bluuebunny/crossref_metadata_2025 huggingface dataset:
Future dry-wet climatic characteristics and drought trends over arid Central Asia
Authors: Cao Linlin , Xu Changchun , Suo Nanji , Song Lingling , Lei Xiaoni
Published: February 2023

Understanding the future drought condition is critical to coping with the challenge of climate change. This study evaluated the simulation capability of 30 Global Climate Models (GCMs) provided by the Coupled Model InterComparison Project Phase 6 (CMIP6) in simulating precipitation (P), potential evapotranspiration (PET) and temperature (T) in arid Central Asia (ACA), and estimated the dry-wet climatic characteristics and trends under four SSP-RCPs (Shared Socio-economic Path-Representative Concentration Path scenarios, SSP126, SSP245, SSP370, and SSP585). Results show that the 30 CMIP6 GCMs have robust simulation ability for precipitation, potential evapotranspiration, and temperature (p < 0.01) over arid Central Asia. The delta-corrected multi-model ensemble mean (Delta-MME) outperforms GWR-corrected one (GWR-MME) and single models. In the future, the precipitation, potential evapotranspiration, and temperature will increase at different rates under the four SSP-RCPs. Uzbekistan, Kazakhstan, Kyrgyzstan and Tajikistan are the regions with faster precipitation and temperature rise, and the northern of arid Central Asia are the main area with the rapid growth of potential evapotranspiration. Arid Central Asia will face more severe drought, especially under high emission scenarios. In the near-term the drought will reduce at a certain extent, but the trend of drought will still be prominent in the mid and long term. Overall, drought in arid Central Asia will show an overall characteristic of decreasing drought number but increasing drought frequency, drought duration, and drought intensity. Drought risk is likely to be higher in Xinjiang of China, Turkmenistan and Uzbekistan. The research can provide a scientific basis for the decision-making of water resources planning and management and socio-economic development of arid Central Asia.
Melt- and fluid-inclusions studies in the Wunugetushan porphyry Cu–Mo deposit, NE China: Constraints on the separation of Cu and Mo
Authors: Lu Wei , Zhang Yuecheng , Du Jingguo , Song Zhiwei
Published: February 2023

The Wunugetushan large porphyry Cu–Mo deposit in NE China is hosted by Mesozoic quartz monzonite porphyry and has a Mo-rich core and Cu-rich rim in space. In this paper, melt inclusions in porphyry intrusions and fluid inclusions in different-stage quartz veins were studied to explore potential parameters leading to Cu–Mo decoupling. Melt inclusions in porphyry intrusions have rhyolitic compositions of 71.7–85.3 wt.% SiO2, 1.9–31.3 ppm Cu and 1.7–2.6 ppm Mo. Hydrothermal activity occurred over three stages: 1) Early Mo mineralization at high temperatures (543°C–560°C) and CO2-rich fluids of intermediate salinity (11.0–17.3 wt.% NaCl equivalent), accompanied by biotitization and minor K-feldspathization; 2) Late Mo mineralization involving high-salinity (up to 77.0 wt.% NaCl equiv.) oxidized fluids at intermediate temperatures (400°C–454°C), with K-feldspathization and minor sericitization; 3) A Cu-mineralization stage with high-salinity (up to 45.6 wt.% NaCl equiv.) and CO2-barren fluids characterized by temperature peaks at 250°C–300°C and 400°C–450°C, accompanied by sericitization and illitization. Given possible variations in melt Cu/Mo ratios during magmatic activity and redox conditions, pH, fluid composition, and temperature during the hydrothermal-fluid stage led to the separation of Cu and Mo, we found that integrated parameters including increased Cu/Mo ratios in residual melt, variations in the redox state and more acidic environment of hydrothermal fluids determine spatial separation of two metals.
How do graduate students approach college teaching? Influences of professional development, teaching assistantships, and Big Five personality traits
Authors: Che Elizabeth S. , Brooks Patricia J. , Schwartz Anna M. , Saltzman Ethlyn S. , Whiteman Ronald C.
Published: February 2023

Introduction

Graduate students engage in college teaching with varied attitudes and approaches. Their teaching practices may be influenced by professional development experiences related to pedagogy, and their personality traits.

Methods

Through an online survey of graduate students teaching undergraduate courses (N = 109, 69.7% women, M age = 30 years, 59% psychology), we examined whether self-reported participation in professional development related to pedagogy, teaching assistantship (TA) experience, academic discipline (psychology vs. other), and Big Five personality traits were associated with variation in teaching practices.

Results

Participation in professional development correlated positively with years of undergraduate teaching experience and with the trait of openness. Hierarchical regressions indicated that professional development served to promote student-focused practices and discouraged lecturing, while TA experience (mostly restricted to psychology instructors) promoted lecturing and discouraged a student-focused approach. Regarding academic discipline, psychology instructors gave higher endorsements to an information transmission, teacher-focused approach to teaching, lectured more, and were less likely to provoke debate than instructors of other disciplines. Such differences may be attributed in part to larger enrollments of psychology courses. Regarding personality traits, both openness and agreeableness were associated with some student-focused practices, while conscientiousness was associated with an information transmission, teacher-focused approach and with practices aligned with backward course design.

