Potential Drivers Research Articles

Identification of genes with oscillatory expression in glioblastoma: the paradigm of SOX2

Quiescence, a reversible state of cell-cycle arrest, is an important state during both normal development and cancer progression. For example, in glioblastoma (GBM) quiescent glioblastoma stem cells (GSCs) play an important role in re-establishing the tumour, leading to relapse. While most studies have focused on identifying differentially expressed genes between proliferative and quiescent cells as potential drivers of this transition, recent studies have shown the importance of protein oscillations in controlling the exit from quiescence of neural stem cells. Here, we have undertaken a genome-wide bioinformatic inference approach to identify genes whose expression oscillates and which may be good candidates for controlling the transition to and from the quiescent cell state in GBM. Our analysis identified, among others, a list of important transcription regulators as potential oscillators, including the stemness gene SOX2, which we verified to oscillate in quiescent GSCs. These findings expand on the way we think about gene regulation and introduce new candidate genes as key regulators of quiescence.

Seventeen-year study reveals fluctuations in key ecological indicators on two reef crests in Cuba.

Reef crests in the Caribbean have lost approximately 80% of the foundational habitat-forming coral Acropora palmata (Lamarck, 1816), with declines registered as early as the 1950s mainly from anthropogenic causes. We studied two reef crests in the northwestern region of Cuba over 17 years (2005 to 2021) to evaluate temporal changes in coral cover, dominated by A. palmata, and their potential drivers. The density of A. palmata generally showed a negative trend at both reefs, with the lowest density recorded in 2021 at 0.2±0.05 col. m-2 at Playa Baracoa and 1.0±0.1 col. m-2 at Rincon de Guanabo. The mean size of the colonies in the two reefs also decreased over time. In Playa Baracoa, the mean diameter of A. palmata colonies decreased from 2012 at 67±5.9 cm to 2013 at 34±2.2 cm, whereas in Rincon de Guanabo, a change in diameter was evident from 2015 at 44.3±2.3 to 2021 at 21.6±0.9 cm. Adult colonies (10 cm-50 cm diameter) predominated in most years on both reefs. The populations of A. palmata on both reefs were healthy, with an average of 70% colonies in good condition during the study period. However, A. palmata cover decreased by almost half by 2021, to 8.6% in Playa Baracoa and 16.8% in Rincon de Guanabo. By contrast, macroalgal cover increased two-fold to 87.1% in Playa Baracoa and four-fold to 77.2% in Rincon de Guanabo. The density of the sea urchin Diadema antillarum was higher in Playa Baracoa than in Rincon de Guanabo. The highest densities were 2.8±0.2 ind. m-2 in Playa Baracoa in 2005 and 0.1±0.03 ind. m-2in Rincon de Guanabo in 2008. Although our results show an overall decline of A. palmata (density and percent cover) and an increase in macroalgae, these two reef crests are in better condition than most reefs in the Caribbean in terms of the density and health of A. palmata populations, and the density of D. antillarum at Playa Baracoa. Our results are important in establishing a management plan to ensure the condition of these reef crests does not degrade further.

The Complement System and C4b-Binding Protein: A Focus onthe Promise of C4BPα as a Biomarker to Predict Clopidogrel Resistance.

The complement system plays a dual role in the body, either as a first-line defense barrier when balanced between activation and inhibition or as a potential driver of complement-associated injury or diseases when unbalanced or over-activated. C4b-binding protein (C4BP) was the first circulating complement regulatory protein identified and itfunctions as an important complement inhibitor. C4BP can suppress the over-activation of complement components and prevent the complement system from attacking the host cells through the binding of complement cleavage products C4b and C3b, working in concert as a cofactor for factor I in the degradation of C4b and C3b, and consequently preventing or reducing the assembly of C3 convertase and C5 convertase, respectively. C4BP, particularly C4BP α-chain (C4BPα), exerts its unique inhibitory effects on complement activation and opsonization, systemic inflammation, and platelet activation and aggregation. It has long been acknowledged that crosstalk or interplay exists between the complement system and platelets. Our unpublished preliminary data suggest that circulating C4BPα exerts its antiplatelet effects through inhibition of both complement activity levels and complement-induced platelet reactivity. Plasma C4BPα levels appear to be significantly higher in patients sensitive to, rather than resistant to, clopidogrel, and we suggest that a plasma C4BPα measurement could be used to predict clopidogrelresistance in the clinical settings.

