bluuebunny/crossref_metadata_2025 huggingface dataset:
Barrier Lyapunov function-based adaptive prescribed performance control of the PMSM used in robots with full-state and input constraints
Authors: Song Yankui , Xia Yu , Wang Jiaxu , Li Junyang , Wang Cheng , Han Yanfeng , Xiao Ke
Published: January 2022

The permanent magnet synchronous motor is extensively used in robots due to its superior performances. However, robots mostly operate in unstructured and dynamically changing environments. Therefore, it is urgent and challenging to achieve high-performance control with high security and reliability. This paper investigates an accelerated adaptive fuzzy neural prescribed performance controller for the PMSM to solve chaotic oscillations, prescribed output performance constraint, full-state constraints, input constraints, uncertain time delays, and unknown external disturbances. First, for ensuring the permanent magnet synchronous motor with higher security, faster response speed, and lower tracking error simultaneously, a novel unified prescribed performance log-type barrier Lyapunov function is proposed to handle both prescribed output performance constraint and full-state constraints. Subsequently, a continuous differentiable constraint function-based model is introduced for solving input constraints nonlinearity. The Lyapunov–Krasovskii functions are utilized to compensate the uncertain time delays. Besides, a type-2 sequential fuzzy neural network is exploited to approximate unknown nonlinearities and unknown gain. For the “explosion of complexity” associated with backstepping, a tracking differentiator is integrated into this controller. Furthermore, a speed function is introduced in the backstepping technique for accelerated convergence. On the basis of above works, the accelerated adaptive backstepping controller is achieved. And the presented controller can ensure that all the closed-loop signals are ultimate boundedness, and all state variables are restricted in the prespecified regions and the permanent magnet synchronous motor successfully escapes from chaotic oscillations. Finally, the simulation results verify the effectiveness of the proposed controller.
Cephalic arch stenosis in the arteriovenous fistula: A retrospective analysis of predisposing factors
Authors: Burnett Cameron Thomas , Nicholls Gemma , Swinbank Amy , Hughes Ian , Titus Thomas
Published: January 2022

Background:

Cephalic Arch Stenosis (CAS) is a frequently observed complication in brachiocephalic and radiocephalic arteriovenous fistulae (AVF) associated with high morbidity and healthcare expenditure. The predisposing factors and preventative strategies for CAS remain unclear. Our aim was to examine predisposing factors for CAS development in the AVF.

Methods:

A retrospective case-control study was performed at Gold University Coast Hospital on patients with AVFs created from 2009 to 2018 with ⩾18 months follow-up. CAS was defined as a >50% narrowing on angiographic assessment with clinically significant symptoms (dialysis dysfunction, arm swelling, prolonged bleeding after access).

Results:

About 187 patients with AVF were included in the analysis (36 brachiocephalic, 151 radiocephalic). CAS developed in 22 of 36 (61%) of brachiocephalic AVF and 9 of 151 (6%) of radiocephalic AVFs. Brachiocephalic AVF were ⩾12 times more likely to develop CAS than radiocephalic AVF (Hazard Ratio (HR) 12.7, 95% CI [5.6–28.3], p < 0.001). Each 1 mL/min increase in flow rate through the AVF, correlated with a 0.07% increase in the probability of development of CAS (HR 1.0007, 95% CI [1.0001–1.0012], p = 0.011). Brachiocephalic AVFs with CAS were associated with a higher number of interventional procedures per access-year compared with their non-CAS counterparts (Median [Interquartile range]: 1.76 [0.74, 3.97] vs 0.41 [0.27, 0.67], p = 0.003).

Conclusion:

Brachiocephalic AVF with higher access flow rates are more likely to develop CAS and earlier than radiocephalic AVF, and in a dose dependent fashion. AVF flow rate is a major factor in CAS development within brachiocephalic AVF and has potential utility in surveillance thresholds for prophylactic blood flow reduction procedures. AVFs with CAS are associated with a greater number of interventional procedures per access-year, heralding higher patient morbidity and healthcare expenditure. Further prospective studies will help define an AVF access flow rate threshold in the implementation of prophylactic strategies for CAS.
Mood as medium: Reconstruction and the material speculations of “new heritage”
Authors: Cooper Timothy P.A.
Published: January 2022

If the politics of aspirational construction appeal to the enchantment of infrastructure, reconstruction usually takes as given an environment of post-conflict, natural disaster, or the degradation of systems of preservation or resource management. If construction and conservation are taken as markers of continuity and political stability what does the urge to build again say about those who exert these ideas in advancement of a set of common goals? Shaped through multi-sited ethnography in Pakistan and the United Arab Emirates, this essay explores the mediation of mood and its material speculations. Concepts borrowed from both the preservation of the moving image and digital forms of heritage restoration provide ways of rethinking the place of reconstruction and coming to a new understanding of its sensual and atmospheric terrain.
Field report: Deployment of a fleet of drones for cloud exploration
Authors: Hattenberger Gautier , Verdu Titouan , Maury Nicolas , Narvor Pierre , Couvreux Fleur , Bronz Murat , Lacroix Simon , Cayez Grègoire , Roberts Gregory C.
Published: January 2022

