bluuebunny/crossref_metadata_2025 huggingface dataset:
The value of quantitative and a new qualitative color pattern shear wave elastography for the differentiation of ACR TI-RADS 4 or 5 category thyroid nodules measuring ≤10 mm
Authors: Yi Ai-jiao , Yang Wei-Wei , Cui Xin-Wu , Dietrich Christoph F. , Wang Bin
Published: January 2024

Objective

This study aims to evaluate the diagnostic performance of quantitative shear wave elastography (SWE) and a new qualitative color pattern SWE for the differentiation of benign and malignant American College of Radiology Thyroid Imaging, Reporting, and Data System (ACR TI-RADS) 4 or 5 category thyroid nodules measuring ≤10 mm.

Materials and methods

From May 2020 to July 2022, a total of 237 patients with 270 thyroid nodules were enrolled, and conventional ultrasound and SWE examinations were performed for each patient. Each ACR TI-RADS 4 or 5 category thyroid nodule measuring ≤10 mm was evaluated by quantitative SWE and a new qualitative color pattern SWE. The diagnostic performance of quantitative SWE parameters, the new qualitative color pattern SWE, and the combination of SWE with ACR TI-RADS, respectively, for the differentiation of benign and malignant ACR TI-RADS 4 or 5 category thyroid nodules measuring ≤10 mm was evaluated and compared.

Results

Among 270 thyroid nodules in 237 patients, 72 (26.67%) thyroid nodules were benign and 198 (73.33%) thyroid nodules were malignant. The qualitative color pattern SWE showed better diagnostic performance than the quantitative SWE parameters. When combining the qualitative color pattern SWE with ACR TI-RADS scores, with the optimal cutoff value of the total points ≥8, the thyroid nodules were considered malignant. The sensitivity, specificity, accuracy, and AUC were 89.90%, 56.94%, 81.11%, and 0.820 (95% CI: 0.768–0.864), respectively. Compared with using qualitative color pattern SWE alone, the combination of qualitative color pattern SWE and ACR TI-RADS had better diagnostic performance, which was significantly different (p < 0.05).

Conclusion

The combination of qualitative SWE color patterns and ACR TI-RADS had high sensitivity and accuracy, which might be a convenient and useful method to differentiate benign and malignant ACR TI-RADS 4 or 5 category thyroid nodules measuring ≤10 mm. It would be helpful for the management of thyroid nodules and improving prognosis.
Treatment modalities favoring outcome in well-differentiated neuroendocrine tumors G3
Authors: Hinterleitner Martina , Pfeiffer Ruben , Trautwein Nils F. , Sipos Bence , Singer Stephan , Nadalin Silvio , Königsrainer Alfred , Lauer Ulrich M. , la Fougère Christian , Zender Lars , Hinterleitner Clemens
Published: January 2024

Introduction

Neuroendocrine neoplasms (NEN) are a rare and heterogenous group of tumors arising from neuroendocrine cells in multiple organs. Neuroendocrine tumors (NET) G3 encompass a small subgroup accounting for less than 10% of all neuroendocrine neoplasms. In contrast to NET G1 and G2 as well as neuroendocrine carcinomas (NEC), in NET G3 data on treatment and patient outcomes are still limited. Especially in a metastasized tumor stage, the role of surgery, peptide receptor radionucleotide therapy (PRRT), and systemic chemotherapy is not clearly defined.

Methods

In this real-life cohort, we consecutively analyzed clinical outcome in NET G3 patients receiving different diagnostic and treatment.

Results and discussion

We found that even metastasized NET G3 patients undergoing surgery, or receiving radiation, somatostatin analogues (SSA), and PRRT showed a clear survival benefit. Interestingly, all treatment regimen were superior to classical chemotherapeutic agents. In addition, somatostatin receptor (SSTR) PET-CT, FDG PET-CT, and repetitive biopsies were shown to be useful diagnostic and prognostic tools in NET G3. Our study demonstrates that patients with highly proliferative NET G3 might benefit from less aggressive treatment modalities commonly used in low proliferative NEN.
Pre-pregnancy body mass index combined with peripheral blood PLGF, DCN, LDH, and UA in a risk prediction model for pre-eclampsia
Authors: Zhou Yanna , Xiao Chunhai , Yang Yiting
Published: January 2024

Objective

This study analyzes the levels of peripheral blood placental growth factor (PLGF), body mass index (BMI), decorin (DCN), lactate dehydrogenase (LDH), uric acid (UA), and clinical indicators of patients with preeclampsia (PE), and establishes a predictive risk model of PE, which can provide a reference for early and effective prediction of PE.

Methods

81 cases of pregnant women with PE who had regular prenatal checkups and delivered in Jinshan Branch of Shanghai Sixth People’s Hospital from June 2020 to December 2022 were analyzed, and 92 pregnant women with normal pregnancies who had their antenatal checkups and delivered at the hospital during the same period were selected as the control group. Clinical data and peripheral blood levels of PLGF, DCN, LDH, and UA were recorded, and the two groups were subjected to univariate screening and multifactorial logistic regression analysis. Based on the screening results, the diagnostic efficacy of PE was evaluated using the receiver operating characteristic (ROC) curve. Risk prediction nomogram model was constructed using R language. The Bootstrap method (self-sampling method) was used to validate and produce calibration plots; the decision curve analysis (DCA) was used to assess the clinical benefit rate of the model.

