneal and peritendinous surgeries in animal models.
Methods
Bio-mechanical, Histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin.
Results
Our results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. We showed that curcumin could decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models.
Conclusion
These results suggest that the anti-inflammatory and anti-fibrotic properties of phytosomal curcumin, has therapeutic potential for preventing PSAB formation.”
Forest Bathing and Hiking benefits for mental health during the Covid-19 pandemic in Mediterranean regions
Authors: Muro Anna , Mateo Corel , Parrado Eva , Subirana-Malaret Montse , Moya Montserrat , Garriga Adrià , Canals Josep , Chamarro Andrés , Sanz Antoni
Published: April 2022

Forest Bathing (FB) is a nature-therapeutic modality that has evidenced positive effects on individuals’ mental health and it is also considered a sustainable touristic activity. However, its benefits have mainly been studied in Asian biomes and more cross-cultural research is needed to evaluate if its benefits are also generalizable to other forests and biomes of the world, such as the Mediterranean. Accordingly, 86 healthy adults of the general population were assessed before and after a FB near Barcelona (Spain) during the COVID-19 pandemic. A control hiking-group of participants was also analysed to contrast the FB effects on anxiety, affect, mood states and mindfulness. Results have shown that the guided practice of FB in Mediterranean-Catalan forests enhances significanlty mindfulness states and positive affect and reduces anxiety and negative affect, with effect sizes being large to very large. Hiking also induced significant changes in all variables tested, but FB showed higher effect sizes. An exploratory analysis also revealed a different profile of the FB participants compared to the hiking practitioners, being highly educated women living in urban areas and with lower basal levels of psychological wellbeing. Accordingly, it is concluded that both Mediterranean FB and hiking (to a lesser degree), might be cost-effective strategies to promote and restore psychological well-being after the Covid-19 pandemic and to promote sustainable tourism in Mediterranean biomes of the European forested and protected areas.
Highway Lane Detection and Vehicle Monitoring
Authors: Satpute Vishal , Das Siddharth , Rexy Joshin
Published: April 2022

It is a well-known fact that perception of road (lane) plays a vital role in assisting drivers by using software that can convey them the possible risks in their surroundings. Lane lines are a significant factor of signaling traffic flow. The strategy of this work is to prevent car accidents on highways mainly due to rash driving that consists of sudden lane departure or not keeping up with the lane in case of curved roads. Hence, we propose a method to reduce these crashes by mounting a calibrated camera on the vehicle which will continuously keep track of the view in front of vehicle and deliver certain relevant warnings to the driver in case of any rash driving or fatal situations. Also, it can be helpful for self-driving cars by providing a wide range of possibilities to learn by software and move vehicle on its own in the lane. We employ image processing techniques to detect and solve some of the most prevalent roadway concerns. The problem statement is broken down into basic building blocks to better understand the comprehensive list of potential techniques within this framework. It comes with a decision model that will provide the driver the required cautions.
Bioinformatic approach to biological processes and metabolic pathways of language gene ROBO1 and co-expressed genes
Authors: Limón-Fernández Héctor Adrián
Published: April 2022

Multiple genes have been associated with normal and abnormal development of brain and language processes; such is the case of ROBO1. It is relevant to clarify the biological processes and metabolic pathways to which this gene contributes and those that are co-expressed with it. The purpose of this study was to describe the biological processes and metabolic pathways involved in the co-expression of ROBO1 in human brain tissue. The data collected for this study were taken from transcriptomics databases (AHBA, SEEK and COXPRESdb), to later elaborate interactomes (STRING) and a determination of the most relevant biological processes and metabolic pathways (DAVID) in the co-expression of ROBO1. The biological processes of axon guidance, neuronal projection and neuronal migration were found to be the ones with the greatest coincidence and significance; in addition to the metabolic pathway of endocytosis. It is concluded that the endocytosis pathway is relevant for the projection and guidance of axons, as well as the formation of neural networks.
Underweight children are agile but lack power
Authors: Verbecque Evi , Coetzee Dané , Smits-Engelsman Bouwien
Published: April 2022