Drones are commonly used for civil applications and are accessible to those with limited piloting skills in several scenarios. However, the deployment of a fleet in the context of scientific research can lead to complex situations that require an important preparation in terms of logistics, permission to fly from authorities, and coordination during the flights. This paper is a field report of the flight campaign held at the Barbados Island as part of the NEPHELAE project. The main objectives were to fly into trade wind cumulus clouds to understand the microphysical processes involved in their evolution, as well as to provide a proof of concept of sensor-based adaptive navigation patterns to optimize the data collection. After introducing the flight strategy and context of operation, the main challenges and the solutions to address them will be presented, to conclude with the evaluation of some technical evolution developed from these experiments.
Perceived Stress Levels and Associated Factors Among SARS-CoV-2-Affected Young Adults Under Home Isolation—A Cross-Sectional Study From Kerala, India
Authors: Nair Anjana Nalina Kumari Kesavan , Nair Jisharaj Vijayakumari Rajasekharan , Swarnabai Siji Vincent , Sudha Reshma Rajan , Mendez Alice Metilda , Amma Leela Itty
Published: January 2022

Introduction

The impact of SARS-CoV-2 is not only on physical health but also on mental health. This pandemic raised concerns of fear, anxiety, and stress among patients affected with the disease. Quarantine and home isolation might have created psychological distress and helplessness in patients due to social and economic reasons. This study aimed in assessing the level of perceived stress and factors associated with it among SARS-CoV-2-affected young adults who were under home isolation.

Methodology

A cross-sectional study was conducted among 147 SARS-CoV-2-affected young adults who were under home isolation during June 2021 to August 2021. A semi-structured proforma was created using KoBo Toolbox for humanitarian response for data collection. Perceived Stress Scale (PSS-10) was used for measurement of stress among COVID-19 patients. The questionnaire was shared in online platform. Data was analyzed using Statistical Package for Social Sciences version 23.0. Significance of association was tested using chi square test and independent sample t test. Logistic regression was done to predict the factors associated with perceived stress.

Results

Out of the 147 study participants, 56.5% were females and 43.5% were males. Symptoms were present in 94 (63.9%) of patients. The mean age of the study participants was 26 (10.5) years. The mean PSS score was 17.5 (6.4). Among the cases under home isolation, 24.5% had low stress levels, 68% had moderate stress levels, and 7.5% had severe stress levels. Feeling of loneliness during home isolation (odds ratio [OR]: 4.7, 95% confidence interval [CI] [1.9-11.63], P = .008), presence of elderly or under-5 children in the same house (OR: 15.45, 95% CI [2.03-117.5], P = .001), and presence of cough ( P = .05) were found to be significantly associated with higher PSS scores. Age and sleep were negatively correlated with stress score.

Conclusion

One-third of the study participants had moderate to severe levels of perceived stress. Age, sleep hours, presence of cough, presence of under-5 children or elderly in the same house, and feeling of loneliness during home isolation were found to be significantly associated with high perceived stress level scores.
Esterification of naphthenic acids with various structures over tungstophosphoric acid-intercalated layer double hydroxide catalysts with various interlayer spacings
Authors: Wu Yan , He Shiang , Li Dongmei , Li Yang , Wang Hao
Published: January 2022

Tungstophosphoric acid-intercalated MgAl layer double hydroxides (LDHs) are active catalysts for removing naphthenic acids (NAs) from petroleum via esterification. Due to their active sites being in the interlayer, the interlayer spacing of LDHs might affect their activity, particularly for NAs with various structures. Herein, two tungstophosphoric acid-intercalated MgAl LDHs with various interlayer spacings (d003 = 1.46 and 1.07 nm) synthesized by varying the ion-exchange time were used as catalysts for esterification between NAs and ethylene glycol. Six NAs with various side chains and rings were used as model compounds to investigate the effects of NA structures and d003 values on the activity of LDHs. In general, NAs with large molecule sizes and steric hindrances are less reactive over the same catalyst. The LDH with a larger d003 value favours the esterification of NAs regardless of their structure, particularly NAs with large molecule sizes and steric hindrances. However, a large d003 is less effective for esterification of NAs with conjugated carboxyl groups. An enlarged interlayer space might facilitate NA molecules to access the interlayer of LDHs so as to come into contact with the catalytic sites, making this process responsible for the enhanced reactivity. The esterification kinetics of cyclohexanecarboxylic acid over these LDHs follow a first-order reaction. The activation energies for the LDHs with large and small d003 values are 26.25 and 32.18 kJ mol–1, respectively.
Genome-wide association study on 13 167 individuals identifies regulators of blood CD34+cell levels
Authors: Lopez de Lapuente Portilla Aitzkoa , Ekdahl Ludvig , Cafaro Caterina , Ali Zain , Miharada Natsumi , Thorleifsson Gudmar , Žemaitis Kristijonas , Lamarca Arrizabalaga Antton , Thodberg Malte , Pertesi Maroulio , Dhapola Parashar , Bao Erik , Niroula Abhishek , Bali Divya , Norddahl Gudmundur , Ugidos Damboriena Nerea , Sankaran Vijay G. , Karlsson Göran , Thorsteinsdottir Unnur , Larsson Jonas , Stefansson Kari , Nilsson Björn
Published: January 2022