Results

There were statistically significant differences in age, pre-pregnancy BMI, gestational weight gain, history of PE or family history, family history of hypertension, gestational diabetes mellitus, and history of renal disease between the two groups (P < 0.05). The results of multifactorial binary logistic stepwise regression revealed that peripheral blood levels of PLGF, DCN, LDH, UA, and pre-pregnancy BMI were independent influences on the occurrence of PE (P < 0.05). The area under the curve of PLGF, DCN, LDH, UA levels and pre-pregnancy BMI in the detection of PE was 0.952, with a sensitivity of 0.901 and a specificity of 0.913, which is better than a single clinical diagnostic indicator. The results of multifactor analysis were constructed as a nomogram model, and the mean absolute error of the calibration curve of the modeling set was 0.023, suggesting that the predictive probability of the model was generally compatible with the actual value. DCA showed the predictive model had a high net benefit in the range of 5% to 85%, suggesting that the model has clinical utility value.

Conclusion

The occurrence of PE is related to the peripheral blood levels of PLGF, DCN, LDH, UA and pre-pregnancy BMI, and the combination of these indexes has a better clinical diagnostic value than a single index. The nomogram model constructed by using the above indicators can be used for the prediction of PE and has high predictive efficacy.
The role of primary cilia in thyroid diseases
Authors: Tian Zijiao , Li Xinlin , Yu Xue , Yan Shuxin , Sun Jingwei , Ma Wenxin , Zhu Xiaoyun , Tang Yang
Published: January 2024

Primary cilia (PC) are non-motile and microtube-based organelles protruding from the surface of almost all thyroid follicle cells. They maintain homeostasis in thyrocytes and loss of PC can result in diverse thyroid diseases. The dysfunction of structure and function of PC are found in many patients with common thyroid diseases. The alterations are associated with the cause, development, and recovery of the diseases and are regulated by PC-mediated signals. Restoring normal PC structure and function in thyrocytes is a promising therapeutic strategy to treat thyroid diseases. This review explores the function of PC in normal thyroid glands. It summarizes the pathology caused by PC alterations in thyroid cancer (TC), autoimmune thyroid diseases (AITD), hypothyroidism, and thyroid nodules (TN) to provide comprehensive references for further study.
Metabolic activity of visceral adipose tissue is associated with age-related macular degeneration: a pilot 18F-FDG PET/CT study
Authors: Choi Kwang-Eon , Joung Chanmin , Pahk Ki Joo , Kim Hyunji , Pahk Kisoo
Published: January 2024

Background

Obesity is known to increase the risk and severity of age-related macular degeneration (AMD). Increased inflamed metabolic activity of visceral adipose tissue (VAT) is considered as a crucial underlying mechanism for the harmful effects of obesity. In this study, we aimed to investigate the inflamed metabolic activity of VAT with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and their association with AMD.

Materials and methods

A total of 57 elderly participants (aged ≥ 50 years) who underwent 18F-FDG PET/CT for health screening and subsequent fundoscopic exam for complaint of recently impaired vision were enrolled. The metabolic activity of VAT was measured from the maximum standardized uptake value (SUVmax) of VAT. The early AMD participant was defined as the participant with either eye satisfying AMD and without any sign of advanced AMD (neovascular AMD or geographic atrophy). The late AMD participant was defined as the participant with either eye satisfying advanced AMD.

Results

VAT SUVmax was highest in participants with late AMD, intermediate in early AMD, and lowest in non-AMD participants. The levels of systemic inflammation surrogate markers were also highest in late AMD group. Furthermore, VAT SUVmax was positively correlated with systemic inflammation surrogate markers and independently associated with the late AMD.

Conclusions

The metabolic activity of VAT evaluated by 18F-FDG PET/CT was associated with the severity of AMD and synchronized with the level of systemic inflammation. Thus, VAT SUVmax could be potentially employed as a surrogate marker of obesity-driven VAT inflammation associated with AMD.
Impact of stress on male fertility: role of gonadotropin inhibitory hormone
Authors: Odetayo Adeyemi F. , Akhigbe Roland E. , Bassey Grace E. , Hamed Moses A. , Olayaki Luqman A.
Published: January 2024

Studies have implicated oxidative stress-sensitive signaling in the pathogenesis of stress-induced male infertility. However, apart from oxidative stress, gonadotropin inhibitory hormone (GnIH) plays a major role. The present study provides a detailed review of the role of GnIH in stress-induced male infertility. Available evidence-based data revealed that GnIH enhances the release of corticosteroids by activating the hypothalamic-pituitary-adrenal axis. GnIH also mediates the inhibition of the conversion of thyroxine (T4) to triiodothyronine (T3) by suppressing the hypothalamic-pituitary-thyroidal axis. In addition, GnIH inhibits gonadotropin-releasing hormone (GnRH), thus suppressing the hypothalamic-pituitary-testicular axis, and by extension testosterone biosynthesis. More so, GnIH inhibits kisspeptin release. These events distort testicular histoarchitecture, impair testicular and adrenal steroidogenesis, lower spermatogenesis, and deteriorate sperm quality and function. In conclusion, GnIH, via multiple mechanisms, plays a key role in stress-induced male infertility. Suppression of GnIH under stressful conditions may thus be a beneficial prophylactic and/or therapeutic strategy.
Joint distribution of lightning and wind speed and its impact on the transmission system
Authors: Xia Yunfeng , Li Bin , Zhou Xuan , Su Sheng
Published: January 2024

