bluuebunny/crossref_metadata_2025 huggingface dataset:
Periostin expression and its supposed roles in benign and malignant thyroid nodules: an immunohistochemical study of 105 cases
Authors: Kusafuka Kimihide , Yamashita Masaru , Iwasaki Tomohiro , Tsuchiya Chinatsu , Kubota Aki , Hirata Kazuki , Murakami Akinori , Muramatsu Aya , Arai Kazumori , Suzuki Makoto
Published: September 2021

Background

Thyroid tumors are often difficult to histopathologically diagnose, particularly follicular adenoma (FA) and follicular carcinoma (FC). Papillary carcinoma (PAC) has several histological subtypes. Periostin (PON), which is a non-collagenous extracellular matrix molecule, has been implicated in tumor invasiveness. We herein aimed to elucidate the expression status and localization of PON in thyroid tumors.

Method

We collected 105 cases of thyroid nodules, which included cases of adenomatous goiter, FA, microcarcinoma (MIC), PAC, FC, poorly differentiated carcinoma (PDCa), and undifferentiated carcinoma (UCa), and immunohistochemically examined the PON expression patterns of these lesions.

Results

Stromal PON deposition was detected in PAC and MIC, particularly in the solid/sclerosing subtype, whereas FA and FC showed weak deposition on the fibrous capsule. However, the invasive and/or extracapsular regions of microinvasive FC showed quite strong PON expression. Except for it, we could not find any significant histopathological differences between FA and FC. There were no other significant histopathological differences between FA and FC. Although PDCa showed a similar PON expression pattern to PAC, UCa exhibited stromal PON deposition in its invasive portions and cytoplasmic expression in its carcinoma cells. Although there was only one case of UCa, it showed strong PON immunopositivity. PAC and MIC showed similar patterns of stromal PON deposition, particularly at the invasive front.

Conclusions

PON may play a role in the invasion of thyroid carcinomas, particularly PAC and UCa, whereas it may act as a barrier to the growth of tumor cells in FA and minimally invasive FC.
Knockdown expression of a MYB-related transcription factor gene, OsMYBS2, enhances production of recombinant proteins in rice suspension cells
Authors: Sinaga Desyanti Saulina , Ho Shin-Lon , Lu Chung-An , Yu Su-May , Huang Li-Fen
Published: September 2021

Background

Transgenic plant suspension cells show economic potential for the production of valuable bioproducts. The sugar starvation-inducible rice αAmy3 promoter, together with its signal peptide, is widely applied to produce recombinant proteins in rice suspension cells. The OsMYBS2 transcription factor was shown recently to reduce activation of the αAmy3 promoter by competing for the binding site of the TA box of the αAmy3 promoter with the potent OsMYBS1 activator. In this study, rice suspension cells were genetically engineered to silence OsMYBS2 to enhance the production of recombinant proteins.

Results

The mouse granulocyte–macrophage colony-stimulating factor (mGM-CSF) gene was controlled by the αAmy3 promoter and expressed in OsMYBS2-silenced transgenic rice suspension cells. Transcript levels of the endogenous αAmy3 and the transgene mGM-CSF were increased in the OsMYBS2-silenced suspension cells. The highest yield of recombinant mGM-CSF protein attained in the OsMYBS2-silenced transgenic suspension cells was 69.8 µg/mL, which is 2.5-fold that of non-silenced control cells. The yield of recombinant mGM-CSF was further increased to 118.8 µg/mL in cultured cells derived from homozygous F5 seeds, which was 5.1 times higher than that of the control suspension cell line.

Conclusions

Our results demonstrate that knockdown of the transcription factor gene OsMYBS2 increased the activity of the αAmy3 promoter and improved the yield of recombinant proteins secreted in rice cell suspension cultures.
The impact of pelvic radiotherapy on the gut microbiome and its role in radiation-induced diarrhoea: a systematic review
Authors: Wang Lina , Wang Xiaohu , Zhang Guangwen , Ma Yan , Zhang Qiuning , Li Zheng , Ran Juntao , Hou Xiaoming , Geng Yichao , Yang Zheng , Feng Shuangwu , Li Chengcheng , Zhao Xueshan
Published: September 2021

Pelvic radiotherapy is the key treatment for pelvic malignancies, usually including pelvic primary tumour lesions and lymphatic drainage areas in the pelvic region. Therefore, the intestinal tract in the radiation field is inevitably damaged, a phenomenon clinically referred to as radiation enteritis, and diarrhoea is the most common clinical symptom of radiation enteritis. Therefore, it is necessary to study the mechanism of radiation-induced diarrhoea. It has been found that the gut microbiome plays an important role in the development of diarrhoea in response to pelvic radiotherapy, and the species and distribution of intestinal microbiota are significantly altered in patients after pelvic radiotherapy. In this study, we searched for articles indexed in the Cochrane Library, Web of Science, EMBASE and PubMed databases in English and CNKI, Wanfang data and SINOMED in Chinese from their inception dates through 13 March 2020 to collect studies on the gut microbiome in pelvic radiotherapy patients. Eventually, we included eight studies: one study report on prostatic carcinoma, five studies on gynaecological carcinoma and two papers on pelvic carcinomas. All studies were designed as self-controlled studies, except for one that compared toxicity to nontoxicity. The results from all the studies showed that the diversity of intestinal flora decreased during and after pelvic radiotherapy, and the diversity of intestinal flora decreased significantly in patients with diarrhoea after radiotherapy. Five studies observed that the community composition of the gut microbiota changed at the phylum, order or genus level before, during, and after pelvic radiotherapy at different time points. In addition, the composition of the gut microbiota before radiotherapy was different between patients with postradiotherapy diarrhoea and those without diarrhoea in five studies. However, relevant studies have not reached consistent results regarding the changes in microbiota composition. Changes in the intestinal flora induced by pelvic radiotherapy and their relationship between changes in intestinal flora and the occurrence of radiation-induced diarrhoea (RID) are discussed in this study, providing a theoretical basis for the causes of RID after pelvic radiotherapy.
Cardiac surgery under cardiopulmonary bypass in pregnancy: report of four cases
Authors: You Youhao , Liu Shenghua , Wu Zhaohong , Chen Dunjin , Wang Gefei , Chen Gangdong , Pan Youguang , Zheng Xing
Published: September 2021

