bluuebunny/crossref_metadata_2025 huggingface dataset:
Pemetrexed induces ROS generation and cellular senescence by attenuating TS-mediated thymidylate metabolism to reverse gefitinib resistance in non-small cell lung cancer
Authors: Guo Renhua , Chen Yun , Zhang Chen , Jin Shidai , Li Jun , Dai Jiali , Zhang Zhihong
Published: October 2022

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are strongly recommended for non-small cell lung carcinoma (NSCLC) patients harboring active EGFR mutations, while drug resistance inevitably makes exploring the resistance mechanisms and seeking effective therapeutic strategies urgent endeavors. Thymidylate synthetase (TYMS or TS) is a dominant enzyme in thymidylate nucleotide metabolism. In this study, based on public database analysis and examination of gene sets from 140 NSCLC patients that received EGFR-TKI therapy, we found a significantly positive correlation between TS expression and overall survival (OS) and disease-free survival (DFS) in lung adenocarcinoma. Twenty-four tissue specimens from NSCLC patients exhibited upregulated TS mRNA expression in NSCLC patients resistant to gefitinib. The human NSCLC cell line PC9, which is sensitive to gefitinib, and relatively resistant PC9/GR cells were used to demonstrate that knockdown of TS restored the sensitivity of resistant cells to gefitinib. Furthermore, pemetrexed effectively suppressed TS-mediated thymidylate metabolism and induced ROS generation and cellular senescence, thereby hampering carcinogenesis and restoring cell sensitivity to gefitinib. The combination of pemetrexed and gefitinib damaged the proliferation, migration and invasion capabilities of gefitinib-resistant cells, exhibiting a synergistic anticancer effect. Our findings illuminate the potential mechanism of TS-triggered gefitinib resistance and indicate that inhibition of TS by pemetrexed can potentiate the effect of gefitinib in NSCLC cells resistant to gefitinib. Pemetrexed combined with gefitinib has potent anti-progression potential in gefitinib-resistant NSCLC. This suggests that NSCLC patients with both high TS expression and EGFR-driving mutations might benefit more from a combination strategy of EGFR-TKIs and pemetrexed-based chemotherapy than EGFR-TKI monotherapy, which has profound clinical implications and considerable therapeutic value.
The distribute impact of labour market and cash transfer policies during the COVID-19 pandemic in Latin America
Authors: Beccaria Luis , Maurizio Roxana , Martinez SIlvana
Published: October 2022

The COVID-19 pandemic has generated an unprecedented economic, health, labour and social crisis in the world. Latin America is one of the regions that has been most strongly affected. The main aim of this paper is to assess the dynamics of family income inequality and its components since the onset of the pandemic in six Latin American countries -Argentina, Brazil, Colombia, Costa Rica, Peru and Uruguay-. The unequalizing impact of the worsening of the labour market during the contraction phase was mainly associated with the significant loss of informal, low-paid, jobs. This effect was offset, at least partially, by the equalizing role of cash transfers policies put in place in the outbreak of the pandemic. An opposite impact of these income sources appears during the recovery phase, as most countries gradually reduced or stopped those transfers as employment and, therefore, labour incomes partially recovered. Nearly two years into the COVID-19 pandemic inequality is higher than 2019 in almost all countries studied exacerbating existing high-income gaps in one of the world's most unequal regions.
A nomogram risk assessment model to predict the possibility of type II endoleak-related re- intervention after endovascular aneurysm repair (EVAR)
Authors: Liu Zongwei , Chen Yonghui , Qin Yafei , Bi Jiaxue , Wang Jiaxin , Niu Fang , Dai Xiangchen
Published: October 2022

Purpose
This study aimed to develop and validate a novel nomogram risk assessment model to predict the possibility of type II endoleak (T2EL)-related re-intervention.
Methods and materials:
The data of 455 patients with abdominal aortic aneurysms who underwent elective endovascular aneurysm repair (EVAR) procedures between January 2018 and December 2021 at our single center were retrospectively reviewed. Following the implementation of exclusion criteria, 283 patients were finally included and divided into T2EL-related re-intervention (n = 42) and non-T2EL (n = 241) groups.
Results
The overall T2EL-related re-intervention rate for 283 patients was 14.8% (42/283). Using multivariate analysis, significant risk factors for re-intervention included age (OR, 1.104; 95% CI, 1.023–1.191; P = 0.011), smoking (OR, 4.249; 95% CI, 1.383–13.052; P = 0.012), hypertension (OR, 4.175; 95% CI, 1.321–13.192; P = 0.015), and number of patent lumbar arteries (OR, 6.270; 95% CI, 3.030–12.974; P < 0.001). The discrimination ability of this risk-predictive model was reasonable (concordance index [C-index] = 0.886; 95% CI, 0.825–0.947). The Hosmer-Lemeshow goodness of fit test was performed on the model, and the chi-square value was 13.832 (P = 0.086), presenting an excellent agreement between the model-predicted and observed values. The receiver operating characteristic (ROC) curve identified that the risk thresholds of re-intervention were a diameter of > 2.77 mm for the diameter of the inferior mesenteric artery and a proportion of < 45.5% for thrombus volume in the aneurysm sac.
Conclusion
This novel nomogram risk assessment model for predicting the possibility of patients’ T2EL-related re-interventions after EVAR should be helpful in discriminating high-risk patients. Two novel risk thresholds may imply a higher possibility of T2EL-related re-intervention after EVAR.
A State-of-the-Art Technique for Malware Detection Based on Deep Learning in IoT Environment
Authors: ALI MUHAMMAD MUMTAZ , ZHENFEI WANG , WEIYAN HOU , SHAUKAT ZEESHAN , SHABBIR AYESHA , RASHEED AQSA , MAQSOOD FAIQA , ZIA QASIM , REHMAN HAMEED UR
Published: October 2022

