bluuebunny/crossref_metadata_2025 huggingface dataset:
An exploration of South African university students’ experience with pre-exposure prophylaxis for HIV: A qualitative study
Authors: Haffejee Firoza , Chetty Lynette , Ghuman Shanaz
Published: June 2022

Background
South Africa is the epicentre of the HIV pandemic, with young women particularly at risk of infection. Pre-exposure prophylaxis (PrEP) is an anti-retroviral drug taken once daily to reduce the risk of HIV infection in HIV-negative people. Oral PrEP was offered in South Africa in 2015, as an additional prevention choice for persons at substantial risk of HIV infection. It was subsequently integrated into an existing HIV prevention programme at a university campus health clinic in 2019. Currently, the experiences of students on PrEP are unknown. This qualitative study investigated reasons for PrEP uptake, compliance, and student perceptions about taking the prophylaxis.
Methods
Students (n = 12), who had previously commenced PrEP, at a university in Kwa-Zulu Natal, South Africa were recruited using purposive sampling. A semi-structured interview guide was used to collect qualitative data. All interviews were audio-recorded, subsequently transcribed and thematically analysed using Tsech’s eight steps.
Results
All participants commenced PrEP in 2019. The following four themes emerged from the study: (1) Sexual risk behavior, (2) reasons for using PrEP, (3) PrEP compliance and (4) the effect of COVID-19 on PrEP use. Five participants indicated that they had multiple concurrent sexual partners whilst all 12 indicated that their partners most likely had sexual relationships with others. Condom use was not regular both before and after commencing PrEP. All the participants thus used PrEP to protect themselves from HIV infection as they realised that they were at a high risk of infection due to their sexual behaviour. In the first year of taking PrEP eight participants were compliant. Those that defaulted, missed the treatment intermittently, when travelling over weekends or rushing to university some mornings. All participants experienced challenges with PrEP compliance after the COVID-19 pandemic, which resulted in closure of the campus health clinic, and difficulties in obtaining the regimen from other clinics.
Conclusions
The high level of risk perception for HIV was a driving factor in commencing PrEP. Difficulties in adherence, particularly due to COVID-19 restrictions were evident.
Chemo- versus immuno-precipitation of G-quadruplex-DNA (G4DNA): a direct comparison of the efficiency of the antibody BG4 versus the small-molecule ligands TASQs for G4 affinity capture
Authors: Feng Yilong , Luo Zhenyu , Sperti Francesco Rota , Valverde Ibai E. , Zhang Wenli , Monchaud David
Published: June 2022

The search for genomic G-quadruplex (G4) motifs is motivated by their involvement in key cellular processes ( e.g ., transcription, replication) and corresponding dysregulations underlying genetic diseases. Sequencing-based methods have been developed to assess G4 DNA formation genome-wide, including G4-seq that detects G4s in purified DNA (so called in vitro ) from human lymphocytes using the G4 stabilizer PDS, and G4 ChIP-seq that detects G4s in the chromatin of human keratinocytes (so called in vivo ) using the G4-specific antibody BG4. We recently reported on the use of a small molecule, BioTASQ, as a proxy for BG4 for assessing the transcriptomic prevalence of G4-RNA in vivo using G4RP-seq. Here, we provide the first direct and unbiased comparison of the G4 capturing ability of small molecules BioTASQ and its new derivative BioCyTASQ versus the antibody BG4, developing G4DP-seq which makes the genome-wide detection of G4s in vitro and in vivo more straightforward, reproducible and reliable.
Autophagic plasmid expressing SIRT3 and SIRT4 to improve Alzheimer’s disease
Authors: Li Shiyu , Deng Jianshan , Mo Xuemei , Sun Hanxu , Wang Jiajia , Dai Zhenning , Chen Youyu , Zheng Weihan , Li Ziyue , Zhong Zhiying , Geng Chengxu , Jiang Zhenyou , Huang Wenhua , Sun Hanxiao
Published: June 2022

Background: Improving mitochondria dysfunction using gene therapy effectively treats Alzheimer’s disease (AD). Meanwhile, the molecular chaperone-mediated autophagy (CMA) mechanism in mammalian cells helps achieve effective and safe gene therapy. Methods: We introduced an internal ribosome entry site (IRES) into a plasmid vector co-expressing Sirtuin (SIRT)3 and SIRT4. This plasmid was then combined with a nucleic acid autophagic peptide (NAP) that activates and expresses CMA under the tetracycline-on (Tet-on) regulation system to construct a two-gene autophagic plasmid pSIRT3/4-NAP. The plasmid was then transfected into 293T cells, and its effect on autophagy mechanisms and dysfunctional mitochondria were assessed. Additionally, the plasmids were encapsulated into nanoparticles with transferrin-coupled cationic liposomes and injected into AD mouse models for behavioral tests and mitochondrial function detection in brain cells.Results: NAP expression is induced by doxycycline (DOX). Thereafter NAP activates the CMA mechanism to remove plasmid DNA in 293T cells. Meanwhile, SIRT3 and SIRT4 are simultaneously expressed in mitochondrial dysfunction cells induced by high glucose concentration, and significantly improve mitochondrial structure and function. Moreover, the liposome-plasmid effectively targets the brain tissue of AD mice, significantly improving mitochondrial dysfunction in the cerebral cortex and hippocampus, and restoring the learning and memory functions. Importantly, following induction by DOX, the intracellular autophagic pathway activates and clears the plasmid.Conclusions: The two-gene autophagic plasmid realizes safe and controllable expression of target genes by activating the intracellular CMA mechanism, thus, providing an effective strategy for controllable gene therapy in AD.
ADAR1p110 promotes Enterovirus D68 replication through its deaminase domain and inhibition of PKR pathway
Authors: Zhang Kehan , Wang Siyuan , Chen Tingting , Tu Zeng , Huang Xia , Fan Xinyue , Liu Jia , Tian Yunbo , Lu Nan , Zhang Guangyuan
Published: June 2022

