bluuebunny/crossref_metadata_2025 huggingface dataset:
Limit Analysis, Numerical and Physical Modelling of Pile Stabilized Slopes
Authors: Mazaheri Ahmadreza , Alipour Rasoul , Paknahad Masoud
Published: April 2021

Vast researches have been performed in the field of earth slope stability analysis including limit equilibrium, strength reduction, and limit analysis methods. All the available methods present slope safety factors in a range with a bit of difference and confirm each other. Validation of analytical results performs with instrumentation in actual slopes existing in the field. Also, another approach that uses for validating results is experimental modeling. The physical modeling requires manufacturing of the intended model in the laboratory concerning the reducing effect of dimensions on the other parameters. This paper investigates slope safety factors against sliding by simulating the slopes in the laboratory and with an image processing system. The test container has dimensions of 1.5×1.5×2 m. The results have illustrated the crest displacement in reinforced slope, with increasing slope angle 13 degrees, is 30 mm in the experimental test and 13 mm in numerical modeling. In the unreinforced slopes, when the slope angle increased by 8 degrees, the experiment test failed, and the factor of safety in the numerical modeling is less than one.
COVID-19 and all-cause-mortality; differential trends between countries and selected states of India
Authors: Menon Jaideep C , Rakesh P Suseela , Bharti Omesh K , Mishra Kaushik , Swain Basanta K , Raina Sunil K , John Denny , Janakiraman Chandrasekhar , Banerjee Amitava
Published: April 2021

Background: By 22nd January 2021, the SARS-CoV-2 virus had infected over 98 million and 10.6 million individuals globally and in India, with 1.7 million and 153, 067 deaths, respectively1. Case Fatality rates (CFR) due to COVID 19 have varied significantly between countries. In order to understand the true impact of the pandemic, we should report coronavirus (COVID-19) mortality in the context of all-cause and non-COVID-19 mortality, and compare with previous years. The consequences of the pandemic have been, and will be, different in different settings within and across countries.Objectives: To compare the all-cause mortality in the year 2020 with previous years in three selected states of India correlate it to the burden of COVID19 and compare all-cause mortality between three states of India to four high income countries.We also compared the number of cases, deaths, CFR, prevalence of NCDs per million and the proportion of population > age 65 in India to four high income countries (HIC)- the UK, US, Spain and Italy.Methods: We provide quantitative data in three states across India (Himachal Pradesh, Kerala and Odisha) and compare with high-income countries to illustrate the importance of context-specific data monitoring and public health responses.Results: There was a 1.9% increase in deaths, with 2.8% decrease in births in 2020, compared to 2019 in Himachal Pradesh, 13.3 and 9.2% decrease in Kerala and 16.7% and 21.4% decrease in Odisha.Conclusion: There was a direct correlation of all cause mortality to CFR on comparison between three states of India and despite the enormous burden of COVID19 in India all-cause mortality was lower compared to previous years in addition to the CFR due to COVID 19 being lower than in selected HICs.
Adsorption characteristics of Cr6+ on microalgae immobilized by different carriers
Authors: Chen Ran , Wang Junjun , Fan Ling , Cui Linlin , Zhang Yejuan , Wu Xueling , Li Jiaokun , Zeng Weimin , Shen Li
Published: April 2021

To solve the problem of harvesting microalgae during heavy metal adsorption, six different carriers were selected in this study to compare the adsorption behavior of microalgae after immobilization. The optimal immobilized carrier-chitosan was obtained under the following conditions of chitosan: acetic acid (2:40), microalgae concentration (10 8 cells/mL), and immobilization time (18 h). The optimal adsorption conditions were as follows: temperature: 30°C, pH: 5.0, adsorption dose: 1.5 g/L, initial ion concentration: 40 mg/L. Fourier transform infrared spectroscopy analysis showed that the specific functional groups of the specific microalgae played an important role in the adsorption process. The kinetic and isothermal model data showed that the adsorption process was mainly chemical adsorption and homogeneous monolayer adsorption. Moreover, X-ray photoelectron spectroscopy analysis showed that the Cr adsorption process involves the reduction of Cr(VI) to Cr(III).
Toxicity of chlortetracycline and oxytetracycline on Vallisneria natans (Lour.) Hare
Authors: Li Jing , Yang Lu , Wu Zhonghua
Published: April 2021

