bluuebunny/crossref_metadata_2025 huggingface dataset:
A matter of origin - identification of SEMA3A, BGLAP, SPP1 and PHEX as distinctive molecular features between bone site-specific human osteoblasts on transcription level
Authors: Zhang Weiping , Rau Sibylle , Kotzagiorgis Konstantinos , Rothweiler René , Nahles Susanne , Gottwald Eric , Rolauffs Bernd , Steinberg Thorsten , Nelson Katja , Altmann Brigitte
Published: September 2022

In oral and maxillofacial bone reconstruction, autografts from the iliac crest represent the gold standard due to their superior clinical performance, compared to autografts derived from other extraoral regions. Thus, the aim of our study was to identify putative differences between osteoblasts derived from alveolar (hOB-A) and iliac crest (hOB-IC) bone of the same donor (nine donors) by means of their molecular properties in 2D and 3D culture. We thereby focused on the gene expression of biomarkers involved in osteogenic differentiation, matrix formation and osteoclast modulation. Furthermore, we examined the transcriptional response to Vit.D3 in hOB-A and hOB-IC. Our results revealed different modulation modes of the biomarker expression in osteoblasts, namely cell origin/bone entity-dependent, and culture configuration- and/or time-dependent modulations. SEMA3A, SPP1, BGLAP and PHEX demonstrated the strongest dependence on cell origin. With respect to Vit.D3-effects, BGLAP, SPP1 and ALPL displayed the highest Vit.D3-responsiveness. In this context we demonstrated that the transcriptional Vit.D3-response concerning SPP1 and ALPL in human osteoblasts depended on the cell origin. The results indicate a higher bone remodeling activity of iliac crest than alveolar osteoblasts and support the growing evidence that a high osteoclast activity at the host-/donor bone interface may support graft integration.
A holistic digital twin simulation framework for industrial facilities: BIM-based data acquisition for building energy modeling
Authors: Gourlis Georgios , Kovacic Iva
Published: September 2022

Energy and resource efficiency as well as reduction of emissions are nowadays significant objectives for production companies. Industry 4.0, through extensive digitalization along the value chain, enables the achievement of these objectives not only in the construction of new facilities but also in existing facilities as well. This requires an interdisciplinary approach, extending over production and logistic processes as well as the building, technical building services, and energy supply systems, consolidated through integrated modeling and simulation-based optimization. The research question this study addresses is how to digitally couple these subsystems and optimize the overall system’s performance in terms of energy and resource efficiency, by distancing from silo-field thinking while using an integrated analysis approach. The article briefly presents a holistic modeling and simulation framework, utilizing modular digital twins (DTs) of all elements that may constitute a given industrial unit. The integration of multiple DTs of these subsystems in a hybrid (continuous and discrete) simulation forms a holistic DT ecosystem of an existing facility. The particular focus of the study is the building representation in this DT ecosystem for energy-efficient production. Based on a methodology including hybrid simulation, building information modeling (BIM), and visual programming, a semi-automated data acquisition workflow was proposed. The hybrid simulation is based on Discrete Event System Specification (DEVS) formalism, where the building is incorporated as a building energy model (BEM). Within the abstracted representation of the overall system, the article explores the possibilities of parametrizing the DT of the building, interconnected with the rest of the factory elements, by acquiring information directly from existing BIM models. Through a comparative case study, the proposed workflow is compared to a manual one in terms of integrity and benefits. The study’s contribution lies in: 1) the detection of the required building level of abstraction for a holistic DT ecosystem, 2) the definition of the interconnections between the building-related counterparts and the rest of the virtual environment as well as the data required for their parameterization, and 3) proposing a semi-automated workflow via virtual programming, for BIM-based creation of the building model within a holistic DT ecosystem.
“Adipose-derived mesenchymal stem cell therapy for the management of female sexual dysfunction: Literature reviews and study design of a clinical trial”
Authors: Hoang Van T. , Nguyen Hoang-Phuong , Nguyen Viet Nhan , Hoang Duc M. , Nguyen Tan-Sinh Thi , Nguyen Thanh Liem
Published: September 2022

