bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgically Managed Malakoplakia of the Spine
Authors: Xu Amy L. , Petrusky Olivia , Babu Jacob , Wang Kevin Y. , Durand Wesley M. , Gross John M. , Neuman Brian J.
Published: September 2021

Case:

A 66-year-old woman with polymyositis and recurrent urinary tract infections presented with lumbar pain and progressive lower extremity neuropathy. Imaging showed lytic destruction of the vertebral bone from L2 to L4 with extension into adjacent musculature. Histological examination demonstrated Michaelis-Gutmann bodies consistent with malakoplakia. The patient underwent revision T12-sacrum posterior fusion, L2-5 laminectomy, and anterior L3-4 corpectomy, followed by L2-4 anterior stabilization and a 6-week course of ceftriaxone. At 3 months postoperatively, she was asymptomatic without recurrence.

Conclusion:

Malakoplakia of bone should be considered in the differential diagnosis of lytic bone lesions and can be effectively treated with surgical debulking with penetrative antibiotics.
Students’ Perceptions of Enhanced e-Assessment Feedback Addressing Common Student Errors in Mathematics
Authors: Sikurajapathi Indunil , Henderson Karen , Gwynllyw Rhys
Published: September 2021

The Common Student Errors Project (CSE Project) has been running at the University of the West of England (UWE, Bristol) since 2017. The main aim of this project is to introduce a method to detect CSEs and to provide tailored feedback in Engineering Mathematics e-Assessment questions. In this case study we briefly describe the process of collecting CSEs related to Engineering Mathematics and delivering personalised enhanced feedback to students who made CSEs on Dewis eAssessment questions. We then present how we carried out a questionnaire to gather student perceptions on the enhanced feedback they received. Finally, we present the outcomes of the questionnaire data, the conclusions on students’ perceptions of the current enhanced feedback and ascertain possible future directions for further development of the enhanced feedback.
Implementing Structured Follow-Up of Neonatal and Paediatric Patients: An Evaluation of Three University Hospital Case Studies Using the Functional Resonance Analysis Method
Authors: Bos Véronique , Roorda Daniëlle , de Sonnaville Eleonore , Boven Menne van , Oosterlaan Jaap , Goudoever Johannes van , Klazinga Niek , Kringos Dionne
Published: September 2021

Background: In complex neonatal and paediatric clinical practice, little is known about long-term patient outcomes and what follow-up care is most valuable for patients. Emma Children’s Hospital, Amsterdam UMC (Netherlands), implemented a follow-up programme called Follow Me for neonatal and paediatric patient groups, to gain more insight into long-term outcomes and to use such outcomes to implement a learning cycle for clinical practice, improve follow-up care and facilitate research. Three departments initiated re-engineering and change processes. Each introduced multidisciplinary approaches to long-term follow-up, including regular standardised check-ups for defined age groups, based on medical indicators, developmental progress, and psychosocial outcomes in patients and their families. This research evaluates the implementation of the three follow-up programmes, comparing predefined procedures (work-as-imagined) with how the programmes were implemented in practice (work-as-done). Methods: This study was conducted in 2019–2020 in the outpatient settings of the neonatal intensive care, paediatric intensive care and paediatric surgery departments of Emma Children’s Hospital. It focused on the organisational structure of the follow-up care. The functional resonance analysis method (FRAM) was applied, using documentary analysis, semi-structured interviews, observations and feedback sessions.Results: One work-as-imagined model and four work-as-done models were described. The results showed vast data collection on medical, developmental and psychosocial indicators in all work-as-done models; however, process indicators for programme effectiveness and performance were missing. In practice there was a diverse allocation of roles and responsibilities and their interrelations to create a multidisciplinary team; there was no one-size-fits-all. Although control and feedback loops for long-term outcomes were specified with respect to the follow-up groups within the programmes, they were found to overlap and misalign with other internal and external long-term outcome monitoring practices. Conclusion: Implementing structured long-term follow-up may provide insights for improving daily practice and follow-up care, with the precondition of standardised measurements. Lessons learned from practice are (1) to address fragmentation in data collection and storage, (2) to incorporate the diverse ways to create a multidisciplinary team in practice, and (3) to include timely actionable indicators on programme effectiveness and performance, alongside medical, developmental and psychosocial indicators.
Differentiated Prevention And Care To Reduce The Risk of HIV Acquisition And Transmission Among Female Sex Workers In Zimbabwe: Study Protocol For The ‘AMETHIST’ Cluster Randomised Trial
Authors: Cowan Frances , Machingura Fortunate , Chabata Sungai T , Ali Sanni , Busza Joanna , Steen Richard , Desmond Nicola , Shahmanesh Maryam , Revill Paul , Mpofu Amon , Yekeye Raymond , Mugurungi Owen , Phillips Andrew N , Hargreaves James R
Published: September 2021