Tetracyclines are frequently detected in water bodies due to their widespread use in aquaculture and animal husbandry. A hydroponic experiment was conducted to explore the phytotoxic effects of Vallisneria natans (Lour.) Hare exposed to various concentrations of chlortetracycline (CTC) and oxytetracycline (OTC) (0, 0.1, 1, 10, 30, 50 and 100 mg/L) for 7 days (7 D) and 14 days (14 D), respectively. The results showed that similar to OTC treatment for 7 D, the relative growth rates (RGR) and catalase (CAT) activity of V. natans , after 7 D of CTC exposure, decreased significantly at 10 mg/L and 30 mg/L, respectively. The content of soluble protein notably decreased when CTC ≥ 10mg/L and OTC ≥ 30mg/L. The hydrogen peroxide (H 2 O 2 ) content was significantly stimulated when OTC ≥ 10mg/L, while it hardly changed when exposed to CTC. After 14 D, the malondialdehyde (MDA) and H 2 O 2 contents of V. natans were significantly higher than those of the control group under high concentration of OTC (≥ 30mg/L), but they didn’t change significantly under high concentration of CTC. The activity of polyphenol oxidase (PPO), under CTC treatment after 14 D, showed first a significant increase then decrease, the maximum value (125% of the control) was notice at 10 mg/L CTC, while it remained unchanged when exposed to OTC. The soluble protein content significantly decreased at 10 mg/L CTC and 0.1 mg/L OTC, respectively. The RGR, CAT and peroxidase (POD) activities, similar to OTC treatment after 14 D, decreased evidently when CTC was 10 mg/L, 30 mg/L and 0.1 mg/L, respectively. CTC and OTC harm the chlorophyll content of V. natans after 14 D, and the reduction of chlorophyll a and carotenoid were more pronounced than chlorophyll b. The results suggest that CTC and OTC both have negative effect on the growth of V. natans , and OTC can cause oxidative damage in V. natans but CTC harm the metabolism process without inducing oxidative damage. Overall, the toxicity of OTC to V. natans is stronger than that of CTC.
Nocturnal digital surveillance in aged populations and its effects on health, welfare and social care provision: a systematic review
Authors: Richardson Matt X. , Ehn Maria , Stridsberg Sara Landerdahl , Redekop Ken , Wamala-Andersson Sarah
Published: April 2021

BackgroundThis systematic review summarized the effects of nocturnal digital surveillance technologies on health, welfare and social care provision outcomes in populations ≥ 50 years, compared to standard care.Primary studies published 2005-2020 that assessed these technologies were identified in 11 databases of peer-reviewed literature and numerous grey literature sources. Five publications out of 629 met inclusion criteria. The Risk of Bias 2.0 and ROBINS-I tools were used for quality assessment. ResultHealth-related outcomes (e.g. injuries, unexplained absences) and social care outcomes (e.g. staff burden) did not differ between interventions and standard care. Quality of life and affect showed improvement with some interventions, as did economic outcomes in one setting. The quality of studies was low however, with a serious to critical risk of bias. ConclusionWe found little evidence for the benefit of nocturnal digital surveillance interventions as compared to standard care in several key outcomes. Higher quality intervention studies should be prioritized in future research to provide more reliable evidence.
Solving the Conundrum of Active Site Density of PGM-free ORR Catalysts in situ Fuel Cells Using Fourier Transform Alternating Current Voltammetry
Authors: Snitkoff Rifael , Friedman Ariel , Yurko Yan , Zelenay Piotr , Bond Alan , Elbaz Lior
Published: April 2021

Advances in the development of Pt-group metal-free (PGM-free) catalysts for oxygen reduction reaction in fuel cells produced active catalysts that allow to reduce the performance gap to the incumbent Pt-based materials. However, the utilization of the state-of-the-art PGM-free catalysts in commercial applications is currently impeded by their relatively low durability. Methods designed to study catalyst degradation in operating fuel cells are critical for the understanding and ultimately solving the durability issues. This work is the first report on the use of Fourier-transformed alternating current voltammetry (FTacV) as an electrochemical method for accurately quantifying the electrochemical site density of PGM-free ORR catalysts, and following their degradation during the operation of polymer electrolyte fuel cells. Using this method we were capable of detecting changes in performance of electrochemically active species (electrocatalytic centers in this case), allowing us, for the first time, to calculate the electrochemical active site density (EASD) which is necessary for the elucidation of the degradation mechanisms of PGM-free ORR catalysts in situ fuel cells.
MOF-Based Nanoagent Enables NIR-Triggered Dual Damage to Mitochondria via Synergistically Reinforced Oxidative Stress and Calcium Overload
Authors: Tian Zhiyuan , Bao Weier , Liu Ming , Meng Jiaqi , Liu Siyuan , Wang Shuang , Jia Rongrong , Wang Yugang , Ma Guanghui , Wei Wei
Published: April 2021

We herein developed a core-shell type antitumor nanoagent based on the synergistically reinforced oxidative stress and calcium overload to mitochondria, both of which were triggered by near-infrared (NIR) light. The folic acid (FA) moiety decorated on MOF shells enabled efficient cellular uptake of nanoagents. The upconversion nanoparticle (UCNP) core converted NIR light to ultraviolet (UV) light with the latter catalyzed Fe3+-to-Fe2+ reduction and simultaneously activated the photoacid generator encapsulated in the cavities of MOFs, which enabled the release of free Fe2+ and photoacidification of intracellular microenvironment, respectively. The overexpressed H2O2 in the mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforced Fenton reactions for producing lethal hydroxyl radicals in mitochondria. Moreover, the photoacidification of plasma induced calcium influx, leading to calcium overload in the mitochondria. The therapeutic potency of the nanoagent based on the dual mitochondrial damage has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.
Exploring the Drivers of Vaccine Hesitancy Toward Childhood and Adolescent Vaccination in Malawi: A Qualitative Study
Authors: Adeyanju Gbadebo Collins , Betsch Cornelia , Adamu Abdu A. , Gumbi Khadijah Sanusi , Head Michael G , Aplogan Aristide , Tall Haoua , Essoh Tene-Alima
Published: April 2021