Stem cell transplantation is a cornerstone in the treatment of blood malignancies. The most common method to harvest stem cells for transplantation is by leukapheresis, requiring mobilization of CD34+ hematopoietic stem and progenitor cells (HSPCs) from the bone marrow into the blood. Identifying the genetic factors that control blood CD34+ cell levels could reveal new drug targets for HSPC mobilization. Here we report the first large-scale, genome-wide association study on blood CD34+ cell levels. Across 13 167 individuals, we identify 9 significant and 2 suggestive associations, accounted for by 8 loci (PPM1H, CXCR4, ENO1-RERE, ITGA9, ARHGAP45, CEBPA, TERT, and MYC). Notably, 4 of the identified associations map to CXCR4, showing that bona fide regulators of blood CD34+ cell levels can be identified through genetic variation. Further, the most significant association maps to PPM1H, encoding a serine/threonine phosphatase never previously implicated in HSPC biology. PPM1H is expressed in HSPCs, and the allele that confers higher blood CD34+ cell levels downregulates PPM1H. Through functional fine-mapping, we find that this downregulation is caused by the variant rs772557-A, which abrogates an MYB transcription factor–binding site in PPM1H intron 1 that is active in specific HSPC subpopulations, including hematopoietic stem cells, and interacts with the promoter by chromatin looping. Furthermore, PPM1H knockdown increases the proportion of CD34+ and CD34+90+ cells in cord blood assays. Our results provide the first large-scale analysis of the genetic architecture of blood CD34+ cell levels and warrant further investigation of PPM1H as a potential inhibition target for stem cell mobilization.
Genome-wide DNA methylation analysis in pediatric acute myeloid leukemia
Authors: Yamato Genki , Kawai Tomoko , Shiba Norio , Ikeda Junji , Hara Yusuke , Ohki Kentaro , Tsujimoto Shin-Ichi , Kaburagi Taeko , Yoshida Kenichi , Shiraishi Yuichi , Miyano Satoru , Kiyokawa Nobutaka , Tomizawa Daisuke , Shimada Akira , Sotomatsu Manabu , Arakawa Hirokazu , Adachi Souichi , Taga Takashi , Horibe Keizo , Ogawa Seishi , Hata Kenichiro , Hayashi Yasuhide
Published: January 2022

We investigated genome-wide DNA methylation patterns in 64 pediatric patients with acute myeloid leukemia (AML). Based on unsupervised clustering with the 567 most variably methylated cytosine guanine dinucleotide (CpG) sites, patients were categorized into 4 clusters associated with genetic alterations. Clusters 1 and 3 were characterized by the presence of known favorable prognostic factors, such as RUNX1-RUNX1T1 fusion and KMT2A rearrangement with low MECOM expression, and biallelic CEBPA mutations (all 8 patients), respectively. Clusters 2 and 4 comprised patients exhibiting molecular features associated with adverse outcomes, namely internal tandem duplication of FLT3 (FLT3-ITD), partial tandem duplication of KMT2A, and high PRDM16 expression. Depending on the methylation values of the 1243 CpG sites that were significantly different between FLT3-ITD+ and FLT3-ITD− AML, patients were categorized into 3 clusters: A, B, and C. The STAT5-binding motif was most frequently found close to the 1243 CpG sites. All 8 patients with FLT3-ITD in cluster A harbored high PRDM16 expression and experienced adverse events, whereas only 1 of 7 patients with FLT3-ITD in the other clusters experienced adverse events. PRDM16 expression levels were also related to DNA methylation patterns, which were drastically changed at the cutoff value of PRDM16/ABL1 = 0.10. The assay for transposase-accessible chromatin sequencing of AMLs supported enhanced chromatin accessibility around genomic regions, such as HOXB cluster genes, SCHIP1, and PRDM16, which were associated with DNA methylation changes in AMLs with FLT3-ITD and high PRDM16 expression. Our results suggest that DNA methylation levels at specific CpG sites are useful to support genetic alterations and gene expression patterns of patients with pediatric AML.
GRAde: a long-read sequencing approach to efficiently identifying the CYP11B1/CYP11B2 chimeric form in patients with glucocorticoid-remediable aldosteronism
Authors: Wu Yu-Ching , Chen Chia-I , Chen Peng-Ying , Kuo Chun-Hung , Hung Yi-Hsuan , Peng Kang-Yung , Wu Vin-Cent , Tsai-Wu Jyy-Jih , Hsu Chia-Lang ,   TAIPAI group
Published: January 2022

Background

Glucocorticoid-remediable aldosteronism (GRA) is a form of heritable hypertension caused by a chimeric fusion resulting from unequal crossing over between 11β‐hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), which are two genes with similar sequences. Different crossover patterns of the CYP11B1 and CYP11B2 chimeric genes may be associated with a variety of clinical presentations. It is therefore necessary to develop an efficient approach for identifying the differences between the hybrid genes of a patient with GRA.

Results

We developed a long-read analysis pipeline named GRAde (GRA deciphering), which utilizes the nonidentical bases in the CYP11B1 and CYP11B2 genomic sequences to identify and visualize the chimeric form. We sequenced the polymerase chain reaction (PCR) products of the CYP11B1/CYP11B2 chimeric gene from 36 patients with GRA using the Nanopore MinION device and analyzed the sequences using GRAde. Crossover events were identified for 30 out of the 36 samples. The crossover sites appeared in the region exhibiting high sequence similarity between CYP11B1 and CYP11B2, and 53.3% of the cases were identified as having a gene conversion in intron 2. More importantly, there were six cases for whom the PCR products indicated a chimeric gene, but the GRAde results revealed no crossover pattern. The crossover regions were further verified by Sanger sequencing analysis.

Conclusions

PCR-based target enrichment followed by long-read sequencing is an efficient and precise approach to dissecting complex genomic regions, such as those involved in GRA mutations, which could be directly applied to clinical diagnosis. The scripts of GRAde are available at https://github.com/hsu-binfo/GRAde.
A case for improved assessment of gut permeability: a meta-analysis quantifying the lactulose:mannitol ratio in coeliac and Crohn’s disease
Authors: Gan Jonathan , Nazarian Scarlet , Teare Julian , Darzi Ara , Ashrafian Hutan , Thompson Alex J.
Published: January 2022

Background

A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn’s disease.