Hormone imbalance and female sexual dysfunction immensely affect perimenopausal female health and quality of life. Hormone therapy can improve female hormone deficiency, but long-term use increases the risk of cardiovascular diseases and cancer. Therefore, it is necessary to develop a novel effective treatment to achieve long-term improvement in female general and sexual health. This study reviewed factors affecting syndromes of female sexual dysfunction and its current therapy options. Next, the authors introduced research data on mesenchymal stromal cell/mesenchymal stem cell (MSC) therapy to treat female reproductive diseases, including Asherman’s syndrome, premature ovarian failure/primary ovarian insufficiency, and vaginal atrophy. Among adult tissue-derived MSCs, adipose tissue-derived stem cells (ASCs) have emerged as the most potent therapeutic cell therapy due to their abundant presence in the stromal vascular fraction of fat, high proliferation capacity, superior immunomodulation, and strong secretion profile of regenerative factors. Potential mechanisms and side effects of ASCs for the treatment of female sexual dysfunction will be discussed. Our phase I clinical trial has demonstrated the safety of autologous ASC therapy for women and men with sexual hormone deficiency. We designed the first randomized controlled crossover phase II trial to investigate the safety and efficacy of autologous ASCs to treat female sexual dysfunction in perimenopausal women. Here, we introduce the rationale, trial design, and methodology of this clinical study. Because aging and metabolic diseases negatively impact the bioactivity of adult-derived MSCs, this study will use ASCs cultured in physiological oxygen tension (5%) to cope with these challenges. A total of 130 perimenopausal women with sexual dysfunction will receive two intravenous infusions of autologous ASCs in a crossover design. The aims of the proposed study are to evaluate 1) the safety of cell infusion based on the frequency and severity of adverse events/serious adverse events during infusion and follow-up and 2) improvements in female sexual function assessed by the Female Sexual Function Index (FSFI), the Utian Quality of Life Scale (UQOL), and the levels of follicle-stimulating hormone (FSH) and estradiol. In addition, cellular aging biomarkers, including plasminogen activator inhibitor-1 (PAI-1), p16 and p21 expression in T cells and the inflammatory cytokine profile, will also be characterized. Overall, this study will provide essential insights into the effects and potential mechanisms of ASC therapy for perimenopausal women with sexual dysfunction. It also suggests direction and design strategies for future research.
Reverse hybrid jig separation efficiency estimation of floating plastics using apparent specific gravity and concentration criterion
Authors: Phengsaart Theerayut , Manositchaikul Chaiwat , Srichonphaisarn Palot , Juntarasakul Onchanok , Maneeintr Kreangkrai , Jeon Sanghee , Park Ilhwan , Tabelin Carlito Baltazar , Hiroyoshi Naoki , Ito Mayumi
Published: September 2022

We developed a technique called the reverse hybrid jig, an advanced physical separation technique that combines the principles of jig and flotation to separate floating plastics. This technique is a promising green technology that is more economical and environmentally friendly compared with the conventional flotation. Although the applicability of this technique to separate PP/PE have been reported, the index to illustrate the possibility of separation for the reverse hybrid jig is still not available. In this study, a reverse apparent concentration criterion (CCRA) is proposed to estimate reverse hybrid jig separation efficiency. This modified concentration criterion can be calculated using the specific gravity (SG) of particle with attached bubbles called the apparent specific gravity (SGA). To determine the volume of attached bubbles on plastic surfaces under water pulsation, a laser-assisted apparatus was used under various conditions, including plastic type, air flow rate, dosage, and type of wetting agent. The results of attached bubble volume measurements were used to calculate the SGA and CCRA. The estimated values were then compared with the results of reverse hybrid jig separation. It was found that higher CCRA resulted in better separation efficiency. In addition, an empirical linear equation for estimating the reverse hybrid jig separation efficiency is proposed.
Revealing bacteria-phage interactions in human microbiome through the CRISPR-Cas immune systems
Authors: Monshizadeh Mahsa , Zomorodi Sara , Mortensen Kate , Ye Yuzhen
Published: September 2022

The human gut microbiome is composed of a diverse consortium of microorganisms. Relatively little is known about the diversity of the bacteriophage population and their interactions with microbial organisms in the human microbiome. Due to the persistent rivalry between microbial organisms (hosts) and phages (invaders), genetic traces of phages are found in the hosts’ CRISPR-Cas adaptive immune system. Mobile genetic elements (MGEs) found in bacteria include genetic material from phage and plasmids, often resultant from invasion events. We developed a computational pipeline (BacMGEnet), which can be used for inference and exploratory analysis of putative interactions between microbial organisms and MGEs (phages and plasmids) and their interaction network. Given a collection of genomes as the input, BacMGEnet utilizes computational tools we have previously developed to characterize CRISPR-Cas systems in the genomes, which are then used to identify putative invaders from publicly available collections of phage/prophage sequences. In addition, BacMGEnet uses a greedy algorithm to summarize identified putative interactions to produce a bacteria-MGE network in a standard network format. Inferred networks can be utilized to assist further examination of the putative interactions and for discovery of interaction patterns. Here we apply the BacMGEnet pipeline to a few collections of genomic/metagenomic datasets to demonstrate its utilities. BacMGEnet revealed a complex interaction network of the Phocaeicola vulgatus pangenome with its phage invaders, and the modularity analysis of the resulted network suggested differential activities of the different P. vulgatus’ CRISPR-Cas systems (Type I-C and Type II-C) against some phages. Analysis of the phage-bacteria interaction network of human gut microbiome revealed a mixture of phages with a broad host range (resulting in large modules with many bacteria and phages), and phages with narrow host range. We also showed that BacMGEnet can be used to infer phages that invade bacteria and their interactions in wound microbiome. We anticipate that BacMGEnet will become an important tool for studying the interactions between bacteria and their invaders for microbiome research.
A prospective, multicenter, single-arm clinical trial cohort to evaluate the safety and effectiveness of a novel stent graft system (WeFlow-JAAA) for the treatment of juxtarenal abdominal aortic aneurysm: A study protocol
Authors: Gao Jiang-Ping , Zhang Hong-Peng , Jia Xin , Xiong Jiang , Ma Xiao-Hui , Wang Li-Jun , Zhang Min-Hong , Xu Yong-Le , Guo Wei
Published: September 2022

Introduction

Juxtarenal abdominal aortic aneurysms (JRAAAs) are challenging to cure by traditional endovascular aortic repair (EVAR). Due to the inherent disadvantages of the customized fenestrated and/or branched aortic endografts (such as delayed cycles with a risk of aneurysm rupture, unavailable in emergency or confine operations), several off-the-shelf devices have been developed for the treatment of JRAAA. However, these devices being used in clinical trials have been proven to have a non-negligible risk of reintervention and inadequate anatomic applicability. We have developed a new off-the-shelf aortic endograft system (WeFlow-JAAA) with a mixed design of inner branches and modified fenestrations. The purpose of this cohort study is to assess the safety and effectiveness of the innovative aortic endograft system.