Background: Vaccine hesitancy is the delay or refusal of vaccines despite the availability of vaccination services. Although it is considered an important global health threat, it has only rarely been systematically studied within the African context. In this study, we explored the factors that influence vaccine hesitancy among caregivers of children and adolescent girls that are eligible for routine childhood immunisation and the human papillomavirus (HPV) vaccine in Malawi. Methods: The study employed a qualitative exploratory research design. In-depth information was obtained from caregivers of children and adolescent girls eligible for routine immunisation (RI) and the HPV vaccine, respectively, as well as national and district-level representatives of the expanded program on immunisation (EPI) and community stakeholders through key informant interviews and focus-group discussions. These participants were purposively selected using predefined criteria A total of 25 key informant interviews and two focus-group discussions with 13 participants were conducted. Data collection took place between April 20 and May 24, 2020. The interviews were audio-recorded, transcribed verbatim, and then analysed using a thematic content analysis approach. Results: The study shows that most of the vaccine-hesitancy drivers for RI also influenced the newly introduced HPV vaccine. Such drivers were inadequate awareness of the vaccination schedule, rumours and conspiracy theories exacerbated by religious beliefs, inability to translate knowledge and attitudes into actual vaccination behaviour, low literacy levels of caregivers, complacency occasioned by the stress of distance and transportation logistics, and disconnection between the community healthcare system and community leaders, among others. Conclusion: This study provides deeper insights into the determinants of vaccine hesitancy within the Malawian context. The findings can inform the design of context-specific interventions by decision-makers. While the study provided behavioural insights regarding vaccination behaviour in Malawi, there is need for further quantitative studies that can assess the prevalence of the determinants as well as their causal relationships to vaccine uptake.
Natural phage communities crosslink different species within the genus Staphylococcus
Authors: Goeller Pauline , Elsener Tabea , Lorgé Dominique , Radulovic Natasa , Bernardi Viona , Naumann Annika , Amri Nesrine , Khatchatourova Ekaterina , Coutinho Felipe Hernandes , Loessner Martin , Gómez-Sanz Elena
Published: April 2021

The importance of the bacteriophage host range builds on its role as an innate barrier, which defines the phages’ impact on bacterial communities and genome diversity. Yet, little is known about host range natural patterns. We characterize 94 novel staphylococcal phages from wastewater and establish their host range on a diversified panel of 117 staphylococci from 29 species. Using this high-resolution phage-bacteria interaction matrix, we unveil a multi-species host range as a dominant trait of the isolated staphylococcal phages. Phage genome sequencing shows this pattern to prevail irrespective of taxonomy. Network analysis between phage-infected bacteria revealed that hosts from multiple species, ecosystems, and drug-resistance phenotypes share numerous phages. This could promote genetic mobilization facilitated by many transfer routes. Lastly, we demonstrate that phages throughout this network package foreign genetic material at various frequencies. Our findings defy a strong host specialism of phages and highlight great possibilities for horizontal gene transfer.
Spatiotemporal Effects of Urban Sprawl on Habitat Quality in the Pearl River Delta from 1990 To 2018
Authors: Wu Jiansheng , Li Xuechen , Luo Yuhang , Zhang Danni
Published: April 2021

Since the implementation of the Chinese economic reforms, economic development in the coastal cities has resulted in serious degradation of habitat quality; however, the concept of "ecological civilization" has improved this situation. For quantitative analysis of the correlation between the Pearl River Delta urban expansion and changes in habitat quality under the influence of the policy, we first analyzed the habitat quality change based on the InVEST model and then measured the impact of construction land expansion on the habitat quality through habitat quality change index (HQCI) and contribution index (CI) indicators. Finally, the correlation between urbanization level and habitat quality was evaluated using geographically weighted regression (GWR) and the Self-organizing feature mapping neural network (SOFM). The results indicated that: (1) during the study period, the habitat quality index decreased from 0.7181 to 0.6672 owing to urban expansion, and the decrease was most significant from 2000 to 2010. (2) The urbanization index had a negative effect on the habitat quality, but this improved after 2000, reflecting the positive effect of policies such as "ecological civilization construction" (3) The importance of ecological civilization varies greatly among cities in the study area: Shenzhen, Dongguan, Foshan, and Zhongshan have the best level of green development. These results reflect the positive role of policies in the prevention of damage to habitat quality caused by economic development and provide a reference for the formulation of sustainable urban development policies with spatial differences.
The potential neuroprotective effect of allicin and melatonin in acrylamide-induced brain damage in rats
Authors: Edres Hanan A. , Taha Nabil M. , lebda Mohamed A. , Elfeky Mohamed S.
Published: April 2021

