bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefícios decorrentes de prática do cuidado farmacêutico em pacientes portadores de diabetes tipo 2: uma revisão sistemática
Authors: Nascimento Denise Sales do , Santos Eliane Bruce dos , Silva Ely Nayra Lopes da , Santos Ícaro da Silva
Published: May 2022

Este estudo aborda os benefícios da prática do cuidado farmacêutico em pacientes portadores de Diabetes Mellitus (DM) tipo 2, uma doença que possui um lento desenvolvimento e longa duração, e que se dá pela intensidade do grau de elevação de açúcar no sangue, que caso não haja tratamento poderá acarretar sérios danos ao organismo humano. Tem como objetivo geral: analisar os benefícios e a importância da atenção farmacêutica junto ao paciente portador da diabetes tipo 2, surgindo a necessidade do farmacêutico na terapia medicamentosa e no tratamento da doença. Para a realização desse trabalho utilizou-se o método de revisão sistemática, de levantamentos contextualizados em banco de dados eletrônicos. Foram utilizadas as palavras-chave: Cuidado Farmacêutico, Diabetes e terapia medicamentosa. Critérios de Inclusão: estudos observacionais e analíticos. Foram excluídos: artigos envolvendo modelos não humanos, processos randomizados. Foram identificados 124 trabalhos, dos quais 63 foram excluídos e 61 selecionados para análise. Inicialmente elegeu-se 23 estudos de interesse, onde 06 estavam foram do foco do estudo, 02 incompletos e 05 em outros idiomas. Foram utilizados 10 estudos tidos como principais e utilizados outros 13 como de apoio argumentativo. Conclui-se que O DM é uma doença socialmente significativa, que causa complicações concomitante com outras complicações afetando a qualidade de vida e laboral do paciente, podendo levar a incapacidade e a morte prematura. A Assistência Farmacêutica visa a prevenção do desenvolvimento de complicações, detecção e controle da DM e acima de tudo o uso racional de medicamentos.
Fatigue strength of Bassi LogicTM and Hyflex EDM endodontic instruments in an artificial canal with an extreme curvature
Authors: Resende Laryssa Coutinho , Maia Caroline Andrade , Santos Alice Machado Carvalho , Campos Gustavo Oliveira , Soares Junior Paulo Roberto Ribeiro , Fernandes Alexandre Moreira
Published: May 2022

The objective of this study was to perform a comparative analysis of the fatigue strength of NiTi instruments in an in vitro model (artificial canal). Ten Hyflex EDM instruments (tip: 10; taper: .05) (Coltene/Whaledent, Altstätten, Switzerland) and ten Bassi LogicTM instruments (tip: 15; taper: .05) (Bassi Endo, Belo Horizonte, Brazil) were used. For the static bending fatigue strength test, we used a stainless-steel artificial canal with a 5-mm curvature radius, 90º curvature, and inner diameter of 1.5 mm. The instruments were run in the artificial canal until the occurrence of fracture. The time was recorded and the number of cycles was calculated. The length of the fragments was measured and three samples from each group were analyzed using scanning electron micrscopy for the characterization of metal fatigue. The data were compared using the nonparametric Man-Whitney test (samples with non-normal distribution), with the significance level set at 5% (p<0.05). Bassi LogicTM instruments tolerated a greater number of cycles compared to the Hyflex EDM (p < 0.05). Significant differences in fragment size were also found between groups (p < 0.05). Mean fragment size was larger among the Hyflex EDM instruments compared to the Bassi LogicTM instruments.The Bassi LogicTM 15.05 exhibited greater fatigue strength in artificial canals with an accentuated curvature compared to Hyflex EDM 10.05.
Curatorial Practice and Public History: Reflections on the ‘World Within Walls’ Exhibition
Authors: NicGhabhann Niamh
Published: May 2022

This essay explores the potential for curatorial practice in a public history context to be engaged as a research practice. It focuses on the development of an exhibition on the history of St Davnet’s Hospital in Monaghan, which first opened as the Monaghan District Lunatic Asylum in 1869. The essay traces the development of this exhibition, and the significance of its location in a local authority museum context. Positioning the exhibition in the context of similar or related public history projects on the subject of psychiatric history, the essay reflects on the processes and practice of curating as a way of generating new insights. In particular, it considers practices of engagement and shared authority that are at the heart of public history practice, as well as contemplating the significance of working with material objects and their associated narratives. This examination of the ‘World Within Walls’ case study identifies curating as a significant research practice that generates new knowledge, rather than as a means of demonstrating or showcasing the results of prior work, particularly in the public history context.
Comparative Study and Possible Phycoremediation of Effluent of JK Pulp and Paper Mill and Select Heavy Metals on Cyanobacteria
Authors: A.P. Tripathy , A. Uma Mahesh , N. Padhi , A.K. Panigrahi
Published: May 2022