Methods

A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn’s disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn’s disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn’s, active Crohn’s, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model.

Results

Pooled LMR in healthy controls was 0.014 (95% CI: 0.006–0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089–0.178) and 0.037 (95% CI: 0.019–0.055). In active and inactive Crohn’s disease, pooled LMRs were 0.093 (95% CI: 0.031–0.156) and 0.028 (95% CI: 0.015–0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783,p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984,p < 0.001), (3) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157,p = 0.001), (4) healthy controls and inactive Crohn’s (SMD = 1.265 95% CI: 0.845 to 1.686,p < 0.001), (5) healthy controls and active Crohn’s (SMD = 2.868 95% CI: 2.112 to 3.623,p < 0.001), and (6) active Crohn’s and inactive Crohn’s (SMD = 1.429 (95% CI: 0.580 to 2.278,p = 0.001). High heterogeneity was observed, which was attributed to variability in protocols used across different studies.

Conclusion

The use of gut permeability measurements in screening and monitoring of coeliac and Crohn’s disease is promising. LMR is useful in performing this function with significant limitations. More robust alternative tests with higher degrees of clinical evidence are needed if measurements of gut permeability are to find widespread clinical use.
Checkpoint inhibitors in metastatic gastric and GEJ cancer: a multi-institutional retrospective analysis of real-world data in a Western cohort
Authors: Schlintl Verena , Huemer Florian , Rinnerthaler Gabriel , Melchardt Thomas , Winder Thomas , Reimann Patrick , Riedl Jakob , Amann Arno , Eisterer Wolfgang , Romeder Franz , Piringer Gudrun , Ilhan-Mutlu Aysegül , Wöll Ewald , Greil Richard , Weiss Lukas
Published: January 2022

Background

Safety and efficacy of immune checkpoint inhibitors in advanced gastric or gastroesophageal junction (GEJ) cancer could be demonstrated in predominantly Asian cohorts, whereas data in Western patients outside of clinical trials are vastly missing.

Methods

In this multi-institutional retrospective analysis conducted at nine oncologic centers in Austria, we tried to assess feasibility of checkpoint inhibitors in advanced gastric/GEJ cancer in a real-world Western cohort.

Results

In total, data from 50 patients with metastatic gastric/GEJ cancer who received nivolumab or pembrolizumab in a palliative setting between November 2015 and April 2020 have been evaluated. The median number of previous palliative therapy lines was two. The median progression-free survival (PFS) and overall survival (OS) were 2.1 (95% CI: 1.4–2.8) and 6.3 (95% CI: 3.3–9.3) months, respectively. There was no statistically significant difference in median OS according to microsatellite or PD-L1 status. However, a trend towards prolonged PFS and OS for the microsatellite instability high subgroup could be observed. Patients with an ECOG Performance Status (PS) ≥ 2 displayed a significantly worse outcome than those with an ECOG PS ≤ 1 (p = .03). Only one patient discontinued immunotherapy due to treatment-related toxicity.

Conclusions

Our results support feasibility of nivolumab and pembrolizumab in pre-treated patients with metastatic gastric and GEJ cancer in a Western real-world cohort. Further phase II/III studies are needed to confirm clinical efficacy.
Assessment of the Cost of the Mediterranean Diet in a Low-Income Region: Adherence and Relationship with Available Incomes
Authors: Rubini Alessia , Vilaplana-Prieto Cristina , Flor-Alemany Marta , Yeguas-Rosa Lorena , Hernández-González Miriam , Félix-García Francisco Javier , Félix-Redondo Francisco Javier , Fernández-Bergés Daniel
Published: January 2022

Background

The Mediterranean Diet (MD) is recognized as heart-healthy, but the economic cost associated with this type of diet has scarcely been studied.

The objective of the present study is to explore the cost and adherence of a low-income region population to the MD and its relationship with income.

Methods

A population-based study was carried out on 2,833 subjects between 25 and 79 years of age, 54% women, selected at random from the municipalities of Vegas Altas, La Siberia and La Serena in the province of Badajoz, Extremadura (Spain).

Average monthly cost of each product included in the MD was computed and related to adherence to the MD using the Panagiotakos Index and average disposable income.

Results

The monthly median cost was 203.6€ (IQR: 154.04-265.37). Food-related expenditure was higher for men (p<0.001), age cohort between 45 and 54 years (p<0.013) and those living in urban areas (p<0.001). A positive correlation between food-related expenditure and the MD adherence was found. Monthly median cost represents 15% of average disposable income, ranging between 11% for the group with low MD adherence and 17% for the group with high MD adherence.

Conclusions

The monthly cost of the MD was positively correlated with the degree of adherence to this dietary pattern. Given that the estimated monthly cost is similar to that of other Spanish regions with a higher income level, the economic effort required to be able to afford the Mediterranean diet is higher. This may represent a barrier to access, which should be analyzed in detail by public decision-makers.
Costs of breast cancer treatment incurred by women in Vietnam
Authors: Ngan Tran Thu , Ngoc Nguyen Bao , Van Minh Hoang , Donnelly Michael , O’Neill Ciaran
Published: January 2022

Background

There is a paucity of research on the cost of breast cancer (BC) treatment from the patient’s perspective in Vietnam.