Discussion

In light of previous evidence that personality traits are malleable, graduate training programs may want to cultivate traits like openness as a means of encouraging graduate students to reflect on their pedagogy and seek ways to improve their teaching through professional development. Relatedly, graduate programs should aim to support students’ participation in professional development related to pedagogy and, in doing so, communicate its value.
A clinical and molecular pathology prediction model for central lymph node metastasis in cN0 papillary thyroid microcarcinoma
Authors: Ma Teng , Wang Lulu , Zhang Xueyan , Shi Yafei
Published: February 2023

Background

The frequency of thyroid cancer has rapidly increased in recent years globally. Thus, more papillary thyroid microcarcinoma (PTMC) patients are being diagnosed, including clinical lymph node-negative (cN0) patients. Our study attempted to develop a prediction model for assessing the probability of central lymph node metastasis (CLNM) in cN0 PTMC patients.

Methods

A total of 595 patients from the Affiliated Hospital of Qingdao University (training cohort: 456 patients) and the Affiliated Hospital of Jining Medical University (verification cohort: 139 patients) who underwent thyroid surgery between January 2020 and May 2022 were enrolled in this study. Their clinical and molecular pathology data were analyzed with multivariate logistic regression to identify independent factors, and then we established a prediction model to assess the risk of CLNM in cN0 PTMC patients.

Results

Multivariate logistic regression analysis revealed that sex, Hashimoto’s thyroiditis (HT), tumor size, extrathyroidal extension, TERT promoter mutations and NRAS mutation were independent factors of CLNM. The prediction model demonstrated good discrimination ability (C-index: 0.757 and 0.753 in the derivation and validation cohorts, respectively). The calibration curve of the model was near the optimum diagonal line, and decision curve analysis (DCA) showed a noticeably better benefit.

Conclusion

CLNM in cN0 PTMC patients is associated with male sex, tumor size, extrathyroidal extension, HT, TERT promoter mutations and NRAS mutation. The prediction model exhibits good discrimination, calibration and clinical usefulness. This model will help to assess CLNM risk and make clinical decisions in cN0 PTMC patients.
Intravitreal anti-vascular endothelial growth factor, laser photocoagulation, or combined therapy for diabetic macular edema: A systematic review and network meta-analysis
Authors: Chen Jiasheng , Wang Haowei , Qiu Weiqiang
Published: February 2023

Purpose

To conduct a network meta-analysis (NMA) comparing the efficacy of anti-vascular endothelial growth factor (VEGF) therapy alone versus laser photocoagulation (LP) therapy alone or anti-VEGF therapy combined with LP therapy for diabetic macular edema (DME).

Methods

PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were systematically searched for studies comparing anti-VEGF therapy alone versus LP therapy alone or anti-VEGF therapy combined with LP therapy for DME. Primary outcomes were mean best-corrected visual acuity (BCVA) and central macular thickness (CMT) change. Relevant data were collected and pooled using NMA.

Results

A total of 13 randomized controlled trials were included in our NMA. Anti-VEGF therapy significantly improved BCVA the most compared to the combined (mean difference [MD] = 1.5; 95% confidence interval [CI]: 0.084, 2.7) and LP (MD = 6.3; 95% CI: 5.1, 7.6) therapies at six months, while there was no difference in reducing CMT at six months between the anti-VEGF and combined therapies (MD = -16; 95% CI: -46, 13). At 12 months, no significant difference was found between the anti-VEGF and combined therapy in terms of BCVA (MD = 0.1; 95% CI: -1.7, 1.5) and CMT (MD = 21; 95% CI: -3.0, 44).

Conclusion

There was no significant difference between the anti-VEGF therapy and combined therapy. For the long-term treatment of patients with DME, combined therapy is recommended.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022376401.
Efficacy of antiresorptive agents bisphosphonates and denosumab in mitigating hypercalcemia and bone loss in primary hyperparathyroidism: A systematic review and meta-analysis
Authors: Rajput Swati , Dutta Aditya , Rajender Singh , Mithal Ambrish , Chattopadhyay Naibedya
Published: February 2023

Purpose

Primary hyperparathyroidism (PHPT) is characterized by increased bone remodeling and hypercalcemia. Parathyroidectomy (PTX), the current standard of care, is recommended in all symptomatic and some groups of asymptomatic patients. Anti-resorptive therapies (bisphosphonates and denosumab) have been used in patients where PTX is refused or contraindicated. In this meta-analysis, we investigated the effectiveness of anti-resorptives in preventing/treating PHPT-induced bone loss and mitigating hypercalcemia.

Method

PubMed, Scopus, and Cochrane Library databases were searched for articles with keywords containing PHPT, bisphosphonates, and denosumab in various combinations. We extracted and tabulated areal BMD (aBMD), serum mineral, and bone turnover parameters from the qualified studies and used comprehensive meta-analysis software for analysis.