Distribution of lightning plays a key role in lightning protection of transmission lines. The design of wind deviation under lightning overvoltage of the transmission tower is an empirical parameter in the transmission line design code. Meteorological data from Hong Kong are investigated to analyze the joint distribution of lightning and wind speed. It has been uncovered that daily cloud-to-ground (CG) flashes follow the Burr distribution, which is highly skewed toward a few days with notable lightning. The lightning and wind follow a Gumbel copula joint distribution. According to empirical and theoretical distribution, there are 239 days with more than 1,000 CG lightning flashes per day, and approximately 20% of these days have a maximum wind speed of approximately or over 15 m/s. In 5 days with the number of CG lightning flashes above 30,000, 3 days have a maximum wind speed of over 15 m/s and the other 2 days have a maximum wind speed of over 10 m/s, which suggests that the severe convection with a squall line contributes much to the likelihood of the days with high wind and lightning storms.
Optimal scheduling of microgrids considering real power losses of grid-connected microgrid systems
Authors: Sun Shengbo , Guo Wei , Wang Qiwei , Tao Peng , Li Gang , Zhao Zhenbing
Published: January 2024

Energy conservation, emission reduction and vigorous development of new energy are inevitable trends in the development of the power industry, but factors such as energy storage loss, solar energy loss and line loss in real power situations have led the problem to a complex direction. To address these intricacies, we use a more precise modeling approach of power loss and propose a collaborative optimization method integrating the Deep-Q-Network (DQN) algorithm with the multi-head attention mechanism. This algorithm calculates weighted features of the system’s states to compute the Q-values and priorities for determining the next operational directives of the energy system. Through extensive simulations that replicate real world microgrid (MG) scenarios, our investigation substantiates that the optimization methodology presented here effectively governs the distribution of energy resources. It accomplishes this while accommodating uncertainty-induced losses, ultimately achieving the economic optimization of MG. This research provides a new approach to deal with problems such as energy loss, which is expected to improve economic efficiency and sustainability in areas such as microgrids.
Enhanced bi-layer scheduling strategies for the cascade hydropower-photovoltaic complementary system using a novel meta-heuristic algorithm
Authors: Shen Li , Wen Yiyu , Wang Qing , Zhang Peng
Published: January 2024

Improving energy efficiency is crucial for China’s power industry to meet global energy conservation and emission reduction goals. The rapid development of photovoltaic (PV) and hydropower has greatly assisted in the construction of China’s novel power system. The stochastic characteristics of PV power generation pose significant challenges to the reliable and economical scheduling of power systems. In fact, the cascade hydropower station can effectively address the issue. To fully utilize the advantages of hydropower, this paper proposes a bi-layer scheduling optimization model for the cascade hydro-PV complementary system considering power market. The upper-layer model simultaneously maximizes the benefit and minimizes the output volatility of the complementary system. The lower-layer model carries out market clearing with the objective of social cost. Besides, PV uncertainty and market price volatility are considered in the decision-making process for power market transactions. To solve the bi-layer model, a novel meta-heuristic algorithm (geometric mean optimizer) is applied, demonstrating excellent performance compared to similar methods. For the complementary system, the results show that its total power output can be improved, and its output volatility can be effectively alleviated.
Evaluating and forecasting methods for assessing the health status of cables under the load of large-scale electric vehicle charging
Authors: Lei He , Rufeng Li , Baofeng Tang , Kaifeng Zhou , Binyu Jia , Lin Xue
Published: January 2024

The assessment of the health status and prediction of the lifespan of cable equipment are critical for ensuring the stability and efficiency of the power grid. This paper develops a temperature-current-capacity-life calculation model for cables, considering the fast and slow charging demands of electric vehicles (EVs). Analyses under scenarios of rapid and slow charging demands are conducted, introducing a cable health index and establishing a health status assessment framework based on this index. The framework accounts for various factors leading to cable faults, offering a comprehensive evaluation of the health status of cables with different fault rates. Building upon this, a prediction method using the Fire Hawk Optimization (FHO) Algorithm and Convolutional Neural Network (CNN) is proposed. This method enhances performance by optimizing the hyperparameters of Bidirectional Gated Recurrent Unit (BiGRU) through FHO, effectively searching and determining the optimal hyperparameter configuration. The impact of different scenarios and varying EV penetration rates on cable temperature is analyzed through case studies, facilitating the assessment and prediction of health status.
Editorial: Enabling technologies and business models for energy communities
Authors: Burgio Alessandro , Jasiński Michał , Leonowicz Zbigniew
Published: January 2024