Methods

Individual-level data about out-of-pocket (OOP) expenditures on use of services were collected from women treated for BC (n = 202) using an online survey and a face-to-face interview at two tertiary hospitals in 2019. Total expenditures on diagnosis and initial BC treatment were presented in terms of the mean, standard deviation, and range for each type of service use. A generalised linear model (GLM) was used to assess the relationship between total cost and socio-demographic characteristics.

Results

19.3% of respondents had stage 0/I BC, 68.8% had stage II, 9.4% had stage III, none had stage IV. The most expensive OOP elements were targeted therapy with mean cost equal to 649.5 million VND ($28,025) and chemotherapy at 36.5 million VND ($1575). Mean total OOP cost related to diagnosis and initial BC treatment (excluding targeted therapy cost) was 61.8 million VND ($2667). The mean OOP costs among patients with stage II and III BC were, respectively, 66 and 148% higher than stage 0/I.

Conclusions

BC patients in Vietnam incur significant OOP costs. The cost of BC treatment was driven by the use of therapies and presentation stage at diagnosis. It is likely that OOP costs of BC patients would be reduced by earlier detection through raised awareness and screening programmes and by providing a higher insurance reimbursement rate for targeted therapy.
LncRNA TP73‐AS1 promotes nasopharyngeal carcinoma progression through targeting miR-342-3p and M2 polarization via exosomes
Authors: Yao Hongchao , Tian Linli , Yan Bingrui , Yang Like , Li Yushan
Published: January 2022

Background

Nasopharyngeal carcinoma (NPC) is a deadly cancer, mainly presenting in southeast and east Asia. Long noncoding RNAs (lncRNAs) play essential roles in cancer progression. Exosomes are critical for intercellular communication. Thus, the aim of this study was to identify the functional lncRNAs in NPC and its relevant mechanisms.

Methods

Data from public databases were utilized to screen for functional lncRNAs in NPC. Functional and mechanical experiments were performed to determine the role of lncRNAs in NPC and its relative molecular mechanisms. Exosomes derived from NPC cells were isolated to determine their function in tumor-associated macrophages.

Results

LncRNA TP73-AS1 was increased in NPC cells and tissues and was associated with a poor prognosis. TP73-AS1 overexpression promoted proliferation, colony formation, and DNA synthesis of NPC cells while TP73-AS1 knockdown showed opposite roles. TP73-AS1 could directly bind with miR-342-3p. MiR-342-3p overexpression attenuated the effect of TP73-AS1 in NPC cells. Furthermore, TP73-AS1 was transferred by exosomes to promote M2 polarization of macrophages. Lastly, exosomal TP73-AS1 enhanced the motility and tube formation of macrophages.

Conclusions

Together, this study suggests that TP73-AS1 promotes NPC progression through targeting miR-342-3p and exosome-based communication with macrophages and that TP73-AS1 might be an emerging biomarker for NPC.
Animal health is often ignored, but indispensable to the human right to health
Authors: Hartnack Sonja
Published: January 2022

Although preventable by vaccines, approximately 60′000 humans die due to canine transmitted rabies annually, mostly in Africa and Asia. The aim of this paper is to advocate for including animal health aspects into considerations of human health and human rights, and for equitable access to rabies vaccination for both animals and humans. An infringement of human - in particular of children’s - right to health will be illustrated with the case of rabies and poor dog management in Uganda.
Self-assembling ferritin nanoparticles coupled with linear sequences from canine distemper virus haemagglutinin protein elicit robust immune responses
Authors: Wang Bo , Li Shuang , Qiao Yongbo , Fu Yu , Nie Jiaojiao , Jiang Shun , Yao Xin , Pan Yi , Zhao Linye , Wu Congmei , Shi Yuhua , Yin Yuhe , Shan Yaming
Published: January 2022

Background

Canine distemper virus (CDV), which is highly infectious, has caused outbreaks of varying scales in domestic and wild animals worldwide, so the development of a high-efficiency vaccine has broad application prospects. Currently, the commercial vaccine of CDV is an attenuated vaccine, which has the disadvantages of a complex preparation process, high cost and safety risk. It is necessary to develop a safe and effective CDV vaccine that is easy to produce on a large scale. In this study, sequences of CDV haemagglutinin (HA) from the Yanaka strain were aligned, and three potential linear sequences, termed YaH3, YaH4, and YaH5, were collected. To increase the immunogenicity of the epitopes, ferritin was employed as a self-assembling nanoparticle element. The ferritin-coupled forms were termed YaH3F, YaH4F, and YaH5F, respectively. A full-length HA sequence coupled with ferritin was also constructed as a DNA vaccine to compare the immunogenicity of nanoparticles in prokaryotic expression.

Result

The self-assembly morphology of the proteins from prokaryotic expression was verified by transmission electron microscopy. All the proteins self-assembled into nanoparticles. The expression of the DNA vaccine YaHF in HEK-293T cells was also confirmed in vitro. After subcutaneous injection of epitope nanoparticles or intramuscular injection of DNA YaHF, all vaccines induced strong serum titres, and long-term potency of antibodies in serum could be detected after 84 days. Strong anti-CDV neutralizing activities were observed in both the YaH4F group and YaHF group. According to antibody typing and cytokine detection, YaH4F can induce both Th1 and Th2 immune responses. The results of flow cytometry detection indicated that compared with the control group, all the immunogens elicited an increase in CD3. Simultaneously, the serum antibodies induced by YaH4F and YaHF could significantly enhance the ADCC effect compared with the control group, indicating that the antibodies in the serum effectively recognized the antigens on the cell surface and induced NK cells to kill infected cells directly.

Conclusions

YaH4F self-assembling nanoparticle obtained by prokaryotic expression has no less of an immune effect than YaHF, and H4 has great potential to become a key target for the easy and rapid preparation of epitope vaccines.