Methods and analysis

This is a prospective, multicenter, single-armed clinical trial cohort study. The enrolment will take place in 29 centers in China, and 106 adult patients with JRAAA will be enrolled in total. Clinical information and CT angiography (CTA) images will be collected and recorded. Patients will be followed up for 5 years. The primary safety endpoint is the rate of no major adverse event within 30 days after index EVAR. The primary efficacy endpoint is the rate of immediate technical success and no JRAAA-related reintervention within 12 months after the procedure.
Myeloid hypoxia-inducible factor HIF1A provides cardio-protection during ischemia and reperfusion via induction of netrin-1
Authors: Heck-Swain Ka Lin , Li Jiwen , Ruan Wei , Yuan Xiaoyi , Wang Yanyu , Koeppen Michael , Eltzschig Holger K.
Published: September 2022

The transcription factor hypoxia-inducible factor HIF1A induces cardioprotection from ischemia and reperfusion injury. Here, we investigate tissue-specific pathways that are critical for HIF1A-elicited tissue protection. Initial studies showed that mice with induced global Hif1a deletion (Hif1aloxP/loxP UbiquitinCre+) have exaggerated myocardial injury during in situ ischemia and reperfusion. Surprisingly, this phenotype was mirrored only in mice with myeloid-specific Hif1a deletion (Hif1aloxP/loxP LysM Cre+). In contrast, mice with myocardial specific (Hif1aloxP/loxP Myosin Cre+), or vascular Hif1a deletion (Hif1aloxP/loxP VEcadherin Cre+) experienced similar levels of injury as controls. Subsequent studies using adoptive transfer of Hif1a-deficient polymorphonuclear neutrophils (PMNs) prior to myocardial injury demonstrated increased reperfusion injury. On the contrary, the adoptive transfer of PMNs treated ex vivo with the hypoxia inducible factor (HIF) stabilizer dimethyloxalylglycine (DMOG) was associated with attenuated myocardial injury. Furthermore, DMOG-mediated cardioprotection was abolished in Hif1aloxP/loxP LysM Cre+ mice, but not in Hif2aloxP/loxP LysM Cre+ mice. Finally, studies of PMN-dependent HIF1A target genes implicated the neuronal guidance molecule netrin-1 in mediating the cardioprotective effects of myeloid HIF1A. Taken together, the present studies identified a functional role for myeloid-expressed HIF1A in providing cardioprotection during ischemia and reperfusion injury, which is mediated, at least in part, by the induction of the netrin-1 neuronal guidance molecule in neutrophils.
Application of multiple testing procedures for identifying relevant comorbidities, from a large set, in traumatic brain injury for research applications utilizing big health-administrative data
Authors: Jana Sayantee , Sutton Mitchell , Mollayeva Tatyana , Chan Vincy , Colantonio Angela , Escobar Michael David
Published: September 2022

Background

Multiple testing procedures (MTP) are gaining increasing popularity in various fields of biostatistics, especially in statistical genetics. However, in injury surveillance research utilizing the growing amount and complexity of health-administrative data encoded in the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), few studies involve MTP and discuss their applications and challenges.

Objective

We aimed to apply MTP in the population-wide context of comorbidity preceding traumatic brain injury (TBI), one of the most disabling injuries, to find a subset of comorbidity that can be targeted in primary injury prevention.

Methods

In total, 2,600 ICD-10 codes were used to assess the associations between TBI and comorbidity, with 235,003 TBI patients, on a matched data set of patients without TBI. McNemar tests were conducted on each 2,600 ICD-10 code, and appropriate multiple testing adjustments were applied using the Benjamini-Yekutieli procedure. To study the magnitude and direction of associations, odds ratios with 95% confidence intervals were constructed.

Results

Benjamini-Yekutieli procedure captured 684 ICD-10 codes, out of 2,600, as codes positively associated with a TBI event, reducing the effective number of codes for subsequent analysis and comprehension.