Pulp and Paper Mill effluent contains toxic heavy metals like Hg, Cd and Pb. These effluent are deadly toxic to the aquatic organisms as these effluents are discharged into River Nagavalli without biological treatment. The main objective of the present study was to assess the Paper mill effluent: its impact on blue green algae (BGA) and whether BGA can be used for detoxification of the effluent waste water. The contaminated river water contained significant amount of heavy metals. An attempt was made to study the impact of heavy metals like Hg, Cd and Pb present in effluent on BGA/cyanobacterium under laboratory controlled conditions and a strategy was planned to study these heavy metals in combination as mixture. All the heavy metals tested showed stimulation and better growth at sub-lethal concentrations (MAC value) but at higher concentrations heavy metals were deadly toxic. The heavy metals when combined produced higher toxicity. No stimulation in the exposed alga was observed in heavy metal combinations. The algae could remove heavy metals from the effluent of the paper mill. The paper mill effluent though highly toxic but showed better behavior at sub-lethal concentrations towards the cyanobacterium. From the observed data it is evident that Westiellopsis was more tolerant than other BGA tested. This alga has potency to grow under stressful conditions and can be safely used for phycoremediation of paper mill effluent after dilution of the effluent. Along with the tested BGA other aquatic macrophytes in combination can be tried for total biological treatment of paper mill effluent before being discharged into the environment.
CONJUGACY OF SEED PRODUCTIVITY MEADOW CLOVER WITH HERBAGE LODGING
Authors: Zolotarev Vladimir
Published: May 2022

Analysis of the problems of increasing the yield of clover seeds shows that, in relation to fodder perennial grasses, the tasks of selection when breeding new varieties are associated with improving the vegetative development of plants. Fodder use provides for the need to further increase the productivity of phytomass, increase the period of active shoot formation, the predominance of vegetative stems in the structure of the herbage, and others. Such natural or selectively induced features of plant development make it difficult to sow varieties for fodder purposes. The growth and development of red clover, the yield value is greatly influenced by the biological characteristics of varieties, as well as agrometeorological conditions during the formation of generative organs, flowering, seed setting and filling. One of the main factors influencing the yield value is the lodging of the herbage. In modern varieties of meadow clover of an intensive type, during the process of growth and accumulation of vegetative mass, lodging of grass stands of varying degrees is usually observed already by the flowering phase, which negatively affects the formation of seed productivity. The purpose of the research is to study the effect of grass stand lodging on the realization of the seed productivity potential of red clover varieties of early and late ripening types. To solve this problem, vertical clover shoots were artificially formed using a special frame. The degree of lodging of seed grass stands of late-ripening clover under field conditions was 56%, and that of early-ripening clover was 36–39%. With the artificial creation of non-lodging grass stands compared to lodging ones, depending on the prevailing weather conditions, the biological yield of meadow clover seeds of late-ripening type increased by 88%, and in early-ripening — in the range from 31 to 48% due to an increase in the number of inflorescences by 14–27% and seeds in heads by 14–28%. To increase the yield of meadow clover seeds, it is necessary to develop and use a complex of agrotechnical techniques that ensure the formation of non-lodging grass stands with optimal plant density per unit area.
ENERGY AND NUTRITIONAL VALUE OF VARIOUS PERENNIAL GRASSES AND THEIR MIXTURES ON SODDY-PODZOLIC SOILS OF THE UPPER VOLGA REGION
Authors: Esedullaev Sabir
Published: May 2022

As a result of many years of research on the energy and nutritional value of various perennial herbs and their mixtures on soddy-podzolic soil in the Upper Volga region, as well as the calculation of the possible gross milk yield when fed, it has been established that festulolium in a single-species sowing is superior to timothy grass both in control and on the background of mineral nutrition. On average, over five years, its green mass yield was 2.7 more, dry matter by 0.41 t/ha, fodder units and metabolic energy yield by 0.54 thousand/ha and 5.6 GJ/ha in control and 3.7, 0.58 t/ha, 0.75 thousand/ha, 7.3 GJ/ha, respectively, against the background with mineral fertilizers. The productivity of variable alfalfa was higher than that of red clover. In mixed crops, the most productive on both agricultural backgrounds was the grass mixture of alfalfa and festulolium, which surpassed the clover-festulolium mixture in the collection of fodder units by 2.48 thousand/ha, exchange energy — by 31.1 GJ/ha in control, by 2.68 thousand/ha and 12.3 GJ/ha, respectively, against the background of mineral nutrition. Mixtures of alfalfa and clover with festulolium are the most balanced in terms of sugar and protein. Their sugar-protein ratio was 1.63 and 1.04 in the control and 1.60 and 1.30 in the presence of mineral nutrition, and the provision of the feed unit with digestible protein corresponded to the zootechnical norm or was close to it. The highest yield of milk, both in terms of exchange energy and sugar, is provided by a mixture of alfalfa with festulolium — 10750 and 12050 liters in the control and 12287 and 13910 liters against the background of mineral nutrition, the smallest is timothy meadow in a single-species sowing.
Synthesis of High-Molecular-Weight Branched Polyethylene Using a Hybrid “Sandwich” Pyridine-Imine Ni(II) Catalyst
Authors: Ge You , Cai Qi , Wang Yuyin , Gao Jiangang , Chi Yue , Dai Shengyu
Published: May 2022

Most pyridine-imine Ni(II) and Pd(II) catalysts tend to yield low-molecular-weight polyethylene and ethylene-based copolymers in olefin insertion polymerization, as the unilateral axial steric structure of such complexes often cannot provide effective shielding of the metal center. In this study, we synthesized a series of hybrid “semi-sandwich” and “sandwich” type pyridine-imine Ni(II) complexes by incorporating diarylmethyl or dibenzosuberyl groups onto 8-aryl-naphthyl motif. The as-prepared Ni(II) complexes afforded highly branched polyethylene with high molecular weights (level of 105 g/mol), and moderate activities (level of 105 g/(molh)) in ethylene polymerization. Most interestingly, compared to “semi-sandwich” Ni(II) complexes bearing (2-diarylmethyl-8-aryl)naphthyl units, the “full-sandwich” counterpart containing (2-dibenzosuberyl-8-aryl)naphthyl motif was able to produce higher-molecular-weight polyethylene with higher branching density. In addition, the effect of remote non-conjugated electronic substituents in diarylmethyl groups of the Ni(II) system was also observed in ethylene polymerization.
Interference With Redox Homeostasis Through a G6PD-Targeting Self-Assembled Hydrogel for the Enhancement of Sonodynamic Therapy in Breast Cancer
Authors: Huang Cuiqing , Xu Yuan , Wang Duo , Chen Zerong , Fang Weimin , Shi Changzheng , Xiao Zeyu , Luo Liangping
Published: May 2022