Graphical Abstract
Pediatric quality of life multidimensional fatigue scale (PedsQL-MFS) detects the effects of a 3-week Inpatient body weight reduction program for children and adolescents with obesity
Authors: Smout Matthew F. , Manzoni Gian Mauro , Tamini Sofia , Marazzi Nicoletta , De Col Alessandra , Pietrabissa Giada , Castelnuovo Gianluca , Molinari Enrico , Sartorio Alessandro
Published: January 2022

Background

Fatigue is a frequent complaint amongst children and adolescents with obesity, and it interferes with adherence to dietary and exercise regimes that could reduce obesity. The present study evaluated the effect of an inpatient 3-week body weight reduction program on body weight and fatigue.

Method

One hundred children and adolescents with obesity (64% female; aged 11–18 years) undertook an inpatient program of personalized diet, daily exercise, education, and counselling.

Results

The sample evidenced a mean reduction in body mass (females:ΔM = 4.3 (sd = 2.1) kg,p < .001), males:ΔM = 6.2 (sd = 2.6) kg,p < .001), BMI standard deviation score (females:ΔM = 0.17 (sd = 0.07), males:ΔM = 0.24 (sd = 0.08),p < .001) and fatigue (females:ΔM = 7.8 (sd = 9.7), males:ΔM = 5.0 (sd = 6.9),p < .001) as measured by the Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL-MFS) and improvements on the Attention problems subscale of the Youth Self Report (total sample:ΔM = 0.89 (sd = 2.44),p < .001). Reliable change analyses revealed fatigue changes were achieved by up to 34% females and 17% males, but the majority did not achieve reliable change and changes in fatigue were not correlated with changes in body mass.

Conclusions

The program achieved clinically significant improvements in some children and adolescents. Future studies should explore predictors of treatment responsiveness.

Trial registrationObservational study. Not registered.
Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation
Authors: Dumesic Daniel A. , Padmanabhan Vasantha , Chazenbalk Gregorio D. , Abbott David H.
Published: January 2022

As a common endocrinopathy of reproductive-aged women, polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. It is linked with insulin resistance through preferential abdominal fat accumulation that is worsened by obesity. Over the past two millennia, menstrual irregularity, male-type habitus and sub-infertility have been described in women and confirm that these clinical features of PCOS were common in antiquity. Recent findings in normal-weight hyperandrogenic PCOS women show that exaggerated lipid accumulation by subcutaneous (SC) abdominal stem cells during development to adipocytes in vitro occurs in combination with reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This PCOS phenotype may be an evolutionary metabolic adaptation to balance energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction. This review integrates fundamental endocrine-metabolic changes in healthy, normal-weight PCOS women with similar PCOS-like traits present in animal models in which tissue differentiation is completed during fetal life as in humans to support the evolutionary concept that PCOS has common ancestral and developmental origins.
Incidence of breast cancer subtypes in immigrant and non-immigrant women in Norway
Authors: Hjerkind Kirsti V. , Johansson Anna L. V. , Trewin Cassia B. , Russnes Hege G. , Ursin Giske
Published: January 2022

Background

Breast cancer incidence differs between non-immigrants and immigrants from low- and middle-income countries. This study investigates whether immigrants also have different subtype-specific incidences.

Methods

We used national health registries in Norway and calculated subtype-specific incidence rate ratios (IRRs) for invasive breast cancer among women aged 20–75 and 20–49 years between 2005 and 2015. Immigrant groups were classified by country of birth broadly defined based on WHO regional groupings. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+ PR+ HER2-), luminal B-like/HER2- (ER+ PR- HER2-), luminal B-like/HER2+ (ER+ PR any HER2+), HER2+ (ER-PR-HER2+) and triple-negative breast cancer (TNBC) (ER-PR-HER2-).

Results

Compared to non-immigrants, incidence of the luminal A-like subtype was lower in immigrants from Sub-Saharan Africa (IRR 0.43 95% CI 0.28–0.66), South East Asia (IRR 0.63 95% CI 0.51–0.79), South Asia (IRR 0.67 95% CI 0.52–0.86) and Eastern Europe (IRR 0.86 95% CI 0.76–0.99). Immigrants from South Asia had higher rates of HER2 + tumors (IRR 2.02 95% CI 1.26–3.23). The rates of TNBC tended to be similar regardless of region of birth, except that women from South East Asia had an IRR of 0.54 (95% CI 0.32–0.91).

Conclusions

Women from Eastern Europe, Sub-Saharan Africa and Asia had different subtype-specific incidences compared to women from high-income countries (including non-immigrants). These differences in tumor characteristics between immigrant groups should be taken into consideration when planning preventive or screening strategies.
Luteolin increases susceptibility to macrolides by inhibiting MsrA efflux pump in Trueperella pyogenes
Authors: Guo Yuru , Huang Chengcheng , Su Hongyu , Zhang Zehui , Chen Menghan , Wang Ruxia , Zhang Dexian , Zhang Luyao , Liu Mingchun
Published: January 2022