Acrylamide (ACR) is an unsaturated monomer that entered in various fields however, it is a potent neurotoxic. The present study target is to explore the neuroprotective efficacy of allicin and melatonin on ACR-induced neurotoxicity. Thirty-six male adult rats were non-selectively separated into six groups: placebo, allicin (20 mg/kg b.w daily per os), melatonin (10 mg/kg b.w 3 times/week per os), ACR (50 mg/kg b.w daily per os), ACR + allicin and ACR + melatonin with the same doses. The assessment of brain biomarkers, neurotransmitters, antioxidative status, Nrf2 signalling pathway, and histopathological analyses were performed following 21 days. ACR exposure enhanced the brain lipid and DNA oxidative damage as well as a reduction in the GSH levels. The obvious brain oxidative injuries was contributed to distinct brain dysfunction that was assured by alteration of brain neurotransmitters (serotonin, dopamine, acetylcholine, and acetylcholinesterase), and pathological brain lesions. Furthermore, ACR exposure increased hydroxy deoxy guanosine (8-OHdG), tumor necrosis factor (TNF) and amyloid protein (AB-42). Finally, the mRNA transcripts of brain Keap-1, Nrf2, and NF-kB were up regulated after ACR intoxication. Interestingly, allicin and melatonin alleviated the ACR-induced brain damage assessed by normalization of the mentioned analyses. The present study demonstrated the protective role of both allicin and melatonin on ACR-prompted neuropathy by alleviation of redox imbalance and enhancement of neurotransmitters as well as relieving DNA damage and anti-inflammatory effect.
Prevalence of Acute Malnutrition And Associated Factors Among Children under Five Years of Age in Rural Kebeles of Shashemene Woreda West Arsi Zone, Oromia Regional State, Ethiopia, 2018
Authors: Endale Aschalew Gatiso , Debela Degfachew Ararso , Kisi Teresa , Ferede Abebe , Shiferaw Niguse
Published: April 2021

BACKGROUND: Acute malnutrition is a devastating public health problem. Globally about, 52 million underfive years old were wasted. One-third of these children live in Africa and Ethiopia is the seventh country among the ten top countries in which wasting is concentrated and currently 10% of under-five children are wasted. Although Ethiopia is implementing different nutritional interventions, but the prevalence of wasting is increasing and there is no scientific study done previously in the study area. So this study aimed to assess the prevalence of Acute Malnutrition and associated factors among children under five years in Rural Kebeles of Shashemene District, West Arsi Zone, Oromia Regional State, Ethiopia, 2018. METHOD: A community based cross-sectional study design with multi stage sampling technique was conducted from July 1-30/2018 on a total of 457Mothers/caretakers of under-five children were interviewed using structured questionnaire and anthropometric measurements of the children were taken using standard procedures. Epi info version 7 was used for data entry and cleaning and SPSS version 21 was used for analysis bivariate and multivariate logistic regression were used to determine the association between dependent and independent variables. World Health Organization (WHO) Anthro software was used to convert nutritional data indices. RESULT: The prevalence of wasting was 91(19.9%) with 95%CI. Mothers with no Antenatal Care (ANC) visits (AOR=2.26, 95%CI 1.14-4.46), mothers who had no autonomous in decision making (AOR=2.42, 95%CI 1.42-4.12), children with diarrheal disease in the last 2 weeks preceding the survey(AOR=2.07,95%CI 1.19-3.59)and deprive colostrum’s (AOR=1.99, 95% CI 1.07- 3.71) were had high risks for Acute malnutrition of their children’s. CONCLUSION AND RECOMMENDATION: This finding showed that, the prevalence of wasting is high; Mothers who had no power in decision making, squeezed out and throw colostrum’s, Mothers who had no ANC visit, child’s history of Diarrhea in the last two weeks were independent determinants of acute malnutrition. So the Woreda Health office and Health Extension Workers should consider empowering women, awareness and accessible antenatal care services, hygiene and sanitation to reduce acute malnutrition.
Performance and Host Association of Spotted Lanternfly (Lycorma Delicatula) among Common Woody Ornamentals
Authors: Uyi Osariyekemwen , A. Keller Joseph , Hoover Kelli
Published: April 2021

Despite the broad host range of Lycorma delicatula, the performance of this invasive pest on non-Ailanthus host plant species is difficult to document realistically without using field conditions given this pest’s requirements for vast amounts of phloem. In spring 2020, we examined the performance of L. delicatula with and without access to Ailanthus altissima by tracking development, survival, host tree association and oviposition in large enclosures planted with one each of Juglans nigra, Salix babylonica and Acer saccharinum along with either one A. altissima or one Betula nigra. We reared nymphs with and without access to A. altissima, released them into the corresponding large enclosures as third instars, and monitored them from early July 2020 through November 2020. Insect survival was higher and development faster with access to A. altissima. Third and fourth instar nymphs were most frequently observed on A. altissima when it was present, while adults were equally associated with A. saccharinum and A. altissima. In the absence of A. altissima, nymphs were most frequently found on S. babylonica, while adults were most often on A. saccharinum. Females with access to A. altissima deposited nearly 7-fold more egg masses than those without access to A. altissima. In another experiment, the offspring of parents that had been reared without access to A. altissima showed similar survival and development time from egg to adult as offspring from parents that never had access to A. altissima. These findings suggest that managers need to be aware that even in the absence of A. altissima in the landscape, several hardwood host trees can be utilized by L. delicatula to develop and reproduce.
Involvement of FLOWERING LOCUS T in microgravity response of Arabidopsis thaliana plants under long- and short-day conditions
Authors: Wang Lihua , Xie Junyan , Wu Yuanyuan , Mou Chenghong , Jiao Yuwei , Dou Yanhui , Zheng Huiqiong
Published: April 2021