The authors have requested that this preprint be removed from Research Square.
A time-resolved fluorescence immunoassay for rapid and precise automatic quality control of human papillomavirus type 68 VLPs in human papillomavirus vaccine
Authors: Li Zhaoyue , Chen Yin , Li Yang , Zhang Zhigao , Zhai Xiangming , Cao Yue , Li Xijiu , Yang Yiqi , Wu Yingsong , Lin Guanfeng
Published: October 2022

The effectiveness and necessity of human papillomavirus (HPV) vaccination to prevent HPV infection and cervical cancer are increasingly recognized by people. The 15-valent HPV vaccine, which protects against almost high-risk types of HPV viruses identified by WHO, has attracted much attention. However, as the valence of vaccines increases, quality control in the HPV vaccine production process is facing more challenges. The precise quality control of the HPV type 68 virus-like particles (VLPs), one of the unique components of the 15-valent HPV vaccine that distinguishes it from existing vaccines, is the new requirement for vaccine manufacturers. Here we developed a novel time-resolved fluorescence immunoassay (TRFIA) for rapid and precise automatic quality control of HPV68 VLPs in HPV vaccine. Two murine monoclonal antibodies specifically targeting the HPV68 L1 protein were used to establish a classical sandwich assay. Except for pretreating the vaccine sample, the whole analysis process was performed by a fully automated machine, which saves detection time and gets rid of manual error. Multiple experiments established that the current novel TRFIA can efficiently and reliably analyses HPV68 VLPs. Present novel TRFIA has exhibited merits with speed, robustness, high sensitivity with a minimum detection value of 0.08 ng/mL, considerable accuracy, a wide detection range (up to 1000 ng/mL) and excellent specificity. It is also expected to provide a new detection method for quality control for each HPV type VLPs. To summarize, the novel TRFIA is of great interest for application in HPV vaccine quality control.
The Antiviral Activity of Triple Motif Protein 38 In Hepatitis B Virus Replication and Gene Expression and Its Association with Treatment Responses During PEG-IFN-α Antiviral Therapy
Authors: Luo Haiying , Hu Xiaoxia , Li Yadi , Lei Dingjia , Tan Guili , Zeng Yueying , Qin Bo
Published: October 2022

Background
Hepatitis B virus (HBV) infection is the most critical factor underlying liver cirrhosis and hepatocellular carcinoma worldwide.The triple motif protein 38 (TRIM38) is an interferon-stimulated gene (ISG) that can indirectly inhibit various DNA and RNA viruses by modulating the type I interferon response.However, the relationship between TRIM38 and HBV infection and therapy is yet to be elucidated.Our study aims to investigate the correlation between TRIM38 expression levels and the efficacy of HBV infection and IFN-α therapy in patients with CHB.
Methods
TRIM38 was overexpressed or knocked down in human hepatoma cells and the cells and supernatant were collected.The levels of HBV RNA, pgRNA and supernatant antigen were detected by qRT-PCR or ELISA to evaluate the inhibitory effect of TRIM38 on HBV.Blood samples of CHB patients who received pegylated interferon-α(PEG-IFN-α) therapy were collected, and PBMC was isolated.The alternation in the gene expression level of TRIM38 was detected by qRT-PCR, and the predictive value of TRIM38 changes during early therapy was evaluated.The induction of antiviral proteins was analyzed by immunoblotting.
Results
In human hepatoma cells, TRIM38 was highly induced by IFN-alpha (IFN-α) and enhanced anti-HBV activity.Furthermore, combined treatment with TRIM38 and IFN-α increased antiviral proteins levels.The overexpression of TRIM38 inhibited while knockdown of TRIM38 elevated HBV replication and gene expression in HepG2 and HepG2.2.15 cells.TRIM38 is negatively correlated with chronic HBV infection.Prospective study showed that high levels of TRIM38 in peripheral blood PBMCs were observed in the early responders, and higher TRIM38 expression co-related with a better response to PEG-IFN-α therapy.
Conclusions
Taken together, our study suggested that TRIM38 plays a vital role in HBV replication and gene expression and TRIM38 may become a new target for the treatment of HBV.
The settlement phase in the common octopus Octopus vulgaris: a complex transition between planktonic and benthic lifestyles
Authors: Roura Alvaro , Castro-Bugallo Alexandra , Martínez-Pérez Miguel
Published: October 2022