Sonodynamics has emerged as a new potential therapy for breast cancer in recent years. However, GSH-mediated redox systems in cancer cells make them tolerable to oxidative stress-related therapy. Herein, in this study, with G6PD, the gatekeeper enzyme of the pentose phosphate pathway, as the regulative target, a self-assembled thermosensitive chitosan-pluronic hydrogel coloaded with ICG (sono-sensitive agent) and RRx-001 (IR@CPGel) was successfully prepared to enhance SDT through interference with redox homeostasis. Both in vitro and in vivo antitumor investigations verified that when integrated with sonodynamic therapy applied in breast cancer treatment, local administration of IR@CPgel could enhance ROS generation under LIFU irradiation and trigger the intrinsic apoptotic pathway of cancer cells, thus effectively inhibiting tumor growth in a safe manner. Moreover, RRx-001 may interfere with redox homeostasis in cancer cells by downregulating G6PD expression. Due to this redox imbalance, proapoptotic signals, such as P21 and P53, were enhanced, and metastasis-related signals, including MMP-2, ZEB1 and HIF-1α, were effectively reduced. Taken together, this work aimed to enhance the efficacy of sonodynamic therapy through local administration of self-assembled IR@CPGel to interfere with redox homeostasis and thus amplify the oxidative stress microenvironment in tumor tissues. In a word, this work provides a new strategy for the SDT enhancement in breast cancer therapy.
Comparative Gut Microbiome in Trachypithecus leucocephalus and Other Primates in Guangxi, China, Based on Metagenome Sequencing
Authors: Que Tengcheng , Pang Xianwu , Huang Hongli , Chen Panyu , Wei Yinfeng , Hua Yiming , Liao Hongjun , Wu Jianbao , Li Shousheng , Wu Aiqiong , He Meihong , Ruan Xiangdong , Hu Yanling
Published: May 2022

The Trachypithecus leucocephalus (white-headed langur) is a highly endangered, karst-endemic primate species, inhabiting the karst limestone forest in Guangxi, Southwest China. How white-headed langurs adapted to karst limestone and special dietary remains unclear. It is the first time to study the correlation between the gut microbiome of primates and special dietary, and environment in Guangxi. In the study, 150 fecal samples are collected from nine primates in Guangxi, China. Metagenomic sequencing is used to analyze and compare the gut microbiome composition and diversity between white-headed langurs and other primates. Our results indicate that white-headed langurs has a higher diversity of microbiome than other primates, and the key microbiome are phylum Firmicutes, class Clostridia, family Lachnospiraceae, and genera Clostridiates and Ruminococcus, which are related to the digestion and degradation of cellulose. Ten genera are significantly more abundant in white-headed langurs and François’ langur than in other primates, most of which are high-temperature microbiome. Functional analysis reveals that energy synthesis-related pathways and sugar metabolism-related pathways are less abundant in white-headed langurs and François’ langur than in other primates. This phenomenon could be an adaptation mechanism of leaf-eating primates to low-energy diet. The gut microbiome of white-headed langurs is related to diet and karst limestone environment. This study could serve as a reference to design conservation breeding, manage conservation units, and determine conservation priorities.
AI Applications and Regulation: Mapping the Regulatory Strata
Authors: Viljanen Mika , Parviainen Henni
Published: May 2022

Many accounts suggest that artificial intelligence (AI) law is still in its infancy with few statutes and other regulatory instruments regulating AI development and use. In this paper, we argue that such accounts are misguided. AI applications exist in a rich regulatory landscape, subject to multiple rules. To demonstrate our claim, we conduct two semi-fictional case studies under Finnish law. In the first case study, we chart the rules that currently would govern and impact AI tool use in recruitment. In the second case study, we map the legal framework for the Finnish COVID-19 contact tracing app. The article makes three contributions to the literature. First, the case studies provide ample evidence that the prevailing orthodoxy misstates the state of AI law. There is AI law on the books and existing laws have a profound impact on AI application design. Second, the mappings provide building material for developing a grounded theory framework for categorizing AI law and its types and modalities, allowing us to formulate a heuristic for understanding AI regulation. We argue that developers and AI application stakeholders should construe AI law as a complex stratigraphy consisting of five layers: data rules that regulate data use, application-specific AI rules that target specific AI applications or application domains, general AI rules that apply to a wide range of AI applications, application-specific non-AI rules that apply to specific activities but not to AI specifically and general non-AI rules that apply generically and across domains. Third, we provide guidance for practitioners for structuring AI compliance processes. We argue that practitioners should keep in mind that the rules and standards differ in their scopes, targets, certainty, and regulatory modalities. Consequently, understanding the AI regulatory landscape requires developing an understanding of multiple rule complexes, their dynamics, and regulatory modalities.
Using Content Coding and Automatic Item Generation to Improve Test Security
Authors: Gierl Mark J. , Shin Jinnie , Firoozi Tahereh , Lai Hollis
Published: May 2022