Background
Severe respiratory and neurological diseases caused byEV-D68 pose a serious threat to public health, but there are currently no effective drugs and vaccines. ADAR1 has been reported to have diverse biological functions in various viral infections, but its role in EV-D68 infection remains undetermined.
Methods
RD cells, 293T cells and Hela cells were used to evaluate the expression level of ADAR1 upon EV-D68 (Ferm strain) and HPIV3 (NIH47885) infection, respectively. The knockdown through siRNA and overexpression of either ADAR1p110 or ADAR1p150 in cell lines above were utilized to determine the role of the two proteins after viral infection. ADAR1p110 dsRBDs deleted mutation was generated by seamless clone kit. The expression patterns of ADAR1, EV-D68 VP1 protein and HPIV3 HN protein were identified by western blotting. TCID50 was applied to detect viral titers. The transcription level of EV-D68 mRNA was analyzed by RT-qPCR and viral 5’UTR-mediated translation was analyzed by dual luciferase reporter gene.
Conclusion
Here, we found that the transcription and expression of ADAR1 was inhibited upon EV-D68 infection. RNA interference of endogenous ADAR1 decreased VP1 protein expression and viral titers, while overexpression of ADAR1p110 but not ADAR1p150 facilitated virus replication. Immunofluorescence assays showed that ADAR1p110 migrated from the nucleus to the cytoplasm after EV-D68 infection. Further, ADAR1p110 lost the pro-viral ability after mutating the key sites in the deaminase domain, and 5’-UTR sequencing of the viral genome revealed that ADAR1p110 probably plays a role in EV-D68 RNA editing. In addition, after knockdown of ADAR1, both p-PKR and p-eIF2α increased. Attenuated translation activity of viral genome 5’-UTR was also shown in dual-luciferase reporter gene assay. At last, deletion of ADAR1p110 dsRBDs increased PKR phosphorylation, which incurs a lower level of VP1 expression, indicating that the promotion of EV-D68 replication by ADAR1p110 is also related to the inhibition of PKR activation by its double stranded RNA binding domains (dsRBDs). Together, our work illustrates ADAR1p110 as a novel pro-viral factor of EV-D68 replication and provides a theoretical basis for EV-D68 antiviral research.
Validation of grip strength as a measure of frailty in rheumatoid arthritis
Authors: Sobue Yasumori , Suzuki Mochihito , Ohashi Yoshifumi , Koshima Hiroshi , Okui Nobuyuki , Funahashi Koji , Ishikawa Hisato , Inoue Hidenori , Kojima Masayo , Asai Shuji , Terabe Kenya , Kishimoto Kenji , Maeda Masataka , Kihira Daisuke , Imagama Shiro , Kojima Toshihisa
Published: June 2022

Rheumatoid arthritis (RA) patients often exhibit finger/wrist joint symptoms and reduced grip strength. This study aimed to validate grip strength as a measure of frailty in RA patients. Subjects were 424 female RA patients (mean age±standard deviation, 66.8±14.5 years). Frailty was defined as a score of ≥8 points on the Kihon Checklist (KCL). Finger/wrist joint symptoms were defined based on tender or swollen joints. Associations between frailty and grip strength were determined using receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis. There were 179 subjects with frailty (42.2%). Multivariable logistic regression analysis revealed that frailty was significantly associated with grip strength independently of finger/wrist joint symptoms. In ROC curves, cut-off scores of grip strength for frailty in subjects without and with finger/wrist joint symptoms were 17 kg (sensitivity, 62.1%; specificity, 69.0%) and 14 kg (sensitivity, 63.2%; specificity, 73.0%), respectively. The results of the present study suggest that grip strength in female RA patients is associated with frailty, with a cut-off score of 17 kg (equivalent to Cardiovascular Health Study criteria, <18 kg) when RA patients have no finger/wrist joint symptoms. However, when RA patients have finger/wrist joint symptoms, measures other than grip strength such as lower limb function should be considered.
Backward propagating quantum repeater protocol with multiple quantum memories
Authors: Sekiguchi Yuhei , Okumura Satsuki , Kosaka Hideo
Published: June 2022

Quantum repeaters with multiple quantum memories provide high throughput, low latency, and high fidelity quantum state (qubit) transfer over long distances. However, conventional quantum repeater protocols require full connections among the multiple quantum memories in a repeater node, which is technically challenging. Here, we propose a quantum repeater protocol based on backward propagating photon emission and absorption, where the quantum memories are multiplexed in the time-domain to speed up a single transmission channel without requiring full connectivity, thereby drastically facilitating physical implementation. Although the protocol is described with nitrogen-vacancy (NV) centers in diamond, it is applicable to various physical systems and opens up the possibility of high-speed high-fidelity quantum networks for distributed quantum computation and the quantum Internet.
Short-term Effects of Solar Storms in Phytoplankton Photosynthesis
Authors: López-Águila Madeleine , Rodríguez-López Lien , Cardenas Rolando , González-Rodríguez Lisdelys
Published: June 2022