Planktonic octopuses undergo a transitional period from a pelagic lifestyle to the predominantly benthic life of the juvenile stage, known as settlement, that is scarcely documented in the wild or captivity. In this work two generations of the common octopus, Octopus vulgaris, were reared in captivity and three different stages were defined for the settlement phase based on morphological, anatomical, and behavioural changes: pre-settlement or “tactile” stage, settlement, and post-settlement or “ninja” stage. Before settlement the swimming planktonic paralarvae are transparent with 65–80 chromatophores, iridophores covering eyes and digestive system, Kölliker organs, circular pupils, ~ 20 suckers, and mantle length (ML) bigger than total length (TL; ML/TL > 60%). The “tactile” stage (ML/TL from 65 − 55% and ~ 20–25 suckers) is marked by the onset of pre-settlement reflexes, where the late paralarvae touch the walls and bottom of the tank and start crawling clumsily. Morphologically, the paralarvae are transparent with increasing chromatophores and iridophores along the arms and the dorsal area of head and mantle. During the settlement stage (~ 55 − 48% ML/TL, and ~ 25–35 suckers), there is an exponential increase of chromatophores in the dorsal area and a marked change in behaviour, with paralarvae showing strong negative phototaxis, looking for shelter when disturbed. The skin is still transparent but new chromatic cells (leucophores) start to develop and the Kölliker organs are almost lost. During the post-settlement stage (~ 48 − 40% ML/TL, > 35 suckers) the chromatic cells keep increasing exponentially, giving a pale look to the skin. The early juveniles have horizontal pupils, with the “eye-bar” and display very fast and coordinated movements like “ninjas”. The start of the benthic phase is marked by the presence of skin sculptural components (papillae and cirrha) and the display of complex chromatic and body patterns.
The association of menopausal hormone therapy with the incidence of urinary tract cancer: a national population-based study
Authors: Yuk Jin-Sung , Yoon Sang-Hee , Yu Ji Hyeong , Kim Jae Yoon
Published: October 2022

This study evaluates the relationship between menopausal hormone therapy (MHT) and the risk of urologic cancer in women. It was conducted for South Korea’s national population based on the National Health Insurance Service Database between January 2002 and January 2019. The types of MHT in this study included tibolone, combined oestrogen plus progestin by the manufacturer (CEPM) or physician (CEPP), and oral and topical oestrogen. Furthermore, select patient characteristics and reproductive factors were reviewed. We performed a Cox proportional hazard analysis to clarify the risk of urologic cancer associated with MHT. According to MHT types, 104,089 were treated with tibolone, 65,597 with CEPM, 29,357 with oral oestrogen, 3,913 with CEPP, and 1,174 with topical oestrogen. Among women on MHT, the incidence of kidney cancer was significantly increased with oral oestrogen (hazard ratio [HR] 1.36, 95% confidence interval [CI]: 1.062–1.735) and topical oestrogen (HR 2.84, 95% CI: 1.270–6.344), whereas other formulations were not associated with kidney cancer. Meanwhile, tibolone significantly decreased the incidence of bladder cancer (HR 0.69, 95% CI: 0.548–0.858), whereas other formulations were not associated with bladder cancer. Our findings suggest that MHT in postmenopausal women affects the incidence of urologic cancers.
Studies on Entire Span Vibration and Local Deformation Characteristicsof Transmission Line under Impact Load
Authors: Zhu He , Chen Wenlong , Han Zhaobing , Liu Cheng , Yang Junqing , Chen Huan
Published: October 2022

In order to study the entire span vibration and local deformation characteristics of transmission conductor under impact load collision, the mathematical model of entire span vibration and local deformation of transmission conductor is established. Considering the influence of conductor local deformation and conductor steel and aluminum strand on Poisson's ratio and elastic modulus, the entire span impact vibration simulation model and local impact deformation simulation model of transmission conductor are established, The macroscopic entire span vibration and local deformation of transmission line are analyzed. The results show that the maximum sag of each position on the transmission line occurs when the impact force acts on that position; The change of impact force has the greatest impact on the maximum value of sag near the suspension point and the least impact on the maximum value of sag near the center of span; Impact has the greatest impact on the outermost aluminum strand. With the deepening of impact, the deformation of each layer decreases gradually, but the deformation area increases gradually; The influence of impact velocity on the deformation of inner aluminum strand increases gradually, but the influence on the deformation of inner steel core is basically unchanged.
Autobiographical memory specificity and restrained eating: examining the influence of priming with images of healthy and unhealthy foods.
Authors: Wallis Deborah Jane , Moss Jessica , Varnam Bethany , Dritschel Barbara , Ridout Nathan
Published: October 2022

Background: Dietary restraint has been linked to deficits in the ability to recall detailed memories of personally experienced events (referred to as autobiographical memory specificity). As priming with healthy foods increases the salience of restraint it would be expected to lead to greater deficits in memory specificity.
Objective: To determine if priming word cues with images of healthy or unhealthy foods would influence the specificity of memory retrieval, and if deficits in memory specificity would be more evident in those reporting higher levels of dietary restraint, or currently dieting.
Methods: Sixty female undergraduates self-reported if they were currently dieting and completed measures of mood, restraint, and disinhibition, and a modified version of the autobiographical memory task. Participants were presented with positive and negative words (unrelated to eating concerns) and asked to retrieve a specific memory in response to each cue. A food image was shown prior to each word cue; half of the participants were primed with images of healthy foods and half with images of unhealthy foods.
Results: As expected, participants primed with healthy foods retrieved fewer specific memories than did those primed with unhealthy foods. However, neither restraint nor current dieting behaviour were associated with memory specificity.
Conclusions: Differences in memory specificity between the priming conditions cannot be explained in terms of increased salience of restraint. However, it is plausible that unhealthy images led to an increase in positive affect, which in turn improved memory specificity.
Level of evidence: Level I: Evidence obtained from: at least one properly designed experimental study
Genomic Variability Correlates with Biofilm Phenotypes in Multidrug Resistant Clinical Isolates of Pseudomonas aeruginosa
Authors: Islam Ovinu Kibria , Islam Israt , Saha Otun , Sultana Munawar , Bockmuhel Dirk , Hossain M Anwar
Published: October 2022