Microgravity have an impact on growth and development of higher plants in space at both vegetative stage and reproductive stage. A great deal of information has been available on the vegetative stage in space, but relatively little is known about the influence of microgravity on plants at the reproductive stage. In this study, we constructed a transgenic Arabidopsis thaliana plants expressing flowering control gene, FLOWERING LOCUS T (FT), together with green fluorescent protein gene(GFP) under control of a heat shock-inducible promoter (HSP17.4), by which we induced FT expression inflight through remote controlling heating shock treatment. Inflight photography data showed that induction of FT expression in plants in space could counteract the impact of microgravity and promote flowering. Whole-genome microarray analysis of gene expression changes in leaves of wild-type and these transgenic plants grown under different photoperiod conditions in space indicated that the function of the photoperiod-related microgravity response genes are mainly involved in protein synthesis and post-translation protein modulation, notably protein phosphorylation. In addition, changes of circadian component gene expression in response to microgravity under different photoperiod indicated that role of circadian oscillator could act as integrators of microgravity response and photoperiodic signals in Arabidopsis plant grown in space.
Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits
Authors: Shiroma Hirotsugu , Shiba Satoshi , Erawijantari Pande Putu , Takamaru Hiroyuki , Yamada Masayoshi , Sakamoto Taku , Kanemitsu Yukihide , Mizutani Sayaka , Soga Tomoyoshi , Saito Yutaka , Shibata Tatsuhiro , Fukuda Shinji , Yachida Shinichi , Yamada Takuji
Published: April 2021

Background: Postoperative colorectal cancer (CRC) patients are at increased risk of developing metachronous CRC. Despite accumulating evidence indicating that the gut microbiota and metabolites can promote CRC carcinogenesis, the influence of surgery for CRC on the gut microbiota and metabolites remains partially understood. We hypothesized that if surgery does not eliminate the bacteria and metabolites promoting CRC carcinogenesis, these bacteria and metabolites might be associated with the development of metachronous CRC. To test this hypothesis, we collected 170 fecal samples from 85 CRC patients in pre- and approximately one year postsurgery status, and performed shotgun metagenomics sequencing and capillary electrophoresis time-of-flight mass spectrometry-based metabolomics analyses and compared pre- and postsurgery status.Results: CRC-associated bacteria such as Parvimonas micra and Fusobacterium nucleatum were significantly (P < 0.005) decreased after surgery. On the other hand, cholate, carcinogenesis-associated deoxycholate, its biotransformed genes (bai operon) from cholate to deoxycholate, and the contributing bacterium (Clostridium scindens) were significantly (P < 0.005) increased. Additionally, these alterations were only observed in postleft surgery. Cholate and glycocholate were significantly (P < 0.005) increased in postright surgery. We also developed a method for potential CRC risk assessment based on the gut microbiota and metabolomic compositions using a random forest machine learning algorithm and then applied it to postoperative patients. The estimated CRC risk based on the random forest algorithm was partially restored postsurgery. Conclusions: Our results indicate that the high potential CRC risk in CRC postoperative patients is associated with metabolites derived from the gut microbiota, which targets interventions to reduce the CRC risk.
A Case of Colonic Micropapillary Carcinoma With a High Frequency of Apoptosis
Authors: Arai Kazumori , Iwasaki Tomohiro , Ishimatsu Hisato , Tsuchiya Chinatsu , Kubota Aki , Sonoda Akihiro , Ohata Ko
Published: April 2021

Purpose: Colorectal micropapillary carcinoma (MPC) exhibits aggressive biological characteristics, with empty spaces and reversed polarity, similar to the poorly differentiated clusters (PDCs) formed from detached cancer cells. Epithelial–mesenchymal transition, which is involved in the cancer cell acquisition of apoptosis resistance, is closely linked with histological findings of MPC, PDCs, and tumor buds (TBs), with MPC and TBs considered as apoptosis-resistant features. However, we encountered a case of colonic MPC with frequent apoptosis.Methods: We examined the case using immunohistochemistry and compared it with two cases of conventional colonic cancer with high PDC and TB presence.Results: In many of the tumor glands (TGs) of the MPC, empty spaces and tumor cell detachment toward the gland interior were observed. Moreover, TG ruptures were scattered, with PDCs adjacent to them. Apoptosis occurred mainly at the TG and PDC peripheries in the middle and deep tumor layers, and transforming growth factor beta 1 (TGF-β1) positivity was evident in those tumor cells. Cells positive for apoptosis-related M30 were distributed mainly in the deep layer with a significant PDC and TB presence. However, apoptosis and M30 positivity were low in the TBs. In the control cases, apoptosis hardly occurred. Furthermore, M30 positivity in the TGs was scattered and barely evident in the PDCs. Aberrant β-catenin positivity was found. In MPC, non-tumorous bud components, especially those in the deep layer, had poor abilities to promptly acquire apoptosis resistance. Conclusion: Apoptosis has the potential to reciprocally produce MPC, PDCs, and TBs, with TGF-β1 involvement.
Can the BMI-Based Dose Regimen be Used to Reduce Injection Activity and to Obtain a Constant Image Quality in Oncological Patients by 18F-FDG Total-Body PET/CT Imaging?
Authors: Xiao Jie , Yu Haojun , Sui Xiuli , Hu Yan , Yanyan Cao , Liu Guobing , Zhang Yiqiu , Hu Pengcheng , Wang Ying , Li Chenwei , Xu Baixuan , Shi Hongcheng
Published: April 2021