It is investigated the potential short-term influence of a solar storm on micro-algal photosynthesis. From the secondary cosmic rays at sea level we focus on muons, given their high penetrating power, and it is considered that a ‘’generic’’ solar storm would imply an increase of 10% in both muon fluxes and their average energy. It is then assumed an exponential decay of muon fluxes down the water column and a direct proportionality between their penetrating power and energy. This allows obtaining a function of ionizing radiation to be embedded in a physical-mathematical model for photosynthesis previously modified by some of us to include particulate ionizing radiation. It is finally shown that solar storms can cause a significant short-term depletion of photosynthesis in both ocean and coastal waters.
Evolution of p53 pathway-related genes provides insights into anticancer mechanisms of natural longevity in cetaceans
Authors: Liu Xing , Yu Zhenpeng , Yang Fei , Huang Xin , Sun Linxia , Ren Wenhua , Yang Guang , Xu Shixia
Published: June 2022

Background: Large, long-lived organisms typically have a higher risk of cancer, but cetaceans, which include the largest and longest-living mammals, may have evolved a mechanism to counter this. However, little is known about the genetic basis underlying this mechanism. Cetaceans, which include the largest and longest-lived mammals, may have evolved effective anticancer mechanisms in response to a high risk of cancer caused by massive somatic cell divisions.Results: The p53 pathway is ideal for studying the mechanisms behind cancer resistance, as nearly all types of cancer have evolved ways to evade this suppressive mechanism. Here, comparative genetic analyses of the 73 genes involved in the p53 pathway were examined in cetaceans to explore potential anticancer mechanisms behind natural longevity. We found that long-lived species have three positively selected genes (APAF1, CASP8, TP73) and three duplicated genes (IGFBP3, PERP, CASP3) involved in the regulation of apoptosis, suggesting that apoptosis regulation may be an important strategy for cancer resistance in these long-lived cetaceans. Inhibition of angiogenesis may be another strategy for protecting cetaceans from cancer because the evolutionary rates of three angiogenesis-regulated genes (SERPINE1, CD82 and TSC2) were significantly related to longevity traits (longevity quotient and maximum lifespan). Interestingly, some tumor suppressor genes were determined to be under positive selection (APAF1 and TP73), have high copy numbers (CASP3 and CCNG1), and be related to body size in the large-bodied and long-lived cetacean lineages. The above is all molecular evidence for Peto's paradox. Conclusions: Our study identified several candidate genes for the p53 pathway with different evolutionary paths in the large, long-lived cetaceans and suggested that tumor suppression in cetaceans might be mediated through multiple synergistic effects rather than a single pathway/target.
Ninja Omicron: BA.1 subvariant showing a BA.2-like pattern using a variant-specific PCR assay due to a single point mutation downstream the spike 69/70 deletion.
Authors: Daviña-Nuñez Carlos , Pérez-Castro Sonia , Martínez-Lamas Lucía , Cabrera-Alvargonzalez Jorge Julio , Rey-Cao Sonia , Carballo-Fernández Raquel , Godoy-Diz Montse , López-Bóveda Leticia , Campo-Pérez Víctor del , Suárez-Luque Silvia , Regueiro-García Benito
Published: June 2022

Background: SARS-CoV-2 variant tracking is key to the genomic surveillance of the pandemic. While next-generation sequencing (NGS) is commonly used for variant determination, it is expensive and time-consuming. Variant-specific PCR (vsPCR) is a faster, cheaper method that detects specific mutations that are considered variant-defining. These tests usually rely on specific amplification when a mutation is present or a specific melting temperature peak after amplification.Case presentation: A discrepant result between vsPCR and NGS was found in seventeen SARS-CoV-2 samples from Galicia, Spain. A cluster of BA.1 Omicron SARS-CoV-2 variant showed a BA.2-like melting temperature pattern due to a point mutation (C21772T) downstream the deletion of the spike aminoacids 69/70. As the 69/70 deletion is widely used for differentiation between BA.1 and BA.2 by vsPCR, C21772T can cause BA.1 samples to be misinterpreted as BA.2. Over a thousand BA.1 sequences in the EpiCoV database contain this mutation. Conclusions: To our knowledge, this is the first case of a point mutation causing a vsPCR algorithm to misclassify BA.1 samples as BA.2. This is an example of how mutations in the targets of vsPCR tests based on melting curve analysis can lead to variant misclassification. NGS confirmation of vsPCR results is relevant for the accuracy of the epidemiological surveillance. In order to overcome the possible impact of novel mutations, diagnostic tools must be constantly updated.
Resistin as a risk factor for mortality in the general population
Authors: Pérez María Cristo Rodríguez , González Delia Almeida , Rodríguez Itahisa Marcelino , Coello Santiago Domínguez , Fernández Francisco J Cuevas , Díaz Buenaventura Brito , de León Antonio Cabrera
Published: June 2022