Background: Female sex workers (FSW) in sub-Saharan Africa are disproportionately affected by HIV and are critical to engage in both HIV prevention and care. Here we describe our approach to evaluation of the AMETHIST intervention for FSW, adapted to the African context and set in Zimbabwe where there is a nationally-scaled programme for sex workers (Sisters). We hypothesise this intervention will raise uptake and adherence to prevention and treatment among FSW resulting in a reduction in their risk of HIV acquisition/transmission.Methods: The AMETHIST intervention (Adapted Microplanning to Eliminate Transmission of HIV in Sex Transactions) aims to provide risk differentiated prevention and care to FSW through microplanning and self help groups. Twenty two towns with the Sisters programme were randomised using restricted randomisation to either the Sisters programme or the Sister programme plus AMETHIST. The primary outcome is composite and is defined as the proportion of HIV positive FSW at risk of HIV transmission combined with the proportion of HIV negative FSW at risk of HIV acquisition. The outcome will be assessed after two years of intervention delivery in a respondent-driven sampling survey (total n=4400; n=200 FSW recruited at each site). Primary analysis will use the ‘RDS-2’ method to estimate cluster summaries and will adapt Hayes and Moulton’s ‘2-step’ method to adjust effect estimates for individual-level confounders and further adjust for cluster baseline prevalence. An in-depth process evaluation guided by our project trajectory will be undertaken.Discussion: Innovative pragmatic trials are needed to generate evidence on effectiveness of combination interventions in HIV prevention and treatment in different contexts. We describe the design and analysis of such a study.Trial Registration: The trial was registered at Pan African Clinical Trials Registry (PACTR202007818077777) on 2 July 2020.
Spatio-Temporal Trend Mapping of Precipitation and its Extremes Across Afghanistan (1951-2010)
Authors: Aliyar Quarban , Dhungana Santosh , Shrestha Sangam
Published: September 2021

The civil war, harsh climate, tough topography and lack of accurate meteorological stations has limited observed data across Afghanistan. In order to fulfill the gap, this study analyzed the trend in precipitation and its extremes using Asian Precipitation Highly Resolved Observational Data Integration Towards Evaluation (APHRODITE) daily dataset between 1951 to 2010 at the spatial resolution of 0.25˚˟0.25˚. Non-parametric modified Mann-Kendall test and Sen’s slope estimator were employed to detect trend and quantify it at the significance level of 5%. Significant decreasing trends were observed only in small clusters of southwestern regions ranging between 0 to -1.5mm/year and northeastern region between -1.5 to -6 mm/year for the annual time series. Similar trend pattern was observed in spring season decreasing at the rate of -0.15 to 0.54 mm/year in northeastern and 0 to -0.15 mm/year southwestern region. Decrease in spring precipitation is expected to affect crop production especially in northeastern region which host 22 % of the arable area. Increasing trend in eastern region at maximum of 0.16 mm/year was observed which could intensify the flooding events. Trend analysis of extreme precipitation indices indicated similar spatial distribution to the mean precipitation, concentrated around southwestern, northeastern, and eastern regions. Increasing frequency of consecutive dry days in western region and very heavy precipitation (R10mm) and extremely heavy precipitation (R20mm) in eastern region are fueling the occurrence of droughts and floods respectively. Taking these findings of erratic nature of rainfall and extreme events into consideration for sustainable management of water resources would be fruitful.
Tranexamic acid for reducing blood loss following vaginal delivery: a double-blind randomized controlled trial.
Authors: Igboke Francis , Lawani Lucky , Obi Vitus , Dimejesi Ikechukwu
Published: September 2021

Background: Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality worldwide with the highest incidence in the developing countries. Tranexamic acid (TXA) is a useful drug for prevention of PPH and merits evaluation in our environment. This study evaluates the efficacy of TXA in reducing blood loss following vaginal delivery.Methods: This was a double-blind randomized placebo-controlled study on the efficacy and safety of intravenous TXA in reducing blood loss in women undergoing vaginal delivery in a tertiary hospital. Data analysis was conducted with IBM SPSS software (version 20, Chicago II, USA). P-value <0.05 was considered statistically significant.Results: The mean estimated blood loss was lower in TXA compared with the placebo group (174.87±119.84 ml versus 341.07±67.97 ml respectively; P<0.0001). PPH (blood loss >500ml) was 5.13% in the study arm compared to the control arm 7.14%- risk ratio (RR) 0.82; 95% [CI 0.38 – 1.79, p=0.5956]. Additional uterotonics was required more in the control group compared to the treatment group 14(16.67%) versus 3(3.85%) of the treatment group, p-value of 0.007. There were no major complications noticed in the treatment group.Conclusion: This study demonstrated that intravenous administration of TXA acid following vaginal delivery reduced blood loss following vaginal delivery. It also reduced the need for additional uterotonics. However, blood loss greater than 500 was not significantly reduced.Pan African Clinical Trial Registry: PACTR202010828881019
A Surrogate Assisted Multi-objective Approach to Social Work Planning
Authors: Nguyen Dinh Duc , Nguyen Long , Nguyen Hoai Xuan , Tran Minh Binh
Published: September 2021

Planning social tasks are essential jobs of every organization, business, and government. With increasing challenges of society, the organization and effective implementation depend on optimizing the plans of the organization and efficient operations of the professional teams in order, time, and specific requirements. In the context of the impact of the COVID-19 pandemic on social activities, developing strategies for the organization and operation of working teams in implementing disease prevention, control, and elimination are research issues that should be raised. This paper model the plan to organize and operate the social-mission working group problem with a multi-objective approach. The problem includes organizing and planning the health workforce to perform tasks in epidemic prevention and implementing guidelines of the Ministry of Health under the administration of the government. These pose a requirement to balance resources, medical equipment, and ancillary equipment to perform tasks according to different priority levels: disease prevention; vaccination; sterilization, isolation, treatment by different locations, and time to ensure effectiveness. The problem is modeled by approaching the multi-objective optimization with three objectives: makespan, performance efficiency, and rate of human resource usage. We also propose a guidance technique to improve the surrogate-assisted multi-objective optimization algorithms on analyzing the factors that influence finding solutions and maintain a balance between local exploration and global exploitation. The enhanced algorithms confirm the proposed model for social tasks against the COVID-19 pandemic.
Influencing factors, scenario prediction and decoupling effect of carbon intensity of the whole process of agricultural products logistics
Authors: Fan Xueru , Yao Guanxin , Zhang Dongmei , Bian Xiaoyu
Published: September 2021