This Research Topic on “Enabling Technologies and Business Models for Energy Communities” presents a comprehensive exploration of critical facets in the realm of sustainable energy transitions. The Research Topic encompasses diverse topics, ranging from smart energy frameworks for urban communities and off-grid renewable energy deployment in Mexico to the impact of institutional support on the coalbed methane industry. It further investigates complex grid investment decisions, solar-based irrigation adoption in water-scarce regions, and risk management in power supply projects. Additionally, the Research Topic delves into financial aspects, exploring the pricing of Public-Private Partnership (PPP) project Asset-backed Securities (ABS) products, the impact of managerial competence on corporate carbon performance, and equity-based predictions for the energy industry. The influence of innovation on fossil fuel abandonment in low and middle-income countries and the significance of climate risk for green innovation in heavy-polluting industries are also examined. A regional perspective is provided on the technological convergence of hydrogen energy, and the interplay between renewable energy, Gross Domestic Product (GDP), and CO2 emissions in highly-globalized countries is scrutinized. Lastly, the effects of green credit policy on the risk of stocks prices crash are investigated. Together, these contributions offer a holistic understanding of the challenges and opportunities in enabling technologies and business models for energy communities, contributing valuable insights for researchers, policymakers, and industry stakeholders striving for a sustainable energy future.
Satellite derived trends and variability of CO2 concentrations in the Middle East during 2014–2023
Authors: Fonseca Ricardo , Francis Diana
Published: January 2024

The Middle East has major sources of anthropogenic carbon dioxide (CO2) emissions, but a dearth of ground-based measurements precludes an investigation of its regional and temporal variability. This is achieved in this work with satellite-derived estimates from the Orbiting Carbon Observatory-2 (OCO-2) and OCO-3 missions from September 2014 to February 2023. The annual maximum and minimum column (XCO2) concentrations are generally reached in spring and autumn, respectively, with a typical seasonal cycle amplitude of 3–8 ± 0.5 ppmv in the Arabian Peninsula rising to 8–10 ± 1 ppmv in the mid-latitudes. A comparison of the seasonal-mean XCO2 values with the CO2 emissions estimated using the divergence method stresses the role played by the sources and transport of CO2 in the spatial distribution of XCO2, with anthropogenic emissions prevailing in arid and semi-arid regions that lack persistent vegetation. In the 8-year period 2015–2022, the XCO2 concentration in the United Arab Emirates (UAE) increased at a rate of about 2.50 ± 0.04 ppmv/year, with the trend empirical orthogonal function technique revealing a hotspot over northeastern UAE and southern Iran in the summer where anthropogenic emissions peak and accumulate aided by low-level wind convergence. A comparison of the satellite-derived CO2 concentration with that used to drive climate change models for different emission scenarios in the 8-year period revealed that the concentrations used in the latter is overestimated, with maximum differences exceeding 10 ppmv by 2022. This excess in the amount of CO2 can lead to an over-prediction of the projected increase in temperature in the region, an aspect that needs to be investigated further. This work stresses the need for a ground-based observational network of greenhouse gas concentrations in the Middle East to better understand its spatial and temporal variability and for the evaluation of remote sensing observations as well as climate models.
Species swarms and their caterpillar colonisers: phylogeny and polyphenols determine host plant specificity in New Guinean Lepidoptera
Authors: Segar Simon T. , Re Jorge Leonardo , Nicholls Louis , Basset Yves , Rota Jadranka , Kaman Ondrej , Sisol Mentap , Gewa Bradley , Dahl Chris , Butterill Phillip , Mezzomo Priscila , Miller Scott E. , Weiblen George , Salminen Juha-Pekka , Novotny Vojtech , Volf Martin
Published: January 2024

The majority of multi-cellular terrestrial life is found in tropical forests and is either an invertebrate or a plant: for decades ecologists have sought to understand why. As global change erodes the list of extant species on our planet quantifying what species remain, along with their origins and ecology, contributes to our ability to preserve ecosystem functioning and resilience. Here we study three feeding guilds of caterpillars (Lepidoptera) and seek to understand the drivers of their diet breadth across four diverse tropical plant genera in Papua New Guinea. Host specificity is central to biodiversity estimates and the resilience of ecological networks. Specifically, we calculate distance-based host specificity in relation to plant phylogenetic relationships alongside chemical and mechanical traits of leaves. In terms of chemical defenses, we focus on the major polyphenol groups, a compound class shared across many plant species. We refine our data exploration using food webs and ordinations to pick out specific traits of relevance to insect host specificity. Our results showed that the degree of specialization for caterpillars took the following order: phylogenetic>polyphenol>mechanical, such that insect specificity was explained best by host phylogeny and polyphenol chemistry in our study system. Leaf mining insects had higher host specificity than those feeding externally. Of the traits studied hexahydroxydiphenoyl derivatives, galloyl derivatives, trichome density, quinic acid derivatives, myricetins and successional index explained the most variation in overall insect community structure. Our findings build on earlier studies of New Guinean rainforest communities and add a mechanistic explanation to previous findings that host genera are functional islands for insect herbivores. Further, we demonstrate that different plant genera combine different defensive traits that appear to drive associated insect diversity. Our approach integrates trait data and phylogeny to explore dimensions of specialization and we welcome metabolomic studies that will provide more detailed explanations for insect-herbivore host use. Finally, chemical diversity is directly linked to organismal diversity and by studying a range of insect herbivore guilds we make a connection between feeding ecology and specialization that will help to predict species interactions and, potentially, the persistence of ecological networks.
Vicissitudes and prospects of green roof research: a two-decade systematic bibliometric review
Authors: Xie Chunping , Liu Dawei , Jim C. Y.
Published: January 2024