Conclusion

Our results illustrate the utility of MTP for data mining and dimension reduction in TBI research utilizing big health-administrative data to support injury surveillance research and generate ideas for injury prevention.
A crustal LVZ in Iceland revealed by ambient noise multimodal surface wave tomography
Authors: Zhang Sen , Zhang Gongheng , Feng Xuping , Li Zhengbo , Pan Lei , Wang Jiannan , Chen Xiaofei
Published: September 2022

The crustal low-velocity zone (LVZ), an important anomaly found in some regional structures of Iceland, is still absent in the Icelandic average velocity structure due to limitations of tomography methods. Using stations from the HOTSPOT experiment and other supplemental stations throughout Iceland, we apply the frequency-Bessel transform method (F-J method) to extract the first two mode dispersion curves from ambient noise data. We obtain an average S-wave velocity (Vs) model of Iceland down to 120 km depth, where two LVZs at depths of 12–22 km and below 55 km are found. The shallow LVZ, whose rationalities are justified using theoretical dispersion curves of certain models to recover themselves, may improve the understanding of the Icelandic average crust. Furthermore, our model shows better representativeness by comparing travel time residuals of the primary wave between observed and synthetic data predicted using different average velocity models. Based on the variations of the Vs gradient, the Icelandic crust with an average thickness of 32 km is divided into the upper crust (0–10 km), middle crust (10–22 km), and lower crust (22–32 km). The asthenosphere starts from the deeper LVZ at 55 km depth, potentially indicating the relatively concentrated melt in this depth range. In this study, crustal LVZs are revealed both in a volcanic active zone and a non-volcanic zone, which may also suggest the LVZ in the average model has more complex origins than the high-temperature zone beneath the central volcanoes. The prevalent thick-cold crustal model of Iceland, considered to rule out the existence of a broad region of partial melt in the crust, also strengthens the possibility of diverse origins. The variations in petrology may also contribute to the crustal LVZ in the average model.
Study on the evolution and prediction of fracture depth of surrounding rock in deep mining roadway based on numerical analysis and borehole detection
Authors: Li Huaibin , Zhao Xingdong , Dai Bibo , Huang Zujun , Zhu Qiankun
Published: September 2022

The failure of surrounding rock in deep hard rock roadway is closely related to mining disturbance. In this study, the 13# stope ramp of −767 m level (at a buried depth of 1,197 m) at Hongtoushan copper mine was taken as the engineering background, a comprehensive analysis method of numerical analysis and borehole detection was put forward, and the evolution law of fracture depth of the ramp surrounding rock under the mining influence was obtained. The results show that the maximum tangential stress and fracture depth of the ramp surrounding rock on both sidewalls increase slowly at the initial mining stage. When the ore body above the ramp is mined, the maximum tangential stress and fracture depth of the ramp surrounding rock on both sidewalls increase rapidly, and the two parameters are positively correlated. Based on this, the ratio of the maximum tangential stress of the surrounding rock to the uniaxial compressive strength of intact rock (σθmax/σc) and the equivalent radius (a) of the roadway were used as parameters, and an equation for the fracture depth of the roadway surrounding rock was proposed. Through the case analysis, the results show that the proposed equation of fracture depth of the roadway surrounding rock has good prediction accuracy. This study enriches the research on the stability and failure mechanism of the roadway surrounding rock under the mining disturbance, and provides new basis for the support design of mining roadways.
Distribution, development, transformation characteristics, and hydrate prospect prediction of the rift basins of northwest Zealandia in the Southwest Pacific
Authors: Song Lijun , Feng Xuliang , Yang Yushen , Li Yamin
Published: September 2022

As the last area with unknown oil exploration potential, Zealandia has attracted the attention of petroleum scientists. Under the constraint of the known rift distribution, the gravity and magnetic anomaly data are utilized to predict the distribution of rift basins, and the balanced cross-section technique and basin simulation technique are utilized to analyze the development of the rift basins and hydrocarbon generation history of source rocks for the hydrate prospect prediction of the rift basins of northwest Zealandia. The time of rifting in Zealandia varies greatly from place to place, and it has experienced extensive rifts, migrated to the east of the Lord Howe Ridge, migrated to the west of the Lord Howe Ridge, migrated to the west of the Dampier Ridge, and finally migrated to both sides of the Lord Howe Ridge and then experienced multiple stages of compression transformation and deep burial transformation. The Upper Cretaceous coal source rock in the rift Ⅱ stage has entered the wet gas generation stage in the deep part of the rift or deeper rift on the eastern side of the Lord Howe Ridge, and the coal-generated wet gas may migrate along the fault and form a gas hydrate in the shallow seabed stable zone.
Perspectives from metabolomics in the early diagnosis and prognosis of gestational diabetes mellitus
Authors: Zhang Muqiu , Yang Huixia
Published: September 2022

Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders in pregnant women. The early detection of GDM provides an opportunity for the effective treatment of hyperglycemia in pregnancy, thus decreasing the risk of adverse perinatal outcomes for mothers and newborns. Metabolomics, an emerging technique, offers a novel point of view in understanding the onset and development of diseases and has been repeatedly used in various gestational periods in recent studies of GDM. Moreover, metabolomics provides varied opportunities in the different diagnoses of GDM from prediabetes or predisposition to diabetes, the diagnosis of GDM at a gestational age several weeks earlier than that used in the traditional method, and the assessment of prognosis considering the physiologic subtypes of GDM and clinical indexes. Longitudinal metabolomics truly facilitates the dynamic monitoring of metabolic alterations over the course of pregnancy. Herein, we review recent advancements in metabolomics and summarize evidence from studies on the application of metabolomics in GDM, highlighting the aspects of the diagnosis and differential diagnoses of GDM in an early stage. We also discuss future study directions concerning the physiologic subtypes, prognosis, and limitations of metabolomics.
Drivers of spatiotemporal disparities in the supply-demand budget of ecosystem services: A case study in the Beijing-Tianjin-Hebei urban agglomeration, China
Authors: Li Zu Zheng , Hu Baoan , Qin Yangyi , Cheng Xiaoqin
Published: September 2022