The reduction of carbon intensity of the whole process of agricultural products logistics is of great significance to the comprehensive control of China's carbon intensity. LMDI decomposition method, STIRPAT model and quantitative decoupling analysis model are used to study the influencing factors, future development scenarios and decoupling effect with economic development of the whole process carbon intensity of agricultural products logistics in China from 2000 to 2017. The countermeasures and suggestions to reduce the carbon intensity of the whole process of agricultural products logistics in China are put forward based on the research results of influencing factors, scenario prediction and decoupling effect.
Strength Deterioration Mechanism of Bentonite Modified Loess After Wetting-Drying Cycles
Authors: Niu Zelin , Xu Jian , Li Yanfeng , Wang Zefeng , Wang Bao
Published: September 2021

The employment of bentonite modified loess (BML) is a common method of constructing the anti-seepage lining of landfills in the loess region of China, and its long-term secure performance is threatened by wetting-drying (W-D) cycles. Taking the remolded loess (RL) and BML with 15% in mass of bentonite as research objects, the W-D cycles test, scanning electron microscope (SEM) test and direct shear test were carried out to analyze the effects of W-D cycles on the microstructure and shear strength of samples. The regression equations between strength and micro-pore structure parameters were established by multivariate linear stepwise regression method. The damage mechanism of BML after W-D cycles was studied by establishing damage degree models based on porosity and cohesion. Results indicate that clay minerals such as montmorillonite in BML absorb water and expand to fill the macropores, resulting in more medium and small pores and more pronounced surface contact of particles. After W-D cycles, the particle arrangement of samples before and after bentonite modification tends to be loose. Both the porosity and fractal dimension increase and tend to stabilize after five cycles. The BML exhibits lower porosity and greater fractal dimension while its cohesion and internal friction angle show more significant decrease after W-D cycles than those of RL. The damage variables based on porosity and cohesion well describe the W-D induced damage of loess before and after modification from macro- and micro-scale perspectives. The damage degree of samples increases with W-D cycles, but the increment decreases.
Attention-Based Deep Multiple Instances Learning For Classifying Circular RNA and Other Long Non-Coding RNA
Authors: Liu Yunhe , Fu Qiqing , peng Xueqing , Zhu Chaoyu , Liu Gang , Liu Lei
Published: September 2021

Circular RNA (circRNA) is a distinguishable circular formed long non-coding RNA (lncRNA), which has specific roles in transcriptional regulation, multiple biological processes. The identification of circRNA from other lncRNA is necessary for relevant research. In this study, we designed attention-based multi-instance learning (MIL) network architecture, which can be fed with raw sequence, to learn the sparse features in sequences and accomplish the identification task for circRNAs. The model outperformed previously reported models. Following the effectiveness validation of the attention score by the handwritten digit dataset, the key sequence loci underlying circRNAs recognition were obtained based on the corresponding attention score. Moreover, the motif enrichment analysis of the extracted key sequences identified some of the key motifs for circRNA formation. In conclusion, we designed a deep learning network architecture suitable for gene sequence learning with sparse features and implemented to the circRNA identification, and the network has a strong representation capability with its indication of some key loci.
CUBN Gene Mutations May Cause Focal Segmental Glomerulosclerosis (FSGS) in Children
Authors: Yang Jing , Xu Yongli , Deng Linxia , Zhou Luowen , Qiu Liru , Zhang Yu , Zhou Jianhua
Published: September 2021

Background: CUBN gene mutation is extremely rare and thought to only presented as tubular proteinuria without glomerular involvement. Here, we present 3 patients with prominent proteinuria and FSGS in renal pathologies caused by novel CUBN gene mutations.Method: Whole exome sequencing was performed in three children. CUBN gene mutations were found and then verified by sanger sequencing. Their clinical, pathological and molecular genetic characteristics were analyzed and correlated accordingly. Results: All three children presented with prominent proteinuria but normal or slightly higher levels of urine β2 microglobulin, without megaloblastic anemia. Renal biopsies showed segmental glomerular sclerosis, glomerular mesangial cells proliferation, effacement of foot processes, podocyte microvillation and interstitial fibrosis. There were four novel CUBN gene mutations in our study, including c.9287T>C (p.L3096P), c.122+1G>A, c.7906C>T (p.R2636*), c.10233G>A (p.W3411*). Except for intron splice-site mutation, all other variants are located in highly conserved sites of CUB domain. Conclusion: In this study, four novel pathogenic mutations of CUBN gene were identified in three prominent proteinuric children. The results demonstrate that CUBN gene mutations may cause pathological changes of podocytes and FSGS, which was not previously reported. Our cases extend the spectrum of renal manifestation and genotype of CUBN gene mutation.
Probabilistic Approach For Health Hazard Assessment of Trihalomethanes Through Successive Showering Events
Authors: Parveen Naseeba T , Chowdhury Shamik , Goel Sudha
Published: September 2021