Urban green roofs have emerged as an innovative nature-based solution for enhancing urban sustainability and resilience. Based on the Web of Science Core Collection database, the scholarly papers on green roofs published in the past two decades were analyzed quantitatively and visualized using bibliometric techniques. The study scope covered research countries, institutions, main journals, crucial authors, highly cited documents, hot topics, and research frontiers. The 3210 publications mined from the bibliographic database on green roofs have increased progressively in the study period, with a significantly faster pace in recent years. The research subjects changed gradually over time, extending into more disciplines and becoming decidedly multidisciplinary. The notable bibliometric features registered a pronounced spatial concentration of research outputs in a small number of countries, regions, research institutions, journals, and researchers, mainly associated with developed metropolises. The number of publications and citation impacts identified the world’s top ten researchers and journals. Well-defined clusters depicted by knowledge graphs indicated a diverse range in the number and strength of inter-node connections for countries, institutions, researchers, and research topics defined by keywords. The research scope focuses on quantifying benefits and costs and optimizing designs to maximize biodiversity, hydrologic, thermal, and energy benefits as urban sustainability and climate-adaptation solutions. Emerging research should enhance biodiversity through optimal plant selection, integrate green roofs with renewable energy systems for sustainability, apply computational tools to enhance designs, evaluate low-cost and locally relevant design options for developing cities, and quantify co-benefits like stormwater reduction and energy savings. Multidisciplinary efforts leveraging simulations, ecosystem services valuation, and participatory community partnerships can advance context-appropriate green roof innovation and evidence-based policymaking to expand adoption in cities worldwide. Quantifying and communicating co-benefits are critical measures to drive wider implementation.
Piezo1 mutant zebrafish as a model of idiopathic scoliosis
Authors: Ramli  , Aramaki Toshihiro , Watanabe Masakatsu , Kondo Shigeru
Published: January 2024

Scoliosis is a condition where the spine curves sideways, unique to humans due to their upright posture. However, the cause of this disease is not well understood because it is challenging to find a model for experimentation. This study aimed to create a model for human idiopathic scoliosis by manipulating the function of mechanosensitive channels called Piezo channels in zebrafish. Zebrafish were chosen because they experience similar biomechanical forces to humans, particularly in relation to the role of mechanical force in scoliosis progression. Here we describe piezo1 and piezo2a are involved in bone formation, with a double knockout resulting in congenital systemic malformations. However, an in-frame mutation of piezo1 led to fully penetrant juvenile-onset scoliosis, bone asymmetry, reduced tissue mineral density, and abnormal intervertebral discs—resembling non-congenital scoliosis symptoms in humans. These findings suggest that functional Piezo channels responding to mechanical forces are crucial for bone formation and maintaining spine integrity, providing insights into skeletal disorders.
Small supernumerary marker chromosomes in prenatal diagnosis—molecular characterization and clinical outcomes
Authors: Joksic Ivana , Toljic Mina , Milacic Iva , Stankovic Andjela , Karadzov Orlic Natasa , Mikovic Zeljko
Published: January 2024

Introduction: Small supernumerary marker chromosomes (sSMCs) are infrequent findings in prenatal diagnostics, however they pose a great challenge for prenatal genetic counseling.

Methods: We report prenatal 12 sSMC cases detected in a single center during 10 years period, their molecular characterization by fluorescence in situ hybridization (FISH) or chromosomal microarray (CMA). Those cases were found among 9620 prenatal diagnostic analyzes by GTG-banding technique. In selected cases, additional UPD testing was also done.

Results: Incidence of sSMCs in our study was 0.12%. sSMC characterization was done by FISH in 9 cases, in the remainder of three CMA was employed. The most common sSMC shape was centric minute, followed by inverted duplication and one case with ring conformation. sSMCs originating from acrocentric chromosomes (chromosomes 14, 21 and 22), sex chromosomes (X, Y) and non-acrocentric autosomal chromosomes (chromosome 4 and 18) were confirmed in 3 cases each; no result could be obtained in 3 further cases.

Discussion: No anomalies were detected by prenatal ultrasound in any of the cases. In 58% of the cases, outcome was reported as normal at birth, while anomalies at birth were described in one case. Only two patients opted for pregnancy termination. Preterm labor occurred in case of twin pregnancy resulting in stillbirth and early neonatal death of twins. Overall, our study highlights the importance of a sSMC characterization by molecular cytogenomic methods in order to make appropriate genotype-phenotype correlations and ensure adequate genetic counseling.
ACCESS: an empirically-based framework developed by the International Nursing CASCADE Consortium to address genomic disparities through the nursing workforce
Authors: Katapodi Maria C. , Pedrazzani Carla , Barnoy Sivia , Dagan Efrat , Fluri Muriel , Jones Tarsha , Kim Sue , Underhill-Blazey Meghan L. , Uveges Melissa K. , Dwyer Andrew A.
Published: January 2024

Introduction: Efforts are needed across disciplines to close disparities in genomic healthcare. Nurses are the most numerous trained healthcare professionals worldwide and can play a key role in addressing disparities across the continuum of care. ACCESS is an empirically-based theoretical framework to guide clinical practice in order to ameliorate genomic disparities.

Methods: The framework was developed by the International Nursing CASCADE Consortium based on evidence collected between 2005 and 2023 from individuals and families of various ethnic backgrounds, with diverse hereditary conditions, and in different healthcare systems, i.e., Israel, Korea, Switzerland, and several U.S. States. The components of the framework were validated against published scientific literature.