Given the knowledge gap in literature on the impact of undernutrition on muscular power and agility in school-aged children, the aim of this study was to compare physical fitness in such underweight- and normal weight children. In this cross-sectional study, 853 children were included (459 boys; mean age: 9.2 (1.8) years). The children were grouped according to their BMI-for-age-and-sex: normal weight (-1≤z-score<2) and underweight (z-score<-1). Within the underweight group, three thinness subgroups were composed: grade 1 (-2≤z-score<-1), grade 2 (-3≤z-score<-2) and grade 3 (z-score<-3). Their agility, muscular endurance and power were assessed with the PERFormance FITness test battery (PERF-FIT). Regardless the country they lived in, the underweight children showed better agility (p=0.012) and muscular endurance (p=0.004) than those with normal weight. They presented with lower muscular power than the normal weight group, shown by significantly shorter overhead throwing distances (p=0.017) and less standing long jump peak power (p<0.001). The standing long jump peak power decreased further with increasing thinness grade (p=0.027).Conclusion: Underweight children are more agile, but have lower muscular power compared to their normal weight peers. Its relationship with motor competence and physical activity, necessitates attention for tackling muscular strength deficiencies in these children, enabling them to meet the basic requirements for a healthy life style later in life.
Skeletal Muscle Proteostasis Promotes Central Nervous System Rejuvenation and Reduces Neuroinflammation during Aging and Neurodegenerative Disease
Authors: Matthews Ian , Birmbaum Allison , Gromova Anastasia , Coutinho Kristen , McGraw Megan , Patterson Dalton , Banks Macy , Nobles Amber , Nguyen Nhaty , Miranda Helen , Spada Albert La , Cortes Constanza
Published: April 2022

Skeletal muscle has recently arisen as a novel regulator of Central Nervous System (CNS) function and aging, secreting bioactive molecules known as myokines with proteostasis and metabolism-modifying functions in targeted tissues, including the CNS. Here we report the generation of a novel transgenic mouse with enhanced skeletal muscle proteostasis via moderate overexpression of master regulator of proteostasis and lysosomal function Transcription Factor E-B. We have discovered that the resulting enhanced muscle proteostasis function significantly ameliorates proteotoxicity, reduces neuroinflammation and promotes transcriptional remodeling of the aging CNS, preserving cognition and memory in aging mice. Enhancing skeletal muscle proteostasis also reduces neuroinflammation and accumulation of tau-associated pathological hallmarks in a mouse model of tau pathology. Our results implicate maintenance of skeletal muscle proteostasis throughout aging to direct regulations of the aging CNS metabolism and function, and suggest that skeletal-muscle originating factors may act as novel therapeutic targets against age-associated neurodegenerative diseases.
Integrating network pharmacology and in vitro experiment to investigate the protective effects of semen cuscutae flavonoid on sertoli cells and blood-testis barrier in male infertility under heat stress
Authors: Liu Chenxiao , Hu Suqin , Liu Dianlong , Xu Yahui , Hu Ke , Guo Jian
Published: April 2022