Assessing the spatiotemporal patterns of ecosystem services (ESs) supply and demand, as well as the drivers thereof during specific time periods, is critical for regional policy making and sustainable management. Taking the Beijing-Tianjin-Hebei (BTH) urban agglomeration of China as an example, we studied four ES supply-demand budgets: carbon storage, water provision, food provision and soil conservation from 2000 to 2015. Through the geodetector model, canonical analysis and Multiscale Geographically Weighted Regression (MGWR) model, the drivers of the ES supply-demand budget were explored. The results showed that the areas supplying high amounts of ESs in the northern region usually did not overlap those areas consuming intensive ESs, which were mainly distributed in metropolitan areas. The anthropological factors, including per capita gross domestic product (Per.GDP) and population density (POP.Den), were the dominant influencing factors for the imbalance between the supply and demand of carbon storage, water provision and food provision, which were mainly distributed in the central and southern regions of the study area. Geomorphological factors (ELE and SLO) were the key driving factors of soil conservation, which was mainly distributed in the eastern regions. In all, our findings could provide comprehensive information for decision-making and ES management.
Fiscal decentralisation and green total factor productivity in China: SBM-GML and IV model approaches
Authors: Zhan Xuegang , Li Rita Yi Man , Liu Xiaoyu , He Fan , Wang Meitao , Qin Yuan , Xia Jing , Liao Wangyunyan
Published: September 2022

This paper uses the SBM-GML model to measure and evaluate green total factor productivity based on the panel data of 30 provinces and cities in China from 2012 to 2018. It examines the impact of different dimensions of financial decentralisation on green total factor productivity. The research results show that: 1) green total factor productivity in China is improved year by year and better in central and western regions; 2) the decentralisation of fiscal revenue and expenditure significantly weakens the increase of green total factor productivity in provincial level; 3) fiscal decentralisation inhibits green total factor productivity in central and western regions with regional heterogeneity; 4) local government competition affects the relationship between fiscal decentralisation and green total factor productivity, weakens the negative effect of fiscal decentralisation on green total factor productivity. Finally, the study aims to promote green total factor productivity and sustainable development from the perspective of financial decentralisation. This paper expands the literature and evidence of financial decentralisation on green total factor productivity and offers suggestions for governments and policymakers working toward sustainable development.
Mapping species diversification metrics in macroecology: Prospects and challenges
Authors: Velasco Julián A. , Pinto-Ledezma Jesús N.
Published: September 2022

The intersection of macroecology and macroevolution is one of today’s most active research in biology. In the last decade, we have witnessed a steady increment of macroecological studies that use metrics attempting to capture macroevolutionary processes to explain present-day biodiversity patterns. Evolutionary explanations of current species richness gradients are fundamental for understanding how diversity accumulates in a region. Although multiple hypotheses have been proposed to explain the patterns we observe in nature, it is well-known that the present-day diversity patterns result from speciation, extinction, colonization from nearby areas, or a combination of these macroevolutionary processes. Whether these metrics capture macroevolutionary processes across space is unknown. Some tip-rate metrics calculated directly from a phylogenetic tree (e.g., mean root distance -MRD-; mean diversification rate -mDR-) seem to return very similar geographical patterns regardless of how they are estimated (e.g., using branch lengths explicitly or not). Model-based tip-rate metrics —those estimated using macroevolutionary mixtures, e.g., the BAMM approach— seem to provide better net diversification estimates than only speciation rates. We argue that the lack of appropriate estimates of extinction and dispersal rates in phylogenetic trees may strongly limit our inferences about how species richness gradients have emerged at spatial and temporal scales. Here, we present a literature review about this topic and empirical comparisons between select taxa with several of these metrics. We implemented a simple null model approach to evaluate whether mapping of these metrics deviates from a random sampling process. We show that phylogenetic metrics by themselves are relatively poor at capturing speciation, extinction, and dispersal processes across geographical gradients. Furthermore, we provide evidence of how parametric biogeographic methods can improve our inference of past events and, therefore, our conclusions about the evolutionary processes driving biodiversity patterns. We recommend that further studies include several approaches simultaneously (e.g., spatial diversification modeling, parametric biogeographic methods, simulations) to disentangle the relative role of speciation, extinction, and dispersal in the generation and maintenance of species richness gradients at regional and global scales.
A comprehensive review of Quercus semecarpifolia Sm.: An ecologically and commercially important Himalayan tree
Authors: Rawat Balwant , Rawat Janhvi M. , Purohit Sumit , Singh Gajendra , Sharma Pradeep Kumar , Chandra Anup , Shabaaz Begum J. P. , Venugopal Divya , Jaremko Mariusz , Qureshi Kamal A.
Published: September 2022