Automatic item generation (AIG) is the process of using models to generate items using computer technology. AIG is a scalable content development method because it relies on the item model as the unit of analysis which means that it is more efficient and economical compared to traditional item development. But to use the generated items effectively, they must be managed properly. Managing a bank that could include millions of items results in problems related to identifying, organizing, and securing the content. As a result, the challenges inherent to managing item models and generated items warrant a shift in banking methodology where the management task must be accomplished using content coding at the model level. The purpose of our paper is to describe and illustrate methods that use content coding to organize and secure generated items in a bank.
Silent but Not Harmless: A Synonymous SLC5A5 Gene Variant Leading to Dyshormonogenic Congenital Hypothyroidism
Authors: Geysels Romina Celeste , Bernal Barquero Carlos Eduardo , Martín Mariano , Peyret Victoria , Nocent Martina , Sobrero Gabriela , Muñoz Liliana , Signorino Malvina , Testa Graciela , Castro Ricardo Belisario , Masini-Repiso Ana María , Miras Mirta Beatriz , Nicola Juan Pablo
Published: May 2022

Background

Congenital iodide transport defect (ITD) is an uncommon cause of dyshormonogenic congenital hypothyroidism characterized by the absence of active iodide accumulation in the thyroid gland. ITD is an autosomal recessive disorder caused by loss-of-function variants in the sodium/iodide symporter (NIS)-coding SLC5A5 gene.

Objective

We aimed to identify, and if so to functionally characterize, novel ITD-causing SLC5A5 gene variants in a cohort of five unrelated pediatric patients diagnosed with dyshormonogenic congenital hypothyroidism with minimal to absent 99mTc-pertechnetate accumulation in the thyroid gland.

Methods

The coding region of the SLC5A5 gene was sequenced using Sanger sequencing. In silico analysis and functional in vitro characterization of a novel synonymous variant were performed.

Results

Sanger sequencing revealed a novel homozygous synonymous SLC5A5 gene variant (c.1326A>C in exon 11). In silico analysis revealed that the c.1326A>C variant is potentially deleterious for NIS pre-mRNA splicing. The c.1326A>C variant was predicted to lie within a putative exonic splicing enhancer reducing the binding of splicing regulatory trans-acting protein SRSF5. Splicing minigene reporter assay revealed that c.1326A>C causes exon 11 or exon 11 and 12 skipping during NIS pre-mRNA splicing leading to the NIS pathogenic variants p.G415_P443del and p.G415Lfs*32, respectively. Significantly, the frameshift variant p.G415Lfs*32 is predicted to be subjected to degradation by nonsense-mediated decay.

Conclusions

We identified the first exonic synonymous SLC5A5 gene variant causing aberrant NIS pre-mRNA splicing, thus expanding the mutational landscape of the SLC5A5 gene leading to dyshormonogenic congenital hypothyroidism.
Severe 25-Hydroxyvitamin D Deficiency May Predict Poor Renal Outcomes in Patients With Biopsy-Proven Diabetic Nephropathy
Authors: Zhou Ting , Shen Li , Li Ze , Jia Junjie , Xing Haifan , Wang Niansong , Jiao Qiong , Fan Ying
Published: May 2022

Aims

This study aims to investigate the role of 25-hydroxyvitamin D (25(OH)D) levels in predicting renal survival in biopsy-proven diabetic nephropathy (DN) with type 2 diabetes mellitus (DM).

Methods

In this retrospective study, a total of 161 biopsy-proven DN patients were enrolled and divided into four groups (normal group: 25(OH)D>20ng/ml; mild group: 10<25(OH)D ≤ 20ng/ml; moderate group: 5<25(OH)D ≤ 10 ng/ml; severe group: 25(OH)D ≤ 5 ng/ml). The effect of the 25(OH)D level on renal survival was evaluated by multivariate Cox regression.

Results

A total of 161 type 2 DM patients with biopsy-proven DN were enrolled in this study. Patients with lower 25(OH)D levels had higher serum creatinine, urinary albumin creatinine ratio (UACR), total cholesterol, and parathyroid hormone levels as well as lower estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and calcium levels and were more prone to diabetic retinopathy (DR). Rather than proteinuria and renal function, glomerular class and interstitial fibrosis and tubular atrophy (IFTA) had a significant correlation with 25(OH)D levels. Multivariate Cox regression indicated that severe deficiency of 25(OH)D levels was associated with adverse renal outcomes. Compared to the level in the normal group, after adjusting for clinicopathological characteristics, a lower 25(OH)D level remained a risk factor for renal outcomes. The HRs were 3.446 (95% CI 0.366-32.406, p=0.279) for the mild group, 8.009 (95% CI 0.791-81.102, p=0.078) for the moderate group, and 14.957(95%CI 1.364-163.995, P=0.027) for the severe group.

Conclusion

Levels of 25(OH)D less than 5 ng/ml were correlated with worse renal function, more pathological injury and poorer renal prognosis in patients with biopsy-proven DN.
Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies
Authors: Kiyozumi Daiji , Ikawa Masahito
Published: May 2022

The physiological roles of proteolysis are not limited to degrading unnecessary proteins. Proteolysis plays pivotal roles in various biological processes through cleaving peptide bonds to activate and inactivate proteins including enzymes, transcription factors, and receptors. As a wide range of cellular processes is regulated by proteolysis, abnormalities or dysregulation of such proteolytic processes therefore often cause diseases. Recent genetic studies have clarified the inclusion of proteases and protease inhibitors in various reproductive processes such as development of gonads, generation and activation of gametes, and physical interaction between gametes in various species including yeast, animals, and plants. Such studies not only clarify proteolysis-related factors but the biological processes regulated by proteolysis for successful reproduction. Here the physiological roles of proteases and proteolysis in reproduction will be reviewed based on findings using gene-modified organisms.
The Effect of Spontaneous LH Surges on Pregnancy Outcomes in Patients Undergoing Letrozole-HMG IUI: A Retrospective Analysis of 6,285 Cycles
Authors: Jiang Shutian , Chen Li , Gao Yining , Xi Qianwen , Li Wenzhi , Zhao Xinxi , Kuang Yanping
Published: May 2022