Results: ACCESS stands for Advocating, Coping, Communication, cascadE Screening, and Surveillance. Each component is demonstrated in concrete examples of clinical practice within the scope of the nursing profession related to genomic healthcare. Key outcomes include advocacy, active coping, intrafamilial communication, cascade screening, and lifelong surveillance. Advocacy entails timely identification of at-risk individuals, facilitating referrals to specialized services, and informed decision-making for testing. Active coping enhances lifelong adaptation and management of disease risk. Effective intrafamilial communication of predisposition to hereditary disease supports cascade testing of unaffected at-risk relatives. Lifelong surveillance is essential for identifying recurrence, changes in health status, and disease trajectory for life-threatening and for life-altering conditions.

Discussion: ACCESS provides a standardized, systematic, situational, and unifying guide to practice and is applicable for nursing and for other healthcare professions. When appropriately enacted it will contribute towards equitable access to genomic resources and services.
Determinants of short birth interval among married multiparous women in Chinaksen district, eastern Ethiopia: a case-control study
Authors: Aleye Bekry , Usso Ahmedin Aliyi , Mengistie Bezatu , Dessie Yadeta , Adem Hassen Abdi , Alemu Addisu , Yuya Mohammed , Mohammed Aminu
Published: January 2024

Background

The short birth interval is a common public health issue that affects women's and children's health in sub-Saharan Africa. Despite a higher burden of short birth intervals reported in Ethiopia, there is limited evidence to indicate the primary risk factors, particularly in rural eastern Ethiopia. Therefore, this study assessed the determinants of the short birth interval among married multiparous women in Chinaksen district, Eastern Ethiopia.

Methods

A community-based case-control study was conducted among randomly selected 210 cases and 210 controls from April 01 to June 30, 2019. The total sample size (219 cases and 219 controls) were calculated using Epi-Info software version 7.2. Data were entered using EpiData version 3.1 and analyzed using SPSS version 27, and multivariable logistic regression analyses conducted to identify the determinants of short birth intervals. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to report the strength of association and statistical significance declared at p-value < 0.05.

Results

The women in the young age group (AOR = 2.33, 95% CI: 1.03, 5.26), missed their antenatal care visits (AOR = 2.23, 95% CI: 1.18, 4.21), failed to utilize postpartum contraceptives (AOR = 5.98, 95% CI: 3.62, 9.89), did not attend postnatal care visit (AOR = 1.86, 95% CI: 1.13, 3.05), nonexclusive breastfed (AOR = 4.05, 95% CI: 2.18, 7.52), short and medium period of breastfeeding (AOR = 4.00, 95% CI: 1.34, 12.10) and (AOR = 3.56, 95% CI: 1.62, 7.82), respectively and female sex of preceding child (AOR = 1.92, 95% CI: 1.18, 3.12) were the important risk factors of short birth interval.

Conclusions

Women's age, antenatal care visits, postnatal care attendance, utilization of postpartum contraceptives, exclusive breastfeeding practice, duration of breastfeeding, and sex of the preceding child were the primary predictors of short birth intervals. Improving the utilization of maternal healthcare services in health facilities would be imperative to prevent and reduce short birth intervals, and its negative consequences.
DNases improve effectiveness of antibiotic treatment in murine polymicrobial sepsis
Authors: Willemsen Jan-Fritjof , Wenskus Julia , Lenz Moritz , Rhode Holger , Trochimiuk Madgalena , Appl Birgit , Pagarol-Raluy Laia , Börnigen Daniela , Bang Corinna , Reinshagen Konrad , Herrmann Martin , Elrod Julia , Boettcher Michael
Published: January 2024

Introduction

Neutrophil extracellular traps (NETs) have various beneficial and detrimental effects in the body. It has been reported that some bacteria may evade the immune system when entangled in NETs. Thus, the aim of the current study was to evaluate the effects of a combined DNase and antibiotic therapy in a murine model of abdominal sepsis.

Methods

C57BL/6 mice underwent a cecum-ligation-and-puncture procedure. We used wild-type and knockout mice with the same genetic background (PAD4-KO and DNase1-KO). Mice were treated with (I) antibiotics (Metronidazol/Cefuroxime), (II) DNAse1, or (III) with the combination of both; mock-treated mice served as controls. We employed a streak plate procedure and 16s-RNA analysis to evaluate bacterial translocation and quantified NETs formation by ELISA and immune fluorescence. Western blot and proteomics analysis were used to determine inflammation.

Results

A total of n=73 mice were used. Mice that were genetically unable to produce extended NETs or were treated with DNases displayed superior survival and bacterial clearance and reduced inflammation. DNase1 treatment significantly improved clearance of Gram-negative bacteria and survival rates. Importantly, the combination of DNase1 and antibiotics reduced tissue damage, neutrophil activation, and NETs formation in the affected intestinal tissue.