Himalayan mountain forests have been a potential candidate for the investigation of perturbations due to the complex geography in which they sustain and the sensitivity of the species toward human disturbance and climate change. Among various tree species, brown oak (Quercus semecarpifolia), a very important component of the Himalayan mountains, has been identified as a keystone species due to its substantial economic and ecological benefits. Maintenance of microclimate and suitable habitats with a rich source of natural resources makes Q. semecarpifolia the most preferred forest for luxuriant growth of ground flora, shelter for fauna, and multipurpose uses by the local people. In a climax community, it plays a critical role in environmental balance both at the local and regional levels. Unfortunately, it has become one of the most overexploited tree species of the Himalayan region over the last few decades due to its high demand for dry season fodder and firewood. The wide range of seedling distribution 348–4,663 individuals ha–1 is evidence of the disturbance accompanied by poor regeneration in Q. semecarpifolia forests. Moreover, litter accumulation and grass cover adversely affect seed germination. The ecological cost of oak forest degradation is perhaps more important and damage is irreversible. Thus, continuous demand and extensive threats accompanied by poor regeneration have drawn the attention of stakeholders to conserve this species. However, propagation protocol, especially the pre-sowing treatment of the species, has not been impressive for large-scale multiplication. This review is comprehensive information on distribution, phenology, regeneration pattern, human threat, conservation approaches, and management of Q. semecarpifolia in the Himalayan region.
Maternal risk factors and neonatal outcomes associated with low birth weight
Authors: Shaohua Yang , Bin Zheng , Mei Liu , Jingfei Zhai , Pingping Qiao , Yanping He , Liping Zhu , Jiexin Yan , Guoshun Mao
Published: September 2022

This study aims to evaluate the incidence of low birth weight (LBW) and related maternal risk factors (during pregnancy or childbirth) and neonatal outcomes. A retrospective cross-sectional study design was used to select 7,421 pregnant women who gave birth in our hospital from January 2018 to June 2021. The data were analyzed using STATA 14.1, and the dependent variable (LBW) and risk were analyzed by the chi-square test of independence. The association between factors is used to determine the factors related to LBW through bivariate and multivariate logistic regression. The incidence of LBW in this study was 4.77%. Compared with single pregnant women, the probability of newborn LBW in married pregnant women is 40% lower (AOR = 0.60 95%CI: 0.40–0.90, p = 0.013). Compared with gestational age less than 37 weeks, the LBW probability of gestational age 37–42 and 42 weeks or older is 85 and 81% lower respectively (AOR = 0.15 95% CI: 0.10–0.24, p = 0.001; AOR = 0.19 95 %CI: 0.09–38, p = 0.001), compared with normal pregnant women, the probability of neonatal LBW among pregnant women with hypertension is 94% higher [AOR = 1.94 (95% CI: 1.39–2.74, p = 0.001). Compared with neonates with normal birth weight, neonates with LBW are at Apgar 1 min And Apgar 5 min score is lower than 7 (AOR = 0.52 95%CI: 0.37–0.73, p = 0.001, AOR = 0.54 95%CI: 0.38–0.75, p = 0.001) higher risk. In conclusion, women’s marital status (single), gestational age (<37 weeks), and combined hypertension are independently associated with LBW, and the higher risk of Apgar 1 min and Apgar 5 min scores <7 is an independent result of LBW.
Trans-cortical vessels in the mouse temporal bulla bone are a means to recruit myeloid cells in chronic otitis media and limit peripheral leukogram changes
Authors: Azar Ali , Bhutta Mahmood F. , Del-Pozo Jorge , Milne Elspeth , Cheeseman Michael
Published: September 2022

Chronic otitis media, inflammation of the middle ear, is a sequel to acute otitis media in ∼8% of children. Chronic otitis media with effusion is the most common cause of childhood deafness and is characterised by effusion of white blood cells into the auditory bulla cavity. Skull flat bones have trans-cortical vessels which are responsible for the majority of blood flow in and out of the bone. In experimental models of stroke and aseptic meningitis there is preferential recruitment of myeloid cells (neutrophils and monocytes) from the marrow in skull flat bones. We report trans-cortical vessels in the mouse temporal bone connect to the bulla mucosal vasculature and potentially represent a means to recruit myeloid cells directly into the inflamed bulla. The mutant mouse strains Junbo (MecomJbo/+) and Jeff (Fbxo11Jf/+) develop chronic otitis spontaneously; MecomJbo/+ mice have highly cellular neutrophil (90%) rich bulla exudates whereas Fbxo11Jf/+ mice have low cellularity serous effusions (5% neutrophils) indicating differing demand for neutrophil recruitment. However we found peripheral leukograms of MecomJbo/+ and Fbxo11Jf/+ mice are similar to their respective wild-type littermate controls with healthy bullae and infer preferential mobilization of myeloid cells from temporal bulla bone marrow may mitigate the need for a systemic inflammatory reaction. The cytokines, chemokines and haematopoietic factors found in the inflamed bulla represent candidate signalling molecules for myeloid cell mobilization from temporal bone marrow. The density of white blood cells in the bulla cavity is positively correlated with extent of mucosal thickening in MecomJbo/+, Fbxo11Jf/+, and EdaTa mice and is accompanied by changes in epithelial populations and bone remodelling. In MecomJbo/+ mice there was a positive correlation between bulla cavity WBC numbers and total bacterial load. The degree of inflammation varies between contralateral bullae and between mutant mice of different ages suggesting inflammation may wax and wane and may be re-initiated by a new wave of bacterial infection. Clearance of white blood cells and inflammatory stimuli from the bulla cavity is impaired and this may create a pro-inflammatory feedback loop which further exacerbates otitis media and delays its resolution.
Molecular prevalence of HBB-associated hemoglobinopathy among reproductive-age adults and the prenatal diagnosis in Jiangxi Province, southern central China
Authors: Luo Haiyan , Huang Ting , Lu Qing , Zhang Liuyang , Xu Yonghua , Yang Yan , Guo Zhen , Yuan Huizhen , Shen Yinqin , Huang Shuhui , Yang Bicheng , Zou Yongyi , Liu Yanqiu
Published: September 2022