Detection of abnormal operation in geothermal binary plant feed pumps using time-series analytics

In this study, we investigate potential pump cavitation events in circulating feed pumps deployed in a geothermal binary power plant using feature-based time series analytics and machine learning. The feed pumps have been in operation for over a decade but have been experiencing episodes wherein the pumps were drawing in lower power even while pump speeds were maintained at the same levels.A workflow combining time-series analytics and first-principle thermodynamics was applied to characterise potential drivers of the abnormal events in the feed pumps. An approach based on systematic time-series feature engineering and semi-supervised machine learning was used to fully annotate the input data and identify twenty (20) undocumented occurrences of the target event. Time-series features extracted from the fully labelled dataset were then used to train forecasting models to identify potential drivers of the target events. Forecasting models trained using pump data outperformed those trained on times-series data from other power plant components (Matthew’s correlation coefficient score of 0.490 vs 0.255). This result indicates that the abnormal events are primarily driven by operating conditions local to the feed pump system. This finding was confirmed by Bayesian A/B testing, showing that the target events were more likely to occur by 22% when four (4) feed pumps were running compared to when only three (3) pumps were in operation. Furthermore, thermodynamic analysis of the state of the working fluid across the feed pumps shows irregularities at the pump inlet, where indications of partial vaporisation of the working fluid have been identified.

Interguild fungal competition in litter and soil inversely modulate microbial necromass accumulation during Loess Plateau forest succession

Microbial interactions determine ecosystem carbon (C) and nutrient cycling, yet it remains unclear how interguild fungal interactions modulate microbial residue contribution to soil C pools (SOC) during forest succession. Here, we present a region-wide investigation of the relative dominance of saprophytic versus symbiotic fungi in litter and soil compartments, exploring their linkages to soil microbial residue pools and potential drivers along a chronosequence of secondary Chinese pine (Pinus tabulaeformis) forests on the Loess Plateau. Despite minor changes in C and nitrogen (N) stocks in the litter or soil layers across successional stages, we found significantly lower soil phosphorus (P) stocks, higher ratios of soil C: N, soil N: P and soil C: P but lower ratios of litter C: N and litter C: P in old (>75 years) than young stands (<30 years). Pine stand development altered the saprotroph: symbiotroph ratios of fungal communities to favor the soil symbiotrophs versus the litter saprotrophs. The dominance of saprotrophs in litter is positively related to microbial necromass contribution to SOC, which is negatively related to the dominance of symbiotrophs in soils. Antagonistic interguild fungal competition in litter and soil layers, in conjunction with increased fungal but decreased bacterial necromass contribution to SOC, jointly contribute to unchanged total necromass contribution to SOC with stand development. The saprotroph: symbiotroph ratios in litter and soil layers are mainly driven by soil P stocks and stand parameters (e.g., stand age and slope), respectively, while substrate stoichiometries primarily regulate microbial necromass accumulation and fungal: bacterial necromass ratios. These results provide novel insights into how microbial interactions at local spatial scales modulate temporal changes in SOC pools, with management implications for mitigating regional land degradation.