Conclusion

The combination of antibiotics with DNase1 ameliorates abdominal sepsis. Gram-negative bacteria are cleared better when NETs are cleaved by DNase1. Future studies on antibiotic therapy should be combined with anti-NETs therapies.
HOXA3 functions as the on-off switch to regulate the development of hESC-derived third pharyngeal pouch endoderm through EPHB2-mediated Wnt pathway
Authors: Fu Yingjie , Zhang Xueyan , Wu Haibin , Zhang Pingping , Liu Shoupei , Guo Tingting , Shan Huanhuan , Liang Yan , Chen Honglin , Xie Jinghe , Duan Yuyou
Published: January 2024

Objectives

Normal commitment of the endoderm of the third pharyngeal pouch (3PP) is essential for the development and differentiation of the thymus. The aim of this study was to investigate the role of transcription factor HOXA3 in the development and differentiation of 3PP endoderm (3PPE) from human embryonic stem cells (hESCs).

Methods

The 3PPE was differentiated from hESC-derived definitive endoderm (DE) by mimicking developmental queues with Activin A, WNT3A, retinoic acid and BMP4. The function of 3PPE was assessed by further differentiating into functional thymic epithelial cells (TECs). The effect of HOXA3 inhibition on cells of 3PPE was subsequently investigated.

Results

A highly efficient approach for differentiating 3PPE cells was developed and these cells expressed 3PPE related genes HOXA3, SIX1, PAX9 as well as EpCAM. 3PPE cells had a strong potential to develop into TECs which expressed both cortical TEC markers K8 and CD205, and medullary TEC markers K5 and AIRE, and also promoted the development and maturation of T cells. More importantly, transcription factor HOXA3 not only regulated the differentiation of 3PPE, but also had a crucial role for the proliferation and migration of 3PPE cells. Our further investigation revealed that HOXA3 controlled the commitment and function of 3PPE through the regulation of Wnt signaling pathway by activating EPHB2.

Conclusion

Our results demonstrated that HOXA3 functioned as the on-off switch to regulate the development of hESC-derived 3PPE through EPHB2-mediated Wnt pathway, and our findings will provide new insights into studying the development of 3PP and thymic organ in vitro and in vivo.
Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy
Authors: Alcantara Marice B. , Tang Wilson S. , Wang Dongfang , Kaniowski Damian , Kang Elaine , Dizman Nazli , Chehrazi-Raffle Alexander , Meza Luis , Zengin Zeynep , Hall Jeremy , Hsu JoAnn , Egelston Colt , Moreira Dayson , Horsager Alan , Pal Sumanta K. , Kortylewski Marcin
Published: January 2024

Introduction

Immune checkpoint blockade (ICB) improved clinical outcomes in renal and bladder cancer patients, but the response rates remain limited especially in metastatic disease. While STAT3 transcription factor is well-known master regulator of tumor immune evasion, little is known about the role of STAT3 in the resistance of renal or bladder cancers to immunotherapy.

Methods

To better understand immune alterations associated with ICB resistance, we assessed blood biomarkers in renal cancer patients classified as responders or non-responders to first line nivolumab/ipilimumab immunotherapy.

Results

We observed that non-responders showed elevated levels of proinflammatory mediators, such as IL-1RA, IL-6, IL-8 and to lesser extent IL-10, which are associated with STAT3 activation and tumor immunosuppression. In addition, we found STAT3 activation primarily in circulating myeloid immune cells such as tolerogenic MDSCs. To assess whether STAT3 inhibition within these cell subsets can promote antitumor immune responses and/or enhance sensitivity to ICB in vivo, we used an original antisense oligonucleotide (ASO) strategy for myeloid-cell selective STAT3 knockdown (CpG-STAT3ASO). Our results in syngeneic models of renal and bladder cancers in mice demonstrated potent antitumor activity of CpG-STAT3ASO alone in contrast to PD1 blockade alone in both models. The CpG-STAT3ASO/anti-PD1 combination improved therapeutic efficacy especially against bladder tumors. Therapeutic efficacy correlated with activation of dendritic cells (DCs) and M1 macrophages in the tumor microenvironment, reduced percentages of regulatory T cells (Tregs) and the expansion of CD8 T cells in both tumor models.

Discussion/Conclusion

Our study underscores the potential of using myeloid-cell targeted CpG-STAT3 inhibitors for genitourinary cancer therapy to disrupt tolerogenic signaling, restore immune cell activity and sensitivity to immune checkpoint inhibitors and/or T cell-based immunotherapies.
A zinc metabolism-related gene signature for predicting prognosis and characteristics of breast cancer
Authors: Hong Jinghui , Li Mengxin , Chen Yichang , Du Ye , Song Dong
Published: January 2024

Background

Breast cancer is one of the most serious and prevalent malignancies. Zinc is commonly known to play a crucial role in the development and progression of breast cancer; however, the detailed mechanisms underlying this role are not well understood. This study aimed to develop a zinc metabolism-related gene (ZMRG) signature based on a multi-database study to predict patient prognosis and investigate the relationship between drug therapy response and immune enrichment.

Methods

Data for breast cancer samples from The Cancer Genome Atlas and Gene Expression Omnibus databases were screened for zinc metabolism-related genes using the Molecular Signature Database. Cox and Least Absolute Shrinkage and Selection Operator regressions were performed to construct a ZMRG signature. To assess the predictive performance of the gene signature, Kaplan–Meier analysis and receiver operating characteristic curves were used. Additionally, we utilised single-sample gene set enrichment analysis, the Tumour Immune Estimation Resource, the Genomics of Drug Sensitivity in Cancer database, and the Cancer Therapeutics Response Portal to investigate the association between the tumour microenvironment and drug sensitivity. Quantitative PCR was used to assess the expression of each gene in the signature in breast cancer cell lines and patient samples.