Background and aims: Hemoglobinopathy associated with the HBB gene, with its two general subtypes as thalassemia and abnormal hemoglobin (Hb) variants, is one of the most prevalent hereditary Hb disorders worldwide. Herein we aimed to elucidate the prevalence of ß-thalassemia and abnormal hemoglobin variants and the prenatal diagnosis of the HBB gene in Jiangxi Province, southern central China.

Methods: Hematological indices and capillary Hb electrophoresis were conducted for 136,149 subjects who were admitted to Jiangxi Maternal and Child Health Hospital and requested for hemoglobinopathy investigation. Routine α- and ß-globin genotyping were performed by gap-polymerase chain reaction (Gap-PCR) and reverse dot-blot (RDB) hybridization for the 11,549 individuals suspected to be thalassemia carriers. For participants whose genotypes could not explain their hematological indices, further Sanger sequencing and Gap-PCR were conducted for the detection of rare or novel variants in related globin genes. Prenatal diagnosis was performed for 77 pregnant couples both carrying ß-thalassemia trait at appropriate gestational ages.

Results: Among the 11,549 subjects, 2,548 individuals were identified with HBB-associated hemoglobinopathy based on molecular analysis. A total of 2,358 subjects were identified as ß-thalassemia heterozygous carriers and nine cases were diagnosed as compound heterozygous ß-thalassemia. Additionally, 125 cases were detected with composite α- and ß-thalassemia and the remaining 56 individuals with abnormal Hb variants in the HBB. A total of 35 types of variants were identified in the HBB gene, including 26 types of ß-thalassemia and nine types of abnormal Hb variants. Four novel variants were firstly reported, including one variant in HBA2 and three variants in HBB. Overall, 77 prenatal samples underwent ß-thalassemia molecular diagnosis; 20 fetuses were identified with normal ß-thalassemia genotypes, 30 fetuses as ß-thalassemia heterozygotes, 11 as homozygotes, and 16 as compound heterozygotes in HBB.

Conclusion: We have demonstrated a relatively high prevalence rate at 1.872% of ß-hemoglobinopathies including common and rare ß-thalassemia as well as abnormal Hb variants among large child-bearing population in the Jiangxi area of southern central China for the first time. Our data presents that prenatal diagnosis is an effective way to prevent and control birth defects of ß-thalassemia.
HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation
Authors: Johansson Tiira , Partanen Jukka , Saavalainen Päivi
Published: September 2022

Varying HLA allele-specific expression levels are associated with human diseases, such as graft versus host disease (GvHD) in hematopoietic stem cell transplantation (HSCT), cytotoxic T cell response and viral load in HIV infection, and the risk of Crohn’s disease. Only recently, RNA-based next generation sequencing (NGS) methodologies with accompanying bioinformatics tools have emerged to quantify HLA allele-specific expression replacing the quantitative PCR (qPCR) -based methods. These novel NGS approaches enable the systematic analysis of the HLA allele-specific expression changes between individuals and between normal and disease phenotypes. Additionally, analyzing HLA allele-specific expression and allele-specific expression loss provide important information for predicting efficacies of novel immune cell therapies. Here, we review available RNA sequencing-based approaches and computational tools for NGS to quantify HLA allele-specific expression. Moreover, we explore recent studies reporting disease associations with differential HLA expression. Finally, we discuss the role of allele-specific expression in HSCT and how considering the expression quantification in recipient-donor matching could improve the outcome of HSCT.
Malnutrition leads to increased inflammation and expression of tuberculosis risk signatures in recently exposed household contacts of pulmonary tuberculosis
Authors: VanValkenburg Arthur , Kaipilyawar Vaishnavi , Sarkar Sonali , Lakshminarayanan Subitha , Cintron Chelsie , Prakash Babu Senbagavalli , Knudsen Selby , Joseph Noyal Mariya , Horsburgh C. Robert , Sinha Pranay , Ellner Jerrold J. , Narasimhan Prakash Babu , Johnson W. Evan , Hochberg Natasha S. , Salgame Padmini
Published: September 2022

Background

Most individuals exposed to Mycobacterium tuberculosis (Mtb) develop latent tuberculosis infection (LTBI) and remain at risk for progressing to active tuberculosis disease (TB). Malnutrition is an important risk factor driving progression from LTBI to TB. However, the performance of blood-based TB risk signatures in malnourished individuals with LTBI remains unexplored. The aim of this study was to determine if malnourished and control individuals had differences in gene expression, immune pathways and TB risk signatures.