Serum resistin has been described as a risk factor associated with mortality in several clinical sets including type 2 diabetes. Mortality studies in the general population are needed to find out the risk of death among those who have been exposed to high levels of this cytokine. In a follow-up study of a cohort of adult population (n=6636) in Spain over a period of fifteen years (447 events/102,255 person-years), serum resistin measurements and death records were obtained. The risks of total deaths, and deaths from cardiovascular and oncological diseases were estimated. Hazard ratios (HR) and its confidence intervals (CI) were calculated using multivariable Cox models, adjusting the effect of 11 traditional risk factors. The risk of total mortality among participants exposed to the highest quintile of resistin was always higher than among those in the lowest quintile (HR varied between 1.55 when smoking was the adjusted factor [95%CI=1.17-2.05], and 1.68 when the adjusted factor was physical activity [95%CI=1.27-2.21]). The maximally adjusted model, accounting for the effect of all traditional factors, corroborated this higher risk of total mortality among people in the highest resistin quintile (HR=1.52; 95%CI=1.13-2.05). The effect of resistin was even higher for cardiovascular deaths (HR=2.14; 95%CI=1.13-4.06), being exceeded only by suffering diabetes (HR=3.04; 95%CI=1.98-4.69) or previous acute coronary syndrome (HR=3.67; 95%CI=2.18-6.18). This findings corroborate the role of resistin as a risk factor for general and cardiovascular mortality in the general population.
Ambient air pollution and emergency department visits and hospitalisation for cardiac arrest: a population-based case-crossover study
Authors: Halldorsdottir Solveig , Finnbjornsdottir Ragnhildur Gudrun , Elvarsson Bjarki Thor , Gunnarsdottir Oddny Sigurborg , Gudmundsson Gunnar , Rafnsson Vilhjálmur
Published: June 2022

Background
The association between ambient air pollution and cardiac arrhythmia has been explored in numerous studies; however, the small subgroup of cardiac arrest has not been closely studied thus far. The aim of the present study was to assess the association between traffic-related ambient air pollution and emergency hospital visits for cardiac arrest.
Methods
A bidirectional time-stratified case-crossover design was used. The setting was the Reykjavik capital area and the study population were the inhabitants 18 years and older identified by zip codes. Cases were those who had made emergency visits to Landspitali University Hospital during the period 2006 to 2017 and who were given the primary discharge diagnosis of cardiac arrest according to The International Classification of Diseases 10th edition (ICD-10), code I46. The pollutants were NO2, PM10, PM2.5, and SO2 with adjustment for H2S, temperature and relative humidity.
Results
The 24-h mean NO2 was 20.7 µg/m3, mean PM10 was 20.5 µg/m3, mean PM2.5 was 12.5 µg/m3, and mean SO2 was 2.5 µg/m3. PM10 level was positively associated with the number of emergency hospital visits (n = 453) for cardiac arrest. Each 10 µg/m3 increase in PM10 was associated with increased risk of cardiac arrest (ICD-10: I46), odds ratio (OR) 1.093 (95%CI 1.033–1.162) on lag 2, and OR 1.118 (95%CI 1.031–1.212) on lag 0–2. Significant associations were shown between exposure to PM10 on lag 2 and on lag 0–2 and increased risk of cardiac arrest in the age, gender, and season strata. Females and those 71 years and older were at higher risk for cardiac arrest, OR 1.193 (95%CI 1.059–1.344), and OR 1.186 (95%CI 1.066–1.320) on lag 2, per 10 µg/m3 increase in PM10, respectively. Significant associations were sporadically found for NO2 and SO2 and emergency hospital visits for cardiac arrest, but these associations were weaker and did not show a discernable pattern.
Conclusions
A new endpoint was used for the first time in this study: cardiac arrest (ICD-10 code I46). Short-term increase in PM10 concentrations was associated with cardiac arrest. The effect seemed higher among the elderly and females. Future ecological studies of this type and their related discussions should perhaps concentrate more on precisely defined endpoints.
Floralozone plays a role in heart failure treatment by down-regulating Vascular Endothelial Growth Factor Receptor 1 Expression
Authors: Yin Ya-ling , Guo Ya-qi , Hou Hong-yan , Que Hua-dong , Li Zi-tian , Fu Yu-tian , Liu Wei-Zhen , Yue Rui-Zhu , Zhu Mo-li , Li peng
Published: June 2022

Background
Floralozone (FL) is medicine with the refreshing aroma of rabbit's ear grass, which can be used to prevent the progression of atherosclerosis and reduces endothelial dysfunction. Vascular endothelial growth factor receptor 1 (VEGFR1) is one of the receptors of vascular endothelial factor (VEGF), which mainly plays a negative role in cardiovascular system regulation mainly by acting as a decoy receptor in endothelial cells. Therefore, the purpose of this study is to evaluate whether FL can down-regulate VEGFR1 expression in treating diabetes-induced heart failure (HF).
Methods
We used high-sugar and high-fat diet and tail vein injection of streptozotocin (STZ) to establish the rat model of HF. After intragastric administration of FL, the left ventricular function, pathological changes, oxidative stress condition in HF rats were assessed by echocardiography, oxidative stress monitoring, hematoxylin-eosin histological staining, argyrophilic staining, Masson staining, lichen red staining. The expression of VEGFR1 in the myocardial tissue of HF rats was detected by immunohistochemistry, immunofluorescence, western blot and RT-PCR analysis
Results
The HF model was established successfully. Through intragastric administration of FL, it was observed the cardiac function of HF rats was significantly improved, ventricular remodeling level was reversed, and the ability of antioxidant stress was enhanced. These therapeutic effects were closely connected with the down-regulation of VEGFR1 expression. ZM306416 is an antagonist of VEGFR1, which can up-regulate VEGFR1 expression and inhibit the protective effect of FL in rats with HF.
Conclusions
These results suggest that FL can play a salutary role in HF rats by down-regulating VEGFR1 expression, inhibiting ventricular remodeling and reducing oxidative stress.
Learning curve for laparoscopic reduction of intussusception in children who failed fluoroscopy- guided air enema
Authors: Liu Y. H. , Sun J. , Lv Z. B. , Xu W. J. , Liu J. B. , Sheng Q. F.
Published: June 2022