Deciphering classification systems for neck pain—Understanding the content of classification systems to enhance physiotherapy management of neck pain

AbstractBackgroundNeck pain is a prevalent and disabling condition. Conservative management of this condition has shown only moderate effects. A solution to improve treatment effectiveness is to sub‐group patients into a classification system (CS) that allows for more personalised care. However, current stratification methods have only shown short‐term efficacy for pain. Given the limitations of these tools, it is pertinent to understand how these CSs are composed to be able to propose alternative patient management solutions.ObjectiveTo identify and examine the different components of classification systems specific to patients with neck‐related conditions.MethodA systematic literature search was performed on 3 databases (PubMed, Scopus and CINAHL). Only systematic reviews, with or without meta‐analysis, and scoping reviews reporting CS with associated treatment for neck pain were included. Bias evaluation was performed through risk of bias in systematic review tools.ResultsFrom the search strategy, 741 citations were retrieved, and seven studies were included. From these studies, 37 CS with associated treatments were extracted. Mobilisations showed that 64% were constructed using physical findings, 61% of CS were guided by symptom modulation, 25% used results of self‐reported questionnaire, 14% used individual characteristics, 14% incorporated cognitive findings, 8% used neurological findings, 3% used results of medical diagnostic test, and 3% incorporated environmental findings. Fear‐avoidance beliefs was the only cognitive parameter considered among CS.ConclusionThis study shows that existing classification systems for neck pain are limited and lack coverage of all potential drivers of pain and disability. The lack of recognition of psychosocial and pain neuroscience parameters may partly explain the limited effectiveness of these tools.

Is It Better for a Publisher to Release an Audiobook after Its E-Book Version?

The e-books industry is mature, and audiobooks are becoming increasingly popular. More and more publishers are coming to realize that audiobooks could be a potential revenue driver and intend to release audiobooks. Considering that there is a certain substitutability between e-books and audiobooks, publishers need to decide how to release a book in its audible version and its e-book version into the market. In this paper, we incorporate the discount factor and the consumers’ acceptance level for audiobooks into the consumer utility by dividing consumers into two types, high-value type and low-value type, and construct two different release models: releasing the audiobook and the e-book simultaneously and releasing the audiobook after the e-book. Using an optimization tool, we investigate pricing strategies of a monopolistic publisher under two different release models. By comparing the theoretical results of the two models, we find that when the consumers’ patience exceeds a certain threshold, releasing a book in its audible version after its e-book version is better for the publisher, and the publisher should adopt a skimming (refers to decreasing markups over time) pricing strategy for the e-book in this case. Further, the publisher should set a higher price for the audiobook than the e-book, whether or not they release the audiobook after the e-book. In addition, we conduct a numerical analysis to investigate how the discount factor, the percentage of high-value consumers, and the high-value consumers’ acceptance level for audiobooks affect the consumer surplus and the social welfare. This study offers publishers some managerial insights into the complex issues involving pricing and release strategies.

Association between vaccination rates and COVID-19 health outcomes in the United States: a population-level statistical analysis

BackgroundPopulation-level vaccine efficacy is a critical component of understanding COVID-19 risk, informing public health policy, and mitigating disease impacts. Unlike individual-level clinical trials, population-level analysis characterizes how well vaccines worked in the face of real-world challenges like emerging variants, differing mobility patterns, and policy changes.MethodsIn this study, we analyze the association between time-dependent vaccination rates and COVID-19 health outcomes for 48 U.S. states. We primarily focus on case-hospitalization risk (CHR) as the outcome of interest, using it as a population-level proxy for disease burden on healthcare systems. Performing the analysis using Generalized Additive Models (GAMs) allowed us to incorporate real-world nonlinearities and control for critical dynamic (time-changing) and static (temporally constant) factors. Dynamic factors include testing rates, activity-related engagement levels in the population, underlying population immunity, and policy. Static factors incorporate comorbidities, social vulnerability, race, and state healthcare expenditures. We used SARS-CoV-2 genomic surveillance data to model the different COVID-19 variant-driven waves separately, and evaluate if there is a changing role of the potential drivers of health outcomes across waves.ResultsOur study revealed a strong and statistically significant negative association between vaccine uptake and COVID-19 CHR across each variant wave, with boosters providing additional protection during the Omicron wave. Higher underlying population immunity is shown to be associated with reduced COVID-19 CHR. Additionally, more stringent government policies are generally associated with decreased CHR. However, the impact of activity-related engagement levels on COVID-19 health outcomes varied across different waves. Regarding static variables, the social vulnerability index consistently exhibits positive associations with CHR, while Medicaid spending per person consistently shows a negative association. However, the impacts of other static factors vary in magnitude and significance across different waves.ConclusionsThis study concludes that despite the emergence of new variants, vaccines remain highly correlated with reduced COVID-19 harm. Therefore, given the ongoing threat posed by COVID-19, vaccines remain a critical line of defense for protecting the public and reducing the burden on healthcare systems.