The multifactorial nature of Pseudomonas aeruginosa biofilm development and genomic variabilities implicates its resistance to conventional antimicrobials and virulence. Therefore, genetic determinants need to be extensively studied to block the early steps of biofilm or already formed biofilms. In this study, a total of 20 multidrug resistant (MDR) clinical P. aeruginosa isolates were evaluated for their biofilm forming abilities and related genes. Of the isolates tested, all of them showed surface attachment tendencies in nutrient limiting conditions, and classified as strong (SBF=45%), moderate (MBF=30%) and weak (WBF=25%) biofilm formers. Complete genome sequencing of representative strong (DMC-27b), moderate (DMC-20c) and weak biofilm former (DMC-30b) isolates was performed. Analysis of biofilm related genes in the sequenced genomes revealed that,80 of the 88 biofilm related genes possess 98–100% sequence identity to the reference PA01 strain. Complete and partial sequence data of LecB proteins from tested isolates indicate that isolates containing PA14-like LecB sequences produced strong biofilms. All of the 7 pel operon protein coding genes in weak biofilm former isolate 30b showed significant nucleotide sequence variation with other tested isolates, and their corresponding proteins are 99% identical with the pel operon proteins of PA7. Bioinformatics analyses identified divergent sequence and structural features that separate PA7 like pel operon proteins from reference PAO1 like pel operon. Congo red and pellicle forming assays revealed that the sequence and structure variations may have interfered with the Pel production pathway and resulted in impaired Pel production in isolate 30b that has a PA7 like pel operon. Expression analysis also showed that both PelB and LecB proteins were about 5 to 6 folds upregulated after 24 hours in SBF 27b in comparison with WBF 30b. Our findings indicate significant genomic divergence in biofilm related genes of P. aeruginosa strains that affect their biofilm phenotypes.
Evidence of a compensatory response in invasive Rusty Crayfish (Faxonius rusticus) following intensive harvest removal from northern Lake Michigan fish spawning reefs
Authors: Kvistad Jake T , Galarowicz Tracy L. , Clapp David F. , Chadderton W. Lindsay , Tucker Andrew J. , Herbert Matthew
Published: October 2022

The goal of a harvest removal program to control invasive species is usually to achieve sustained reductions in population abundance. Yet removal efforts may be counteracted by density-dependent processes by increasing available resources and reducing stage-specific mortality. We tested a harvest removal strategy for invasive Rusty Crayfish (Faxonius rusticus) focused on nearshore cobble reefs, used by several native fishes as spawning habitats, in Lake Michigan with a before-after control-impact (BACI) study design. We removed 3182 Rusty Crayfish, primarily adults (> 20 mm carapace length), at two sites over two harvest seasons, expending 17,825 trap days in effort. While the BACI analysis results suggested that a statistically significant reduction in Rusty Crayfish densities assessed from diver quadrat surveys was achieved on one reef (Little Traverse Bay Crib), suppression effects were highly variable across sites. In addition, reduced densities were sustained over the egg maturation period for native fish and into the following year after removal ceased. However, by late summer/early fall between consecutive suppression efforts in 2018 and 2019 we observed a threefold increase in pre-removal densities. Size-frequency histograms from diver quadrat surveys showed higher abundance of juvenile size classes over the following spring and summer at Little Traverse Bay Crib compared to its paired reference site, suggesting a compensatory response. Evidence of compensation was corroborated by stock-recruitment analysis and a coincident increase in ovarian egg counts at Little Traverse Bay Crib between 2018 and 2019. With a proviso that we only conducted two seasons of consecutive suppression, our results emphasizes the effects of density-dependent processes in invasive species management and raises questions about efficacy of adult-only removal strategies.
Use of a-priori information to minimize uncertainties in surface wave inversion and subsequent site response analysis
Authors: Desai Aniket , Jakka Ravi S , Foti Sebastiano
Published: October 2022

The authors have requested that this preprint be removed from Research Square.
Wetlands Mapping with Deep ResU-Net CNN and Open-Access Multisensor and Multitemporal Satellite Data in Alberta’s Parkland and Grassland Region
Authors: Onojeghuo Alex Okiemute , Onojeghuo Ajoke Ruth
Published: October 2022

Wetlands are a valuable ecosystem that provides various services to flora and fauna. This study developed and compared deep and shallow learning models for wetland classification across the climatically dynamic landscape of Alberta’s Parkland and Grassland Natural Region. This approach to wetland mapping entailed exploring multi-temporal (combination of spring/summer and fall months over four years – 2017 to 202) and multisensory (Sentinel 1 and 2 and Advanced Land Observing Satellite - ALOS) data as input in the predictive models. This input image consisted of S1 dual-polarization vertical-horizontal bands, S2 near-infrared and shortwave infrared bands and ALOS-derived Topographic Wetness Index. The study explored the ResU-Net deep learning (DL) model and two shallow learning models, namely random forest (RF) and support vector machine (SVM). We observed a significant increase in the average F1-score of the ResNet model prediction (0.77) compared to SVM and RF prediction of 0.65 and 0.64, respectively. The SVM and RF models showed a significant occurrence of mixed pixels, particularly marshes and swamps confused for upland classes (such as agricultural land). Overall, it was evident that the ResNet CNN predictions performed better than the SVM and RF models. The outcome of this study demonstrates the potential of the ResNet CNN model and exploiting open-access satellite imagery to generate credible products across large landscapes.
Clinician perspectives on offering services to adolescents with mental health problems in a National Referral Hospital in Kenya
Authors: Wambua Grace Nduku , Kumar Manasi , Falkenström Fredrik , Cuijpers Pim
Published: October 2022