Results

Of the 1,914 articles screened, 13 were eligible for meta-analysis. In the pooled analysis, 12 months of anti-resoptives (bisphosphonates and denosumab) therapy significantly increased aBMD at the lumbar spine (Standard difference in means (SDM)=0.447, 95% CI=0.230 to 0.664, p=0.0001), femoral neck (SDM=0.270, 95% CI=0.049 to 0.491, p=0.017) and increased serum PTH (SDM=0.489, 95% CI=0.139 to 0.839, p=0.006), and decreased serum calcium (SDM=-0.545, 95% CI=-0.937 to -0.154, p=0.006) compared with baseline. 12 months of bisphosphonate use significantly increased aBMD only at the lumbar spine (SDM=0.330, 95% CI=0.088 to 0.571, p=0.007) with a significant increased in serum PTH levels (SDM=0.546, 95% CI= 0.162 to 0.930, p=0.005), and a decreased in serum calcium (SDM=-0.608, 95% CI=-1.048 to -0.169, p=0.007) and bone-turnover markers (BTMs) compared with baseline. Denosumab use for 12 months significantly increased aBMD at both the lumbar spine (SDM=0.828, 95% CI=0.378 to 1.278, p=0.0001) and femur neck (SDM=0.575, 95% CI=0.135 to 1.015, p=0.010) compared with baseline. Mean lumbar spine aBMD (SDM=0.350, 95% CI=0.041 to 0.659, p=0.027) and serum PTH (SDM=0.602, 95% CI= 0.145 to 1.059, p=0.010) were significantly increased after 12 months of alendronate use compared with placebo. When compared with baseline, alendronate significantly decreased BTMs after 12 months and increased aBMD without altering the PTH and calcium levels after 24 months.

Conclusion

Anti-resorptives are effective in mitigating bone loss and hypercalcemia in PHPT while maintaining or increasing aBMD. PTX reversed all changes in PHPT and normalized PTH levels.
A combined model based on secondary decomposition technique and grey wolf optimizer for short-term wind power forecasting
Authors: Su Zhongde , Zheng Bowen , Lu Huacai
Published: February 2023

Short-term wind power forecasting plays an important role in wind power generation systems. In order to improve the accuracy of wind power forecasting, many researchers have proposed a large number of wind power forecasting models. However, traditional forecasting models ignore data preprocessing and the limitations of a single forecasting model, resulting in low forecasting accuracy. Aiming at the shortcomings of the existing models, a combined forecasting model based on secondary decomposition technique and grey wolf optimizer (GWO) is proposed. In the process of forecasting, firstly, the complete ensemble empirical mode decomposition adaptive noise (CEEMDAN) and wavelet transform (WT) are used to preprocess the wind power data. Then, least squares support vector machine (LSSVM), extreme learning machine (ELM) and back propagation neural network (BPNN) are established to forecast the decomposed components respectively. In order to improve the forecasting performance, the parameters in LSSVM, ELM, and BPNN are tuned by GWO. Finally, the GWO is used to determine the weight coefficient of each single forecasting model, and the weighted combination is used to obtain the final forecasting result. The simulation results show that the forecasting model has better forecasting performance than other forecasting models.
Quantitative evaluation of waste sorting management policies in China’s major cities based on the PMC index model
Authors: Xu Jiangtao , Zhang Zaisheng , Xu Yanqing , Liu Li , Pei Tong
Published: February 2023

Municipal Solid Waste governance in China entered a new phase in March 2017 when the Chinese government began requiring major cities to enforce waste sorting as well as to develop a system of laws, regulations, and standards regarding waste sorting. This study used text mining and the Policy Modeling Consistency (PMC) Index model to develop an evaluation system of Municipal Solid Waste sorting management policies that included 10 first-level variables and 51 second-level variables to quantitatively evaluate the texts of waste sorting management policies in 11 major cities, and then the PMC surface of policy texts was constructed to analyze the strengths and weaknesses of individual policies according to the PMC index values. The results revealed that there were no excellent level or bad level policies among the 11 policies, with an average PMC index value of 7.71. Overall, the 11 policy texts all set out clear goals and programs in accordance with local conditions, but there are some differences across policies in terms of indicators, including policy content, policy function, policy evaluation, restriction and incentives. This study provides a fresh viewpoint on the policy evaluation of waste sorting management and offers some insight for policymakers, who should pay attention to waste separation, focus on key indicators of the policy, and enhance the effectiveness of the policy response. In addition, the applicability of the evaluation model and the difficulties associated with waste sorting governance of China in post-epidemic are discussed.
Relationship between FDI inflow, CO2 emissions, renewable energy consumption, and population health quality in China
Authors: Zhang Ziwei , Nuță Florian Marcel , Dimen Levente , Ullah Irfan , Xuanye Si , Junchen Yao , Yihan Zhou , Yi Chen
Published: February 2023

China has received significant foreign direct investment in the last few decades; the FDI inflow could affect the environment, income, and people’s health. Therefore, this paper aims to investigate the relationship between FDI, renewable energy consumption, CO2 emissions, and Population health quality in China for the period 1980–2020. We applied the VECM method for the data analysis for the short and long-run effects of the independent variables. In the short run, FDI and CO2 emissions did not affect health quality in China; however, in the long run, FDI and CO2 emissions improved life expectancy. Renewable energy has both run and long implications for the health quality in China. These results reflect that FDI creates more jobs in China and improves the overall income of Chinese citizens, contributing to more accessible healthcare services in the long run. Therefore, the government should provide incentives to increase the FDI inflow, which uses renewable energy in production. Furthermore, to mitigate the CO2 emissions government should implement a carbon tax on the industries which has substantial CO2 emissions in the country.
Can environmental information disclosure reduce air pollution? Evidence from China
Authors: Xiong Lei , Long Hongyu , Zhang Xiang , Yu Chenyang , Wen Zezhou
Published: February 2023