Background: Semen cuscutae is one of the common drugs used in treating male infertility (MI) in Traditional Chinese Medicine (TCM), and semen cuscutae flavonoid (SCF) is the main active component of semen cuscutae. The mechanism of SCF on sertoli cells (SCs) and blood-testis barrier (BTB) in male infertility under heat stress have not been clarified yet. Methods: Here, network pharmacology were used to explore the targets and signaling pathways of SCF in the treatment of MI. Then, in vitro experiments were integrated to verify the results of network pharmacology. In the in vitro experiments, the cell viability was measured by performing the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Ki67 and AR expression were detected by performing immunohistochemistry staining, and AR, Akt, CK-18, and Occludin levels were measured using western blotting. The Akt inhibitor assay was further performed to elucidate the signaling pathway underlying the function of SCF.Result: The data showed a total of 136 potential therapeutic targets of SCF, including HPS90AA1, SRC, JUN, TP53, MAPK1, AKT1, etc., were identified. In vitro experiments suggested that SCF significantly improved the viability of SCs, upregulated the expression of AR, Akt, Occludin, and Ki67, and downregulated the expression of CK-18. After adding the Akt inhibitor to block the PI3K-Akt signaling pathway, the effect of SCF decreased, indicating that SCF regulates the PI3K-Akt signaling pathway via AR, and then regulates occludin, Ki67, and CK-18. Gene ontology (GO) enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) pathway analyses also suggested that SCF regulates cell proliferation and differentiation mainly via the PI3K-Akt signaling pathway. Conclusions: We suggested that the active components of SCF can promote AR expression, and regulate the PI3K-Akt signaling pathway and its downstream factors (occludin, Ki67, and CK-18), to regulate the viability, proliferation, differentiation, and BTB permeability of SCs, ultimately protecting reproductive ability.
The Percentage of ALK-Positive Cells and the Efficacy of First-Line Alectinib in Advanced Non-small Cell Lung Cancer: Is it a novel factor for stratification? (Turkish Oncology Group Study)
Authors: Hizal Mutlu , Bilgin Burak , Paksoy Nail , Atcı Muhammed Mustafa , Kahraman Seda , Kılıçkap Saadettin , Keskinkılıç Merve , Ayhan Murat , Eren Önder , Mustafayev Fatma Nihan Akkoç , Yaman Şebnem , Bayram Ertuğrul , Ertürk İsmail , Özcan Erkan , Korkmaz Mustafa , Akagündüz Baran , Erdem Dilek , Telli Tuğba Akın , Aksoy Asude , Üskent Necdet , Baytemür Naziyet Köse , Gülmez Ahmet , Aydın Dinçer , Şakalar Teoman , Arak Hacı , Tatlı Ali Murat , Ergün Yakup , Ak Naziye , Ünal Çağlar , Özgün Mehmet Alpaslan , Yalçın Bülent , Öztop İlhan , Algın Efnan , Sakin Abdullah , Aydıner Adnan , Yumuk Perran Fulden , Şendur Mehmet Ali Nahit
Published: April 2022

Introduction: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI.Materials and Methods: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥40% and low-positive group <40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells.Results: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n=78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n=113) but it was 10.8 months in the low-positive group (n=98) (HR: 0.39; 95% CI, 0.25-0.60, p<0.001). The median OS in the high positive group was not reached, whereas it was 22.8 months in the low positive group (HR: 0.37; 95% CI, 0.22-0.63, p<0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p=0.002). According to the cutoff values of <20%, 20-39%, 40-59%, and ≥60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥60% group.Conclusion: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs.
Geochemical Provenance of an Indo-Arabian Stone Anchor from Manikapatna, East Coast of India: Implications for Medieval Maritime Trade of India
Authors: Tripati Sila , Ray Jyotiranjan S. , Behera Rudra Prasad , Babu Prakash , Mahala Milan Kumar , Kocherla Murali , Khedekar Vijay
Published: April 2022

India is one of the oldest maritime nations in the world, and the overseas contacts date back to the third millennium BCE. Besides several archaeological vestiges, numerous stone anchors of various types have been documented during maritime archaeological explorations along the Indian littoral. During a recent maritime archaeological exploration, a broken Indo-Arabian stone anchor, of the Medieval period, was discovered along the Manikapatna coast of Odisha, Indian eastern littoral. In an attempt to determine the provenance of the anchor, we carried out a detailed petrographic, geochemical (major/trace elements) and Sr-Nd isotopic investigation. The results of our study reveal that the stone of the anchor had been cut out of a geologically young, vesicular, alkali basalt lava flow. Source fingerprinting done using petrographic, geochemical and isotopic data, suggests that contrary to the general perception, the anchor rock did not come from any local rock formations. All data point to the most likely scenario that it was sourced from one of the Deccan Traps lava flows of Palitana in the Saurashtra region of Gujarat, western India. This confirms the Medieval maritime trading between western and eastern Indian states.
Effect of heating on protein denaturation, water state, microstructure, and textural properties of Antarctic krill (Euphausia superba) meat
Authors: Sun Peizi , Lin Junxin , Ren Xiang , Zhang Biao , Liu Jiaxin , Zhao Yanfen , Li Dongmei
Published: April 2022