Background

To date, no consensus has been reached on whether to wait for spontaneous luteinizing hormone (LH) surge to occur or to trigger ovulation regardless of the presence of an LH surge for achieving higher success rate in intrauterine insemination (IUI) cycles. Therefore, we hope to investigate the effect of the presence of a spontaneous LH surge on pregnancy outcomes in letrozole–human menopausal gonadotropin (LE-HMG) IUI cycles.

Methods

In this retrospective cohort study, a total of 6,285 LE-HMG IUI cycles were included between January 2010 and May 2021. Cycles were categorized into three groups: the trigger + LH surge group, the trigger only group, and the LH surge only group. The primary outcome measure was the clinical pregnancy rate. A logistic regression analysis was performed to explore other risk factors affecting the clinical pregnancy rate.

Results

No significant differences were observed in biochemical pregnancy rate (P =0.640), clinical pregnancy rate (P =0.702), ongoing pregnancy rate (P =0.842), and live birth rate (P =0.951) among the three groups. The binary logistic regression analysis also confirmed that the existence of an LH surge was not associated with clinical pregnancy. There was a difference in ectopic pregnancy rates (P =0.045), but logistic regression showed that the presence of a spontaneous LH surge has no association with ectopic pregnancy. Nonetheless, patients with lead follicles within 18.1-20.0 mm/20.1-22.0 mm and a long duration of LE treatment were less likely to get ectopic pregnant compared with patients with 14.1-16.0 mm lead follicles and shorter LE treatment (OR: 0.142, 95% CI: 0.023–0.891, P =0.037; OR: 0.142, 95% CI: 0.022–0.903, P =0.039; OR: 0.445, 95% CI: 0.235–0.840, P = 0.013).

Conclusions

The presence of a spontaneous LH surge in triggered LE-HMG IUI cycles does not appear to improve pregnancy rates. Thus, we suggest that waiting for an LH surge to occur is not necessary in triggered LE-HMG IUI cycles.
Long-Term Oncological Outcomes of Papillary Thyroid Cancer and Follicular Thyroid Cancer in Children: A Nationwide Population-Based Study
Authors: van de Berg Daniël J. , Kuijpers Anke M. J. , Engelsman Anton F. , Drukker Caroline A. , van Santen Hanneke M. , Terwisscha van Scheltinga Sheila C. E. J. , van Trotsenburg A. S. Paul , Mooij Christiaan F. , Vriens Menno R. , Nieveen van Dijkum Els J. M. , Derikx Joep P. M.
Published: May 2022

Introduction

Pediatric thyroid carcinoma is a rare malignancy and data on long-term oncological outcomes are sparse. The aim of this study was to describe the long-term oncological outcomes of pediatric papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) in a national cohort, and to identify risk factors for recurrence.

Methods

We conducted a nationwide, retrospective cohort study, in which we combined two national databases. Patients aged <18 years, diagnosed with PTC or FTC in the Netherlands between 2000 and 2016, were included. pT-stage, pN-stage, multifocality and angioinvasion were included in a Cox-regression analysis for the identification of risk factors for recurrence.

Results

133 patients were included: 110 with PTC and 23 with FTC. Patients with PTC most often presented with pT2 tumors (24%) and pN1b (45%). During a median follow-up of 11.3 years, 21 patients with PTC developed a recurrence (19%). Nineteen recurrences were regional (91%) and 2 were pulmonary (9%). No risk factors for recurrence could be determined. One patient who developed pulmonary recurrence died two years later. Cause of death was not captured. Patients with FTC most often presented with pT2 tumors (57%). One patient presented with pN1b (4%). In 70%, no lymph nodes were collected. None of the patients with FTC developed a recurrence or died.

Conclusion

Pediatric PTC and FTC are two distinct diseases. Recurrence in pediatric PTC is common, but in FTC it is not. Survival for both pediatric PTC and FTC is very good.
Neutronics and Thermohydraulics Coupling Analysis on Novel Organic Cooled Reactor Based on Single-Channel Model
Authors: Wang Feng , Gu Xinyue , Guan Delun , Dou Wang
Published: May 2022

A conceptual design for a 100 MW(th) organic cooled reactor is proposed with the application of organic fluid HB-40 as a coolant. In order to obtain the axial and radial power distribution, a physical model for the proposed core is developed using the Monte Carlo particle transport code MCNP. Moreover, a single-channel model is developed using multi-physics simulation software COMSOL to calculate the temperature distribution of the fuel elements and corresponding coolant channels. A neutronics-thermohydraulics coupling calculation method is established to couple the MCNP code and COMSOL software by means of mesh mapping and data transfer. Through coupling calculation, the high fidelity power and temperature distribution can be obtained. The key thermohydraulics parameters of the hottest channel in the core are investigated, and the changes after coupling calculation are analyzed. The proposed core design and coupling method can be used as a reference for further optimization of organic cooled reactors.
Quantifying Spatio-Temporal Dynamics of African Dust Detection Threshold for PM10 Concentrations in the Caribbean Area Using Multiscale Decomposition
Authors: Plocoste Thomas , Euphrasie-Clotilde Lovely , Calif Rudy , Brute France-Nor
Published: May 2022