Trueperella pyogenes (T. pyogenes) is an opportunistic pathogen associated with a variety of diseases in many domestic animals. Therapeutic treatment options for T. pyogenes infections are becoming limited due to antimicrobial resistance, in which efflux pumps play an important role. This study aims to evaluate the inhibitory activity of luteolin, a natural flavonoid, on the MsrA efflux pump and investigate its mechanism. The results of antimicrobial susceptibility testing indicated that the susceptibility of msrA-positive T. pyogenes isolates to six macrolides increased after luteolin treatment, while the susceptibility of msrA-negative isolates showed no change after luteolin treatment. It is suspected that luteolin may increase the susceptibility of T. pyogenes isolates by inhibiting MsrA activity. After 1/2 MIC luteolin treatment for 36 h, the transcription level of the msrA gene and the expression level of the MsrA protein decreased by 55.0–97.7% and 36.5–71.5%, respectively. The results of an affinity test showed that the equilibrium dissociation constant (KD) of luteolin and MsrA was 6.462 × 10–5 M, and hydrogen bonding was predominant in the interaction of luteolin and MsrA. Luteolin may inhibit the ATPase activity of the MsrA protein, resulting in its lack of an energy source. The current study illustrates the effect of luteolin on MsrA in T. pyogenes isolates and provides insight into the development of luteolin as an innovative agent in combating infections caused by antimicrobial-resistant bacteria.
Neurological management and work-up of neurotoxicity associated with CAR T cell therapy
Authors: Möhn Nora , Bonda Viktoria , Grote-Levi Lea , Panagiota Victoria , Fröhlich Tabea , Schultze-Florey Christian , Wattjes Mike P. , Beutel Gernot , Eder Matthias , David Sascha , Körner Sonja , Höglinger Günter , Stangel Martin , Ganser Arnold , Koenecke Christian , Skripuletz Thomas
Published: January 2022

Introduction

Treatment with CD19 chimeric antigen receptor (CAR) T cells is an innovative therapeutic approach for patients with relapsed/refractory diffuse large B cell lymphoma (r/rDLBCL) and B-lineage acute lymphoblastic leukemia (r/rALL). However, convincing therapeutic response rates can be accompanied by cytokine release syndrome (CRS) and severe neurotoxicity termed immune effector cell-associated neurotoxicity syndrome (ICANS).

Methods

Single center, prospective observational study of fifteen consecutive r/r DLBCL patients treated with Tisagenlecleucel within 1 year at Hannover Medical School. Extensive neurological work-up prior to CAR T cell infusion included clinical examination, cognitive testing (Montreal-Cognitive-Assessment), brain MRI, electroencephalogram, electroneurography, and analysis of cerebrospinal fluid. After CAR T cell infusion, patients were neurologically examined for 10 consecutive days. Afterwards, all patients were assessed at least once a week.

Results

ICANS occurred in 4/15 patients (27%) within 6 days (4–6 days) after CAR T cell infusion. Patients with ICANS grade 2 (n = 3) exhibited similar neurological symptoms including apraxia, expressive aphasia, disorientation, and hallucinations, while brain MRI was inconspicuous in either case. Treatment with dexamethasone rapidly resolved the clinical symptoms in all three patients. Regarding baseline parameters prior to CAR T cell treatment, patients with and without ICANS did not differ.

Conclusions

In our cohort, ICANS occurred in only every fourth patient and rather low grade neurotoxicity was found during daily examination. Our results demonstrate that a structured neurological baseline examination and close monitoring are helpful to detect CAR T cell related neurotoxicity already at an early stage and to potentially prevent higher grade neurotoxicity.
Phase II Trial of Inotuzumab Ozogamicin in Children and Adolescents With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia: Children's Oncology Group Protocol AALL1621
Authors: O'Brien Maureen M. , Ji Lingyun , Shah Nirali N. , Rheingold Susan R. , Bhojwani Deepa , Yuan Constance M. , Xu Xinxin , Yi Joanna S. , Harris Andrew C. , Brown Patrick A. , Borowitz Michael J. , Militano Olga , Kairalla John , Devidas Meenakshi , Raetz Elizabeth A. , Gore Lia , Loh Mignon L.
Published: January 2022

PURPOSE

Children's Oncology Group trial AALL1621 was conducted to prospectively determine the safety and efficacy of inotuzumab ozogamicin (InO) in pediatric and adolescent patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS

This single-arm phase II trial enrolled patients age 1-21 years with R/R CD22-positive B-ALL. In cycle 1, InO dosing was 0.8 mg/m2 intravenously on day 1 and 0.5 mg/m2 on days 8 and 15 of a 28-day cycle with response evaluation at day 28. Using a two-stage design, the trial was continuously monitored for dose-limiting toxicities and sinusoidal obstruction syndrome (SOS). CD22 expression was retrospectively evaluated by central flow cytometry.

RESULTS

Forty-eight patients were evaluable for response and toxicity; 19 had complete response (CR) and nine CR with incomplete count recovery (CRi) after cycle 1 (CR/CRi rate: 58.3%; two-sided 90% CI, 46.5 to 69.3). Twenty-seven of 28 patients with CR or CRi had minimal residual disease measured by flow cytometry; 18 (66.7%) had minimal residual disease < 0.01%. Seven of 28 patients (25%) with CR or CRi had delayed count recovery past day 42 in cycle 1. Three (6.3%) patients had grade 3 ALT elevation and one patient had grade 3 hyperbilirubinemia in cycle 1. Of 21 patients undergoing hematopoietic stem-cell transplantation after InO, 6 (28.6%) developed grade 3 SOS. Partial CD22 expression and lower CD22 site density were associated with lower likelihood of response to InO.