Trihalomethanes (THMs) are common disinfection byproducts in chlorinated tap waters. They can cause various cancers and non-cancerous health hazards. Ingestion, dermal contact, and inhalation are the three exposure routes considered in the THM hazard/risk assessments. Among these, inhalation hazard is generally calculated by assuming the initial concentration as zero. This assumption fails to address the case of continuous showers that can happen in shared showering facilities such as student hostels or gymnasiums. In the present study, the leftover THM concentration from the previous bath was considered to assess the chronic daily intakes (CDI) and hazard index (HI) of the successive showers. For this, tap water of a university campus was analyzed to understand the extend of THMs at consumer points and the result obtained was used for the hazard assessment. Total THM concentration varied from 0.51 to 68.9 µg L-1. To address the variability of the model input parameters, 50,000 iterations of Monte Carlo simulation were carried out. A maximum HI of 7.94E-02 ± 3.63E-02 and 6.69E-02 ± 3.08E-02 was observed for 1st shower for females and males. This value was found as exponentially increasing up to the 5th shower and thereafter the rate was decreasing. The methodology followed in the present study successfully determines the risk and hazard of THMs through successive showers.
African Heritage Sites threatened by coastal flooding and erosion as sea-level rise accelerates
Authors: Vousdoukas Michalis , Clarke Joanne , Ranasinghe Roshanka , Reimann Lena , Khalaf Nadia , Duong Trang , Ouweneel Birgitt , Sabour Salma , Iles Carley , Trisos Christopher , Feyen Luc , Simpson Nicholas
Published: September 2021

Important heritage sites along the African coast are at risk from the threats associated with rising sea levels. Here, we quantify the exposure of natural and cultural heritage sites in Africa to coastal flooding and erosion in the 21st century. We develop a comprehensive database of 284 coastal African Heritage Sites (AHS), composed of 213 natural and 71 cultural heritage sites, which is then combined with coastal flooding and erosion projections to assess exposure to coastal extreme events for a moderate (RCP4.5) and high (RCP8.5) greenhouse gas emissions scenario. We find that 56 AHS are presently at risk from a 100-year extreme sea-level event, with a total exposed heritage area of 2,222 km2. Most of the currently exposed AHS are located in Northern and Western Africa. By mid-century, the number of exposed AHS is projected to increase more than 3 times to reach 191 and 198 under moderate and high emissions respectively. In the second half of the century, the number of exposed sites stabilizes, but the median exposed area increases to 6.6 to 8.5 times the present-day value, under moderate and high emissions, respectively. Mitigation from high to moderate emissions will reduce the end-century median exposed area and number of very highly exposed sites by 20% and 25% respectively.
Comparison of Percutaneous Coronary Intervention and Optimal Medical Therapy on Outcomes in Patients with Chronic Coronary Total Occlusion
Authors: Zhou Fuliang , Sun Lufan , Liu Qiushuang , Wu Nan , Jia Dalin
Published: September 2021

Background: Nowadays the optimal strategy for patients with chronic total occlusion (CTO) has not been well established. This meta-analysis aims to evaluate effect of PCI and optimal medical therapy (OMT) on clinical outcomes in these patients. Methods: Pubmed, Embase and Cochrane Library were searched for studies about patients who had CTO and received PCI or medical therapy as initial strategy, from inception to February 2020. Results of pooled analysis were expressed by risk ratios (RR) and 95% confidence intervals (CI), which were calculated by random effects or fixed effects model according to heterogeneity. Sensitivity analysis was performed by removing one study a time. Funnel plot and Egger’s value were used to appraise publication bias. All analysis were calculated by Revmen5.0 and Stata15.0 software.Results: Total 11studies were included in our meta-analysis, 4 RCTs and 7 observation studies using PSM. Total 5664 patients with CTO were enrolled. 2904 patients underwent PCI and 2760 patients received OMT. Pooled analysis indicated that compared with OMT, PCI was associated with lower risk of cardiac death (RR 0.59,95%CI 0.45-0.77, P<0.001). However, there was no significant discrimination in MACE (RR 0.83, 95% CI 0.64-1.06, P=0.14), myocardial infarction (RR 0.98, 95%CI 0.78-1.24, P=0.86), repeat revascularization (RR 0.95, 95%CI 0.71-1.25, P=0.71), and stroke (RR 0.62, 95%CI 0.29-1.34, P=0.22). Sub-analysis by ethnicity showed that PCI was associated with lower incidence of MACE compared with OMT in West European (RR 0.48, 95% CI 0.28-0.84, P=0.01), but not in East Asian (RR 0.94,95% CI 0.77-1.16, P=0.58). Conclusions: Compared with OMT, PCI is associated with lower risk of cardiac death. However, there was no significant difference in MACE, MI, repeated revascularization and stroke. Sub-analysis indicates that PCI is favor of West European.
High Hemoglobin Level is a Risk Factor for Maternal and Fetal Outcomes of Pregnancy in Chinese Women: A Retrospective Cohort Study
Authors: Wu Lanlan , Sun Ruifang , Liu Yao , Liu Zengyou , Chen Hengying , Shen Siwen , Wei Yuanhuan , Deng Guifang
Published: September 2021