Background: The aim of this paper was to explore clinicians’ perspectives on the provision of psychotherapy to adolescents referred for care in a public health facility, with a focus on identifying both facilitators and barriers to the treatment process.
Method: The study was conducted at the Youth Clinic of the Mental Health Department at Kenyatta National Hospital (KNH) in Nairobi. Ten clinicians participated in the interviews. Interviews were recorded and transcribed verbatim for coding. A reflexive thematic approach was utilized for analysis.
Findings: Our analysis identified five overarching but interrelated themes. The clinicians describe different facilitators and barriers to the therapeutic process within each theme. They included (i) awareness of mental health issues was limited among adolescents and caregivers with the internet offering new source of information for adolescents, (ii) community awareness of available help was also inadequate with adolescents and caregivers often preferring a quick solution as opposed to time-consuming therapy, (iii) dose of treatment and perception of adequacy identified as conflict areas for all stakeholders involved, with 3 sessions often being prescribed by the schools, with clinicians describing them as inadequate, (iv) premature termination of the process which was influenced by user perceptions and attitudes toward treatment and finally (v) the clinicians identified that a good therapeutic relationship was important for good therapeutic outcomes.
Discussion: Our findings give us insight into the therapeutic process, giving an understanding of some of the barriers and facilitators as experienced by clinicians working with adolescents in Kenya. Issues such as low mental health literacy have greater impact on not only help-seeking behaviors in the group, but appropriate utilization of services for their benefit. This work yields important insights that can be used to improve adolescent mental health services.
Childhood maltreatment and emotion regulation in everyday life: An experience sampling study
Authors: Miu Andrei C. , Bîlc Mirela I. , Szentágotai-Tătar Aurora , Pop Claudia Felicia , Ion Andrei
Published: October 2022

Childhood maltreatment is a major risk factor for psychopathology, and increasing evidence suggests that emotion regulation (ER) is one of the underlying mechanisms. However, most of this evidence comes from cross-sectional studies and single assessments of habitual ER strategies. In the present study, we investigated the relation between history of childhood maltreatment, positive and negative affect, and multiple dimensions of spontaneous ER (strategy use, ER success, effort, and goals) in everyday life, using experience sampling method (3 assessments/day, for 10 consecutive days), in a sample of healthy volunteers (N = 118). Multilevel modeling results indicated that childhood maltreatment was associated with lower positive affect and higher negative affect. Childhood maltreatment was also related to lower use of reappraisal and savoring (but not suppression, rumination and distraction), reduced ER success (but not effort), as well as lower levels of and higher within-individual variability of hedonic (but not instrumental) ER goals. These results provide ecological evidence that individuals with a history of childhood maltreatment are characterized by differences in multiple ER dimensions.
Adverse cardiovascular, limb, and renal outcomes in patients with diabetes after peripheral artery disease revascularization treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors Cover title: SGLT2i versus DPP4i in T2D patients after PAD revascularization
Authors: Lee Hsin-Fu , Chuang Chi , Li Pei-Ru , Yeh Yung-Hsin , Chan Yi-Hsin , See Lai-Chu
Published: October 2022

Aims
The effectiveness and limb safety of sodium glucose co-transporter 2 inhibitors (SGLT2i) for patients with type-2 diabetes (T2D) who have received peripheral artery disease (PAD) revascularization are unknown.
Methods and results
In this nationwide retrospective cohort study, we identified a total of 2,455 and 8,695 patients with T2D who had undergone PAD revascularization and received first prescriptions for SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i), respectively, between May 1, 2016, and December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates between the two study groups. Patients were followed up from the drug index date until the occurrence of specified outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first. After PSM, we observed that compared with DPP4i, SGLT2i were associated with comparable risks of ischemic stroke, acute myocardial infarction, and heart failure hospitalization but were associated with a lower risk of cardiac death (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.40–0.90]; p = 0.0126). Regarding major limb outcomes, SGLT2i were associated with comparable risks of repeated revascularization and lower limb amputation compared with DPP4i. SGLT2i were associated with a lower risk of composite renal outcomes (HR: 0.40; 95% CI: 0.27–0.59; p < 0.0001) compared with DPP4i.
Conclusion
In a real-world study of patients with T2D who had undergone PAD revascularization, SGLT2i were associated with lower risks of cardiac death and composite renal outcomes but not associated with increased risks of adverse limb eventscompared with DPP4i.
The modified generalized Tresca yield condition with application to mode I perfectly plastic crack problems
Authors: Unger David J.
Published: October 2022