Towards Understanding the Development of Breast Cancer: The Role of RhoJ in the Obesity Microenvironment.

Obesity is a growing pandemic with an increasing risk of inducing different cancer types, including breast cancer. Adipose tissue is proposed to be a major player in the initiation and progression of breast cancer in obese people. However, the mechanistic link between adipogenicity and tumorigenicity in breast tissues is poorly understood. We used in vitro and in vivo approaches to investigate the mechanistic relationship between obesity and the onset and progression of breast cancer. In obesity, adipose tissue expansion and remodeling are associated with increased inflammatory mediator's release and anti-inflammatory mediators' reduction.. In order to mimic the obesity micro-environment, we cultured cells in an enriched pro-inflammatory cytokine medium to which we added a low concentration of beneficial adipokines. Epithelial cells exposed to the obesity micro-environment were phenotypically transformed into mesenchymal-like cells, characterized by an increase in different mesenchymal markers and the acquisition of the major hallmarks of cancerous cells; these include sustained DNA damage, the activation of the ATR-Chk2 pathway, an increase in proliferation rate, cell invasion, and resistance to conventional chemotherapy. Transcriptomic analysis revealed that several genes, including RhoJ, CCL7, and MMP9, acted as potential major players in the observed phenomenon. The transcriptomics findings were confirmed in vitro using qRT-PCR and in vivo using high-fat-diet-fed mice. Our data suggests RhoJ as a potential novel molecular driver of tumor development in breast tissues and a mediator of cell resistance to conventional chemotherapy through PAK1 activation. These data propose that RhoJ is a potential target for therapeutic interventions in obese breast cancer patients.

Adolescent sexual and reproductive health and rights for ethnic minority girls in Vietnam.

There has been significant progress in improved adolescent sexual and reproductive health and rights (ASRHR) for girls across low- to- middle-income countries (LMICs). However, progress has been uneven, and disparities persistent across and within countries. For example, Vietnam is one of only nine countries to have achieved the 2015 maternal mortality rate (MMR) target of the Millennium Development Goals (MDGs) as a nation, but for some sub-populations, progress has been much slower, and MMR is more than twice that the national average. Ensuring equity is a current focus of the Sustainable Development Goals (SDGs) agenda that seeks to Leave No One Behind. This paper explores some of these inequities and potential drivers for ethnic minority adolescent girls in Vietnam, with a specific focus on the Tay community, the largest ethnic minority group in Vietnam. This paper highlights the challenges to progress, including areas where there is still limited evidence about the range of socio-cultural factors that may determine sexual and reproductive health outcomes for Tay adolescent girls. In the era of the SDGs, Vietnam's national policy platforms and current aid architecture provide a solid basis on which to build research, policy and practice investments that improve the health of adolescent ethnic minority girls in Vietnam.

Liver sinusoidal endothelial cells as potential drivers of liver fibrosis (Review).

Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. It is a critical pre‑stage condition of severe hepatopathy, characterized by excessive accumulation of extracellular matrix components and ongoing chronic inflammation. To date, early prevention of liver fibrosis remains challenging. As the most abundant non‑parenchymal hepatic cell population, liver sinusoidal endothelial cells (LSECs) are stabilizers that maintain the intrahepatic environment. Notably, LSECs dysfunction appears to be implicated in the progression of liver fibrosis via numerous mechanisms. Following sustained liver injury, they lose their fenestrae (cytoplasmic pores) and change their crosstalk with other cellular interactions in the hepatic blood environment. LSEC‑targeted therapy has shown promising effects on fibrosis resolution, opening up new opportunities for anti‑fibrotic therapy. In light of this, the present study summarized changes in LSECs during liver fibrosis and their interactions with hepatic milieu, as well as possible therapeutic approaches that specially target LSECs.