Background

Open heart surgery during pregnancy is relatively rare at home and abroad, and there is a higher risk and probability of maternal and infant death. How to carry out heart valve replacement under cardiopulmonary bypass (CPB) under the premise of ensuring the safety of mother and child is the focus of attention at home and abroad.

Case introduction

We reported four cases of cardiac surgeries under CPB during pregnancy performed in our hospital from March 2020 to March 2021. Two of the patients continued their pregnancy after cardiac surgery under CPB. Three patients had infective endocarditis and the other one had an ascending aortic aneurysm. Three patients underwent heart valve placement with the mechanical mitral valve when the other one underwent Bentall surgery. The operations of four cases were all successful, and further follow-up evaluation of the pregnant women and fetuses showed no abnormalities. The patients' detailed information is shown in the following table.

Conclusion

Heart disease during pregnancy should be treated actively and proactively when the patient has obvious symptoms. Heart valve replacement under CPB will be the first choice, and this may become the primary surgical treatment for symptomatic heart disease during pregnancy.
Inward- versus outward-focused bioeconomy strategies for British Columbia’s forest products industry: a harvested wood products carbon storage and emission perspective
Authors: Xie Sheng H. , Kurz Werner A. , McFarlane Paul N.
Published: September 2021

Background

British Columbia’s (BC) extensive forest resources provide climate change mitigation opportunities that are available to few other jurisdictions. However, as a consequence of the Mountain Pine Beetle outbreak and large-scale wildfires, BC is anticipating reduced roundwood harvest for the next decades. Progress towards more climatically efficient utilization of forest resources is needed. This research quantitatively compared the greenhouse gas emission consequences of nine harvested wood products trade and consumption strategies. Inward-focused strategies use wood products within Canada to achieve emission reduction objectives, while outward-focused strategies encourage exports of wood products.

Results

In the business-as-usual baseline scenario, average emissions arising from BC-originated harvested wood products between 2016 and 2050 were 40 MtCO2e yr−1. The estimated theoretical boundaries were 11 MtCO2e yr−1 and 54 MtCO2e yr−1, under the scenarios of using all harvests for either construction purposes or biofuel production, respectively. Due to the constrained domestic market size, inward-focused scenarios that were based on population and market capacity achieved 0.3–10% emission reductions compared to the baseline. The international markets were larger, however the emissions varied substantially between 68% reduction and 25% increase depending on wood products’ end uses.

Conclusions

Future bioeconomy strategies can have a substantial impact on emissions. This analysis revealed that from a carbon storage and emission perspective, it was better to consume BC’s harvests within Canada and only export those products that would be used for long-lived construction applications, provided that construction market access beyond the US was available. However, restricting export of wood products destined for short-lived uses such as pulp and wood pellets would have significant economic and social impacts. On the other hand, inward-focused strategies had a small but politically and environmentally meaningful contribution to BC’s climate action plan. This study also revealed the conflicts between a demand-driven bioeconomy and targeted environmental outcomes. A hierarchical incentive system that could co-exist with other market drivers may help achieve emission reduction goals, but this would require a better quantitative understanding of wood products’ substitution effects. While the analyses were conducted for BC, other regions that are net exporters of wood products may face similar issues.
Elosulfase alfa in the treatment of mucopolysaccharidosis type IVA: insights from the first managed access agreement
Authors: Stevens Bob , Kenny Tom , Thomas Sophie , Morrison Alexandra , Jarrett James , Jain Mohit
Published: September 2021

Managed access agreements provide a crucial mechanism whereby real-world data can be collected systematically to reduce uncertainty around available clinical and economic data, whilst providing the opportunity to identify patient sub-populations who are most likely to benefit from a new treatment. This manuscript aims to share learnings from the first managed access agreement, which was initiated following positive conditional approval in 2015 from the National Institute for Health and Care Excellence (NICE) for elosulfase alfa, an enzyme replacement therapy for the treatment of mucopolysaccharidosis type IVA (MPS IVA). This managed access agreement enabled the collection of comprehensive real-world data for patients with MPS IVA, with results demonstrating that patients starting elosulfase alfa treatment showed gains similar to those seen in the pivotal trial for outcomes including endurance, respiratory and cardiac function, pain, quality of life measures and urinary keratan sulfate levels. In addition, former trial patients continued to see benefits in both clinical assessments and quality of life/activities of daily living nine years after beginning treatment. Key strengths of the process included recruitment of a high proportion of MPS IVA patients treated in England (72/89 known eligible patients) with a wide range of ages (2–58 years). Participation of a patient organisation (the MPS society) ensured that the patient voice was present throughout the process, whilst a contract research organisation (Rare Disease Research Partners) ensured that patients were represented when interpreting agreement criteria and during patient assessment meetings. Longer-term follow-up will be required for several MPS IVA outcomes (e.g. skeletal measures) to further reduce uncertainty, and continued follow-up of patients who had stopped treatment was found to be challenging. The burden associated with this managed access agreement was found to be high for patients, physicians, patient organisations, NHS England and the manufacturer, therefore costs and benefits of future agreements should be considered carefully before initiation. Through evaluation of the strengths and limitations of this process, it is hoped that learnings from this managed access agreement can be used to inform future agreements.
Kynurenine derivative 3-HAA is an agonist ligand for transcription factor YY1
Authors: Shi Zhaopeng , Gan Guifang , Xu Xiang , Zhang Jieying , Yuan Yuan , Bi Bo , Gao Xianfu , Xu Pengfei , Zeng Wenbin , Li Jixi , Ye Youqiong , Zhou Aiwu , Zhang Naixia , Liu Wen , Lin Shuhai , Mi Jun
Published: September 2021