Background Laparoscopic reduction in the treatment of intussusception in children who failed fluoroscopy-guided air enema has gained popularity recently. The question arises as to how many laparoscopic procedures are required before the technique is safely performed. This study aimed to evaluate and quantify the learning curve associated with laparoscopic reduction for intussusception at the authors’ center. Methods We performed a retrospective analysis of consecutive patients undergoing laparoscopic reduction by the same surgeon at our center between August 2014 and December 2020. Patient data including age, gender, BMI (body mass index), ASA (American Society of Anesthesiologists fitness grade), clinical manifestation, preoperative air enema attempts, operative time, anatomic type of intussusception, length of intussusception, No. of intussusception, recurrence of intussusception, pathologic lead point, concomitant procedure, complications, conversion, length of postoperative stay were analyzed over time to evaluate the learning curve.Results A total of 34 patients received laparoscopic reduction of intussusception during the study period. The two groups were comparable, with their baseline demographics and clinical characteristics remained similar over time. Complications were experienced by 27% of the first 15 patients, which decreased to 0% during the next 19 patients (p = 0.029). The median operative time between the first 15 patients (45 min) and the next 19 patients (65 min) was not significantly different (p = 0.822). The median postoperative hospital stay was 4 days for the first 15 patients and 6 days for the next 19 patients (p = 0.253). The conversion rates were not significantly different between the first 15 patients (13%) and next 19 patients (16%) (p = 1.0).Conclusions The complication rate was sharply decreased after 15 laparoscopic procedures. This indicates that the learning curve for laparoscopic reduction for intussusception of an experienced surgeon is approximately 15 cases.
The frequency and fitness of m6A-associated variants may be modulated by thermodynamic stability of the overlapping G-quadruplex
Authors: Gulec Cagri
Published: June 2022

Background: Post-transcriptional modifications like m6A, and secondary structures like G-quadruplex (G4), play an important role in RNA processing. Despite an emerging number of studies focusing on m6A and G4 separately, there are less studies about their synergy. Since m6A is known to be enzymatically created in DRACH-motif, and genetic variants may create a novel DRACH-motif or abolish a pre-existing DRACH-motif, we can suppose that the variants may affect gene product level through modulating m6A-G4 colocalization, which consequently may affect fitness and change allele frequency. To test this hypothesis, rare and common variants in selected human genes were investigated in terms of their effect on m6A-G4 colocalization.Methods: Genomic sequences and variant features were fetched from GRCh37/hg19 and Biomart-Ensembl databases, respectively. Genomic coordinates of experimentally identified G4 sequences were yielded from two studies. Counting the number of putative motifs and statistical analysis were performed with appropriate libraries of Python3.7.Results: Common variants creating novel m6A-motif were found more frequently inside than outside G4, and displayed unequal distribution throughout pre-mRNA. Unequal distribution of m6A-creating variants seemed to be related to their effect on thermodynamic stability of the overlapping-G4. Conclusions: Selective m6A-G4 colocalization suggests that m6A-motifs are favorable when overlapping with G4. Besides, thermodynamic stability may lead to unequal distribution of m6A-G4 colocalization, favorable in 5-prime-side, but not in 3-prime-side. We can conclude that the fitness, and consequently frequency of an m6A-creating variant is prone to become higher or lower depending on its position and effect on the overlapping-G4 stability.
Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma
Authors: Xing Jiahua , Jia Ziqi , Han Yan
Published: June 2022

Background
Cutaneous melanoma (CM), a kind of skin cancer with a high rate of advanced mortality, exhibits a wide variety of driver and transmitter gene alterations in the immunological tumor microenvironment (TME) associated with tumor cell survival and proliferation.
Methods
We analyzed the immunological infiltration of TME cells in normal and malignant tissues using 469 CM and 556 normal skin samples. We used a single sample gene set enrichment assay (ssGSEA) to quantify the relative abundance of 28 cells, developed a riskScore prognostic model using the LASSO COX regression model, and performed small molecule drug screening and molecular docking validation, which was finally validated using qRT-PCR and IHC.
Results
We developed a prognosis model around seven essential protective genes for the first time, dramatically elevated in tumor tissues, as did immune cell infiltration. The results of multivariate Cox regression demonstrated that riskScore is an independent and robust prognostic indicator, and its predictive usefulness in immunotherapy was verified. Additionally, we identified Gabapentin as a possible small molecule therapeutic for CM.
Conclusions
A riskScore model was developed in this work to analyze patient prognosis, TME cell infiltration features, and treatment responsiveness. The development of this model aid in predicting patient response to immunotherapy, but it also has significant implications for the development of novel immunotherapeutic agents and the promotion of tailored treatment regimens.
Application of Real-time MRI-guided Linear Accelerator in Stereotactic Ablative Body Radiotherapy for Non- Small Cell Lung Cancer: One Step Forward to Precise Targeting
Authors: Kang Hye Jin , Kwak Yoo-Kang , Kim Myungsoo , Lee So Jung
Published: June 2022