Previous studies have focused on the reduction effect of regulation-based instruments and economic-based instruments on air pollution, ignoring the importance of environmental information disclosure. Based on the Ambient Air Quality Standards (AAQS), a quasi-natural policy implemented in 2012, this paper assesses the effect of environmental information disclosure on air pollution through a dynamic spatial difference-in-difference (DID) model using panel data of 269 cities from 2006 to 2017 in China. We find that the implementation of the AAQS results in a 3% reduction of local PM2.5 concentration and a 3.3% reduction of PM2.5 concentration in the surrounding cities. Further analysis suggests that environmental information disclosure reduces air pollution through enhancing public environmental concerns, green innovation, and industrial upgrading. We also explore the moderating effect of government environmental regulation and heterogeneity analysis in different regions. Our findings suggest that government should further develop the scope and quality of environmental quality information disclosure. Moreover, the local government should provide more support for the green transformation of enterprises and provide necessary support during the transition period. In addition, long-term sustainable environmental protection policies must be able to mobilize regional initiatives for green development.
Increased survival of honey bees consuming pollen and beebread is associated with elevated biomarkers of oxidative stress
Authors: Yazlovytska Liudmyla S. , Karavan Volodymyr V. , Domaciuk Marcin , Panchuk Irina I. , Borsuk Grzegorz , Volkov Roman A.
Published: February 2023

Introduction

Significant losses of honey bee colonies have been observed worldwide in recent decades. Inadequate nutrition is considered to be one of the factors that can reduce honey bee resistance to abiotic and biotic environmental stresses. Accordingly, we assessed the impact of food composition on worker bee survival.

Methods

Bees in cages were fed six different diets, and then their survival, levels of thiobarbituric acid reactive substances and protein carbonyl groups, catalase and lysozyme activities were evaluated.

Results and Discussion

After 17 days of feeding, the lowest mortality was observed in the group of bees that received sucrose solution with the addition of willow pollen or artificial rapeseed beebread or artificial willow beebread (diets 4–6). The highest mortality was found in bees that consumed only sucrose solution (diet 1) or the sucrose solution supplemented with a mixture of amino acids (diet 2), which can be explained by the lack of vitamins and microelements in these diets. In the group of bees that received the sucrose solution with rapeseed pollen (diet 3), mortality was intermediate. To check whether the decrease in insect survival could be related to oxidative damage, we evaluated biomarkers of oxidative stress. Consumption of pollen (diets 3 and 5) and artificial beebread (diets 4 and 6) enhances protein carbonylation in worker bees. Feeding bees artificial beebread also resulted in increase in lipid peroxidation and catalase activity, which is probably due to the presence of hydrogen peroxide in the honey contained in beebread. Remarkably, the increase in biomarkers of oxidative stress was not accompanied by adverse but positive effects on insect survival. A lack of amino acids and proteins in the diet 1 did not cause oxidative stress, but led to an increase in lysozyme activity in hemolymph, a biomarker of immune system status. In conclusion, we believe that the increase in oxidative stress biomarkers we found do not indicate oxidative damage, but rather reflect the changes in redox balance due to consumption of certain dietary options.
An integrated physiological perspective on anthropogenic stressors in the Gulf coast toad (Incilius nebulifer)
Authors: Monroe Dillon J. , Barny Lea A. , Wu Alice , Minbiole Kevin P. C. , Gabor Caitlin R.
Published: February 2023

Anthropogenic environmental change, including climate change and urbanization, results in warmer temperatures in both terrestrial and aquatic habitats and changes in community assemblages including invasive species introductions, among many other alterations. Anurans are particularly susceptible to these changes because generally they have a biphasic lifecycle and rely on aquatic and terrestrial habitats for survival. Changes such as warmer water temperature can result in direct and carryover effects, after metamorphosis that decrease fitness. However, Gulf Coast toads (Incilius (Bufo) nebulifer) are expanding their range, including into anthropogenically disturbed areas. We hypothesize that I. nebulifer copes with warmer water, reduced water levels, and invasive species by altering their physiology and/or behavior. Corticosterone is the primary glucocorticoid in amphibians, and it modulates many aspects of physiology and behavior, potentially including lipid storage and hop performance, during unpredictable (stressful) events. As a true toad, I. nebulifer also produces bufadienolide toxins that aid in its antipredator defense and may have tradeoffs with corticosterone. In a fully factorial design, we measured baseline corticosterone levels in tadpoles in response to two treatments: decreased water levels and increased water temperatures. After metamorphosis, we measured the corticosterone profile and other associated responses to exposure to the predatory red imported fire ant (Solenopsis invicta; RIFA). We found that tadpoles had elevated baseline corticosterone release rates when reared in warmer water and reduced water levels. Toadlets also had elevated baseline corticosterone release rates when exposed to any combination of two of the three treatments but when exposed to all three treatments toadlets instead showed elevated magnitude of their stress response. Predator avoidance (as measured by hop performance) was reduced after exposure to RIFA. Tadpoles from warmer water developed more quickly and were smaller in mass after metamorphosis. Toadlets had reduced production of two of the three detected bufadienolides and increased energy storage (lipids) after exposure to warmer water and reduced growth after exposure to reduced water levels. We found direct and carryover effects of common anthropogenic changes in I. nebulifer that may aid in their ability to persist despite these changes.
Using dense Sentinel-2 time series to explore combined fire and drought impacts in eucalypt forests
Authors: Hislop Samuel , Stone Christine , Gibson Rebecca K. , Roff Adam , Choat Brendan , Nolan Rachael H. , Nguyen Trung H. , Carnegie Angus J.
Published: February 2023