The 3-hydroxyanthranilic acid (3-HAA), a derivative of kynurenine, was reported to suppress tumor growth. However, the function of 3-HAA largely remains unclear. Here, we report that 3-hydroxyanthranilic acid (3-HAA) is lower in tumor cells, while adding exogenous 3-HAA induces apoptosis in hepatocellular carcinoma by binding YY1. This 3-HAA binding of YY1 leads to phosphorylation of YY1 at the Thr 398 by PKCζ, concomitantly enhances YY1 chromatin binding activity to increase expression of target genes. These findings demonstrate that 3-HAA is a ligand of YY1, suggesting it is a promising therapeutic candidate for HCC.
Restricted visitation policies in acute care settings during the COVID-19 pandemic: a scoping review
Authors: Moss Stephana J. , Krewulak Karla D. , Stelfox Henry T. , Ahmed Sofia B. , Anglin Melanie C. , Bagshaw Sean M. , Burns Karen E. A. , Cook Deborah J. , Doig Christopher J. , Fox-Robichaud Alison , Fowler Robert , Hernández Laura , Kho Michelle E. , Kredentser Maia , Makuk Kira , Murthy Srinivas , Niven Daniel J. , Olafson Kendiss , Parhar Ken Kuljit S. , Patten Scott B. , Rewa Oleksa G. , Rochwerg Bram , Sept Bonnie , Soo Andrea , Spence Krista , Spence Sean , Straus Sharon , West Andrew , Parsons Leigh Jeanna , Fiest Kirsten M.
Published: September 2021

Background

Restricted visitation policies in acute care settings because of the COVID-19 pandemic have negative consequences. The objective of this scoping review is to identify impacts of restricted visitation policies in acute care settings, and describe perspectives and mitigation approaches among patients, families, and healthcare professionals.

Methods

We searched Medline, Embase, PsycINFO, Healthstar, CINAHL, Cochrane Central Register of Controlled Trials on January 01/2021, unrestricted, for published primary research records reporting any study design. We included secondary (e.g., reviews) and non-research records (e.g., commentaries), and performed manual searches in web-based resources. We excluded records that did not report primary data. Two reviewers independently abstracted data in duplicate.

Results

Of 7810 citations, we included 155 records. Sixty-six records (43%) were primary research; 29 (44%) case reports or case series, and 26 (39%) cohort studies; 21 (14%) were literature reviews and 8 (5%) were expert recommendations; 54 (35%) were commentary, editorial, or opinion pieces. Restricted visitation policies impacted coping and daily function (n = 31, 20%) and mental health outcomes (n = 29, 19%) of patients, families, and healthcare professionals. Participants described a need for coping and support (n = 107, 69%), connection and communication (n = 107, 69%), and awareness of state of well-being (n = 101, 65%). Eighty-seven approaches to mitigate impact of restricted visitation were identified, targeting families (n = 61, 70%), patients (n = 51, 59%), and healthcare professionals (n = 40, 46%).

Conclusions

Patients, families, and healthcare professionals were impacted by restricted visitation polices in acute care settings during COVID-19. The consequences of this approach on patients and families are understudied and warrant evaluation of approaches to mitigate their impact. Future pandemic policy development should include the perspectives of patients, families, and healthcare professionals.

Trial registration: The review was registered on PROSPERO (CRD42020221662) and a protocol peer-reviewed prior to data extraction.
Acupuncture as adjunctive therapy for acute renal colic caused by urinary calculi: study protocol for a randomized controlled trial
Authors: Cao Ying , Tu Jian-Feng , Shi Guang-Xia , Wang Li-Qiong , Jia Lian-Cheng , Li Bo , Liu Bao-Li , Yao Wei-Hai , Pei Xiao-Lu , Qu Zhi-Cheng , Liu Cun-Zhi
Published: September 2021

Background

Acute renal colic caused by urinary calculi (ARCUC) has a considerable impact on the quality of life. Acupuncture might be a potential treatment option. However, the evidence is limited. We will conduct this trial to evaluate the efficacy and safety of acupuncture as adjunctive treatment to diclofenac for ARCUC.

Methods/design

A total of 80 eligible patients who are diagnosed with urinary stone renal colic will be randomly allocated to the acupuncture group or the sham acupuncture group. Each patient will receive 1 session of acupuncture or sham acupuncture. The primary outcome will be the response rate of patients achieving a reduction of > 50% on visual analog score (VAS) from baseline to 10 min after treatment. Secondary outcomes will include the VAS, remedial analgesia, re-visit and admission rate, blinding assessment, credibility and expectancy, and adverse event. All patients who receive randomization will be included in the intent-to-treat analysis.