Purpose: Tumor motion is a major challenge in stereotactic ablative body radiotherapy (SABR) for non-small cell lung cancer (NSCLC), causing excessive irradiation to compensate for this motion. Real-time tumor tracking with a magnetic resonance imaging-guided linear accelerator (MR-Linac) could address this problem. This study aimed to assess the effects and advantages of MR-Linac in SABR for the treatment of lung tumors. Methods: Overall, 41 patients with NSCLC treated with SABR using MR-Linac between March 2019 and December 2021 were included. For comparison, 40 patients treated with SABR using computed tomography-based modalities were also enrolled. The SABR dose ranged from 48 Gy to 60 Gy in 3-5 fractions. The primary endpoint was a lower radiation volume compared to CT-based SABR. The secondary endpoint was the local control rate of SABR using the MR-Linac. Results: The median follow-up time was 19 months (range: 3-105 months). There was no significant difference in the gross tumor volume between the MR and CT groups (7.1 ± 9.3 cm3 vs 8.0 ± 6.8 cm3, p=0.643), but the planning target volume was significantly smaller in the MR group (20.8 ± 18.8 cm3 vs 34.1 ± 22.9 cm3, p=0.005). The 1-year local control rates for the MR and CT groups were 92.1% and 75.4%, respectively (p=0.07), and the 1-year overall survival rates were 87.4% and 87.0%, respectively (p=0.30).Conclusion: Lung SABR with MR-Linac can reduce the radiation field without compromising the local control rate. Further follow-up is needed to assess the long-term effects.
IL-13R130Q modulates human airway smooth muscle cell phenotype to contribute to severe asthma
Authors: He Yafang , Pan Qin , Li Luanluan , Liu Quanhua , Bao Yi-xiao , Zhang Jianhua
Published: June 2022

Background
A small percentage of asthma patients experience severe and refractory asthma that responds poorly to standard therapy. However, this percentage is increasing and better treatment options are therefore needed. Our previous study showed that cultured human airway smooth muscle cells treated with IL-13 R130Q, a naturally occurring IL-13 variant, displayed enhanced functional activities compared to wild-type (WT) IL-13. The present study aims to determine whether IL-13 R130Q could modulate the ASMC phenotype to further contribute to severe asthma.
Methods
Human bronchial smooth muscle cells (hBSMCs) were treated with increasing concentrations of IL-13R130Q or WT IL-13 for 24 h. Endogenous expressions of IL-5 and IL-4 were characterized with Enzyme-linked immunosorbent assay analysis. Acetylcholine-induced changes in intracellular calcium concentration were analyzed with the fluorescent probe Fluo-3/AM with flow-cytometric analysis. Cell proliferation was quantified using the CCK-8 kit and cell migration using the Boyden chamber assay.
Results
IL-13 R130Q induced significantly higher levels of proliferation, migration, and contraction, as well as secretion of IL-4 and IL-5 in hBSMCs compared to WT IL-13.
Conclusions
Taken all together, our data indicate that IL-13R130Q may contribute to severe asthma through phenotypic modulation of hBSMCs.
The Effect of Grinding Time on Moisture Sorption, Particle Size Distribution, and Phenolic Bioaccessibility of Carob Powder
Authors: Červenka Libor , Frühbauerová Michaela , Muriqi Sali , Palarčík Jiří , Velichová Helena
Published: June 2022

Carob pods were ground for 30–180 s in a vibratory grinder. Particle size, colour, moisture sorption properties, antioxidant properties, and phenolic contents were examined. A static three-stage in vitro (oral, gastric, and intestinal) digestion process was performed to determine the fate of phenolic compounds and the antioxidant properties of the carob powder samples.The median values (D50) of particle size decreased after 60 s of grinding (87.9 μm), then increased to 135.1 μm. Lightness showed a negative correlation with D50 and aw, while redness and yellowness values decreased with the reduction of particle size and water activity. The smaller the particle size, the higher the equilibrium moisture content of carob powder. Phenolic acids (vanillic, ferulic, cinnamic) and flavonoids (luteolin, naringenin, apigenin) were found in all samples of carob powder. The grinding time influenced their content with maximum values in carob pods ground for 180 s. Similar observations were made when assessing antioxidant capacity. The in vitro digestion process improved the bioaccessibility of catechin content in all samples. However, the bioaccessibility of phenolic compounds, total phenolic and flavonoid content decreased with the increase in grinding time. Our findings revealed that the grinding of carob pods for 180 s improved the extractability of phenolics, however, their bioaccessibility was reduced. It is sufficient to ground carob pod for 30 s, which ensures good availability of nutraceuticals and lower energy cost for grinding.
In-Pocket 3D Graphs Enhance Ligand-Target Compatibility in Generative Small-Molecule Creation
Authors: Kang Seung-gu , Weber Jeffrey , Morrone Joseph , Zhang Leili , Huynh Tien , Cornell Wendy
Published: June 2022

Proteins in complex with small molecule ligands represent the core of structure-based drug discovery. However, three-dimensional representations are absent from most deep-learning-based generative models. We here present a graph-based generative modeling technology that encodes explicit 3D protein-ligand contacts within a relational graph architecture. The models combine a conditional variational autoencoder that allows for activity-specific molecule generation with putative contact generation that provides predictions of molecular interactions within the target binding pocket. We show that molecules generated with our 3D procedure are more compatible with the binding pocket of the dopamine D2 receptor than those produced by a comparable ligand-based 2D generative method, as measured by docking scores, expected stereochemistry, and recoverability in commercial chemical databases. Predicted protein-ligand contacts were found among highest-ranked docking poses with a high recovery rate. This work shows how the structural context of a protein target can be used to enhance molecule generation.
Health-related Quality of Life Among Adult Patients With Cancer in Uganda
Authors: Naamala Allen , Eriksson Lars E. , Orem Jackson , Nalwadda Gorrette K. , Kabir Zarina Nahar , Wettergren Lena
Published: June 2022