Following one of the driest years on record, millions of hectares of forests in southeast Australia were burned in the 2019–2020 “Black Summer” wildfires. In addition to the areas burned, drought related canopy collapse, dieback and tree mortality was widely observed. In this paper, we present a method to map canopy damage due to drought and fire across a large area. Sentinel-2 satellite imagery was used in a monthly time series to highlight areas of forest where the Normalized Burn Ratio index was significantly below a pre-disturbance “stable” period. The stable period was defined as the 3 years prior to 2019 and the disturbance thresholds are based on bioregion specific standard deviations below pre-disturbance means. The novel methods enabled drought impacted forests to be identified, including those which were subsequently burned by wildfire. Across the 20 Mha of forests studied, 9.9 Mha (49%) fell below the disturbance threshold. Of that, 5.8 Mha was disturbed by fire and a further 4.1 Mha by drought outside of the fire extent. Within the fire extent, almost 0.9 Mha was identified as being significantly drought affected prior to being burned. An analysis of spectral recovery following substantial rainfall from February 2020 onward indicates that most of the areas impacted by both drought and fire have similar rates of recovery to those impacted only by fire. There are some areas, however, where the combined effects of the “double disturbance” appears to be hindering recovery. The methods presented here are easily transferrable and demonstrate an approach for monitoring forest disturbance at higher temporal and spatial scales than those typically used.
Potential alternative tree species to Fraxinus excelsior in European forests
Authors: Lévesque Mathieu , Bustamante Eduardo José Ignacio , Queloz Valentin
Published: February 2023

Common ash (Fraxinus excelsior L.) is a keystone tree species in Europe. However, since the 1990s, this species has been experiencing widespread decline and mortality due to ash dieback [Hymenoscyphus fraxineus (T. Kowalski) Baral, Queloz and Hosoya]. Besides H. fraxineus, emerald ash borer (Agrilus planipennis Fairmaire), an invasive alien pest already devastating ash trees in western Russia, is spreading westward and becoming an emerging threat to the remaining European ash populations. While efforts to control ash dieback continue to be a priority, it is becoming crucial to compensate for the loss of ash and its ecosystem services by elaborating restoration strategies, including the search for alternative native and non-native tree species. This review summarizes available knowledge on potential alternative tree species to common ash to help forest managers to cope with ash dieback. Although using natural regeneration and promoting tree species diversity can reduce the impacts of ash dieback in European forests, our review indicates that no native species alone or in combination can fully replace the ecological niche of common ash and its associated ecosystem services (e.g., biodiversity and timber). To fill this gap, forest managers have considered using non-native ash species that are tolerant to both H. fraxineus and A. planipennis and have similar ecological and forestry values as common ash. Of the 43 ash species reviewed, few non-native ash species (e.g., Fraxinus mandshurica Rupr. and Fraxinus platypoda Oliv.) have similar ecological characteristics to common ash and are tolerant to H. fraxineus and A. planipennis. However, the performance of non-native ash species in European forests, their invasiveness potential, and the risk of hybridization with native ash species are still unknown. With the current state of knowledge, it is thus too early to recommend the use of non-native ash species as a suitable option to deal with ash dieback. The priority should be the conservation, regeneration, and breeding of tolerant common ash populations to H. fraxineus, as well as the use of the natural regeneration of other native tree species. Our review highlights the need for controlled experimental plantations to better understand the regeneration ecology and invasiveness potential of non-native ash species prior to their utilization in natural forests.
Diversity of clinical phenotypes in a cohort of Han Chinese patients with PAX6 variants
Authors: Huang Lijuan , Peng Jiajia , Xie Yan , Zhou Yunyu , Wang Xiaolin , Wang Hui , Gui Jingang , Li Ningdong
Published: February 2023

The PAX6 gene plays an important role in ocular development. Mutations of the PAX6 gene may result in a series of ocular abnormalities, including congenital aniridia, anterior segment dysgenesis (ASD), progressive corneal opacification, glaucoma, and hypoplasia of the fovea and optic nerve, leading to reduced visual acuity and even blindness. This study aimed to describe the diversity of clinical features caused by PAX6 pathogenic variants in 45 Han Chinese patients from 23 unrelated families. All patients underwent detailed clinical assessment. Genetic testing was performed to identify pathogenic variations in the PAX6 gene by next-generation sequencing, minigene splicing assay, RT-qPCR, and long-range PCR. Twenty pathogenic variations were detected in the PAX6 gene from 12 pedigrees and 11 sporadic patients, of which 12 were previously reported and 8 were novel. The clinical phenotypes obtained as a result of the PAX6 gene mutations were complicated and vary among patients, even among those who carried the same variants. Genetic testing is helpful for differential diagnosis. Our genetic findings will expand the spectrum of pathogenic variations in the PAX6 gene. PAX6 pathogenic variants not only cause defects in ocular tissues, such as the iris and retina, but also lead to maldevelopment of the whole eye, resulting in microphthalmia.
Prognosis and personalized medicine prediction by integrated whole exome and transcriptome sequencing of hepatocellular carcinoma
Authors: Li Debao , Lei Lei , Wang Jinsong , Tang Bo , Wang Jiuling , Dong Rui , Shi Wenjiong , Liu Guo , Zhao Tingting , Wu Yuzhang , Zhang Yi
Published: February 2023