Antarctic krill (Euphausia superba) is an important source of biomass and high-quality protein. However, heat treatment of Antarctic krill negatively impacts its quality and compromises its utilization in the food industry. This study aimed to investigate the mechanisms underlying changes in Antarctic krill meat characteristics and physicochemical properties treated at different temperatures and holding times. Findings indicate that at higher temperatures and holding times, hardness and cooking loss of Antarctic krill meat increased dramatically. The low-field nuclear magnetic resonance (LF-NMR) analysis revealed that the loss of immobile water increased, whereas SDS-PAGE analysis showed that the content of myosin heavy chain decreased significantly, and that protein degradation occurred. Fourier transform infrared spectroscopy (FT-IR) and intrinsic fluorescence spectra indicated that α-helix motifs were transformed into β-sheets, and that more hydrophobic groups were exposed. The scanning electron microscopy (SEM) results showed that Antarctic krill meat formed corrugated folded regions after heat treatment without forming a three-dimensional water-entrapped structure, which led to significant water loss, resulting in rapid deterioration Antarctic krill meat. These results provide the basis for a deeper understanding of processing characteristics of Antarctic krill meat.
Ablation of CX3CR1-expressing Immune Cells after Radiation Attenuates Tumor Progression and Sensitizes Cancer Cells to S-phase Specific Chemotherapy
Authors: Ben-Mordechai Tamar , Lawrence Yaacov R. , Symon Zvi , Shimoni-Sebag Ariel , Amit Uri
Published: April 2022

Introduction: Chemokine (C-X3-C Motif) Receptor 1 (CX3CR1) is present on a subset of the immune cells in the tumor microenvironment (TME) and plays an essential and diverse role in cancer progression. However, its potential function in the irradiated TME remains unknown.Materials and Methods: Mouse lung cancer model was performed by subcutaneously inoculating Lewis Lung Carcinoma (LLC) cells expressing luciferase (Luc-2) and mCherry cells in CX3CR1GFP/GFP , CX3CR1DTR/+ , and wild–type (WT) mice. Bioluminescence imaging, clonogenic assay, and flow cytometry were used to assess tumor progression, proliferation, and cell composition after radiation.Results: Radiation provoked a significant influx of CX3CR1-expressing immune cells, notably monocytes, into the TME. Co-culturing irradiated LLC cells with CX3CR1-deficient monocytes and macrophages resulted in reduced clonogenic survival and increased apoptosis of the cancer cells. Interestingly, depletion of CX3CR1 in macrophages led to a redistribution of the irradiated LLC cells in the S-phase, parallel to increased expression of cyclin E1, required for cell cycle G1/S transition. In addition, deletion of CX3CR1 expression in macrophages altered the cytokine secretion with a decrease of interleukin-6, a crucial mediator of cancer cell survival and proliferation. Next, LLC cells were injected subcutaneously into CX3CR1DTR/+ mice, sensitive to diphtheria toxin (DT), and WT mice. After injection, tumors were irradiated with 8Gy, and mice were treated with DT, leading to conditional ablation of CX3CR1-expressing cells. After three weeks, CX3CR1 depleted mice displayed reduced tumor progression. Furthermore, combining the S-phase specific chemotherapy gemcitabine with CX3CR1 cell ablation resulted in additional attenuation of tumor progression.Conclusion: CX3CR1-expressing mononuclear cells invade the TME after radiation therapy in a mouse lung cancer model. CX3CR1 cell depletion attenuates tumor progression following radiation and sensitizes the tumor to S–phase-specific chemotherapy. Thus, we propose a novel strategy to improve radiation sensitivity by targeting the CX3CR1-expressing immune cells.
Safety and efficacy of allogeneic hematopoietic stem cell transplantation in R/R B-NHL patients with disease progression after CAR-T therapy
Authors: Cong Mengya , Ai Sicheng , Kang Liqing , Jin Mao , Zhu Ying , Li Caixia , Jin Zhengming , Yu Lei , Wu Depei , Huang Haiwen
Published: April 2022