AimTo investigate prevalence of clinical cases with regard to health-related quality of life (HRQoL) and its association with socio-demographic and clinical factors among adult patients attending specialized cancer care in Uganda.MethodsA cross-sectional study was performed with 385 patients cared for at Uganda Cancer Institute (response rate 95%). HRQoL was measured using EORTC QLQ-C30 including its subscales measuring functioning and symptoms as well as overall health status and quality of life (QoL). Predetermined thresholds indicating clinical importance were applied to identify patients exhibiting functional impairments and symptoms at a level meriting concern (clinical cases). Socio-demographic and clinical characteristics were collected through study-specific items and medical records, respectively. Multivariable logistic regression models identified factors associated with being a clinical case in seven selected subscales of the EORTC QLQ-C30 (Physical, Role, Social and Emotional Function, Global health status/QoL, Pain and Fatigue). ResultsThe mean age of the study participants, in - and outpatients with various cancers, was 48 years. The majority reported their functioning at levels indicating clinical caseness (68%−87%), as well as significant pain (80%), and fatigue (63%). Higher age and lack of education were associated with clinical caseness. Clinical characteristics related to caseness included having an advanced disease stage, being hospitalized, receiving palliation, not on active cancer treatment as well as diagnosed with head/neck cancers.Conclusion The study demonstrated that more than two thirds of adult patients cared for at a specialized cancer facility in Uganda rate HRQoL at levels meriting concern. The large proportion of patients with pain calls for implementation of guidelines such as the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Adult Cancer Pain, to improve pain management in Uganda. A majority of the patients reported fatigue at a clinical level which can be addressed by educational interventions to teach patients self-care strategies to conserve energy.
Cross-codex Learning for Reliable Large Scale Scribe Identification in Medieval Manuscripts
Authors: Weißmann Julius , Seidl Markus , Dietrich Anya , Haltrich Martin
Published: June 2022

Historic scribe identification is a substantial task for obtaining information about the past. Uni-form script styles, such as the Carolingian minuscule, make it a difficult task for classification to focuse on meaningful features. Therefore, we demonstrate in this paper the importance of cross-codex training data for CNN based text-independent off-line scribe identification, to overcome codex dependent overfitting. We report three main findings: First, we found that preprocessing with masked grayscale images instead of RGB images increased the F1-score of the classification results drastically. Second, we trained different neural networks on our complex data, validating time and accuracy differences in order to define the most reliable net-work architecture. With AlexNet, the network with the best trade-off between F1-score and time, we achieved for individual classes F1-scores of up to 0,96 on line level and up to 1.0 on page level in classification. Third, we could replicate the finding that the CNN output can be further improved by implementing a reject option, giving more stable results. We present the results on our large scale open source dataset – the Codex Claustroneoburgensis database (CCl-DB) – containing a significant number of writings from different scribes in several codices. We demonstrate for the first time on a dataset with such a variety of codices that paleographic decisions can be reproduced automatically and precisely with CNNs. This gives manifold new and fast possibilities for paleographers to gain insights into unlabeled material, but also to develop further hypotheses.
Preliminary Survey on the Health and Management Practices Among Small-scale Cage Tilapia Farmers on Lake Volta
Authors: Abarike E. D. , Atuna R. A. , Dandi S. O. , Agyekum S. , Appenteng P. , Alhassan E.H. , Akongyuure D.N.
Published: June 2022

The study investigated the health and management strategies adopted by fish farmers on Lake Volta to control disease outbreaks. 30 fish farmers were randomly selected within stratum II of the Lake Volta and interviewed using semi-structured questionnaires and oral discussions to collect information on their knowledge, experiences and measures used in controlling the spread of fish diseases. Farmers face challenges including poor water quality and seed and incidence of diseases. 56% of farmers reported they have experienced up to 70% losses of their fish due to diseases. 80% of farmers use antibiotics, herbs and probiotics as a treatment regimen to control diseases. Farmers expressed low confidence in using expert advice in the control of diseases. For better management of fish health, it may be necessary to develop a comprehensive fish health management plan by the collaborative efforts of stakeholders in the management of disease incidence in the aquaculture industry in Ghana.
Designing a decision aid for cancer prevention
Authors: Milton Shakira , Macrae Finlay , McIntosh Jennifer G , Saya Sibel , Alphonse Pavithran , Yogaparan Thivagar , Karnchanachari Napin , Novy Kitty , Nguyen Peter , Lau Phyllis , Forbes Carmody , Cummings Kara-Lynne , Emery Jon David
Published: June 2022

Objectives
Australian guidelines recommend people aged 50 to 70-years-old, consider taking low-dose aspirin to reduce their risk of colorectal cancer. The aim was to design sex-specific decision aids (DAs) with clinician and consumer input including expected frequency trees (EFTs) to communicate risks and benefits of taking aspirin.
Methods
Semi-structured interviews were conducted with clinicians. Focus groups were conducted with consumers. The interview schedules covered ease of comprehension, design, potential effects on decision making, and approaches to implementation of the DAs. Thematic analysis was employed; independent coding by two researchers was inductive. Themes were developed through consensus between authors.
Results
Sixty-four clinician were interviewed over six-months in 2019. Twelve consumers, aged 50 to 70 years, participated in two focus groups in February and March 2020.
Design of Overhead Tank with Carbon Fibre/Fiber Rebar as Reinforcement and Time History Analysis using STAAD-Pro software.
Authors: CHONDIKAR KRUSHNARTH
Published: June 2022