Digitalization of Family Planning Services: A Reality or Fantasy?

This position paper examines the changing environment of digitalizing family planning services, investigating how established healthcare paradigms might be transformed via the incorporation of new technology. The increasing use of digital technologies in the healthcare sector has brought attention to the provision of family planning services, leading to an examination of the practicality and achievability of this technological advancement. The study explores several aspects of this discussion, such as the present condition of family planning services, technical advancements, obstacles to digitalization, user viewpoints, and policy deliberations. The story begins by analysing the wider digitalization patterns in healthcare, setting the stage for the convergence of technology and reproductive health. The study critically examines the significance of digital technologies in family planning, including both the potential advantages and difficulties they may provide. It tackles the obstacles related to privacy, access, and cultural factors, in contrast to the optimistic potential of developing technology. The article showcases case studies and success stories that demonstrate the effectiveness of digital family planning, offering significant insights for future implementation. The report finishes by endorsing a series of policy proposals designed to navigate the complex interaction between technology, ethics, and healthcare infrastructure. These proposals prioritise the need of explicit rules, purposeful investments in digital literacy and accessibility, and smooth integration into current healthcare systems. This study examines the digitization of family planning services, highlighting its role as both a technical innovation and a potential driver of social change. It emphasises the importance of individual empowerment and well-being in discussions about reproductive health.

Identifying spatiotemporal trends of SARS-CoV-2 RNA in wastewater: from the perspective of upstream and downstream wastewater-based epidemiology (WBE).

Recently, many efforts have been made to address the rapid spread of newly identified COVID-19 virus variants. Wastewater-based epidemiology (WBE) is considered a potential early warning tool for identifying the rapid spread of this virus. This study investigated the occurrence of SARS-CoV-2 in eight wastewater treatment plants (WWTPs) and their sewerage systems which serve most of the population in Taoyuan City, Taiwan. Across the entire study period, the wastewater viral concentrations were correlated with the number of COVID-19 cases in each WWTP (Spearman's r = 0.23-0.76). In addition, it is confirmed that several treatment technologies could effectively eliminate the virus RNA from WWTP influent (> 90%). On the other hand, further results revealed that an inverse distance weighted (IDW) interpolation and hotspot model combined with the geographic information system (GIS) method could be applied to analyze the spatiotemporal variations of SARS-CoV-2 in wastewater from the sewer system. In addition, socio-economic factors, namely, population density, land use, and income tax were successfully identified as the potential drivers which substantially affected the onset of the COVID-19 outbreak in Taiwan. Finally, the data obtained from this study can provide a powerful tool in public health decision-making not only in response to the current epidemic situation but also to other epidemic issues in the future.

Human‐associated genetic landscape of walnuts in the Himalaya: implications for conservation and utilization

AbstractAimsA comprehensive understanding of the genetic variation of walnuts (Juglans regia and J. sigillata) in the Himalaya and its potential drivers are essential for the conservation and sustainable utilization of these plant genetic resources. In this study, we aimed to uncover the genetic landscape of walnuts and potential drivers in the Himalaya for better utilization, awareness, sustainable management and conservation of the extant genetic resources of walnuts in the vast Himalayan landscape.LocationThe Himalaya biodiversity hotspot.MethodsA total of 1410 wild or feral walnut trees from 65 populations of J. regia and J. sigillata across four countries in the Himalaya were collected. The genetic diversity, population structure, hybridization and gene flow were thoroughly investigated based on the chloroplast genome and 31 nuclear microsatellite markers. The patterns and drivers of the walnut genetic landscape were further explored.ResultsWe detected three genetic groups of J. regia (JR1, JR2, JR3), one of J. sigillata (JS) and two hybrid types (JR1 × JS and JR3 × JS) of walnut in the Himalaya, with the western Himalaya identified as the genetic diversity hotspot of J. regia. The spatial genetic pattern of the J. regia was significantly influenced by geographic and climatic factors. Human‐mediated dispersal probably promoted the hybridization and gene introgression between J. regia and J. sigillata, which reshaped the genetic landscape of walnut populations in the Himalaya.Main ConclusionsThe extant genetic landscape of walnuts in the Himalaya was driven by natural and anthropogenic forces. Regarding conservation, the western and eastern Himalaya are the genetic reservoir of J. regia and J. sigillata, and hence, pure individuals should be urgently protected from frequent hybridization and introgression. In addition, we propose the utilization of natural hybrid resources coupled with new breeding techniques that combine genomic and phenotypic data.