Discussion

The finding of this trial will provide evidence on the efficacy and safety of acupuncture for the treatment of ARCUC. The results of this study will be published in peer-reviewed journals.

Trial registration

ClinicalTrials.gov ChiCTR 1900025202. Registered on August 16, 2019.
Level and factors associated with physical activity among university teacher: an exploratory analysis
Authors: Kwiecień-Jaguś Katarzyna , Mędrzycka-Dąbrowska Wioletta , Kopeć Monika , Piotrkowska Renata , Czyż-Szypenbejl Katarzyna , Hansdorfer-Korzon Rita , Lemska Magdalena , Jarzynkowski Piotr
Published: September 2021

Background

Physical inactivity is one of the primary factors that leads to obesity and overweight. What is more, it is becoming an increasingly common problem among the population of those who work. The causes of obesity and the lack of physical activity are multifactorial. The aims of the study were: to (1) measure the level of physical activity among the university staff, (2) evaluate what factors have a significant influence on undertaking the physical activity and lack of.

Methods

A cross-sectional study was conducted via the Internet questionnaires among university staff in Northern Poland and Pomeranian Region. Taking into consideration the climate and cultural factors in Poland, a physical activity test with the usage of IPAQ scale was performed between September and November 2018 and between March and June 2019. The data was collected on the basis of the standardized long form of the IPQA questionnaire, the GSE Scale and the interview questionnaire including questions about sex, age and health assessment.

Results

The study group consisted of 276 respondents, including 143 women (51.8%) and 133 men (48.2%). The average age of the respondents was 42.22 with SD ± 11.01. The weight status was categorized with the use of BMI index. 51.3% (142) of the respondents had normal body mass, 93 (33.8%) were overweight, while 23 (8.4%) were obese. The mean BMI index was 25.23 points (SD ± 4.04). One hundred and twenty five (45.1%) respondents were the employees of the Medical University, and 54.9% were employed by the Technical University. Detailed analyses using Spearman correlation test confirmed the presence of a statistically higher level of physical activity among respondents employed at the Medical University (M 513.37; SD ± 609.13) than the employees of Technical University (M 378.38; SD ± 328.26). The odds ratio analysis shows that a low level of physical activity in the group of technical university staff has a significant correlation with the other social behavior which is the alcohol consumption.

Conclusion

This study confirms that the number of points obtained in the IPAQ scale, classified the academics in the workgroup presenting low physical activity which does not exceed 600 MET-min/week. The most common form of activity in this group was walking. There was no correlation between physical activity and self-efficacy, age, marital status or the number of children.
Integrative genomics analysis of nasal intestinal-type adenocarcinomas demonstrates the major role of CACNA1C and paves the way for a simple diagnostic tool in male woodworkers
Authors: Gallet Patrice , Oussalah Abderrahim , Pouget Celso , Dittmar Gunnar , Chery Celine , Gauchotte Guillaume , Jankowski Roger , Gueant Jean Louis , Houlgatte Rémi
Published: September 2021

Background

Nasal intestinal-type adenocarcinomas (ITAC) are strongly related to chronic wood dust exposure: The intestinal phenotype relies on CDX2 overexpression but underlying molecular mechanisms remain unknown. Our objectives were to investigate transcriptomic and methylation differences between healthy non-exposed and tumor olfactory cleft mucosae and to compare transcriptomic profiles between non-exposed, wood dust-exposed and ITAC mucosa cells.

Methods

We conducted a prospective monocentric study (NCT0281823) including 16 woodworkers with ITAC, 16 healthy exposed woodworkers and 13 healthy, non-exposed, controls. We compared tumor samples with healthy non-exposed samples, both in transcriptome and in methylome analyses. We also investigated wood dust-induced transcriptome modifications of exposed (without tumor) male woodworkers’ samples and of contralateral sides of woodworkers with tumors. We conducted in parallel transcriptome and methylome analysis, and then, the transcriptome analysis was focused on the genes highlighted in methylome analysis. We replicated our results on dataset GSE17433.

Results

Several clusters of genes enabled the distinction between healthy and ITAC samples. Transcriptomic and IHC analysis confirmed a constant overexpression of CDX2 in ITAC samples, without any specific DNA methylation profile regarding the CDX2 locus. ITAC woodworkers also exhibited a specific transcriptomic profile in their contralateral (non-tumor) olfactory cleft, different from that of other exposed woodworkers, suggesting that they had a different exposure or a different susceptibility. Two top-loci (CACNA1C/CACNA1C-AS1 and SLC26A10) were identified with a hemimethylated profile, but only CACNA1C appeared to be overexpressed both in transcriptomic analysis and in immunohistochemistry.

Conclusions

Several clusters of genes enable the distinction between healthy mucosa and ITAC samples even in contralateral nasal fossa thus paving the way for a simple diagnostic tool for ITAC in male woodworkers. CACNA1C might be considered as a master gene of ITAC and should be further investigated.