Background: R/R B-NHL patients with disease progression after CAR-T therapy have poor prognosis and no standard chemotherapy regimen has been defined. We aimed to explore whether receiving allo-HSCT could improve the outcomes of R/R B-NHL patients who have disease progression after CAR-T therapy.Methods: From October 2017 to June 2021, we retrospectively report outcomes of R/R B-NHL patients with disease progression after CAR-T cell treatment, then receiving allo-HSCT. Results: Among 9 patients, 4 were males and 5 females, with a median age of 44 (27-52) years. 5 patients were diagnosed refractory/relapsed diffuse large B cell lymphoma, 1 patient was Burkitt lymphoma, 1 was B lymphoblastic lymphoma, 1 was transformed DLBCL and 1 was gray zone lymphoma. 8/9 donors were haploidentical family member, 1/9 donor was identical sibling. The median time from CAR-T treatment to transplantation was 2.3 (1.0-12.3) months. 9/9 patients obtained complete engraftment. The median time of neutrophil implantation was 12 (11- 19) days, and 13 (9-20) days of platelet implantation. The median follow-up was 7.9 (3.4-48.6) months. 4/9 patients received CR and 1/9 patient received PR during the follow up. The objective response rate (ORR) was 55.6%. The six-months overall survivaln (OS) and progression-free survival (PFS) were 66.7% and 33.3%, respectively. 1 case experienced acute graft-versus-host disease（aGVHD）grade Ⅱ, 1 case with aGVHD grade Ⅲ. Among 5 survivals, localized chronic GVHD occurred in 1 patient. During the follow up, four patients have died and the causes were disease relapses and progressions (2 patients), acute renal failure (1 patient), severe pulmonary infection (1 patient). No-relapse mortality was 22.2%.Conclusion: The present study demonstrated that allo- HSCT is a feasible and safe choice with favorable outcome for R/R B-NHL patients with disease progression after CAR-T therapy.
Surgery versus radiotherapy in octogenarians with stage Ⅰa non‑small cell lung cancer: Propensity score‑matching analysis of SEER database
Authors: Ni Lianfang , lin Gang , Zhang Zhigang , Sun Dan , Liu Zhonghui , Liu Xinmin
Published: April 2022

Purpose
To compare the overall survival (OS) and cancer-specific survival (CSS) of surgery with radiotherapy in octogenarians with stage Ⅰa non–small cell lung cancer (NSCLC).
Methods
Patients aged ≥ 80 years with clinical stage Ⅰa (T1N0M0) NSCLC from 2012 to 2017 were identified from the population-based Surveillance, Epidemiology, and End Results (SEER) database. Included patients were divided into surgery and radiotherapy group. Multivariate Cox regression was used to identify factors associated with survival. Propensity score‑matching (PSM) analysis was used to adjust treatment groups. OS and CSS were compared among groups by the Kaplan–Meier analysis.
Results
A total of 1641 patients were identified, with 46.0% received surgery and 54.0% radiotherapy. Compared with surgery, patients treated with radiotherapy were older, later diagnosed, and had more squamous cell carcinoma, unknown grade and increased tumor size. Radiotherapy was associated with a significantly worse OS as compared with surgery (hazard ratio 2.426; 95% CI, 2.003 to 2.939; P < .001). After PSM, the OS (P < 0.001) and CSS (P < 0.001) was higher in the surgery group. The 1-, 3-, and 5-year OS rates of surgery and radiotherapy group were 90.0%, 76.9%, 59.9%, and 86.0%, 54.3%, 28.0%, respectively. The 1-, 3-, and 5-year CSS rates of surgery and radiotherapy group were 94.5%, 86.1%, 78.0% and 90.7%, 74.5%, 61.0%, respectively. No differences in the OS (P = 0.146) and CSS (P = 0.675) were found between the matched surgery without lymph node examination (LNE) and radiotherapy group.
Conclusions
Surgery with lymph node dissection offers better OS and CSS than radiotherapy in octogenarians with stage Ⅰa NSCLC.
Suppression of the telomerase RNA component induces autophagy and ferroptosis in lung cancer via regulation of AMP-activated protein kinase
Authors: Zhou NAME：Honglian , Liu Zijian , Huang Xiaobi , Yu Hui , Huang Zhong , Chen Yongyang , Liu Hongyi , Xu Xiaohong , Yang Zhixiong , Su Wenmei
Published: April 2022