Integrated Overtaking Model and Safety Analysis for Truck Platooning Requirements on Two-Lane Undivided Highways

Truck platooning is a promising solution for enhancing efficiency and reducing fuel consumption in freight transportation. However, overtaking truck platoons poses safety challenges that need to be addressed. This paper employs an overtaking model incorporating lane change dynamics, and a collision risk assessment to evaluate the safety risks involved in overtaking truck platoons. The safety assessment is presented through a numerical analysis that considers three aspects: roadway geometry, traffic conditions, and driver behavior. Scenarios representing different truck platoon lengths, driver behavior, and opposing traffic conditions are evaluated, highlighting their impact on safety. Two major findings from the assessment are that the overtaking distance and time increase linearly as the truck platoon length increases, and potential driver hesitation and the presence of opposing vehicles are shown to increase collision risks. Safety implications are that the length of truck platoons needs to be regulated on two-lane undivided highways; and driver behavior should be considered in the safety assessment and regulation of truck platooning, but further investigations are needed. From the perspective of overtaking, this paper emphasizes the need for safety guidelines and regulations for truck platooning. Policymakers, transportation agencies, and industry stakeholders may utilize the findings to establish standardized safety measures and protocols.

Methylglyoxal-Derived Nucleoside Adducts Drive Vascular Dysfunction in a RAGE-Dependent Manner.

Diabetic kidney disease (DKD) is a leading cause of death in patients with diabetes. An early precursor to DKD is endothelial cell dysfunction (ECD), which often precedes and exacerbates vascular disease progression. We previously discovered that covalent adducts formed on DNA, RNA, and proteins by the reactive metabolic by-product methylglyoxal (MG) predict DKD risk in patients with type 1 diabetes up to 16 years pre-diagnosis. However, the mechanisms by which MG adducts contribute to vascular disease onset and progression remain unclear. Here, we report that the most predominant MG-induced nucleoside adducts, N2-(1-carboxyethyl)-deoxyguanosine (CEdG) and N2-(1-carboxyethyl)-guanosine (CEG), drive endothelial dysfunction. Following CEdG or CEG exposure, primary human umbilical vein endothelial cells (HUVECs) undergo endothelial dysfunction, resulting in enhanced monocyte adhesion, increased reactive oxygen species production, endothelial permeability, impaired endothelial homeostasis, and exhibit a dysfunctional transcriptomic signature. These effects were discovered to be mediated through the receptor for advanced glycation end products (RAGE), as an inhibitor for intracellular RAGE signaling diminished these dysfunctional phenotypes. Therefore, we found that not only are MG adducts biomarkers for DKD, but that they may also have a role as potential drivers of vascular disease onset and progression and a new therapeutic modality.

High-sensitivity analysis of clonal hematopoiesis reveals increased clonal complexity of potential-driver mutations in severe COVID-19 patients.