Trial registration: NIH ClinicalTrials, NCT0281823, registered May 23d 2016, https://www.clinicaltrials.gov/NCT0281823.
Differences in allergic symptoms after the consumption of egg yolk and egg white
Authors: Uneoka Kei , Horino Satoshi , Ozaki Ayafumi , Aki Haruka , Toda Masako , Miura Katsushi
Published: September 2021

Hen’s eggs are one of the most common causes of food allergy. Although hen’s eggs are known to cause more gastrointestinal symptoms than other foods, it is not known whether there is a difference in organ-specific symptoms between egg yolk (EY) and egg white (EW). The present study aimed to determine whether there are organ-specific differences in the immediate symptoms of EY and EW in patients with hen’s egg allergies. We retrospectively investigated the immediate symptoms and treatment contents of those who had a positive result in an oral food challenge (OFC) of boiled whole EY or 10 g of boiled EW in our hospital from January 2013 to July 2019. We compared 80 patients in the EY-OFC-positive group with 106 patients in the EW-OFC-positive group. The EY-OFC-positive group had significantly fewer respiratory symptoms and significantly more gastrointestinal symptoms than the EW-OFC-positive group and had significantly more gastrointestinal symptoms only. In terms of treatment, significantly fewer patients in the EY-OFC-positive group required beta 2-agonist inhalation, and a significantly higher proportion of patients did not require treatment. Compared to EW, EY is more likely to cause gastrointestinal symptoms and less likely to cause respiratory symptoms. It may be necessary to discriminate between EY and EW allergy during diagnosis.
A semiquantitative color Doppler ultrasound scoring system for evaluation of synovitis in joints of patients with blood-induced arthropathy
Authors: Zhang Ningning , Yang Sheng , Zwagemaker Anne-Fleur , Huo Aihua , Li Ying-Jia , Zhou Fang , Hilliard Pamela , Squire Sandra , Bouskill Vanessa , Mohanta Arun , Zhou Alex , Jarrin Jose , Wu Runhui , Sun Jing , Luke Brian , Moineddin Rahim , Blanchette Victor S. , Peng Yun , Doria  Andrea S.
Published: September 2021

Background

Intra-articular bleeds in patients with inherited bleeding disorders lead to active synovitis which may progress to a chronic state over time. We explored the diagnostic value of color Doppler ultrasound in detecting synovitis in boys with bleeding disorders.

Results

Sixty boys with hemophilia and 3 boys with type 3 von Willebrand disease aged 5 to 18 years (median 12.3 years) were imaged by gray-scale and color Doppler ultrasound (US) in three centers (Beijing, China [n = 22], Guangzhou, China [n = 12] and Toronto, Canada [n = 29])) in this observational study. Images were independently reviewed by two radiologists blinded to clinical data using a subjective semi-quantitative scoring system and objective measurements of synovial thickness and vascularity. Inter-reader reliability for using subjective versus objective color Doppler US methods for assessing synovial vascularity was excellent for the subjective method and moderate/lower range of substantial for the objective method. Agreement between degree of vascularity on color Doppler and extent of synovial hypertrophy on gray-scale US was overall poor for Canada data and moderate for China data. Correlations between degree of vascularity on color Doppler and synovial hypertrophy on gray-scale US, and clinical constructs (total and itemized HJHS scores and total Pettersson X-ray scores) for assessment of blood-induced arthropathy were all poor.

Conclusion

Color Doppler US is a valuable scoring method for evaluating reactive synovitis in joints of subjects with inherited bleeding disorders and holds potential for assessing post-bleed reactive synovitis once further information on its association with timing of the joint bleed becomes available in the literature.
Cost-effectiveness of artificial intelligence aided vessel occlusion detection in acute stroke: an early health technology assessment
Authors: van Leeuwen Kicky G. , Meijer Frederick J. A. , Schalekamp Steven , Rutten Matthieu J. C. M. , van Dijk Ewoud J. , van Ginneken Bram , Govers Tim M. , de Rooij Maarten
Published: September 2021

Background

Limited evidence is available on the clinical impact of artificial intelligence (AI) in radiology. Early health technology assessment (HTA) is a methodology to assess the potential value of an innovation at an early stage. We use early HTA to evaluate the potential value of AI software in radiology. As a use-case, we evaluate the cost-effectiveness of AI software aiding the detection of intracranial large vessel occlusions (LVO) in stroke in comparison to standard care. We used a Markov based model from a societal perspective of the United Kingdom predominantly using stroke registry data complemented with pooled outcome data from large, randomized trials. Different scenarios were explored by varying missed diagnoses of LVOs, AI costs and AI performance. Other input parameters were varied to demonstrate model robustness. Results were reported in expected incremental costs (IC) and effects (IE) expressed in quality adjusted life years (QALYs).

Results

Applying the base case assumptions (6% missed diagnoses of LVOs by clinicians, $40 per AI analysis, 50% reduction of missed LVOs by AI), resulted in cost-savings and incremental QALYs over the projected lifetime (IC: − $156, − 0.23%; IE: + 0.01 QALYs, + 0.07%) per suspected ischemic stroke patient. For each yearly cohort of patients in the UK this translates to a total cost saving of $11 million.