Objective
Long non-coding RNAs (lncRNAs) are involved in tumorigenesis. The telomerase RNA component (TERC) is an lncRNA that functions as an essential template for the addition of the telomere repeat.The aims of our study were to determine the biological function and mechanism of TERC in lung adenocarcinoma.
Methods
RNA-seq analyses were used to compare the expression levels of TERC in cancerous and adjacent normal lung tissues. Functional assays of TERC in LUAD cell lines were performed by siRNA-mediated knockdown. Cell proliferation, migration and invasion were evaluated by WST-1 and transwell assays. Reactive oxygen species (ROS) levels were determined by flow cytometry and examined by fluorescence microscopy, and the morphology of mitochondria was observed using transmission electron microscopy. Protein expression was analyzed by western blot. The formation of autophagosomes was monitored by fluorescence microscopy following expression of fluorescent-tagged LC3.
Results
RNA-seq analyses show that the expression of TERC is upregulated in lung cancer tissues. Knockdown of TERC inhibits migration and invasion of LUAD cells. Mechanistic analyses indicate that silencing of TERC increases the expression of autophagy-related proteins LC3B, Beclin-1 and AMP-activated protein kinase (AMPK) meanwhile the expression of p62 protein, as well as ferroptosis-regulated proteins GPX4 and SLC7A11 were diminished. Importantly, inhibition of AMPK function counterbalances the effects of TERC knockdown on autophagy and ferroptosis in LUAD cells.
Conclusions
These findings reveal that suppression of TERC in lung cancer promotes autophagy and ferroptosis via regulation of AMPK. They help to understand the mechanism underlying TERC activity in tumorigenesis.
Validation of the vault prediction model based on the sulcus-to-sulcus diameter and lens thickness: A 925-eye prospective study
Authors: Zhu Qiu-Jian , Xing Xiao-Ying , Zhu Man-Hui , Ma Lie , Yuan You , Song E
Published: April 2022

Background: To verify the accuracy and stability of the prediction formula based on the ciliary sulcus diameter and lens thickness and to analyse factors influencing the prediction results.Methods: In total, 925 eyes from 506 subjects were enrolled in this prospective study between July 1, 2020, and June 30, 2021. Subjects were divided into four seasons, each spanning three months. The target vault was set to be between 300 μm and 700 μm according the prediction formula. The actual vault was measured one month postoperatively. The Bland–Altman test, 95% confidence intervals (95% CI) and 95% limits of agreement (95% LoA) were used to evaluate the agreement between the predicted vault and the actual vault. Eyes with absolute prediction errors greater than 300 μm were further analysed.Results: The mean predicted vaults for the four seasons were 503 ± 99, 494 ± 96, 481 ± 92 and 502 ± 93 μm, while the mean actual vaults were 531 ± 189, 491 ± 179, 464 ± 179 and 529 ± 162 μm, respectively. The predicted and actual vaults of the overall subjects were 493 ± 95 and 500 ± 180 μm, respectively. Of the 925 eyes, 861 eyes (93.08%), 42 eyes (4.54%), and 22 eyes (2.38%) showed a normal vault, high vault, and low vault, respectively. Bland–Altman plots showed that the mean difference between the actual vault and predicted vault overall (± 95% LoA) was 6.43 ± 176.2 μm (-339 to 352 μm). Three UBM features may lead to large prediction errors (more than 300 μm): wide iris-ciliary angle (ICA), iris concavity and anteriorly positioned ciliary body.Conclusions: This study demonstrated the accuracy and stability of the prediction formula through the validation of a large sample size and a long time span. Wide ICA, iris concavity and anteriorly positioned ciliary body may have an effect on vault.
Use of mathematical modeling in enzymatic hydrolysis in elephant grass pretreatment
Authors: Godinho Emmanuel , Hasan Salah Din Mahmud , Baumgartner Tatiana Rodrigues da Silva , Kaminski Thiago Spinardi , Candelaria Murilo Henrique Hernandez , Silveira Flávia Taguti , Reginato Marco Antonio
Published: April 2022