Basic properties of a newly defined yield criterion are explored and then applied to plane stress, mode I, perfectly plastic crack problems. This yield condition began as a perturbation of the traditional Tresca yield condition. In a previous study, a relationship was found for a yield criterion that spanned the Tresca to the von Mises yield criteria in the principal stress plane. In this study, a distinct but related yield criterion is used for those cases where the yield criterion lies on or outside the von Mises yield condition in the principal stress plane. For these cases, the associated mathematics becomes more complicated than those cases where the yield condition lies within or on the von Mises yield condition in the principal stress plane. The perfectly plastic mode I crack problem is solved for this modified version of the generalized Tresca yield condition. It is found that the maximum normal stress for this yield condition is higher than that for the equivalent mode I crack problem under the von Mises yield condition. Material parameters associated with the generalized Tresca yield condition are found for both the BCC and FCC crystal structures based on models proposed previously in the literature.
Mathematics Subject Classification. 74A45, 74C05
A Quantitative Strategic Planning Framework for Artificial Groundwater Recharge of Esfarayen Aquifer in Iran based on Fuzzy AHP
Authors: Farzi Abolfazl , Boostani Abtin , Maghsodi Reza , Nameni Reza
Published: October 2022

This article studies the Artificial Groundwater Recharge (AGR) of the Esfarayen aquifer, in Iran, from the perspective of the strategic planning process. For this purpose, a SWOT systematic analysis was performed for the AGR of this aquifer, and its strengths, weaknesses, opportunities, and threats (SWOT) were identified. These factors were analyzed and ranked using Mikhailov's fuzzy analytic hierarchy process (AHP) and based on this analysis, prior strategies were proposed. The results showed that the share of two groups of threats and opportunities in higher priority factors was more than the two groups of strengths and weaknesses, so that the shares of threats and opportunities in the first half of the list of factors were 87.5% and 70% of the factors of these groups, respectively. Also, strengths have been ranked higher than weaknesses. Therefore, in selecting appropriate strategies for the future of the AGR of Esfarayen aquifer, priority should be given to ST type strategies; strategies that use the strengths of the system to try to eliminate external threats to the system. After ST type strategies, due to the high importance of opportunities, SO type strategies can also be adopted for the AGR of Esfarayen aquifer.
Whole genome characterization of an avian calicivirus from broiler chicken farms in Iran: First report
Authors: Zamani Niusha Haji , Ghalyanchilangeroudi Arash , Kafi Zahra Ziafati , Dizaji Reza Esmaeelzadeh , Sadri Naser , Sarmadi Soroush , Hosseini Hossein , Ghafouri Seyed Ali
Published: October 2022

Caliciviruses are (+) RNA viruses with a worldwide distribution and wide host range, including humans and birds. The family caliciviridae consists of eleven genera, two of which, bavovirus and nacovirus, are found in chickens affected by stunting syndrome. In this study, for the first time the presence of calicivirus in Iranian broiler flocks was investigated by viral metagenomics method. Fecal samples were collected from broiler chicken farms affected with diarrhea from Gilan province Iran. Our results showed that some of the diseased chickens carried a genus of calicivirus belonging to bavovirus. The complete 7824 nt genome of this bavovirus, named UT Shahhosseini1 2018, was sequenced and characterized. Phylogenetic analysis revealed that our calicivirus shared 87% similarity to the closest strains, including the German calicivirus chicken/V0021/Bayern/2004, suggesting that the avian- derived strain belongs to the bavoviruses. Conserved motifs shared between bavoviruses further confirmed this finding. Phylogenetic analysis of nonstructural (NS) and VP proteins also revealed similar values. This is the first report and first complete genome sequence of bavovirus in Iran. However, further studies are needed to obtain a better epidemiological picture of the abundance avian-origin caliciviruses of in Iranian bird populations, including poultry. The pathogenic potential of these caliciviruses to affect poultry production should also be investigated.
A Rapid UHPLC-MS/MS Multiresidue Method to Determine Pesticides in Zucchini Based on Dilution of QuEChERS Raw Extracts
Authors: Reis Giovane S. dos , Santos Pimpernelli J. dos , Floriano Luana , Oliveira Júlia A. , Adaime Martha B. , Prestes Osmar D. , Zanella Renato
Published: October 2022

Zucchini is one of the most cultivated and consumed vegetables in the world and often requires pesticide treatment. In this context, a simple and straightforward method for determining pesticide residues in zucchini was proposed based on an effective QuEChERS extraction approach followed by dilution of the unclean extract and analysis by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). During the development of the sample preparation step, the cleanup of the extract using dispersive solid-phase extraction with different sorbents was compared with the analysis of unclean extract. Different dilution rates of the raw extract with ultrapure water were evaluated, and a dilution of 5 times presented adequate analysis performance, minimizing the matrix effect. The established method was suitable for 99 pesticides presenting satisfactory results for trueness, with recoveries ranging from 70 to 120% and precision in terms of relative standard deviations (RSD) ≤ 20%. Practical method limit of quantification ranged from 0.005 to 0.010 mg kg− 1 for all compounds. The method was successfully applied to 20 commercial samples of zucchini, and 15 samples showed the presence of 12 different pesticides, especially the insecticide imidacloprid. The method proved to be simple and effective for routine analysis.
Gold nanocrystals modified electrochemical aptasensor for ultra-trace level detection of malathion in environmental samples
Authors: Bala Rajni , Lalhall Alisha , Sharma Rohit K. , Wangoo Nishima
Published: October 2022