Due to African dust, the Caribbean area is known to have one of the highest incidences of asthma on the planet. Consequently, it is crucial to dissociate the impact of local sources from large scale sources in this region. The aim of this study was to estimate the PM10 detection threshold for dusty events using a statistical approach and a dynamic approach. To carry out this analysis, PM10 time series from Martinique (MAR), Guadeloupe (GPE) and Puerto-Rico (PR) were used between 2006 and 2016. The statistical analysis highlighted that the distance from the African coast is a key feature for PM10 concentrations distribution with the highest at MAR (26.52 μg/m3) and the lowest at PR (24.42 μg/m3). The probability density function analysis showed that MAR-GPE-PR distributions converge towards a same point between the first and the second maximum probability value at 28 μg/m3. The dynamical analysis with the Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) and the Improved CEEMDAN (ICEEMDAN) validated the 28 μg/m3 found with the statistical analysis. The analysis of HYSPLIT back trajectories confirmed this threshold. Thus, our results indicated that 28 μg/m3 is the PM10 detection threshold for African dust in the Caribbean basin. It will therefore be a good indicator allowing the competent authorities to take the appropriate decisions to protect vulnerable populations during dusty events.
Effects of Nutrient Levels on Microbial Diversity in Sediments of a Eutrophic Shallow Lake
Authors: Zhu Weitang , Liu Jing , Li Qihui , Gu Peng , Gu Xiaohui , Wu Lingling , Gao Yang , Shan Jun , Zheng Zheng , Zhang Weizhen
Published: May 2022

Microorganisms can both indicate the water quality characteristics and the health of the aquatic environment, which have an important influence on the cycling of organic carbon, nitrogen (N), and phosphorus (P) in nature. In this study, we took Taihu Lake, a typical eutrophic lake in China, as the research object, and monitored the northern (Changzhou City) and southern (Changxing County) regions of Taihu Lake for three consecutive years (2019–2021), respectively. We also analyzed the microbial diversity in sediments, and then summarized the effects of different nutrient environments on microorganisms in the aquatic environment. The results showed that the pollution level in the northern part of Taihu Lake was higher than that in the southern region of Taihu Lake, where the pollution was mainly in summer (June–July). The pollution in the southern region of Taihu Lake is relatively stable between 2019 and 2021; the changes in the northern part of Taihu Lake are relatively significant. Microbial diversity in the study area was negatively correlated with the degree of eutrophication of water bodies; microbial abundance was positively correlated with nutrient levels. The functional difference analysis indicated that the microorganisms in the sediments of Taihu Lake in the study area were involved in the nutrient transport and transformation, and played an important role in the purification of the lake water body. This study reveals the relationship between water eutrophication and microbial diversity, and then provides a theoretical basis for the management of eutrophic lakes.
DEAD-Box Helicase 27 Triggers Epithelial to Mesenchymal Transition by Regulating Alternative Splicing of Lipoma-Preferred Partner in Gastric Cancer Metastasis
Authors: Jin Yirong , Yang Suzhen , Gao Xiaoliang , Chen Di , Luo Tingting , Su Song , Shi Yanting , Yang Gang , Dong Lei , Liang Jie
Published: May 2022

DEAD-box helicase 27 (DDX27) was previously identified as an important mediator during carcinogenesis, while its role in gastric cancer (GC) is not yet fully elucidated. Here, we aimed to investigate the mechanism and clinical significance of DDX27 in GC. Public datasets were analyzed to determine DDX27 expression profiling. The qRT-PCR, Western blot, and immunohistochemistry analyses were employed to investigate the DDX27 expression in GC cell lines and clinical samples. The role of DDX27 in GC metastasis was explored in vitro and in vivo. Mass spectrometry, RNA-seq, and alternative splicing analysis were conducted to demonstrate the DDX27-mediated molecular mechanisms in GC. We discovered that DDX27 was highly expressed in GCs, and a high level of DDX27 indicated poor prognosis. An increased DDX27 expression could promote GC metastasis, while DDX27 knockdown impaired GC aggressiveness. Mechanically, the LLP expression was significantly altered after DDX27 downregulation, and further results indicated that LPP may be regulated by DDX27 via alternative splicing. In summary, our study indicated that DDX27 contributed to GC malignant progression via a prometastatic DDX27/LPP/EMT regulatory axis.
The Effect of miRNA Gene Regulation on HIV Disease
Authors: Chinniah Romona , Adimulam Theolan , Nandlal Louansha , Arumugam Thilona , Ramsuran Veron
Published: May 2022

Over many years, research on HIV/AIDS has advanced with the introduction of HAART. Despite these advancements, significant gaps remain with respect to aspects in HIV life cycle, with specific attention to virus-host interactions. Investigating virus-host interactions may lead to the implementation of novel therapeutic strategies against HIV/AIDS. Notably, host gene silencing can be facilitated by cellular small non-coding RNAs such as microRNAs paving the way for epigenetic anti-viral therapies. Numerous studies have elucidated the importance of microRNAs in HIV pathogenesis. Some microRNAs can either promote viral infection, while others can be detrimental to viral replication. This is accomplished by targeting the HIV-proviral genome or by regulating host genes required for viral replication and immune responses. In this review, we report on 1) the direct association of microRNAs with HIV infection; 2) the indirect association of known human genetic factors with HIV infection; 3) the regulation of human genes by microRNAs in other diseases that can be explored experimentally to determine their effect on HIV-1 infection; and 4) therapeutic interactions of microRNA against HIV infection.
Unraveling T Cell Responses for Long Term Protection of SARS-CoV-2 Infection
Authors: Wu Dongyuan , Zhang Runzhi , Datta Susmita
Published: May 2022