The objective of this work was to test the Fenton reaction on pretreatment of elephant grass aiming the final results of cellulose increase and the delignification process. A subsequent study of the enzymatic hydrolysis of the pretreated elephant grass and the mathematical modeling of hydrolysis was performed. A Doehlert-type experimental design was used into the pretreatment stage, and the best result were obtained at the central point with an average of 53.80% of cellulose and 10.00% of lignin. The enzymatic hydrolysis of pre-treated grass with Fenton reaction was performed, with a commercial enzyme (Celluclast® 1.5L), where the best yield (17.39%) of reducing sugars was obtained with 20 g L-1 of enzyme in 72 h and higher productivity (2.51 g L-1 h-1) observed in 2 h. It was possible to adjust the proposed mathematical model to the hydrolysis process. It was observed that, for higher concentrations of enzyme, the proposed mathematical model adjusts better the experimental results (R2 = 0.974). It can be observed with these results, that there was an increment in the economic profitability of the enzymatic hydrolysis process due to the relation of the operational parameters, so that it can be used in new projects and industrial applications.
Current situation and influencing factors of disease uncertainty in parents of children with Sturge-Weber syndrome
Authors: Du Na , Wu Yue , Xiong Shan-Shan , Ji Hong , Huang Lu-Lu , Guo Wen-Yi , Zeng Chang-Juan
Published: April 2022

Purpose
To investigate the current situation and influencing factors of disease uncertainty in parents of children with Sturge-Weber syndrome (SWS).
Methods
A total of 105 parents of children with SWS completed a self-designed general information questionnaire, generalized anxiety questionnaire (GAD−7), patient health questionnaire (PHQ−2), stress perception scale (PSS−4), simple coping scale (SCSQ) and disease uncertainty scale (PPUS).
Results
The total uncertainty score of parents of children with SWS was 79.07 ± 13.24, and the average item score was 2.82 ± 0.47. Multiple linear regression analysis showed that anxiety and simple coping were the main influencing factors of parents' disease uncertainty in children with SWS (P < 0.05).
Conclusions
The parents of children with SWS have a high level of disease uncertainty. Medical staff should pay attention to the source of parents' disease uncertainty and carry out targeted interventions, which are of great importance in reducing parents' disease uncertainty.
Prioritization of Roads based on their safety levels by multi-Criteria approach techniques
Authors: Gupta Ashutosh , Mishra A K
Published: April 2022

Road safety is a critical issue that affects not just road authorities but the whole country. Road accidents are on the rise in developing countries such as India. It is mostly owing to a larger number of car accidents on Indian roadways. As a result, roadways must be prioritized according on their severity levels. A study was conducted in the current research work to prioritize the safety requirements of specific selected highways in the Gorakhpur area of Uttar Pradesh, India. The safety standards of chosen roadways were ranked using a multi-criteria methodology. In addition, an extensive investigation was undertaken on the road with the poorest safety conditions in order to rank various stretches. Analytical Hierarchy Process (AHP), Simple Additive Weightage (SAW), and Fuzzy AHP were employed as multi-criteria decision-making techniques. The outcomes of the aforementioned instruments are compared. The technique given here is meant to assist decision-makers in prioritizing roads based on their safety ratings in order to reduce road traffic accidents.
Optimization of End-to-end Supply Chain Costs to Maximize Revenue and Profits From Supply Chain Operations
Authors: Damodaram A.K. , Reddy. L. Venkateswara , Davanam Ganesh , Thejasree P.
Published: April 2022