Results

Five ZMRGs were identified (ATP7B, BGLAP, P2RX4, SLC39A11, and TH) and a risk profile was constructed for each. Two risk groups, high- and low-risk, were identified in this way, and the high-risk score subgroups were found to have worse prognosis. This risk profile was validated using the GSE42568 dataset. Tumour microenvironment and drug sensitivity analyses showed that the expression of these five ZMRGs was significantly associated with immune response. The high-risk group showed substantial immune cell infiltration and enrichment of immune pathways, and patients were more sensitive to drugs commonly used in breast cancer.

Conclusion

The ZMRG signature represents a new prognostic predictor for patients with breast cancer, and may also provide new insights into individualised treatment of breast cancer.
J-shaped association of dietary catechins intake with the prevalence of osteoarthritis and moderating effect of physical activity: an American population-based cohort study
Authors: Fu Yuesong , Li Lu , Gao Jing , Wang Fazheng , Zhou Zihan , Zhang Yiwei
Published: January 2024

Background

Catechins are a class of natural compounds with a variety of health benefits, The relationship between catechins and the prevalence of osteoarthritis (OA) is unknown. This study investigated the associations between daily intake of catechins and the prevalence of OA among American adults and assessed the moderating effect of physical activity (PA).

Methods

This study included 10,039 participants from the National Health and Nutrition Examination Survey (2007–2010,2017-2018). The logistic regression, weighted quantile sum (WQS) regression, and restricted cubic spline (RCS) regression models were conducted to explore the associations between daily intake of catechins and the prevalence of OA. Moreover, interaction tests were performed to assess the moderating effect of PA.

Results

After multivariable adjustment, the weighted multivariable logistic regression and RCS regression analyses revealed significant J-shaped non-linear correlations between intakes of epigallocatechin and epigallocatechin 3-gallate had significant associations with the prevalence of OA among in U.S. adults. WQS regression analysis showed that excessive epigallocatechin intake was the most significant risk factor for OA among all subtypes of catechins. In the interaction assay, PA showed a significant moderating effect in the relationship between epigallocatechin intake and OA prevalence.

Conclusions

The intake of gallocatechin and gallocatechin 3-gallate had a significant negative correlation with the prevalence of OA and the dose-response relationship was J-shaped.PA below 150 MET-min/week and the threshold intakes of 32.70mg/d for epigallocatechin and 76.24mg/d for epigallocatechin 3-gallate might be the targets for interventions to reduce the risk of developing OA.
PRMT5 regulates epigenetic changes in suppressive Th1-like iTregs in response to IL-12 treatment
Authors: Jadon Nidhi , Shanthalingam Sudarvili , Tew Gregory N. , Minter Lisa M.
Published: January 2024

Background

Induced regulatory T cells (iTregs) are a heterogeneous population of immunosuppressive T cells with therapeutic potential. Treg cells show a range of plasticity and can acquire T effector-like capacities, as is the case for T helper 1 (Th1)-like iTregs. Thus, it is important to distinguish between functional plasticity and lineage instability. Aplastic anemia (AA) is an autoimmune disorder characterized by immune-mediated destruction of hematopoietic stem and progenitor cells in the bone marrow (BM). Th1-like 1 iTregs can be potent suppressors of aberrant Th1-mediated immune responses such as those that drive AA disease progression. Here we investigated the function of the epigenetic enzyme, protein arginine methyltransferase 5 (PRMT5), its regulation of the iTreg-destabilizing deacetylase, sirtuin 1 (Sirt1) in suppressive Th1-like iTregs, and the potential for administering Th1-like iTregs as a cell-based therapy for AA.

Methods

We generated Th1-like iTregs by culturing iTregs with IL-12, then assessed their suppressive capacity, expression of iTreg suppression markers, and enzymatic activity of PRMT5 using histone symmetric arginine di-methylation (H3R2me2s) as a read out. We used ChIP sequencing on Th1 cells, iTregs, and Th1-like iTregs to identify H3R2me2s-bound genes unique to Th1-like iTregs, then validated targets using CHiP-qPCR. We knocked down PRMT5 to validate its contribution to Th1-like iTreg lineage commitment. Finally we tested the therapeutic potential of Th1-like iTregs using a Th1-mediated mouse model of AA.

Results

Exposing iTregs to the Th1 cytokine, interleukin-12 (IL-12), during early events of differentiation conveyed increased suppressive function. We observed increased PRMT5 enzymatic activity, as measured by H3R2me2s, in Th1-like iTregs, which was downregulated in iTregs. Using ChIP-sequencing we discovered that H3R2me2s is abundantly bound to the Sirt1 promoter region in Th1-like iTregs to negatively regulate its expression. Furthermore, administering Th1-like iTregs to AA mice provided a survival benefit.

Conclusions

Knocking down PRMT5 in Th1-like iTregs concomitantly reduced their suppressive capacity, supporting the notion that PRMT5 is important for the superior suppressive capacity and stability of Th1-like iTregs. Conclusively, therapeutic administration of Th1-like iTregs in a mouse model of AA significantly extended their survival and they may have therapeutic potential.