Due to the COVID-19 pandemic, the global need for vaccines to prevent the disease is imperative. To date, several manufacturers have made efforts to develop vaccines against SARS-CoV-2. In spite of the success of developing many useful vaccines so far, it will be helpful for future vaccine designs, targetting long-term disease protection. For this, we need to know more details of the mechanism of T cell responses to SARS-CoV-2. In this study, we first detected pairwise differentially expressed genes among the healthy, mild, and severe COVID-19 groups of patients based on the expression of CD4+ T cells and CD8+ T cells, respectively. The CD4+ T cells dataset contains 6 mild COVID-19 patients, 8 severe COVID-19 patients, and 6 healthy donors, while the CD8+ T cells dataset has 15 mild COVID-19 patients, 22 severe COVID-19 patients, and 4 healthy donors. Furthermore, we utilized the deep learning algorithm to investigate the potential of differentially expressed genes in distinguishing different disease states. Finally, we built co-expression networks among those genes separately. For CD4+ T cells, we identified 6 modules for the healthy network, 4 modules for the mild network, and 1 module for the severe network; for CD8+ T cells, we detected 6 modules for the healthy network, 4 modules for the mild network, and 3 modules for the severe network. We also obtained hub genes for each module and evaluated the differential connectivity of each gene between pairs of networks constructed on different disease states. Summarizing the results, we find that the following genes TNF, CCL4, XCL1, and IFITM1 can be highly identified with SARS-CoV-2. It is interesting to see that IFITM1 has already been known to inhibit multiple infections with other enveloped viruses, including coronavirus. In addition, our networks show some specific patterns of connectivity among genes and some meaningful clusters related to COVID-19. The results might improve the insight of gene expression mechanisms associated with both CD4+ and CD8+ T cells, expand our understanding of COVID-19 and help develop vaccines with long-term protection.
An Integrated Immune-Related Bioinformatics Analysis in Glioma: Prognostic Signature’s Identification and Multi-Omics Mechanisms’ Exploration
Authors: Fan Xin , Zhang Lingling , Huang Junwen , Zhong Yun , Fan Yanting , Zhou Tong , Lu Min
Published: May 2022

As the traditional treatment for glioma, the most common central nervous system malignancy with poor prognosis, the efficacy of high-intensity surgery combined with radiotherapy and chemotherapy is not satisfactory. The development of individualized scientific treatment strategy urgently requires the guidance of signature with clinical predictive value. In this study, five prognosis-related differentially expressed immune-related genes (PR-DE-IRGs) (CCNA2, HMGB2, CASP3, APOBEC3C, and BMP2) highly associated with glioma were identified for a prognostic model through weighted gene co-expression network analysis, univariate Cox and lasso regression. Kaplan-Meier survival curves, receiver operating characteristic curves and other methods have shown that the model has good performance in predicting the glioma patients’ prognosis. Further combined nomogram provided better predictive performance. The signature’s guiding value in clinical treatment has also been verified by multiple analysis results. We also constructed a comprehensive competing endogenous RNA (ceRNA) regulatory network based on the protective factor BMP2 to further explore its potential role in glioma progression. Numerous immune-related biological functions and pathways were enriched in a high-risk population. Further multi-omics integrative analysis revealed a strong correlation between tumor immunosuppressive environment/IDH1 mutation and signature, suggesting that their cooperation plays an important role in glioma progression.
LRBA Deficiency Can Lead to Lethal Colitis That Is Diminished by SHIP1 Agonism
Authors: Sudan Raki , Fernandes Sandra , Srivastava Neetu , Pedicone Chiara , Meyer Shea T. , Chisholm John D. , Engelman Robert W. , Kerr William G.
Published: May 2022

Humans homozygous for inactivating LRBA (lipopolysaccharide (LPS)-responsive beige-like anchor) mutations or with compound heterozygous mutations exhibit a spectrum of immune-related pathologies including inflammatory bowel disease (IBD). The cause of this pathology remains undefined. Here we show that disruption of the colon epithelial barrier in LRBA-deficient mice by dextran sulfate sodium (DSS) consumption leads to severe and uniformly lethal colitis. Analysis of bone marrow (BM) chimeras showed that susceptibility to lethal colitis is primarily due to LRBA deficiency in the immune compartment and not the gut epithelium. Further dissection of the immune defect in LRBA-deficient hosts showed that LRBA is essential for the expression of CTLA4 by Treg cells and IL22 and IL17 expression by ILC3 cells in the large intestine when the gut epithelium is compromised by DSS. We further show that SHIP1 agonism partially abrogates the severity and lethality of DSS-mediated colitis. Our findings indicate that enteropathy induced by LRBA deficiency has multiple causes and that SHIP1 agonism can partially abrogate the inflammatory milieu in the gut of LRBA-deficient hosts.
Lymphoproliferation in Inborn Errors of Immunity: The Eye Does Not See What the Mind Does Not Know
Authors: Sharma Saniya , Pilania Rakesh Kumar , Anjani Gummadi , Sudhakar Murugan , Arora Kanika , Tyagi Rahul , Dhaliwal Manpreet , Vignesh Pandiarajan , Rawat Amit , Singh Surjit
Published: May 2022