Methods

We utilized data from 50 tuberculin skin test positive household contacts of persons with TB - 18 malnourished participants (body mass index [BMI] < 18.5 kg/m2) and 32 controls (individuals with BMI ≥ 18.5 kg/m2). Whole blood RNA-sequencing was conducted to identify differentially expressed genes (DEGs). Ingenuity Pathway Analysis was applied to the DEGs to identify top canonical pathways and gene regulators. Gene enrichment methods were then employed to score the performance of published gene signatures associated with progression from LTBI to TB.

Results

Malnourished individuals had increased activation of inflammatory pathways, including pathways involved in neutrophil activation, T-cell activation and proinflammatory IL-1 and IL-6 cytokine signaling. Consistent with known association of inflammatory pathway activation with progression to TB disease, we found significantly increased expression of the RISK4 (area under the curve [AUC] = 0.734) and PREDICT29 (AUC = 0.736) progression signatures in malnourished individuals.

Conclusion

Malnourished individuals display a peripheral immune response profile reflective of increased inflammation and a concomitant increased expression of risk signatures predicting progression to TB. With validation in prospective clinical cohorts, TB risk biomarkers have the potential to identify malnourished LTBI for targeted therapy.
Case report: Severe deep ulcer on the left abdomen mimicking mycosis fungoides caused by Trichophyton tonsurans in a patient with novel CARD9 mutation
Authors: Tan Jingwen , Yu Qian , Gao Zhiqin , Yang Hong , Chen Qilong , Yang Lianjuan
Published: September 2022

Dermatophytosis is the most common type of superficial fungal infection caused by dermatophytes. Occasionally, the fungus invades deep into the dermis or other tissues, causing deep dermatophytosis. Deep dermatophytosis is often associated with Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in patients. Here, we report the first case of deep dermatophytosis with a rare mycosis fungoides manifestation caused by T. tonsurans in a patient with a novel mutation in exon 4 of CARD9. The condition presented with heterozygous K196E mutation, which leads to deficiency of innate and adaptive immune responses in the patient, and caused intractable severe lesions. The patient received treatment with multiple antifungal drugs and was ultimately alleviated by posaconazole. These findings extend the pathogen spectrum of deep dermatophytosis linked with CARD9 deficiency and enriched their phenotypic spectrum.
Cross-reactivity between vaccine antigens from the chitin deacetylase protein family improves survival in a mouse model of cryptococcosis
Authors: Hester Maureen M. , Oliveira Lorena V. N. , Wang Ruiying , Mou Zhongming , Lourenco Diana , Ostroff Gary R. , Specht Charles A. , Levitz Stuart M.
Published: September 2022

Meningitis due to the fungal pathogen Cryptococcus neoformans is estimated to cause nearly 200,000 deaths annually, mostly in resource-limited regions. We previously identified cryptococcal protein antigens which, when delivered in glucan particles, afford vaccine-mediated protection against an otherwise lethal infection. Many of these proteins exhibit significant homology to other similar cryptococcal proteins leading us to hypothesize that protection may be augmented by immunologic cross-reactivity to multiple members of a protein family. To examine the significance of protein cross-reactivity in vaccination, we utilized strains of Cryptococcus that are genetically deficient in select antigens, yet are still lethal in mice. Vaccination with a protein without homologs (e.g., Mep1 and Lhc1) protected against challenge with wild-type Cryptococcus, but not against a deletion strain lacking that protein. Contrastingly, vaccination with a single chitin deacetylase (Cda) protein protected against the corresponding deletion strain, presumably due to host recognition of one or more other family members still expressed in this strain. Vaccination with a single Cda protein induced cross-reactive antibody and interferon-gamma (IFNγ) immune responses to other Cda protein family members. Paradoxically, we saw no evidence of cross-protection within the carboxypeptidase family of proteins. Factors such as in vivo protein expression and the degree of homology across the family could inform the extent to which vaccine-mediated immunity is amplified. Together, these data suggest a role for prioritizing protein families in fungal vaccine design: increasing the number of immune targets generated by a single antigen may improve efficacy while diminishing the risk of vaccine-resistant strains arising from gene mutations.
CAR-T cell therapy for hematological malignancies: Limitations and optimization strategies
Authors: Huang Jiawen , Huang Xiaobing , Huang Juan
Published: September 2022

In the past decade, the emergence of chimeric antigen receptor (CAR) T-cell therapy has led to a cellular immunotherapy revolution against various cancers. Although CAR-T cell therapies have demonstrated remarkable efficacy for patients with certain B cell driven hematological malignancies, further studies are required to broaden the use of CAR-T cell therapy against other hematological malignancies. Moreover, treatment failure still occurs for a significant proportion of patients. CAR antigen loss on cancer cells is one of the most common reasons for cancer relapse. Additionally, immune evasion can arise due to the hostile immunosuppressive tumor microenvironment and the impaired CAR-T cells in vivo persistence. Other than direct antitumor activity, the adverse effects associated with CAR-T cell therapy are another major concern during treatment. As a newly emerged treatment approach, numerous novel preclinical studies have proposed different strategies to enhance the efficacy and attenuate CAR-T cell associated toxicity in recent years. The major obstacles that impede promising outcomes for patients with hematological malignancies during CAR-T cell therapy have been reviewed herein, along with recent advancements being made to surmount them.