Hepatocellular carcinoma (HCC) is a clinically and genetically heterogeneous disease. To better describe the clinical value of the main driver gene mutations of HCC, we analyzed the whole exome sequencing data of 125 patients, and combined with the mutation data in the public database, 14 main mutant genes were identified. And we explored the correlation between the main mutation genes and clinical features. Consistent with the results of previous data, we found that TP53 and LRP1B mutations were related to the prognosis of our patients by WES data analysis. And we further explored the associated characteristics of TP53 and LRP1B mutations. However, it is of great clinical significance to tailor a unique prediction method and treatment plan for HCC patients according to the mutation of TP53. For TP53 wild-type HCC patients, we proposed a prognostic risk model based on 11 genes for better predictive value. According to the median risk score of the model, HCC patients with wild-type TP53 were divided into high-risk and low-risk groups. We found significant transcriptome changes in the enrichment of metabolic-related pathways and immunological characteristics between the two groups, suggesting the predictability of HCC immunotherapy by using this model. Through the CMap database, we found that AM580 had potential therapeutic significance for high-risk TP53 wild-type HCC patients.
Comprehensive molecular characterizations of stage I–III lung adenocarcinoma with tumor spread through air spaces
Authors: Ye Ronghao , Yu Yongfeng , Zhao Ruiying , Han Yuchen , Lu Shun
Published: February 2023

Purpose: The aim of this study is to investigate integrative genomic spectra of stage I–III lung adenocarcinoma with tumor spread through air spaces (STAS).

Methods: We retrospectively identified 442 surgically resected lung adenocarcinoma patients of pathological stage I–III in Shanghai Chest Hospital from January 2018 to February 2021. Surgically resected tissues were used for next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes to profile comprehensive molecular characterizations.

Results: A total of 442 cases were analyzed, including 221 (50%) STAS-positive (SP) and 221 (50%) STAS-negative (SN) lung adenocarcinoma patients. In total, 440 cases (99.6%) were positive for the overall mutational spectrum, and the higher mutational genes were EGFR, TP53, KRAS, ALK, SMAD4, and ERBB2 (62%, 42%, 14%, 10%, 7%, and 7%, respectively). Compared with the SN population, there was significantly lower EGFR alteration in the single-nucleotide variant (SNV) mutation spectrum (52.5% vs 69.7%, p < 0.001) and significantly higher TP53 alteration in the SP population (49.8% vs 34.8%, p = 0.002). EGFR L858R missense mutation (19.5% vs 37.6%, p < 0.001) and ERBB2 exon 20 indel mutation (1.8% vs 5.9%, p = 0.045) were more frequent in the SN population. The detection rate of ALK fusion rearrangements in the SP population was significantly higher than that in the SN population (13.1% vs 2.3%, p < 0.001). In the analysis of signaling pathways, no significant difference was discovered between SP and SN patients. No difference in 1-year disease-free survival was observed between SP and SN patients in this study.

Conclusion: Significant differences exist in stage I–III lung adenocarcinoma patients with STAS in molecular characterizations.
Causes, survival rates, and short-term outcomes of preterm births in a tertiary hospital in a low resource setting: An observational cohort study
Authors: Mocking Martina , Adu-Bonsaffoh Kwame , Osman Kwabena A. , Tamma Evelyn , Ruiz Alexa M. , van Asperen Ruth , Oppong Samuel A. , Kleinhout Mirjam Y. , Gyamfi-Bannerman Cynthia , Browne Joyce L.
Published: February 2023

Background

Prematurity is the most important cause of death among children under the age of five years. Globally, most preterm births occur in Sub-Saharan Africa. Subsequent prematurity leads to significant neonatal morbidity, mortality and long-term disabilities. This study aimed to determine the causes, survival rates and outcomes of preterm births up to six weeks of corrected age in Ghana.

Materials and methods

An observational prospective cohort study of infants born preterm was conducted in a tertiary hospital in Accra, Ghana from August 2019 to March 2020. Inclusion was performed within 48 h after birth of surviving infants; multiple pregnancies and stillbirths were excluded. Causes of preterm birth were categorized as spontaneous (including preterm pre-labour rupture of membranes) or provider-initiated (medically indicated birth based on maternal or fetal indications). Survival rates and adverse outcomes were assessed at six weeks of corrected age. Recruitment and follow-up were suspended due to the COVID-19 outbreak. Descriptive statistics and differences between determinants were calculated using Chi-squared tests or Kruskal-Wallis test.

Results

Of the 758 preterm deliveries, 654 (86.3%) infants were born alive. 179 were enrolled in the cohort and were analyzed. Nine (5%) were extremely preterm [gestational age (GA) < 28 weeks], 40 (22%) very preterm (GA 28–31 weeks), and 130 (73%) moderate to late preterm (GA 32–37 weeks) births. Most deliveries (n = 116, 65%) were provider-initiated, often due to hypertensive disorders in pregnancy (n = 79, 44.1%). Sixty-two infants were followed-up out of which fifty-two survived, presenting a survival rate of 84% (n = 52/62) at six weeks corrected age in this group. Most infants (90%, n = 47/52) experienced complications, predominantly consisted of NICU admission (92%) and interval illnesses (21%) including jaundice and sepsis.