The abnormal concentrations of organophosphorus pesticides (OPs) in agricultural residues have raised serious concerns regarding food safety and environmental pollution. The trace level detection of these toxic OPs has therefore garnered great attention in the past few decades. Herein, gold nanocrystals modified electrochemical aptasensor has been reported for the detection of a widely used organophosphorus pesticide, malathion. By virtue of the high specificity of the aptamer towards malathion and enhanced surface area provided by the nanocrystals, the designed probe exhibits excellent selectivity and sensitivity for malathion. The conformational changes of aptamer due to its specific binding to malathion induces a large variation in the electrochemical responses of the redox moiety, methylene blue. The gold nanocrystals@aptamer probe exhibits excellent sensitivity in the linear range from 1 pm to 100 nm with 1 pM as the detection limit. Owing to its high reliability and robustness in the spiked samples, the developed nanoprobe paves the way for ultra-trace level detection of malathion in environmental samples.
Head and neck mucosal melanoma: radiological considerations and UK imaging guidelines
Authors: Algudkar Ashwin , Harrington Kevin , Kerawala Cyrus , Bagwan Izhar , Dafydd Derfel ap
Published: October 2022

Purpose
Awareness of head and neck mucosal melanoma (HNMM) is important, as incorrect work-up can impact on the investigation and management of this rare and aggressive cancer. Following on from the 2020 HNMM UK guidelines, we set out the imaging recommendations and their rationale. To illustrate the key imaging characteristics, we also include a case series from our centre.
Methods
All HNMM cases managed at our institution from January 2016 to January 2021 were identified and the available imaging for each patient was reviewed. For each patient, the age, gender and location of primary tumour was recorded together with key staging and diagnostic imaging parameters.
Results
A total of 14 patients were identified. The median age was 65 years with a female to male ratio of 1.33:1. Primary tumours were sinonasal in location in 93% of cases, with 7% of patients having metastatic neck nodes at presentation and 21% of cases having distant metastatic disease at presentation.
Conclusion
This data set is in general concordance with other published series regarding the sinonasal origin of the vast majority of HNMM tumours along with the proportion of patients with metastatic neck nodes and distant metastases at presentation. We recommend dual-modality imaging with computed tomography (CT) and magnetic resonance imaging (MRI) of primary tumours whenever possible. In the systematic staging of HNMM, positron emission tomography (PET)-CT should be strongly considered, together with MRI of the brain. Pre-biopsy imaging of HNMM tumours is advisable whenever possible.
HEProfiler: An In-Depth Profiler of Approximate Homomorphic Encryption Libraries
Authors: Takeshita Jonathan , Koirala Nirajan , McKechney Colin , Jung Taeho
Published: October 2022

Fully Homomorphic Encryption (FHE) allows computation on encrypted data. Various software libraries have implemented the approximate-arithmetic FHE scheme CKKS, which is highly useful for applications in machine learning and data analytics; each of these libraries have differing performance and features. It is useful for developers and researchers to learn details about these libraries' performance and their differences. Some previous work has profiled FHE and CKKS implementations for this purpose, but these comparisons are limited in their fairness and completeness.

In this article, we compare four major libraries supporting the CKKS scheme.
Working with the maintainers of each of the PALISADE, Microsoft SEAL, HElib, and HEAAN libraries, we devise methods for fair comparisons of these libraries, even with their widely varied development strategies and library architectures. To show the practical performance of these libraries, we present HEProfiler, a simple and extensible framework for profiling C++ FHE libraries. Our experimental evaluation is complete in both the scope of tasks tested and metrics evaluated, allowing us to draw conclusions about the behaviors of different libraries under a wide range of real-world workloads. This is the first work giving experimental comparisons of different bootstrapping-capable CKKS libraries.
Edge-HetIoT Defense against DDoS attack using LearningTechniques
Authors: Mahadik Shalaka S , Pawar Pranav , Muthalagu Raja
Published: October 2022

The heterogeneous nature of the internet-of-thing (IoT) is gaining popularity and, simultaneously, faces rising security issues. The distributed denial of service (DDoS) attack is the most significant security threat addressed in the research. The research proposes edge-heterogeneous IoT (HetIoT) centric defense IDS that aids the HetIoT infrastructure in detecting and blocking victim traffic near the network edge. The Edge-HetIoT defense IDS helps to address significant issues such as performance and security due to proximity to the local network. The research focuses on six learning techniques, including five machine learning (ML) classifiers, namely, ID3, NB, RF, LR, and AdaBoost, and the proposed deep learning (DL)-based hybrid model (i.e., CNN+LSTM). These learning techniques are trained and tested using the real-time benchmark-dataset CICDDoS2019 and consider binary and multiclass (14 classes) classification. The performance is analyzed and evaluated against six classifiers to determine which classification model performs best in detecting and classifying various DDoS attacks. The proposed DL-based hybrid model outperforms when compared against ID3, NB, RF, LR, and AdaBoost. The proposed DL-based hybrid model successfully detects and classifies MSSQL, NetBIOS, TFTP, NTP, Syn, and Portmap attacks with 100% precision, recall, and f1-score. The overall weighted average precision, recall, and f1-score for the proposed DL-based hybrid model are 92%, 89%, and 90%, respectively.
Non-destructive evaluation of cellulose paper degradation using water-soluble carbohydrates
Authors: Hwang Yujin , Kang Kyu-Young , Yang Bong Suk , Potthast Antje , Jeong Myung-Joon
Published: October 2022