Conclusions

AI tools for LVO detection in emergency care have the potential to improve healthcare outcomes and save costs. We demonstrate how early HTA may be applied for the evaluation of clinically applied AI software for radiology.
Meniscal ramp lesions: an illustrated review
Authors: Taneja Atul K. , Miranda Frederico C. , Rosemberg Laercio A. , Santos Durval C. B.
Published: September 2021

The purpose of this review is to describe the anatomy and lesions affecting the peripheral portion of posterior horn of medial menisci (ramp lesions), along with illustrations and MRI cases. We will correlate imaging features with arthroscopic classification of ramp lesions. Also, postoperative and chronic changes related to meniscocapsular tears will be presented, as well as biomechanical consequences and treatment approach.
Computed tomography-based multiple body composition parameters predict outcomes in Crohn’s disease
Authors: Zhou Ziling , Xiong Ziman , Xie Qingguo , Xiao Peng , Zhang Qingpeng , Gu Jian , Li Jing , Hu Daoyu , Hu Xuemei , Shen Yaqi , Li Zhen
Published: September 2021

Background

The efficacy of computed tomography-based multiple body composition parameters in assessing disease behavior and prognosis has not been comprehensively evaluated in Crohn’s disease. This study aimed to assess the association of body composition parameters with disease behavior and outcomes in Crohn’s disease and to compare the efficacies of indexes derived from body and lumbar spinal heights in body composition analysis.

Results

One hundred twenty-two patients with confirmed Crohn’s disease diagnoses and abdominal computed tomography scans were retrospectively included in this study. Skeletal muscle, visceral, and subcutaneous fat indexes were calculated by dividing each type of tissue area by height2 and lumbar spinal height2. Parameters reflecting the distribution of adiposity were also assessed. Principal component analysis was used to deal with parameters with multicollinearity. Patients were grouped according to their disease behavior (inflammatory vs. structuring/penetrating) and outcomes. Adverse outcome included need for intestinal surgery or anti-TNF therapy. Predictors of disease course from multiple parameters were evaluated using multivariate analysis. Indexes derived from body and lumbar spinal heights were strongly correlated (r, 0.934–0.995; p < 0.001). Low skeletal muscle-related parameters were significantly associated with complicated disease behavior in multivariate analysis (p = 0.048). Complicated disease behavior (p < 0.001) and adipose tissue parameters-related first principal component (p = 0.029) were independent biomarkers for predicting adverse outcomes.

Conclusions

Skeletal muscle and adipose tissue principle component were associated with complicated Crohn’s disease behavior and adverse outcome, respectively. Indexes derived from body and lumbar spinal heights have similar efficacies in body composition analysis.
AKT signaling is associated with epigenetic reprogramming via the upregulation of TET and its cofactor, alpha-ketoglutarate during iPSC generation
Authors: Sekita Yoichi , Sugiura Yuki , Matsumoto Akari , Kawasaki Yuki , Akasaka Kazuya , Konno Ryo , Shimizu Momoka , Ito Toshiaki , Sugiyama Eiji , Yamazaki Terushi , Kanai Eriko , Nakamura Toshinobu , Suematsu Makoto , Ishino Fumitoshi , Kodera Yoshio , Kohda Takashi , Kimura Tohru
Published: September 2021

Background

Phosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival and tumorigenesis. The activation of AKT signaling promotes the cellular reprogramming including generation of induced pluripotent stem cells (iPSCs) and dedifferentiation of primordial germ cells (PGCs). Previous studies suggested that AKT promotes reprogramming by activating proliferation and glycolysis. Here we report a line of evidence that supports the notion that AKT signaling is involved in TET-mediated DNA demethylation during iPSC induction.

Methods

AKT signaling was activated in mouse embryonic fibroblasts (MEFs) that were transduced with OCT4, SOX2 and KLF4. Multiomics analyses were conducted in this system to examine the effects of AKT activation on cells undergoing reprogramming.

Results

We revealed that cells undergoing reprogramming with artificially activated AKT exhibit enhanced anabolic glucose metabolism and accordingly increased level of cytosolic α-ketoglutarate (αKG), which is an essential cofactor for the enzymatic activity of the 5-methylcytosine (5mC) dioxygenase TET. Additionally, the level of TET is upregulated. Consistent with the upregulation of αKG production and TET, we observed a genome-wide increase in 5-hydroxymethylcytosine (5hmC), which is an intermediate in DNA demethylation. Moreover, the DNA methylation level of ES-cell super-enhancers of pluripotency-related genes is significantly decreased, leading to the upregulation of associated genes. Finally, the transduction of TET and the administration of cell-permeable αKG to somatic cells synergistically enhance cell reprogramming by Yamanaka factors.

Conclusion

These results suggest the possibility that the activation of AKT during somatic cell reprogramming promotes epigenetic reprogramming through the hyperactivation of TET at the transcriptional and catalytic levels.
Transplantation of mesenchymal stem cells ameliorates systemic lupus erythematosus and upregulates B10 cells through TGF-β1
Authors: Chun Wang , Tian Jilai , Zhang Ying
Published: September 2021

Background

Considerable experimental and clinical evidences have proved that human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation was powerful in systemic lupus erythematosus (SLE) treatment. MSCs could upregulate regulatory B cells (Bregs) in the mice model of the other immune disease. However, the regulation of MSCs on Bregs in SLE environment remains unclear.

Methods

To assess the abilities of UC-MSCs to treat SLE, MSCs were transferred intravenously to 17- to 18-week-old MRL/lpr mice. Four weeks later, mice were sacrificed. Survival rates, anti-dsDNA antibodies and renal histology were evaluated. CD4+ T helper (Th) cell subgroups and interleukin (IL)-10+ Bregs (B10) in the spleen were quantitated by flow cytometry. The changes of transforming growth factor (TGF)-β1, IL-6 and indoleamine 2,3-dioxyenase (IDO) mRNAs expressed by MSCs after co-cultured with B cells were detected using real-time polymerase chain reaction (RT-PCR). MSCs were infected by lentivirus carrying TGF-β1 shRNAs, then MSCs with low expression of TGF-β1 were conducted for co-culture in vitro and transplantation experiments in vivo.