Conclusions

The incidence of adverse outcomes associated with preterm birth in a tertiary facility with NICU capacity is high. Larger longitudinal studies are needed for an in-depth understanding of the causes and longer-term outcomes of preterm birth, and to identify effective strategies to improve outcomes in resource constrained settings.
A systematic review of diagnostic, prognostic, and risk blood and urine biomarkers of transplant-associated thrombotic microangiopathy
Authors: Schoettler Michelle L. , Bhatt Harshil , Vasu Sumithira
Published: February 2023

Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of allogeneic and autologous hematopoietic cellular therapy (HCT), associated with significant morbidity and mortality. Although the central drivers of the disease are thought to be endothelial damage and complement activation, no specific diagnostic biomarkers have been identified. TA-TMA is typically diagnosed using criteria comprised of non-specific clinical and laboratory features. Some patients will have a self-remitting course, but more than half develop multi-organ dysfunction or die, making prognostic biomarkers critical. Prevention of TA-TMA, an approach central to other HCT complications such as graft-versus-host disease, is largely untested in part due to a lack of identified early high-risk biomarkers. We conducted a systematic review to summarize the diagnostic, early risk, and prognostic biomarkers of TA-TMA. We screened the titles and abstracts of 1524 citations. After screening out duplications, we read the abstracts of 979 papers and fully reviewed 132 full-text publications. Thirty-one publications fulfilled the inclusion criteria of more than five patients with TA-TMA and a reported measure of association with diagnosis, prognosis, or risk of later development of the disease. Fourteen studies (45%) were with adults, 12 (39%) were with children <18 years old, three included both children and adults, and two did not report age. There were 53 biomarker or biomarker signature entries, and a total of 27 unique biomarkers. Only four biomarkers reported sensitivity and specificity. The single biomarker with the most robust data was sC5b-9, which conferred diagnostic, prognostic, and risk implications. Studies of combinations of biomarkers were rare. No meta-analyses were performed because of significant heterogeneity between studies. The limitations of studies included small sample size, study designs with a high risk of bias (i.e., case–control), the timing of sample collection, and the selection of controls. Furthermore, only two (6%) studies included a training and validation cohort. Cut-off points are needed to stratify groups, as most biomarkers do not have normal values, or normal values cannot be assumed in the HCT setting. In the future, multi-institutional, collaborative efforts are needed to perform rigorously designed, prospective studies with serially enrolled patients, with samples collected at the time of TA-TMA diagnosis, careful selection of controls, and validation of selected biomarkers and cut-off points in a separate cohort.
Interleukin 27 is a novel cytokine with anti-inflammatory effects against spondyloarthritis through the suppression of Th17 responses
Authors: Jouhault Quentin , Cherqaoui Bilade , Jobart-Malfait Aude , Glatigny Simon , Lauraine Marc , Hulot Audrey , Morelle Guillaume , Hagege Benjamin , Ermoza Kétia , El Marjou Ahmed , Izac Brigitte , Saintpierre Benjamin , Letourneur Franck , Rémy Séverine , Anegon Ignacio , Boissier Marie-Christophe , Chiocchia Gilles , Breban Maxime , Araujo Luiza M.
Published: February 2023

Introduction

Spondylarthritis (SpA) development in HLA-B27/human β2-microglobulin transgenic rat (B27-rat) is correlated with altered conventional dendritic cell (cDC) function that promotes an inflammatory pattern of CD4+T cells, including a biased expansion of pro-inflammatory Th17 population and imbalance of regulatory T cells cytokine profile. Transcriptomic analysis revealed that cDCs from B27-rats under express IL-27, an anti-inflammatory cytokine which induces the differentiation of IL-10+ regulatory T cells and inhibits Th17 cells.

Methods

Here, we first investigated whether in vitro addition of exogenous IL-27 could reverse the inflammatory pattern observed in CD4+ T cells. Next, we performed preclinical assay using IL-27 to investigate whether in vivo treatment could prevent SpA development in B27-rats.

Results

in vitro addition of IL-27 to cocultures of cDCs and CD4+ T cell subsets from B27-rats reduced IL-17 and enhanced IL-10 production by T cells. Likewise, IL-27 inhibited the production of IL-17 by CD4+ T cells from SpA patients. Interestingly, in vivo treatment with recombinant IL-27 starting before SpA onset, inhibited SpA development in B27-rats through the suppression of IL-17/TNF producing CD4+ T cells.

Discussion

Overall, our results reveal a potent inhibitory effect of IL-27 and highlight this cytokine as a promising new therapeutic target in SpA, especially for SpA patients non responders to currently approved biotherapies.
Antibody Fc-chimerism and effector functions: When IgG takes advantage of IgA
Authors: Cottignies-Calamarte Andréa , Tudor Daniela , Bomsel Morgane
Published: February 2023