The Construction and Design industry is always trying to find new and better technologies, ways, materials and equipment. One such technology/material is the using Carbon Fibre/fiber as Reinforcement for design the structure which is a new material in this industry that brings alternative for steel in the designing of the structure and offers design opportunities to enhance the performance of the structure with encouraging innovation. The use of this material in designing of the structure reflects economical. Most of the studies showed that the need of water and storage of water in tanks is essential and increasing now days all over the world. For that demands, we designs the huge storage water tanks structures. Designing the huge storage water tanks by traditional/conventional/regular way has limits, but it should not been limited to a certain extent structural point of view. Efficient overhead water tanks would not be possible with a traditional/conventional/regular approach. Storage tanks are different structure by their special architectural features and configurations. Materials having high strength and innovative structural systems are needed to be developed to resist the challenges created by construction the huge storages of water tanks in regions of highly dense populated area. In present work, design of the overhead tank using carbon fibre/fiber as reinforcement, has been checked against the several loads, time history analysis and the maximum considered level criteria by performing the linear and nonlinear procedures with the help of STAAD-Pro software. In further work, the performance of overhead tank using carbon fibre/fiber as reinforcement will be checked at the several loads, time history analysis and the maximum considered level criteria.
Anti-inflammatory activity of omega-3-polyunsaturated fatty acid oil extract on acute inflammation in animal models.
Authors: Omale J. A. , Ezeanyika L. U. S , Omale A
Published: June 2022

Safety concerns for persistent long-term use of anti- inflammatory drugs must be considered when prescribing pain relief medications for acute, chronic and degenerative pain conditions due to the side effects. Therefore supplementation using natural forms of anti-inflammatories such as omega − 3- fatty acids (n-3 fatty acids) is more about therapeutic safety than it is of efficacy. In this study, standard methods (Carageenan, Arachidonic acid and PGE2) were used to determine the nutritional intervention of n-3 fish oil extract (due to its eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA contents) in experimental animal models for acute inflammatory models. Obtained results showed marked inhibition of inflammation by the fish oil brought about by EPA and DHA content of the oil. Resolution of carragenan-induced paw edema inflammation after 24hrs was 78.57%, 57.14%, 50.00%, 100.00% and 92.85% percentage inhibition for groups 1, 2, 3, 4, and 5 respectively. Arachidonic acid-induced ear edema was 30, 24, 27, 37 and 40% inhibition while 44.16, 52.48, 61.34,74 and 80.05% were for PGE-2 assay. The results show that the active components in omega-3 polyunsaturated fatty acids, which are eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), are capable of interrupting the prostaglandin metabolic pathway by competing with arachidonic acids for the COX active site thereby inhibiting their synthesis.
Designing Optimal Hub-and-Spoke Network Considering Flow Delay Cost: The Case of Urban Express Delivery in Eastern China
Authors: Bangjun Wang , Quoqiang Shen , Long Zhou , Wei Zhao
Published: June 2022

With respect to a traditional point-to-point (P-P) network, a hub-and-spoke (H-S) not only uses a smaller number of links/paths, but also utilizes the scale economy advantage on consolidated flows on hub-hub links and at hubs. However, the inevitable delays through hubs have always been a critical concern. Therefore, this paper develops an H-S model considering flow delay costs and applies the model to a logistics case in east Jiangsu province, China. The model is based on the well-known H-S network model proposed by O'Kelly et al., which first introduced the concept of flow delay cost in hub location and network design. In this research, the flow delay cost is defined as the cost associated with delay caused by flow transfers at hubs. The integer quadratic term in our model’s objective function is linearized using the algebraic method suggested by Shen (1994). Our model is applied to a local logistics firm, who plans to develop an H-S network for its 13-node express package delivery operation, using the Particle Swarm Optimization (PSO) algorithm. The results show using the H-S can save more than 14.1% of the total cost annually. The model also provides an applied case to the H-S configuration, especially for urban express delivery logistics in China.
Relationship of History and Music: Traces of Historical Events in Kurdish Music and Evdalê Zeynikê
Authors: ÇİFÇİ Tekin
Published: June 2022

History comes across as a product of the effort to create social memory, written or verbal. It is based on information and documents and avoids emotional biases. Music, on the other hand, is a multifaceted phenomenon and its aim to entertain shapes it. On one hand, it interprets emotions, and on the other hand it bears the social, cultural and historical codes of the society to which it belongs. For this reason, it is possible to discover specific details of historical events in the kilams/songs of dengbêjs, important exponents of the Kurdish music of orality. This study focuses on unveiling traces of historical events in the songs of the dengbêjs, in context of the relationship between history and music. Information and documents dealing with the Kozanoğlu events in kilam/songs are compared. A good example of the importance of the dengbêjs in Kurdish history is taken from when in the 19th century, the Ottoman state established a military unit called Fırka-i Islahiye as a part of its policy of asserting its full dominance in rural areas, and also to carry out compulsory resettlement policies. In order to support the operation, the Kurdish chief Sürmeli Memed Pasha set out, taking with him under his auspices Evdale Zeynikê, a dengbej singer. However, the Kurdish troops reaching Kozan were defeated due to the climatic conditions and the cholera epidemic. Witnessing all the events, Evdale Zeynikê sang kilam/songs for every stop on the route and on the death of the Pasha. Throughout this account, which is based in Kurdish culture and immured with a strong dengbêj tradition, it is possible to find details of Kurdish history in the kilams/songs of the dengbêjs.