Results

UC-MSCs transplantation could efficiently downregulate 24 h proteinuria and anti-dsDNA antibodies, correct Treg/Th17/Th1 imbalances and increase the frequency of B10 cells. The expression of TGF-β1 in MSCs was significantly increased after co-culture with B cells. Downregulation of TGF-β1 in MSCs could significantly attenuate the upregulation of B10 by MSCs in vitro and in vivo. Downregulation of TGF-β1 also compromised the immunomodulation effects of MSCs on Th17 and Treg cells and the therapeutic effects of MSC transplantation.

Conclusions

UC-MSCs could protect against SLE in mice and upregulate IL-10+ Bregs via TGF-β1.
GenUI: interactive and extensible open source software platform for de novo molecular generation and cheminformatics
Authors: Sicho M. , Liu X. , Svozil D. , van Westen G. J. P.
Published: September 2021

Many contemporary cheminformatics methods, including computer-aided de novo drug design, hold promise to significantly accelerate and reduce the cost of drug discovery. Thanks to this attractive outlook, the field has thrived and in the past few years has seen an especially significant growth, mainly due to the emergence of novel methods based on deep neural networks. This growth is also apparent in the development of novel de novo drug design methods with many new generative algorithms now available. However, widespread adoption of new generative techniques in the fields like medicinal chemistry or chemical biology is still lagging behind the most recent developments. Upon taking a closer look, this fact is not surprising since in order to successfully integrate the most recent de novo drug design methods in existing processes and pipelines, a close collaboration between diverse groups of experimental and theoretical scientists needs to be established. Therefore, to accelerate the adoption of both modern and traditional de novo molecular generators, we developed Generator User Interface (GenUI), a software platform that makes it possible to integrate molecular generators within a feature-rich graphical user interface that is easy to use by experts of diverse backgrounds. GenUI is implemented as a web service and its interfaces offer access to cheminformatics tools for data preprocessing, model building, molecule generation, and interactive chemical space visualization. Moreover, the platform is easy to extend with customizable frontend React.js components and backend Python extensions. GenUI is open source and a recently developed de novo molecular generator, DrugEx, was integrated as a proof of principle. In this work, we present the architecture and implementation details of GenUI and discuss how it can facilitate collaboration in the disparate communities interested in de novo molecular generation and computer-aided drug discovery.
Lipocalin 2 regulates expression of MHC class I molecules in Mycobacterium tuberculosis-infected dendritic cells via ROS production
Authors: Choi Ji-Ae , Cho Soo-Na , Lee Junghwan , Son Sang-Hun , Nguyen Doan Tam , Lee Seong-Ahn , Song Chang-Hwa
Published: September 2021

Background

Iron has important roles as an essential nutrient for all life forms and as an effector of the host defense mechanism against pathogenic infection. Lipocalin 2 (LCN2), an innate immune protein, plays a crucial role in iron transport and inflammation. In the present study, we examined the role of LCN2 in immune cells duringMycobacterium tuberculosis(Mtb) infection.

Results

We found that infection with Mtb H37Ra induced LCN2 production in bone marrow-derived dendritic cells (BMDCs). Notably, expression of MHC class I molecules was significantly reduced in LCN2−/−BMDCs during Mtb infection. The reduced expression of MHC class I molecules was associated with the formation of a peptide loading complex through LCN2-mediated reactive oxygen species production. The reduced expression of MHC class I molecules affected CD8+T-cell proliferation in LCN2−/−mice infected with Mtb. The difference in the population of CD8+effector T cells might affect the survival of intracellular Mtb. We also found a reduction of the inflammation response, including serum inflammatory cytokines and lung inflammation in LCN2−/−mice, compared with wild-type mice, during Mtb infection.

Conclusions

These data suggest that LCN2-mediated reactive oxygen species affects expression of MHC class I molecules in BMDCs, leading to lower levels of CD8+effector T-cell proliferation during mycobacterial infection.
On some geometric properties for the combination of generalized Lommel–Wright function
Authors: Zayed Hanaa M. , Bulboacă Teodor
Published: September 2021

The scope of our investigation is to study the geometric properties of the normalized form of the combination of generalized Lommel–Wright function $J_{\nu ,\lambda }^{\mu ,m}$

J

ν
,
λ

μ
,
m

defined by $\mathfrak{J}_{\nu ,\lambda }^{\mu ,m}(z):=\Gamma ^{m}(\lambda +1) \Gamma (\lambda +\nu +1)2^{2\lambda +\nu } z^{1-(\nu /2)-\lambda } \mathcal{I}_{\nu ,\lambda }^{\mu ,m}(\sqrt{z})$

J

ν
,
λ

μ
,
m

(
z
)
:
=

Γ
m

(
λ
+
1
)
Γ
(
λ
+
ν
+
1
)

2

2
λ
+
ν

z

1
−
(
ν
/
2
)
−
λ

I

ν
,
λ

μ
,
m

(

z

)
, where $\mathcal{I}_{\nu ,\lambda }^{\mu ,m}(z):=(1-2\lambda -\nu )J_{\nu , \lambda }^{\mu ,m}(z)+z (J_{\nu ,\lambda }^{\mu ,m}(z) )^{ \prime }$