Being aware that the supply chain costs claim a substantial share in the final product cost, organizations, in an effort to improve revenue and increase profitability, should minimize supply chain costs invariably. Besides other costs, supply chain costs vary from time to time depending on the sourcing, transportation, and inventory-related costs. Improving the operational efficiency of the supply chain has become the primary objective for increasing profitability from supply chain operations in present-day context. In reality, supply chain operations are complex with uncertainty predominantly influencing various costs associated with supply chains affecting return on investments and profitability. Supply chain cost optimization should enable the supply chain managers to ensure that the supply chain is ‘responsive’, ‘agile’, and ‘reinvented’ for present and future operations. Optimization of supply chain costs bestows improving operating efficiency that promotes improvements in revenue and increment in profits. The present article aims at considering various supply chains cost parameters such as total operating costs, profit, revenue, logistics costs, and information sharing costs for optimization of supply chain costs using multi-objective optimization. A generic three-stage supply chain model with usual entities like suppliers, manufacturers, and customer zones is assumed in the present article. A trade-off curve among the selected objective function sets and relevant constraints was developed and presented in the article. The trade-off curve provides the basis for decision-makers to better understand the supply chain optimization effect on the selected objective function set elements to make the present and future supply chains promote startling ‘profitability’ and increase revenue generation in operations.
Developing TB Vaccines for People with HIV: A Roadmap: Meeting Consensus Report
Authors: Miner Maurine D. , Hatherill Mark , Mave Vidya , Currier Judith , Eron Joseph , Gray Glenda E. , Nachman Sharon , Kim Peter , Read Sarah , White Richard , Hessling Anneke , Cobelens Frank , Patel Sheral , Frick Mike , Bailey Theodore , Seder Robert , Flynn Joanne , Rengarajan Jyothi , Kaushal Deepak , Hanekom Willem , Schmidt Alexander , Scriba Thomas , Nemes Elisa , Andersen-Nissen Erica , Landay Alan , Dorman Susan , Aldrovandi Grace , Cranmer Lisa M. , Day Cheryl , Rangaka Lele , Garcia-Basteiro Alberto , Fiore-Gartland Andrew , Mogg Robin , Kublin James G. , Gupta Amita , Churchyard Gavin
Published: April 2022

Many new TB vaccine candidates in the development pipeline need to be studied in people with HIV. People with HIV are at high risk of developing Mycobacterium tuberculosis (Mtb) infection and TB disease and tend to develop less robust vaccine induced immune responses. Many questions remain unanswered regarding priority vaccine indications, clinical trial design, measures of safety, immunogenicity, and efficacy considerations for people with HIV. To address these gaps, a roadmap for developing TB vaccines for people with HIV was developed through a series of symposia that posed framing questions to a panel of international experts for discussion. Framing questions specific to people with HIV included: 1) What is the use case or rationale for developing TB vaccines?; 2) What is the landscape of TB vaccines?; 3) Which vaccine candidates should be prioritized ?; 4) What are the TB vaccine trial design considerations?; 5) What is the role of immunological correlates of protection?; and 6) What are the gaps in preclinical models for studying TB vaccines? We provide a summary of our roadmap with the intention of informing TB vaccine development and the prioritization of clinical trials for inclusion of people with HIV.
Endovascular balloon occlusion of the aorta in the complex of damage control resuscitation in patients with acute massive blood loss: a retrospective propensity score matched analysis
Authors: Shchegolev A. V. , Reva Viktor A. , Pochtarnik A. A. , Samokhvalov I. M. , Hörer T. M.
Published: April 2022

INTRODUCTION. An increase of quality improvement program for severe polytrauma hypotensive patients is associated with new techniques of “endovascular resuscitation” of which resuscitative endovascular balloon occlusion of the aorta (REBOA) to be the most widespread and effective. OBJECTIVE. Treatment outcomes after damage control resuscitation and endovascular resuscitation strategies were evaluated in comparison between Russian and “foreign” cohorts. MATERIALS AND METHODS. A retrospective and propensity score matched analysis was performed to compare Russian (n = 24) and foreign (n = 241) cohorts of extremely severely injured trauma patients (in extremis) admitted to trauma centers during the period of 2013–2020. All hemodynamically unstable trauma patients admitted in shock, with signs of systemic hypoperfusion and non-compressible torso hemorrhage, were enrolled into the study. RESULTS. In average, REBOA was performed 22 minutes after admission in both groups. In most cases (65–75 %), occlusion of the thoracic aorta was performed, what resulted in a significant increase of blood pressure by 40–50 mm Hg from baseline and allowed temporary hemodynamic stabilization to initiate surgery and blood replacement therapy. Early fluid and blood replacement therapy was significantly different between groups. Total volume of fluid and blood replacement therapy was significantly higher in the foreign group (p = 0.001), mostly due to blood components: red packed blood cells and platelets (p < 0.05 before and after REBOA). No colloids were infused in the foreign group at all (p < 0.001). Early blood transfusion was found to improve survival until 50 % (95% CI, 43–56 %) (р = 0.002). CONCLUSIONS. REBOA seems to be an effective adjunct for temporary hemodynamic stabilization of extremely severe injured patients, but its effectiveness is likely to be defined by quality and quantity of infusion and transfusion strategy as well as by intensive care in whole.