Inborn errors of immunity (IEIs) are a group of heterogeneous disorders characterized by a broad clinical spectrum of recurrent infections and immune dysregulation including autoimmunity and lymphoproliferation (LP). LP in the context of IEI may be the presenting feature of underlying immune disorder or may develop during the disease course. However, the correct diagnosis of LP in IEI as benign or malignant often poses a diagnostic dilemma due to the non-specific clinical features and overlapping morphological and immunophenotypic features which make it difficult to treat. There are morphological clues to LP associated with certain IEIs. A combination of ancillary techniques including EBV-associated markers, flow cytometry, and molecular assays may prove useful in establishing a correct diagnosis in an appropriate clinical setting. The present review attempts to provide comprehensive insight into benign and malignant LP, especially the pathogenesis, histological clues, diagnostic strategies, and treatment options in patients with IEIs.
Advances in the Management of Primary Membranous Nephropathy and Rituximab-Refractory Membranous Nephropathy
Authors: Teisseyre Maxime , Cremoni Marion , Boyer-Suavet Sonia , Ruetsch Caroline , Graça Daisy , Esnault Vincent L. M. , Brglez Vesna , Seitz-Polski Barbara
Published: May 2022

Primary membranous nephropathy (pMN) is an auto-immune disease characterized by auto-antibodies targeting podocyte antigens resulting in activation of complement and damage to the glomerular basement membrane. pMN is the most common cause of nephrotic syndrome in adults without diabetes. Despite a very heterogeneous course of the disease, the treatment of pMN has for many years been based on uniform management of all patients regardless of the severity of the disease. The identification of prognostic markers has radically changed the vision of pMN and allowed KDIGO guidelines to evolve in 2021 towards a more personalized management based on the assessment of the risk of progressive loss of kidney function. The recognition of pMN as an antibody-mediated autoimmune disease has rationalized the use immunosuppressive drugs such as rituximab. Rituximab is now a first line immunosuppressive therapy for patients with pMN with proven safety and efficacy achieving remission in 60-80% of patients. For the remaining 20-40% of patients, several mechanisms may explain rituximab resistance: (i) decreased rituximab bioavailability; (ii) immunization against rituximab; and (iii) chronic glomerular damage. The treatment of patients with rituximab-refractory pMN remains controversial and challenging. In this review, we provide an overview of recent advances in the management of pMN (according to the KDIGO 2021 guidelines), in the understanding of the pathophysiology of rituximab resistance, and in the management of rituximab-refractory pMN. We propose a treatment decision aid based on immunomonitoring to identify failures related to underdosing or immunization against rituximab to overcome treatment resistance.
Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity
Authors: Pande Kalyan , Hollingsworth Scott A. , Sam Miranda , Gao Qinshan , Singh Sujata , Saha Anasuya , Vroom Karin , Ma Xiaohong Shirley , Brazell Tres , Gorman Dan , Chen Shi-Juan , Raoufi Fahimeh , Bailly Marc , Grandy David , Sathiyamoorthy Karthik , Zhang Lan , Thompson Rob , Cheng Alan C. , Fayadat-Dilman Laurence , Geierstanger Bernhard H. , Kingsley Laura J.
Published: May 2022

The SARS-CoV-2 pandemic and particularly the emerging variants have deepened the need for widely available therapeutic options. We have demonstrated that hexamer-enhancing mutations in the Fc region of anti-SARS-CoV IgG antibodies lead to a noticeable improvement in IC50 in both pseudo and live virus neutralization assay compared to parental molecules. We also show that hexamer-enhancing mutants improve C1q binding to target surface. To our knowledge, this is the first time this format has been explored for application in viral neutralization and the studies provide proof-of-concept for the use of hexamer-enhanced IgG1 molecules as potential anti-viral therapeutics.
Increase of Deep Intraepithelial Lymphocytes in the Oxyntic Mucosa of Patients With Potential and Overt Autoimmune Gastritis
Authors: Lenti Marco Vincenzo , Vanoli Alessandro , Miceli Emanuela , Arpa Giovanni , Di Stefano Michele , Soriano Simone , Capuano Francesca , Gentile Antonella , Aronico Nicola , Coppola Luigi , Pasini Alessandra , Luinetti Ombretta , Mauro Aurelio , Paulli Marco , Klersy Catherine , Corazza Gino Roberto , Di Sabatino Antonio
Published: May 2022

Pathological correlates of potential autoimmune gastritis (AIG), defined by anti-parietal cell antibody (PCA) positivity in the absence of gastric atrophy, have never been described. We herein aimed to assess intraepithelial lymphocyte (IEL) infiltration in gastric corpus of AIG patients. From 2000 to 2021, among 53 potential AIG patients, we focused on nine (median age 61 years, IQR 53-82; four females) who subsequently developed overt AIG. IEL infiltration of the oxyntic mucosa was assessed before and after developing overt AIG by measuring deep and superficial CD3+ IEL. AIG patients with different degrees of corpus atrophy, healthy controls (HC), active H. pylori gastritis, celiac disease (CD), and Hashimoto’s thyroiditis patients were included as controls. Of note, deep, but not superficial, CD3+ IEL count was higher (p<0.001) in potential AIG compared to HC and H. pylori gastritis. Deep CD3+ IEL infiltration did not change before or after the evolution into atrophy (median 9.6, IQR 8.8-12.4, vs 11.3, IQR 9.4-12.9). No difference was found in deep CD3+ IEL infiltration among potential, mild, and severe AIG, and compared to Hashimoto’s thyroiditis or CD. A deep CD3+ IEL cut-off of >7/100 epithelial cells allowed discrimination of any AIG stage and severity (AUC=0.842). We conclude that an increased deep CD3+ IEL infiltration of the oxyntic mucosa could represent a marker of potential AIG. Prospective studies including a larger number of potential AIG patients are needed.