I

ν
,
λ

μ
,
m

(
z
)
:
=
(
1
−
2
λ
−
ν
)

J

ν
,
λ

μ
,
m

(
z
)
+
z

(

J

ν
,
λ

μ
,
m

(
z
)
)

′

and $$ J_{\nu ,\lambda }^{\mu ,m}(z)= \biggl(\frac{z}{2} \biggr)^{2\lambda + \nu } \sum_{n=0}^{\infty } \frac{(-1)^{n}}{\Gamma ^{m} (n+\lambda +1 )\Gamma (n\mu +\nu +\lambda +1 )} \biggl(\frac{z}{2} \biggr)^{2n}, $$

J

ν
,
λ

μ
,
m

(
z
)
=

(

z
2

)

2
λ
+
ν

∑

n
=
0

∞

(
−
1
)

n

Γ
m

(
n
+
λ
+
1
)
Γ
(
n
μ
+
ν
+
λ
+
1
)

(

z
2

)

2
n

,
with $m\in \mathbb{N}$
m
∈
N
, $\mu >0$
μ
>
0
and $\lambda ,\nu \in \mathbb{C}$
λ
,
ν
∈
C
, including starlikeness and convexity of order α ($0\leq \alpha <1$
0
≤
α
<
1
) in the open unit disc using the two-sided inequality for the Fox–Wright functions that has been proved by Pogány and Srivastava in (Comput. Math. Appl. 57(1):127–140, 2009). Further, the orders of starlikeness and convexity are also evaluated using some classical tools. We then compare the orders of starlikeness and convexity given by both techniques to illustrate the efficacy of the approach. In addition, we proved that for some values of α, if $\lambda >-1$
λ
>
−
1
then $\operatorname{Re} (\mathfrak{J}_{\nu ,\lambda }^{\mu ,m}(z)/z )>\alpha $
Re
(

J

ν
,
λ

μ
,
m

(
z
)
/
z
)
>
α
, $z\in \mathbb{U}$
z
∈
U
, and if $\lambda \ge (\sqrt{10}-6 )/4$
λ
≥
(

10

−
6
)
/
4
then the function $(\mathfrak{J}_{\nu ,\lambda }^{\mu ,m}(z^{2})/z )\ast \sin z$
(

J

ν
,
λ

μ
,
m

(

z
2

)
/
z
)
∗
sin
z
is close-to-convex with respect to $1/2\log ((1+z)/(1-z) )$
1
/
2
log
(
(
1
+
z
)
/
(
1
−
z
)
)
where ∗ stands for the Hadamard product (or convolution) of two power series.
A rational delegating computation protocol based on reputation and smart contract
Authors: Ma Juan , Chen Yuling , Wang Ziping , Liu Guoxu , Zhu Hongliang
Published: September 2021

The delegating computation has become an irreversible trend, together comes the pressing need for fairness and efficiency issues. To solve this problem, we leverage game theory to propose a smart contract-based solution. First, according to the behavioral preferences of the participants, we design an incentive contract to describe the motivation of the participants. Next, to satisfy the fairness of the rational delegating computation, we propose a rational delegating computation protocol based on reputation and smart contract. More specifically, rational participants are to gain the maximum utility and reach the Nash equilibrium in the protocol. Besides, we design a reputation mechanism with a reputation certificate, which measures the reputation from multiple dimensions. The reputation is used to assure the client’s trust in the computing party to improve the efficiency of the protocol. Then, we conduct a comprehensive experiment to evaluate the proposed protocol. The simulation and analysis results show that the proposed protocol solves the complex traditional verification problem. We also conduct a feasibility study that involves implementing the contracts in Solidity and running them on the official Ethereum network. Meanwhile, we prove the fairness and correctness of the protocol.
Oncolytic viruses for triple negative breast cancer and beyond
Authors: Jin Shengye , Wang Qin , Wu Hao , Pang Da , Xu Shouping
Published: September 2021

Biological therapy is considered an alternative treatment capable of eliciting the same effects on tumors as surgery, radiotherapy, and chemotherapy. As a major player in biological therapy, oncolytic viruses (OVs) have attracted great attention and achieved good results. Specifically, the successful application of OVs in head and neck cancer, as well as melanoma, promoted its research in triple negative breast cancer (TNBC). TNBC is a high-risk molecular type of breast cancer, characterized by strong invasion, easy recurrence, and metastasis. Due to the absence of estrogen and progesterone receptors, as well as the absence of overexpression or gene amplification of human epidermal growth factor receptor 2 (HER2), endocrine therapy and anti HER-2 targeted therapy have proven ineffective. Although chemotherapy has shown substantial efficacy in some TNBC patients, the occurrence of drug resistance and poor prognosis have prompted the exploration of new and effective treatment methods. The emerging concept of OVs provides a new platform to treat TNBC. Indeed, several studies have confirmed the therapeutic effects of OVs in TNBC. Numerous studies have also investigated the efficacy of OVs in other malignances, including solid tumor clinical trials, thus further demonstrating the promising application of oncolytic virotherapy for TNBC. The primary focus of the current review is the examination of OV mechanisms underlying their antitumor properties, while also summarizing the ongoing progress in OV research regarding TNBC treatment, as well as the various combinatorial strategies comprising OVs and other therapies. We also briefly introduce specific relevant clinical trials and discuss some of the progress in the research of novel OVs for the treatment of other malignancies, thereby affirming the significant therapeutic potential of OVs for the treatment of TNBC, as well as other cancers.