Background
To examine the association of hemoglobin (Hb) levels during gestation with the risk of selected adverse pregnancy outcomes in Chinese women.
Methods
A total of 1911 singleton mothers were included. Hb levels were measured during the second (16-18th weeks) and third (28-30th weeks) trimesters of pregnancy, and pregnancy outcomes were followed. Statistical analysis was performed using multivariate logistic regression.
Results
After multivariable adjustment, Hb levels > 130 g/L in the second trimester increased the risk of low-birth-weight infants (LBW) (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.12–5.77). In the third trimester of gestation, compared with women whose Hb levels between 110–119 g/L, women with Hb levels > 130 g/L had an increased risk of LBW (OR, 2.17; 95% CI, 1.05–4.48) and small-for-gestational-age infants (SGA) (OR, 1.98; 95% CI, 1.04–3.78). In addition, maternal Hb levels of < 110 g/L or > 130 g/L at the second week that were restored vs not restored in the third trimester decreased the risk of preterm birth (PTB) by 80% (95% CI, 0.07–0.58) and 86% (95% CI, 0.03–0.84), respectively.
Conclusion
Maternal Hb > 130 g/L was associated with increased risk of adverse pregnancy outcomes. Reduction of PTB risk was observed with correction of Hb level during the third trimester.
Acute Toxicity Assays Using Danio Rerio and Daphnia Magna To Assess Hot-Spring Drainage in The Shibukuro and Tama Rivers (Akita, Japan)
Authors: Suwa Kyo , Takahashi Chiho , Horie Yoshifumi
Published: September 2021

We investigated the lethal toxicity of Shibukuro and Tama river water near the inflow of Tamagawa hot-spring water in Akita Prefecture, Japan. We first measured heavy metal concentrations in both rivers. We detected iron, arsenic, and aluminum; the concentrations of each tended to decrease from upstream to downstream. We next examined the influence of river water on zebrafish Danio rerio and water flea Daphnia magna. We observed lethal effects in both species, with Daphnia magna more sensitive to toxicity than Danio rerio. For both species, the toxic effects of river water decreased with increasing distance downstream from the inflow of hot-spring water. Our results show that the heavy metals discharged from Tamagawa hot spring have a negative effect on aquatic organisms.
Epidemiology of Neuroendocrine Neoplasmas in Japan: Based on Analysis of Hospital-Based Cancer Registry Data, 2009 – 2015
Authors: Koizumi Tomonobu , Otsuki Kengo , Tanaka Yuriko , Kanda Shintaro
Published: September 2021

Purpose: Neuroendocrine neoplasms are rare disease and could originate from throughout the body, however, there have been little epidemiological studies in Japan, especially the organ distribution. This study was to examine the epidemiological information of neuroendocrine neoplasms in the Japanese population using data from a hospital-based cancer registry. Methods: Using data from the national database of hospital-based cancer registries, we examined the organ distribution, the stage and initial treatment of neuroendocrine neoplasms newly diagnosed and treated in designated and non-designated cancer care hospitals between 2009 and 2015. In the present study, neuroendocrine neoplasms consisted of neuroendocrine tumors and carcinoma. Results: A total of 33,215 (17485 neuroendocrine carcinomas and 15730 neuroendocrine tumors) cases were diagnosed. The majority in neuroendocrine carcinoma occur in lung (31.1%) followed in decreasing frequency by stomach (12.9%), pancreas (7.5%), rectum (6.7%) and esophagus (5.8%). On the other hand, the half of neuroendocrine tumor originated rectum (50.9%) and followed by pancreas (13.9%), duodenum (9.0%), lung/bronchus (8.9%), and stomach (8.7%). Neuroendocrine carcinoma presented at more advanced stage and higher age than neuroendocrine tumors.　Most cases of neuroendocrine tumors were treated surgically, while half of neuroendocrine carcinomas were treated with non-surgical therapy consisting of chemotherapy with or without radiotherapy. Conclusions: Our results demonstrated that neuroendocrine neoplasms could originate from various organs and the site distribution was different between neuroendocrine carcinoma and tumor. The national database of hospital-based cancer registries in Japan is a valuable source for evaluating the organ distribution of the rare systemic disease.
Single cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia
Authors: Ulukaya Gulay , Thomas Beena , Bhasin Swati , Mumme Hope , Dwivedi Bhakti , Perumalla Pruthvi , Sarkar Debasree , Sabnis Himalee , Park Sunita , DeRyckere Deborah , RaiKar Sunil , Pauly Melinda , Summers Ryan , Castellino Sharon , Wechsler Daniel , Porter Christopher , Graham Douglas , Bhasin Manoj
Published: September 2021

Relapse- and continuous complete remission (CCR)-associated pediatric acute myeloid leukemia (AML) patient bone marrows collected at the time of diagnosis (Dx), end of induction (EOI) and relapse were analyzed by single cell RNA sequencing. A novel AML blasts-associated 7-genes signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH) displayed a strong correlation with blast percentages and overall survival in the TARGET AML dataset (HR=2.3; P-value=.007). Distinct clusters of AML-blasts at Dx were observed for relapse- and CCR-associated samples with differential expression of genes associated with survival. Relapse-associated samples demonstrated enrichment of exhausted T cells and M2 macrophages as opposed to inflammatory M1 macrophages in CCR-associated samples at Dx. EOI treatment resistant blast cells overexpressed fatty acid oxidation, tumor growth and stemness genes. Also, a relapse-associated EOI samples T cells subset showed downregulation of MHC Class I and regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse-/CCR-associated tumor microenvironment transcriptome landscape.
Selective inhibition of microRNA processing by a herpesvirus-encoded microRNA triggers virus reactivation from latency
Authors: Hennig Thomas , Prusty Archana , Kaufer Benedikt , Whisnant Adam , Lodha Manivel , Enders Antje , Thomas Julius , Kasimir Francesca , Grothey Arnhild , Herb Stefanie , Juerges Christopher , Meister Gunter , Erhard Florian , Dolken Lars , Prusty Bhupesh
Published: September 2021

Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation thereof 1,2. A long appreciated, yet elusively defined relationship exists between the lytic-latent switch and viral non-coding RNAs 3,4. Here, we identify miRNA-mediated inhibition of miRNA processing as a novel cellular mechanism that human herpesvirus 6A (HHV-6A) exploits to disrupt mitochondrial architecture, evade intrinsic host defense and drive the latent-lytic switch. We demonstrate that virus-encoded miR-aU14 selectively inhibits the processing of multiple miR-30 family members by direct interaction with the respective pri-miRNA hairpin loops. Subsequent loss of miR-30 and activation of miR-30/p53/Drp1 axis triggers a profound disruption of mitochondrial architecture, which impairs induction of type I interferons and is necessary for both productive infection and virus reactivation. Ectopic expression of miR-aU14 was sufficient to trigger virus reactivation from latency thereby identifying it as a readily drugable master regulator of the herpesvirus latent-lytic switch. Our results show that miRNA-mediated inhibition of miRNA processing represents a generalized cellular mechanism that can be exploited to selectively target individual members of miRNA families. We anticipate that targeting miR-aU14 provides exciting therapeutic options for preventing herpesvirus reactivations in HHV-6-associated disorders like myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and Long-COVID.
Cancer-Associated Fibroblasts Promote Oral Squamous Cell Carcinoma Progression Through LOX-Mediated Matrix Stiffness
Authors: Zhang Jia-Yi , Zhu Wei-Wen , Wang Meng-Yao , Zhai Run-Dong , Wang Qiong , Shen Wei-Li , Liu Lai-Kui
Published: September 2021

Background: Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, have prominent roles in the development of solid tumors as stromal targets. However, the underlying mechanism of CAFs’ function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we investigated the role of lysyl oxidase (LOX) expression in CAFs in tumor stromal remodeling and the mechanism of its effect on OSCC progression. Methods: Immunohistochemistry was performed to detect the expression and correlation of the α - SMA and LOX in OSCC specimens, as well as the correlation with clinicopathological parameters. The expression of LOX in CAFs were detected by RT-qPCR and western blot. The effects of LOX in CAFs on the biological characteristics of OSCC cell line were investigated using CCK-8, wound-healing, Transwell migration and invasion assay. Next, CAFs cells were co-cultured with type I collagen in vitro, and collagen contraction test, microstructure observation and rheometer were used to detect the effect of CAFs on remodeling collagen matrix. Then, collagen with different stiffness were established to investigate the effect of matrix stiffness on the invasion and EMT of OSCC cells. Moreover, we explored whether the increase of matrix stiffness promote the progress of OSCC through activating focal adhesion kinase (FAK) phosphorylation pathway.Results: In OSCC specimens, α-SMA, the specific markers of CAFs, and LOX were highly expressed in tumor stromal tissues, and they were significantly correlated with the degree of malignant differentiation. LOX was highly expressed in CAFs, and its knockdown impaired proliferation, migration, invasion and EMT process of OSCC cells. The expression of LOX in CAFs can catalyze collagen crosslinking and increase matrix stiffness. Furthermore, LOX-mediated increase in collagen stiffness induced morphological changes and promoted invasion and EMT process in OSCC cells by activating FAK phosphorylation pathway. Conclusions: Our findings suggest that CAFs highly express LOX in OSCC and can remodel the matrix collagen microenvironment, and an increase in LOX-mediated matrix stiffness promotes OSCC development through FAK phosphorylation pathway. Thus, LOX may be a potential target for the early diagnosis and therapeutic treatment of OSCC.
Bryozoans from the early Cambrian Chengjiang Biota
Authors: Wei Fan , Lei Xiangtong , Li Gaorong , Zhao Yang , Hou Xian-guang , Cong Peiyun
Published: September 2021

Bryozoa are colonial, aquatic, generally sessile coelomate metazoans, with a retractable lophophore and U-shaped digestive tract. They are widely distributed and highly diverse in extant marine and freshwater environments. Current confident fossils of the earliest bryozoan only occur in the Early Ordovician, although molecular estimation date their origin in or prior to the early Cambrian, rendering the origin and early evolution of bryozoans are intensely debated. Here, we describe two cyclostomes, Panpipora yunnanensis gen. et. sp. nov. and Corynotrypa sp., having been recovered from the Cambrian Chengjiang Biota (~ 518 m.y.) in Southwest China. The bryozoans represent the earliest fossils of Bryozoa, predating the record of the phylum by more than 30 million years. Our finding reveals that the Bryozoa, as all other skeletonised metazoans, first evolved during the Cambrian Explosion, and it is congruent with estimation of molecular clock that the cyclostomes is the earliest biomineralised clade. Corynotrypa might be derived from unmineralized ctenostomes by stolonal mineralization and change of growth direction of polypides from vertical to creeping. The unmineralised frontal exterior wall might be a share character existed in all ancestral clades. Encrusting specimens that inhabited in muddy environments have been confirmed here, further suggesting that encrusting bryozoans underwent a profound ecological migration from soft- to hard-bottom facies from Cambrian to Ordovician.
The Atmospheric River Threat to Antarctic Peninsula Ice-Shelf Stability
Authors: Wille Jonathan , Favier Vincent , Jourdain Nicolas , Kittel Christoph , Turton Jenny , Agosta Cecilie , Gorodetskaya Irina , Picard Ghislain , Codron Francis , Amory Charles , Fettweis Xavier , Blanchet Juliette , Jomelli Vincent
Published: September 2021