CONCLUSION

InO is effective and well tolerated in heavily pretreated children and adolescents with R/R CD22-positive B-ALL. SOS after hematopoietic stem-cell transplantation and prolonged cytopenias were notable. CD22 modulation was identified as a mechanism of resistance. Expanded study of InO combined with chemotherapy is underway.
Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease
Authors: Bleakley Marie , Sehgal Alison , Seropian Stuart , Biernacki Melinda A. , Krakow Elizabeth F. , Dahlberg Ann , Persinger Heather , Hilzinger Barbara , Martin Paul J. , Carpenter Paul A. , Flowers Mary E. , Voutsinas Jenna , Gooley Theodore A. , Loeb Keith , Wood Brent L. , Heimfeld Shelly , Riddell Stanley R. , Shlomchik Warren D.
Published: January 2022

PURPOSE

Graft-versus-host disease (GVHD) causes morbidity and mortality following allogeneic hematopoietic cell transplantation. Naive T cells (TN) cause severe GVHD in murine models. We evaluated chronic GVHD (cGVHD) and other outcomes in three phase II clinical trials of TN-depletion of peripheral blood stem-cell (PBSC) grafts.

METHODS

One hundred thirty-eight patients with acute leukemia received TN-depleted PBSC from HLA-matched related or unrelated donors following conditioning with high- or intermediate-dose total-body irradiation and chemotherapy. GVHD prophylaxis was with tacrolimus, with or without methotrexate or mycophenolate mofetil. Subjects received CD34-selected PBSC and a defined dose of memory T cells depleted of TN. Median follow-up was 4 years. The primary outcome of the analysis of cumulative data from the three trials was cGVHD.

RESULTS

cGVHD was very infrequent and mild (3-year cumulative incidence total, 7% [95% CI, 2 to 11]; moderate, 1% [95% CI, 0 to 2]; severe, 0%). Grade III and IV acute GVHD (aGVHD) occurred in 4% (95% CI, 1 to 8) and 0%, respectively. The cumulative incidence of grade II aGVHD, which was mostly stage 1 upper gastrointestinal GVHD, was 71% (95% CI, 64 to 79). Recipients of matched related donor and matched unrelated donor grafts had similar rates of grade III aGVHD (5% [95% CI, 0 to 9] and 4% [95% CI, 0 to 9]) and cGVHD (7% [95% CI, 2 to 13] and 6% [95% CI, 0 to 12]). Overall survival, cGVHD-free, relapse-free survival, relapse, and nonrelapse mortality were, respectively, 77% (95% CI, 71 to 85), 68% (95% CI, 61 to 76), 23% (95% CI, 16 to 30), and 8% (95% CI, 3 to 13) at 3 years.

CONCLUSION

Depletion of TN from PBSC allografts results in very low incidences of severe acute and any cGVHD, without apparent excess risks of relapse or nonrelapse mortality, distinguishing this novel graft engineering strategy from other hematopoietic cell transplantation approaches.
MRI findings suggestive of Alzheimer’s disease in patients with primary open angle glaucoma – a single sequence analysis using rapid 3D T1 spoiled gradient echo
Authors: Hanafiah Mohammad , Johari Bushra , Ab Mumin Nazimah , Musa Azlan Azha , Hanafiah Hazlenah
Published: January 2022

Objective:

Primary open-angle glaucoma (POAG) is a degenerative optic neuropathy disease which has somewhat similar pathophysiology to Alzheimer’s disease (AD). This study aims to determine the presence of medial temporal atrophy and parietal lobe atrophy in patients with POAG compared to normal controls using medial temporal atrophy (MTA) scoring and posterior cortical atrophy (PCA) scoring system on T1 magnetization-prepared rapid gradient-echo.

Methods:

50 POAG patients and 50 normal subjects were recruited and an MRI brain with T1-magnetization-prepared rapid gradient-echo was performed. Medial temporal lobe and parietal lobe atrophy were by MTA and PCA/Koedam scoring. The score of the PCA and MTA were compared between the POAG group and the controls.

Results:

There was a significant statistical difference between PCA score in POAG and the healthy control group (p-value = 0.026). There is no statistical difference between MTA score in POAG compared to the healthy control group (p-value = 0.58).

Conclusion:

This study suggests a correlation between POAG and PCA score. Potential application of this scoring method in clinical diagnosis and monitoring of POAG patients.

Advances in knowledge:

The scoring method used in AD may also be applied in the diagnosis and monitoring of POAG MRI brain, specifically rapid volumetric T1 spoiled gradient echo sequence, may be applied in POAG assessment.
TIPOLOGIAS DOS PROCESSOS DE COOPERAÇÃO EM GRUPOS DE MICROCRÉDITO: O CASO DO PROGRAMA CREDIAMIGO
Authors: Pontes Matheus Dantas Madeira , Pontes Thayanne Lima Duarte
Published: January 2022

O objetivo do trabalho é identificar a tipologia predominante do processo de cooperação no programa Crediamigo. Por meio de entrevistas em profundidade com diferentes atores da instituição financeira, agência intermediadora e microempresários, constatou-se que o processo de cooperação intencional se sobressai no programa. Os entrevistados ilustraram que há razões estratégicas para o nascimento da cooperação, pois a reputação é o principal critério da seleção de parceiros, e o acesso aos recursos financeiros é o objetivo maior da cooperação e que o relacionamento e a interação entre agentes são os fatores de sucesso do programa. Oportunidades de melhoria para o programa foram identificadas, tais como uma maior atenção para capacitação e orientação dos microempresários participantes, além de fomentar a cooperação intra e intergrupos, para reforçar as capacidades produtivas e competitivas dos negócios. O microcrédito produtivo é essencial para o enfrentamento da vulnerabilidade econômica entre os microempresários, constituindo-se em peça importante para a competitividade empresarial.