Recent advances in the development of therapeutic antibodies (Abs) have greatly improved the treatment of otherwise drug-resistant cancers and autoimmune diseases. Antibody activities are mediated by both their Fab and the Fc. However, therapeutic Abs base their protective mechanisms on Fc-mediated effector functions resulting in the activation of innate immune cells by FcRs. Therefore, Fc-bioengineering has been widely used to maximise the efficacy and convenience of therapeutic antibodies. Today, IgG remains the only commercially available therapeutic Abs, at the expense of other isotypes. Indeed, production, sampling, analysis and related in vivo studies are easier to perform with IgG than with IgA due to well-developed tools. However, interest in IgA is growing, despite a shorter serum half-life and a more difficult sampling and purification methods than IgG. Indeed, the paradigm that the effector functions of IgG surpass those of IgA has been experimentally challenged. Firstly, IgA has been shown to bind to its Fc receptor (FcR) on effector cells of innate immunity with greater efficiency than IgG, resulting in more robust IgA-mediated effector functions in vitro and better survival of treated animals. In addition, the two isotypes have been shown to act synergistically. From these results, new therapeutic formats of Abs are currently emerging, in particular chimeric Abs containing two tandemly expressed Fc, one from IgG (Fcγ) and one from IgA (Fcα). By binding both FcγR and FcαR on effector cells, these new chimeras showed improved effector functions in vitro that were translated in vivo. Furthermore, these chimeras retain an IgG-like half-life in the blood, which could improve Ab-based therapies, including in AIDS. This review provides the rationale, based on the biology of IgA and IgG, for the development of Fcγ and Fcα chimeras as therapeutic Abs, offering promising opportunities for HIV-1 infected patients. We will first describe the main features of the IgA- and IgG-specific Fc-mediated signalling pathways and their respective functional differences. We will then summarise the very promising results on Fcγ and Fcα containing chimeras in cancer treatment. Finally, we will discuss the impact of Fcα-Fcγ chimerism in prevention/treatment strategies against infectious diseases such as HIV-1.
Myeloidderived suppressor cells: Escorts at the maternal–fetal interface
Authors: Pang Bo , Hu Cong , Li Huimin , Nie Xinyu , Wang Keqi , Zhou Chen , Yi Huanfa
Published: February 2023

Myeloid-derived suppressor cells (MDSCs) are a novel heterogenous group of immunosuppressive cells derived from myeloid progenitors. Their role is well known in tumors and autoimmune diseases. In recent years, the role and function of MDSCs during reproduction have attracted increasing attention. Improving the understanding of their strong association with recurrent implantation failure, pathological pregnancy, and neonatal health has become a focus area in research. In this review, we focus on the interaction between MDSCs and other cell types (immune and non-immune cells) from embryo implantation to postpartum. Furthermore, we discuss the molecular mechanisms that could facilitate the therapeutic targeting of MDSCs. Therefore, this review intends to encourage further research in the field of maternal–fetal interface immunity in order to identify probable pathways driving the accumulation of MDSCs and to effectively target their ability to promote embryo implantation, reduce pathological pregnancy, and increase neonatal health.
Effects of chemotherapy and immunotherapy on microbial diversity in TME and engineered bacterial-mediated tumor therapy
Authors: Zheng Heng , Chen Xianxian , Li Qiyang , Liu Yuqi , Cai Jinzhong
Published: February 2023

Tumor microbiota is a group of microorganisms located in tumor tissues with rich diversity that can promote tumorigenesis and development, and different types of tumors have different tumor microbiotas, which has important implications for tumor research, detection, and clinical treatment. In this review, we examine the diversity of the tumor microbiota, discuss the impact of chemotherapy and immunotherapy on tumor microbiota diversity, and summarize recent advances in the use of genetically engineered bacteria for the treatment of tumors. In addition, we propose key questions that need to be further addressed by the tumor microbiota.
Association of systemic immune inflammatory index with all-cause and cause-specific mortality in hypertensive individuals: Results from NHANES
Authors: Cao Yang , Li Pengxiao , Zhang Yan , Qiu Miaohan , Li Jing , Ma Sicong , Yan Yudong , Li Yi , Han Yaling
Published: February 2023

Background

The relationship between the systemic immune inflammatory index (SII) and the prognosis of hypertensive patients is unclear. This study aims to explore the association of SII with all-cause and cause-specific mortality in patients with hypertension.

Methods

This study included 8524 adults with hypertension from the National Health and Nutritional Examination Surveys (NHANES) 2011–2018, and followed for survival through December 31, 2019. Cox proportional hazards models were used to investigate the associations between SII and mortality from all causes, cardiovascular disease (CVD), and cancer. Restricted cubic spline, piecewise linear regression, subgroup and sensitivity analyses were also used.

Results

During a median follow-up of 4.58 years, 872 all-cause deaths occurred. After adjusting for covariates, higher SII was significantly associated with an elevated risk of CVD mortality. There was a 102% increased risk of CVD mortality per one-unit increment in natural log-transformed SII (lnSII) (P < 0.001). Consistent results were also observed when SII was examined as categorical variable (quartiles). The associations of SII with all-cause and cancer mortality were detected as U-shaped with threshold values of 5.97 and 6.18 for lnSII respectively. Below thresholds, higher SII was significantly associated with lower all-cause mortality (HR=0.79, 95%CI=0.64-0.97) and cancer mortality (HR=0.73, 95%CI=0.53-1.00). Above thresholds, SII was significantly positive associated with all-cause mortality (HR=1.93, 95%CI=1.55-2.40) and cancer mortality (HR=1.93, 95%CI=1.22-3.05). The results were robust in subgroup and sensitivity analyses.

Conclusion

Higher SII (either as a continuous or categorical variable) were significantly associated with a higher risk of CVD mortality. The U-shaped associations were observed between SII and all-cause and cancer mortality.