Purpose PET image quality is influenced by the patient size according to the current guideline. The purpose was to propose an optimized dose regimen to yield a constant image quality independent of patient size to meet the clinical needs.Methods A first patient cohort of 78 consecutives for oncological patients (59.7±13.7 years) who underwent a total-body PET/CT scan were retrospectively enrolled to develop the regimen. The patients were equally distributed in four BMI groups according to WHO criteria. The liver SNR (Signal noise ratio, SNRL) was obtained through manually drawing ROIs and normalized (SNRnorm) by the injected activity and acquisition time. And fits of SNRnorm against different patient-dependent parameters were performed to determine the best correlating parameter and fit method. A qualitative assessment on image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL. And thus, an optimized regimen was proposed and validated by a second patient cohort with prospectively enrolled 38 oncological patients. Results The linear fit showed SNRnorm was the strongest correlation (R2 = 0.69) with the BMI than other patient-dependent parameters. The qualitative assessment revealed a SNRL of 14.0 as a threshold to achieve a sufficient image quality. The optimized dose regimen was determined as a quadratic relation with BMI: Injected activity = 39.2 MBq/(-0.03*BMI+1.49)2. In the validation study, the SNRL no longer decreased with the increase of BMI. There was no significant difference of the image quality, the SNRL, between different BMI groups (p > 0.05). In addition, the injected activity was reduced by 75.6±2.9 %, 72.1±4.0 %, 67.1±4.4 % and 64.8±3.5 % compared to the first cohort for the four BMI groups, respectively.Conclusion The study recommended a quadratic relation between the 18F-FDG injected activity and the patient’s BMI and propose a regimen for total-body PET imaging. In the regimen, the image quality can maintain in a constant level independent of patient size and meet the clinical requirement even with a reduced injected activity.
First Record of Migonemyia Vaniae (Galati, Fonseca & Marassá, 2007) (Diptera, Psychodidae, Phlebotominae) in the State of Rio De Janeiro.
Authors: Balthazar Thamiris , Santana Antônio de , Costa Luiz , Mallet Jacenir , Vilela Maurício
Published: April 2021

Entomological surveillance studies in areas that have not yet been evaluated become important for the survey of local fauna, where new taxons or species records can be observed. In an investigation carried out at the Jequitibá headquarters of the Três Picos State Park, the presence of the species Migonemyia vaniae was observed, until then described and recorded only in the state of São Paulo, thus, we report the first encounter of the species in the state of Rio de Janeiro. Two male specimens of Mg vaniae with CDC light traps (HP model) were captured. Specimens of Mg vaniae and Migonemyia migonei were submitted to the clarification process and mounted between slide and coverslip in Berlese and identified under microscope following the Galati classification. Morphometric analyses of the ejaculatory pump and edeagais ducts and photographs of the structures were performed in order to compare the differences between species and record the first report of the species Mg vaniae in the state of Rio de Janeiro.
Analysis of the Pan-Asian Subgroup of patients in the NALA Trial: A Randomized Phase III NALA Trial Comparing Neratinib + Capecitabine (N+C) vs Lapatinib + Capecitabine (L+C) in Patients with HER2+ Metastatic Breast Cancer (mBC) Previously Treated with Two or more HER2-Directed Regimens
Authors: Dai Ming-Shen , Feng Yin Hsun , Chen Shang Wen , Masuda Norikazu , Yau Chung Cheung Thomas , Chen Shou Tung , Lu Yen Shen , Yap Yoon Sim , Ang Peter Cher Siang , Chu Sung Chao , Kwong Ava , Lee Keun Seok , Ow Samuel , Kim Sung Bae , Lin Johnson , Chung Hyun Cheol , Ngan Roger , Kok Victor C. , Rau Kun Ming , Sangai Takafumi , Ng Ting Ying , Tseng Ling Ming , Bryce Richard , Keyvanjah Kiana , Bebchuk Judith , Chen Mei Chieh , Hou Ming-Feng
Published: April 2021

Purpose: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+ breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib + capecitabine (N+C) against lapatinib + capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein.Methods: 621 centrally-assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240mg qd) + C (750mg/m2 bid, day 1-14) with loperamide prophylaxis, or to L (1250mg qd) + C (1000mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally-assessed progression free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety.Results: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P=0.0014), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P=0.039). Both median OS (23.8 versus 18.7 months; P=0.185) and DoR (11.1 versus 4.2 months; P<0.0001) were extended with N+C, compared to L+C. Diarrhea was the most frequent treatment-emergent adverse event (TEAE) in both arms (78.8 versus 51.0%). The incidence of grade 3/4 TEAEs and TEAEs leading to treatment discontinuation was comparable between the two arms.Conclusion: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. Clinical Trial Registration: NCT01808573
Mathematical Model With Phosphate Activation Effect Validates Batch (R)-phenylacetylcarbinol Biotransformation Process Utilizing Candida Tropicalis Pyruvate Decarboxylase in Phosphate Buffer 
Authors: Khemacheewakul Julaluk , Taesuwan Siraphat , Nunta Rojarej , Techapun Charin , Phimolsiripol Yuthana , Rachtanapun Pornchai , Jantanasakulwong Kittisak , Porninta Kritsadaporn , Sommanee Sumeth , Mahakuntha Chatchadaporn , Chaiyaso Thanongsak , Seesuriyachan Phisit , Reungsang Alissara , Trinh Ngoc Thao Ngan , Wangtueai Sutee , Sommano Sarana Rose , Leksawasdi Noppol
Published: April 2021