The disintegration of the ice shelves along the Antarctic Peninsula have spurred much discussion on the various processes leading to their eventual dramatic collapse, but without a consensus on an atmospheric forcing that could connect these processes. Here, using an atmospheric river (AR) detection algorithm along with a regional climate model and satellite observations, we show that particularly intense ARs have a ~40% probability of inducing extreme events of temperature, surface melt, sea-ice disintegration, or large swells; all processes proven to induce ice-shelf destabilization. This was observed during the collapses of the Larsen A, B, and overall, 60% of calving events triggered by ARs from 2000-2020. The loss of the buttressing effect from these ice shelves leads to further continental ice loss and subsequent sea-level rise. Understanding how ARs connect various disparate processes cited in ice-shelf collapse theories is essential for identifying other at-risk ice shelves like the Larsen C.
Study On The Single Point Incremental Sheet Forming of AISI 321 Variable Wall Angle Geometry
Authors: Afzal Muhammad Jawad , Israr Asif , Akram Muhammad Soban , Muqeet Abdul
Published: September 2021

For rapid prototyping, design validation and small batch productions process with low tooling cost is preferred. Single Point Incremental Forming (SPIF) is a die-less sheet metal forming process which requires only low cost forming tool driven by CNC machine in a toolpath to form required geometry at room temperature from sheet blank clamped in a low cost and low stiffness clamping system. In this study, effect of process parameters such as tool radius, feed rate and lubrication are considered on the formability of the truncated profile of AISI 321 Variable Wall Geometry (VWA). Set parameters conditions with 2 level layers are optimized using numerical and statistical approach. Experimentation on the same setup is carried out by selecting the most, least and mid favorable solutions optimized on the basis of forming forces and stresses in the sheet. Geometrical accuracy, sheet thinning, and forming forces are compared analytically, numerically and experimentally addressing the inadequacy of analytically models for Variable Wall Angle Geometries.
Multi-Center Evaluation of Artificial Intelligent Imaging And Clinical Models For Predicting Neoadjuvant Chemotherapy Response In Breast Cancer
Authors: Qi Tan Hong , Hian Ong Hiok , Kumaran Arjunan Muthu , Tan Tira J. , Cong Ryan Shea Tan Ying , Su-Xin Ghislaine Lee , Hsuen Elaine Lim , Hui Raymond Ng Chee , Chert Richard Yeo Ming , Tching Faye Lynette Lim Wei , Zewen Zhang , Hui Christina Yang Shi , Xin Wong Ru , Kai Gideon Ooi Su , Hao Lester Leong Chee , Ming Tan Su , Preetha Madhukumar , Yirong Sim , Mien Veronique Tan Kiak , Yeong Joe , Yong Wong Fuh , Yiyu Cai , Nei Wen Long
Published: September 2021

Background:Neoadjuvant chemotherapy (NAC) plays an important role in the management of locally advanced breast cancer. It allows for downstaging of tumours, potentially allowing for breast conservation. NAC also allows for in-vivo testing of the tumours’ response to chemotherapy and provides important prognostic information. There are currently no clearly defined clinical models that incorporate imaging with clinical data to predict response to NAC. Thus, the aim of this work is to develop a predictive AI model based on routine CT imaging and clinical parameters to predict response to NAC. Methods:The CT scans of 324 patients with NAC from multiple centers in Singapore were used in this study. Four different radiomics models were built for predicting pathological complete response (pCR): first two were based on textural features extracted from peri-tumoral and tumoral regions, the third model based on novel space-resolved radiomics which extract feature maps using voxel-based radiomics and the fourth model based on Deep Learning (DL). Clinical parameters were included to build a final prognostic model. Results:The best performing models were based on space-resolved and deep learning approaches. Space-resolved radiomics improves the clinical AUCs of pCR prediction from 0.743 (0.650 to 0.831) to 0.775 (0.685 to 0.860) and our DL model improved it from 0.743 (0.650 to 0.831) to 0.772 (0.685 to 0.853). The tumoral radiomics model performs the worst with no improvement of the AUC from the clinical model. The peri-tumoral combined model gives moderate performance with an AUC of 0.765 (0.671 to 0.855). Conclusions:Radiomics features extracted from diagnostic CT augments the predictive ability of pathological complete response when combined with clinical features. The novel space-resolved radiomics and deep learning radiomics approaches outperformed conventional radiomics techniques.
Cyberattacks Detection and Analysis in a Network Log System Using XGBoost with ELK Stack
Authors: Yang Chao-Tung , Chan Yu-Wei , Liu Jung-Chun Liu , Kristiani Endah , Lai Cing-Han
Published: September 2021