To evaluate the deterioration of paper cultural heritage artifacts using non-destructive methods, aqueous extracts from Korean traditional paper, ‘Hanji’, and pure cellulose paper were used in this study. We quantified the water-soluble low-molecular-weight carbohydrates (cello-oligosaccharides) in paper extracts. The degree of polymerization (DP) of aged paper was also evaluated from the absolute molecular weight of the cellulose. The content of water-soluble low-molecular-weight carbohydrates depended on the cellulose degradation. Therefore, the cellulose hydrolysis rate could be predicted from the linear relationship between the cellulose hydrolysis rate and water-soluble carbohydrate contents. The DP calculated from the predicted cellulose hydrolysis rate showed little difference from the actual DP value. Therefore, among the many non-destructive analysis methods, this methodology can also be used as an indirect method to evaluate cellulose degradation by quantifying the carbohydrates dissolved in extracts from Hanji and pure cellulose paper.
Dolutegravir based therapy showed CD4+ T cell count recovery and viral load suppression among ART naïve HIV positive individuals: A longitudinal evaluation
Authors: Gebremedhin Teshager , Ayenalem Melak , Adem Mohammed , Geremew Demeke , Aleka Yetemwork , Kiflie Amare
Published: October 2022

Background
Recently, dolutegravir (DTG)-based combined therapy, a more effective and safer first-line antiretroviral therapy (ART), has been recommended by the World Health Organization (WHO) for the treatment of Human Immunodeficiency Virus (HIV) since July 2018. However, its effectiveness in CD4 + T-cells count recovery and viral load suppression has not been studied yet in Ethiopia, where HIV is endemic. Therefore, we aimed to assess the effect of DTG-based therapy on CD4 + T-cell count and viral load count among HIV-positive patients in Ethiopia.
Methods
A longitudinal prospective cohort study was conducted from July 2020–February 2021. 109 HIV-positive individuals who are ART naive but plan to initiate DTG-based therapy were recruited. HIV viral ribonucleic acid (RNA) copies were determined using a CD4 + T-cell count and quantitative polymerase chain reaction (PCR). To compute the difference in viral load and CD4 + T-cell counts between the baseline, 3rd, and 6th months, a Friedman test was used.
Results
The study included 109 HIV-positive people who had never received antiretroviral medication. Participants taking DTG-based treatment showed significantly decreasing median (IQR) values of viral load count (copies/mL) from 446,812 (237,649.5–732,994.5) at baseline to 34 (23.5–46) at 3 months and 0.0 (0–19) at 6 months of treatment follow-up. Although the treatment increases the proportion of participants with HIV-1 RNA 50 copies/mL from 0 (0% at baseline) to 87 (79.8%) and 100 (91.7%) at the 3rd and 6th months of treatment, respectively, On the other hand, the CD4+ T-cell count increased significantly during treatment: median (IQR): 209 (81.5–417.5) versus 291 (132–522) versus 378 (181.–632.5) cells/L at baseline, the 3rd and 6th months of the treatment follow-up period, respectively.
Conclusion
We found dolutegravir-based therapy was a promising option with high virological suppression rates and CD4+ T-cell count recovery demonstrating a restoration of cellular immunity. More over Viral load suppression rates were high after the initiation of the treatment.
Predicting the Difficulty of EFL Reading Comprehension Tests Based on Linguistic Indices
Authors: Rafatbakhsh Elaheh , Ahmadi Alireza
Published: October 2022

Estimating the difficulty of reading texts is critical in second language education and assessment. This study was aimed at examining various text features that might influence the difficulty level of a high-stakes reading comprehension test and predict test takers’ scores. To this end, the responses provided by 17900 test takers on the reading comprehension subsection of a major high-stakes test, the Iranian National University Entrance Exam for the Master’s Program were examined. Overall, 63 reading passages in different versions of the test from 2017-2019 were studied with a focus on 16 indices that might help explain the reading difficulty and test takers’ scores. The results showed that the content word overlap index and the Flesch-Kincaid Reading Ease formula had significant correlations with the observed difficulty and could therefore be considered better predictors of test difficulty compared to other variables. The findings suggest the use of various indices to estimate the reading difficulty before administering tests to ensure the equivalency and validity of tests.
Effect of Water Flow Rate on Nursing Spat Mussels, Mytilus galloprovincialis
Authors: Kassila Jawad , Khallaf Niaama , Knibass Khalid , Aamri Fatima El , Ouagajjou Yassine
Published: October 2022

Hatchery production of mussel seeds could be a solution to ensure reliable supply and introduce opportunities for selective breeding. To overcome the prohibitively expensive cost of hatchery-reared spat, it is necessary to optimize several factors in hatchery conditions. The water flow rate is among the main parameters for regulating the growth of nursing hatchery-reared juvenile mussels. In this study, three water flow rates of 2.5, 5 and 10 l.min− 1 were compared to investigate their effects on growth and survival of mussel spats reared in an upwelling culture system. The results highlighted that spat mussels reared at the water flow rate of 10 l min− 1 showed the highest performance in length, width and live weight, while juveniles deployed at water flow rates of 2.5 and 5 l min− 1 exhibited the lowest (p < 0.05). At the end of the experiment, no mortality was recorded in all treatments. The size fraction of spat mussels larger than 8 mm significantly increased (p < 0.05) at water flow rate of 10 l min− 1. However, the size frequency distribution of mussels from rates of 2.5 and 5 l min− 1 was found to exhibit a similar pattern at the end of study (p > 0.05). After four weeks of nursing, at water flow rates of 2.5, 5 and 10 l min− 1, size fraction > 8 mm were 3.5 ± 1.57, 4.4 ± 0.99 and 43.3 ± 1.22% respectively. However, the fraction of spat oysters smaller than 6 mm significantly increased (p < 0.05) when the rate of water flow decreased.