The new (R) - phenylacetylcarbinol (PAC) batch biotransformation kinetics for partially purified Candida tropicalis TISTR 5350 pyruvate decarboxylase (PDC) were characterized and validated with a comprehensive mathematical model in 250 mL scale with 250 mM phosphate buffer / pH 7.0. PDC could convert initial 100 / 120 mM benzaldehyde / pyruvate substrates to the statistical significantly highest (p £ 0.05) maximum PAC concentration (95.8 ± 0.1 mM) and production rate (0.639 ± 0.001 mM min-1). A parameter search strategy aimed at minimizing overall residual sum of square (RSST) based on a system of six ordinary differential equations was applied to PAC biotransformation profiles with initial benzaldehyde / pyruvate concentration of 100/120 and 30/36 mM. Ten important biotransformation kinetic parameters were then elucidated including the zeroth order activation rate constant due to phosphate buffer species (ka) of (9.38 ± < 0.01) × 10-6 % relative PDC activity min-1 mM-1. The validation of this model to independent biotransformation kinetics with initial benzaldehyde / pyruvate concentration of 50 / 60 mM resulted in relatively good fitting with RSST, mean sum of square error (MSE), and coefficient of determination (R2) values of 662, 17.4, and 0.9863, respectively.Novelty: The existing (R) - phenylacetylcarbinol (PAC) biotransformation model in literatures did not include activation effect of buffering species into the enzyme deactivating rate equation, thereby background deactivation and buffering activation effects could not be discerned. A new mathematical model which incorporated activation effect, using 250 mM phosphate buffer as an example, was able to predict and validate PAC batch biotransformation systems reasonably well and could pave the way for model applications in more complex processes.
Intra-articular Injection of SHP2 Inhibitor SHP099 Promotes the Repair of Rabbit Full-thickness Cartilage Defect
Authors: Sun Ziying , Xu Xingquan , Lv Zhongyang , Li Jiawei , Sun Heng , Sun Kuoyang , Tan Guihua , Yan Wenqiang , Yang Yannick Xiaofan , Wu Rui , Xu Jia , Guo Hu , Jiang Qing , Shi Dongquan
Published: April 2021

Background Cartilage repair has been a challenge in the field of orthopedics for decades, highlighting the great significance of investigating potential therapeutic drugs. In this study, we explored the effect of SHP2 inhibitor, SHP099, as a small molecule drug on cartilage repair.Methods Human synovial mesenchymal stem cells (SMSCs) were isolated and their three-way differentiation potential was examined. After treated with chondrogenic medium, the chondrogenic effect of SHP099 on SMSCs was examined by Western blot, qPCR, and immunofluorescence (IF). To explore chondrogenic effects of SHP099 in vivo, full-thickness cartilage defects with microfracture were constructed in the right femoral trochlear of New Zealand White rabbits. Intra-articular injection of SHP099 or normal saline were performed twice a week for 6 weeks. Cartilage repair were evaluated by hematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining. Immunohistochemistry (IHC) for collagen II (COL2) was also conducted to verify the abandance of cartilage extracellular matrix after SHP099 treatment. The mechanism involving yes associated protein (YAP) and WNT signaling was investigated in vitro.Result The SMSCs isolated from human synovium represented optimal multi-differentiation potential. SHP099 increased chondrogenic markers (SOX9, COL2) expression and decreased hypertrophic markers (COL10, RUNX2) in SMSCs. The inhibition of YAP and WNT signaling was also observed. Moreover, compared with the normal saline group at 6 weeks, intra-articular injection of SHP099 resulted in better defect filling which formed more hyaline cartilage-like tissue with more glycosaminoglycan (GAG) and COL2.Conclusion SHP099 promotes the repair of rabbit full-thickness cartilage defect, representing a potential therapeutic drug for cartilage repair.
Detecting global influence of transcription factor interactions on gene expression in lymphoblastoid cells using neural network models
Authors: Patel Neel , Bush William S.
Published: April 2021

Background Transcription factor(TF) interactions are known to regulate target gene(TG) expression in eukaryotes via TF regulatory modules(TRMs). Such interactions can be formed due to co-localizing TFs binding proximally to each other in the DNA sequence or over long distances between distally binding TFs via chromatin looping. While the former type of interaction has been characterized extensively, long distance TF interactions are still largely understudied. Furthermore, most prior approaches have focused on characterizing physical TF interactions without accounting for their effects on TG expression regulation. Understanding TRM based TG expression regulation could aid in understanding diseases caused by disruptions to these mechanisms. In this paper, we present a novel neural network based TRM detection approach that consists of using multi-omics TF based regulatory mechanism information to generate features for building non-linear multilayer perceptron TG expression prediction models in the GM12878 immortalized lymphoblastoid cells.Results We estimated main effects of 149 individual TFs and interaction effects of 48 distinct combinations of TFs forming TRMs based on their influence on TG expression. We identified several well-known and discovered multiple previously uncharacterized TF interactions within our detected set of TRMs. We further characterized the pairwise TRMs using long distance chromatin looping and motif co-occurrence data. We found that nearly all the TFs constituting TRMs detected by our approach interacted via chromatin looping, and that these TFs further interacted with promoters to influence TG expression through one of four possible regulatory configurations. Conclusion Here, we have provided a framework for detecting TRMs using neural network models containing multi-omics TF based regulatory features. We have also described these TRMs based on their regulatory potential along with presenting evidence for the possibility of TF interactions forming the TRMs occurring via chromatin looping.
Identifying potential novel insights for COVID-19 pathogenesis and therapeutics using an integrated bioinformatics analysis of host transcriptome
Authors: El-aarag Salem , Mahmoud Amal , ElHefnawi Mahmoud
Published: April 2021