The usage of artificial intelligence and machine learning methods on cyberattacks increasing significantly recently. For the defense method of cyberattacks, it is possible to detect and identify the attack event by observing the log data and analyzing whether it has abnormal behavior or not. This paper implemented the ELK Stack network log system (NetFlow Log) to visually analyze log data and present several network attack behavior characteristics for further analysis. Additionally, this system evaluated the extreme gradient enhancement (XGBoost), Recurrent Neural Network (RNN), and Deep Neural Network (DNN) model for machine learning methods. Keras was used as a deep learning framework for building a model to detect the attack event. From the experiments, it can be confirmed that the XGBoost model has an accuracy rate of 96.01% for potential threats. The full attack data set can achieve 96.26% accuracy, which is better than RNN and DNN models.
The Relationship Among Integrin Alpha 7, CD133 and Nestin as Well as Their Correlation With Clinicopathological Features and Prognosis in Astrocytoma Patients
Authors: Li Changtai , Liu Jiao , Yang Wei , Chen Chongyi , Wu Bo
Published: September 2021

Objective: Integrin alpha 7 (ITGA7), a potential glioma stem cell marker, regulates several other stem cell markers including CD133 and Nestin in several cancers, meanwhile its high expression is related to poor prognosis in multiple solid tumor patients. However, few studies report correlation of ITGA7 with prognosis in astrocytoma patients. Hence, this study aimed to determine the astrocytoma-tissue ITGA7, CD133 and Nestin expressions to explore their relationship and clinical value for astrocytoma management. Methods: Totally, 124 patients with primary astrocytoma were included. Their tumor tissue ITGA7, CD133 and Nestin expressions were determined by immunohistochemical (IHC) assay and scored by intensity and density ranging from 0-12 points. Besides, their clinical features (such as world health organization (WHO) grade, isocitrate dehydrogenase (IDH) mutation, and adjuvant therapy etc.) were collected, also their overall survival (OS) were analyzed by follow-up data. Results: The mean IHC scores for ITGA7, CD133 and Nestin were 4.9±2.5, 2.1±2.6 and 5.8±2.6, respectively. Moreover, ITGA7 high expression correlated with absence of IDH mutation (P=0.004), advanced WHO grade (P=0.001) and shorter OS (P=0.005). Besides, ITGA7 positively correlated with CD133 (P=0.001) and Nestin (P=0.001) expressions. Regarding CD133 and Nestin, their high expression also correlated with increased WHO grade and shorter OS. Furthermore, multivariant Cox’s regression analysis displayed that only CD133 high expression (P=0.021) could independently predict reduced OS, while ITGA7 or Nestin high expression could not. Conclusion: ITGA7, CD133 and Nestin are intercorrelated, also their high expressions associate with deteriorating disease conditions and poor prognosis in astrocytoma patients.
Bio-composites for Fused Filament Fabrication. Effects of Maleic Anhydride Grafting on Poly(Lactic Acid) and Microcellulose
Authors: Rigotti Daniele , Fambri Luca , Pegoretti Alessandro
Published: September 2021

Composite filaments consisting of poly(lactic acid) (PLA) and micro crystalline cellulose (MCC) were successfully used for additive manufacturing (AM) by fused filament fabrication (FFF). PLA and MCC bio-composites were obtained by direct mixing in a melt compounder; maleic anhydride (MAH) was also grafted onto PLA in reactive mixing stage to evaluate its effect on the final properties of the printed material. Filaments with various concentrations of MCC (up to a maximum content of 10 wt%) were produced with a single screw extruder and used to feed a commercial desktop FFF printer. Upon grafting of PLA with MAH, a more coherent interfacial morphology between PLA and MCC was detected by electron microscopy analysis. The thermal degradation of the PLA was unaffected by the presence of MCC and MAH. According to differential scanning calorimetry and dynamic mechanical analysis results, micro-cellulose acted as nucleating agent for PLA. In fact, the crystallization peak shifted towards lowers temperature and a synergistic effect when MCC was added to PLA grafted with MAH was observed possibly due to the increase of the chain mobility. Micro cellulose led to an increase in the stiffness of the material in both filaments and 3D printed specimen, however, a different fracture behavior was observed due to the peculiar structure of printed samples.
First-Principles Study of (CsMA)NaSbX6 (MA= Methylammonium; X=Cl, Br, I) Organic-Inorganic Hybrid Double Perovskites For Optoelectronic Applications
Authors: Johnson Austin , Gbaorun F. , Ikyo B.A.
Published: September 2021

Significant interests have been drawn to organic-inorganic hybrid double perovskites towards the commercialization of Pb-free non-toxic perovskites because of their unique optoelectronic properties than their inorganic counterparts. In this study, the structural, electronic and optical properties as well as stability of (CsMA)NaSbX6(MA= methylammonium; X= Cl, Br, I) were investigated using first-principles density functional theory (DFT). Results of the DFT method reveal that the investigated compounds have tunable bandgaps, high absorption coefficients and high refractive indices. Findings also show that the iodide-based compound, (CsMA)NaSbI6 shows superior optoelectronic properties compared to the bromide and chloride- based compounds, (CsMA)NaSbBr6 and (CsMA)NaSbCl6. Specifically, results of the study predict the (CsMA)NaSbI6 organic-inorganic hybrid double perovskite to be a promising candidate for optoelectronic applications due to its high absorption coefficient (in the order of 106cm-1), dielectric constant (approx.4.43), imaginary part of the refractive index (2.83) as well as the high formation energy depicting its stability. These results can be utilized for synthesis of sustainable and non-toxic optoelectronic devices.