Whether Clonal Hematopoiesis (CH) represents a risk factor for severity of the COVID-19 disease remains a controversial issue. We report the first high- sensitivity analysis of CH in COVID-19 patients (threshold of detection at 0.5% vs 1 or 2% in previous studies). We analyzed 24 patients admitted to ICU for COVID-19 (COV-ICU) and 19 controls, including healthy subjects and asymptomatic SARS-CoV2-positive individuals. Despite the significantly higher numbers of CH mutations identified (80% mutations with <2% variant allele frequency, VAF), we did not find significant differences between COV-ICU patients and controls in the prevalence of CH or in the numbers, VAF or functional categories of the mutated genes, suggesting that CH is not overrepresented in patients with COVID-19. However, when considering potential drivers CH mutations (CH-PD), COV-ICU patients showed higher clonal complexity, in terms of both mutation numbers and VAF, and enrichment of variants reported in myeloid neoplasms. However, we did not score an impact of increased CH-PD on patient survival or clinical parameters associated with inflammation. These data suggest that COVID-19 influence the clonal composition of the peripheral blood and call for further investigations addressing the potential long-term clinical impact of CH on people experiencing severe COVID-19. We acknowledge that it will indispensable to perform further studies on larger patient cohorts in order to validate and generalize our conclusions. Moreover, we performed CH analysis at a single time point. It will be necessary to consider longitudinal approaches with long periods of follow-up in order to assess if the COVID-19 disease could have an impact on the evolution of CH and long-term consequences in patients that experienced severe COVID-19.

Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

Genetically based variation in heat tolerance covaries with climate in a globally important disease vector

IntroductionVector-borne diseases (VBDs) are an increasingly important global health concern in the face of climate change. Understanding the ecology and evolution of vector species is critical to predicting and combating VBD. Vectorial capacity models, used to forecast disease transmission, traditionally assume traits are constant among populations, and little is known about whether different vector populations vary in thermal tolerance. To test for geographic variation in upper thermal tolerance, we determined the critical thermal maximum (CTmax) of Aedes albopictus, a globally distributed mosquito and competent vector for many viruses including West Nile, chikungunya, and dengue.MethodsWe studied CTmax for eight different populations spanning four climate zones across the Eastern United States using common garden experiments to isolate genetic variation. To explore potential drivers of this variation we then tested the relationship between climatic variables measured near each population source and CTmax.ResultsWe found significant differences across populations for both adults and larvae, and these differences were more pronounced for adults. Larvae had higher CTmax values compared to adults. Several climatic variables improved models of CTmax for both adults and larvae including mean and max seasonal temperature, annual precipitation, and relative humidity. Annual precipitation appears to be particularly important and has a positive linear relationship with CTmax.DiscussionThe differences between life stages likely result from different selection pressures experienced in their terrestrial and aquatic habitats. Importantly, the assumption that mosquito populations within a species have the same upper thermal limits does not hold in this case, thus it is important to use population-specific CTmax values, among other important physiological parameters that may vary, to more accurately model and forecast VBDs.

The dynamic role of technological innovations and energy structure in China's industrial coal consumption growth: a joint production theoretical decomposition analysis.

China's energy-intensive industries utilize the leading proportion of coal to meet the demand for its industrial outputs, while on the other hand, these industries also assure the provision of livelihood to millions of people, and capping the share of coal consumption for these industries can adversely affect the industrial and economic growth of China. Thus, to achieve the Pareto improvement between environmental pollution and industrial output growth, it is essential to comprehend the patterns of coal consumption in these industries. Hence, the present research intended to analyze the potential drivers of coal consumption by applying a joint LMDI, DEA, and the production theoretical decomposition approach. Findings indices that, first, industrial output growth was the crucial driver to simulate the industrial coal consumption, while the potential coal intensity and coal technology changes exhibited the reverse effect. Second, the coal inputs and industrial output efficiency, along with the improvements in technological gaps, were found to be the imperative factors in decelerating coal consumption. Third, the energy industrial group was discovered to have more potentials of coal conversation as compared to the non-energy industrial group. Moreover, results also indicated that coal pure technical efficiency is accelerating coal growth, which revealed that coal can be saved by enhancing coal allocative efficiency. These findings laid the empirical ground to design a feasible coal conservation policy for achieving the imperative goals of environmental protection without compromising industrial output growth.