The molecular mechanisms underlying the pathogenesis of COVID-19 has not been fully discovered. This study aims to decipher potentially hidden parts of the pathogenesis of COVID-19, potential novel drug targets, and to identify potential drug candidates. Two gene expression profiles (GSE147507-GSE153970) were analyzed and overlapping differentially expressed genes (DEGs) were selected for which top enriched transcription factors and kinases were identified and pathway analysis was performed. Protein-protein interaction (PPI) of DEGs was constructed, hub genes were identified and module analysis was also performed. DGIdb database was used to identify drugs for the potential targets (hub genes and the most enriched transcription factors and kinases for DEGs). A drug-potential target network was constructed and drugs are ranked according to the degree. L1000FDW web-based utility was used to identify drugs that can reverse transcriptional profiles of COVID-19. We identified drugs currently in clinical trials and novel potential 8 drugs. Besides the well-known pathogenic pathways, It was found that axon guidance is a potential pathogenic pathway. Sema7A, which may exacerbate hypercytokinemia, is considered a potential novel drug target. Another potential novel pathway is related to TINF2 overexpression which may induce potential telomere dysfunction and hence DNA damage that may exacerbate lung fibrosis.
The World Health Organisation’s Caregiver Skills Training Programme for Autism and Developmental Disorders: Adapting and Pretesting in Hong Kong
Authors: Wong Paul W.C. , Lam Yan Yin , Lau Janet Siu , Fok Hung Kit
Published: April 2021

Background The World Health Organisation Caregiver Skills Training programme (WHO-CST) was developed to strengthen a caregiver’s skills in supporting their child’s development and the caregiver’s well-being. The WHO-CST Hong Kong (HK) was adapted to support families with children suspected of having autism spectrum disorder (ASD) while the families were waiting for a confirmed diagnosis.Aim This sequential mixed methods study aimed to explore the adaptation process, using a formative qualitative method. It assessed the acceptability, feasibility, and perceived benefits of the WHO-CST, using caregivers’ qualitative and quantitative prepost feedback.Methods Data examined included (1) two consultation meetings with stakeholders; (2) a detailed review of translated and adapted WHO-CST HK materials by Master Trainees (MTs) (n = 10) trained by WHO representatives; (3) need assessment focus group interviews with caregivers (n = 15) of children with ASD; and (4) prepost CST programme qualitative focus group interviews and quantitative evaluation (n = 11).Results Consultation with stakeholders suggested that the programme is acceptable for the local community, but the home visit and fidelity components were initially considered to be challenges for the feasibility and sustainability of the programme. Thematic analyses of the focus group interview with caregivers generated six subthemes from preprogramme focus group interviews and five subthemes from postprogramme focus group interviews. The programme was reported to be helpful for caregivers’ skills development and for aiding children’s verbal and social skills development. There was also improvement in caregivers’ mental health after completing the programme.Conclusion The prepilot evaluation findings of WHO-CST HK indicate that it is feasible and acceptable to implement the programme in a metropolitan area where families have busy working schedules. The findings indicate potential programme developments for supporting families in communities in high income countries.
Graphene Coated Scaffold for Bone Tissue Engineering: Physicochemical and Osteogenic Characterizations
Authors: Bahrami Sajad , Baheiraei Nafiseh , Shahrezaee Mostafa
Published: April 2021

Variety of bone-related diseases and injures and limitations of traditional regeneration methods need to introduce new tissue substitutes. Tissue engineering and regeneration combined with nanomedicine can provide different natural or synthetic and combined scaffolds with bone mimicking properties for implant in the injured area. In this study, we synthesized collagen (Col) and reduced graphene oxide coated collagen (Col-rGO) scaffolds and evaluated their in vitro and in vivo effects on bone tissue repair. Col and Col-rGO scaffolds were synthesized by chemical crosslinking and freeze-drying methods. The surface topography, mechanical and chemical properties of scaffolds were characterized and showed three-dimensional (3D) porous scaffolds and successful coating of rGO on Col. rGO coating enhanced mechanical strength of Col-rGO scaffolds compared with Col scaffolds by 2.8 folds. Furthermore, Col-rGO scaffolds confirmed that graphene addition not only did not any cytotoxic effects but also enhanced human bone marrow-derived mesenchymal stem cells (hBMSCs) viability and proliferation with 3D adherence and expansion. Finally, scaffolds implantation into rabbit cranial bone defect for 12 weeks showed increased bone formation, confirmed by Hematoxylin-Eosin (H&E) and alizarin red staining. Altogether, the study showed that rGO coating improves Col scaffold properties and could be a promising implant for bone injuries.