bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel medication decision gene signature predicts response to individualized therapy and prognosis outcomes in hepatocellular carcinoma patients
Authors: Yuan Jingsheng , Liu Zijian , Wu Zhenru , Yan Lvnan , Yang Jiayin , Shi Yujun
Published: October 2022

Molecular targeted therapy has shown potential in hepatocellular carcinoma (HCC) patients, and immunotherapy applications are developing rapidly. However, clinical guidance for making individualized therapy decisions for HCC patients remains lacking. MDH (Medication Decision in HCC) gene signatures comprising 70 genes were screened using transcriptomic data from multikinase inhibitor (TKI)-resistant HCC cells and HCC patient-derived xenograft model (PDX) models. Four MDH subtypes with distinct biological and clinical characteristics were defined by unsupervised cluster analysis of HCC data from The Cancer Genome Atlas (TCGA) database. To facilitate individualized and reasonable clinical guidance for each HCC patient, we constructed the MDH score. Comprehensive analysis suggested high MDH scores were associated with TKI resistance, a high proportion of stromal cell infiltration and poor survival outcomes. We recommend concomitant stromal activity intervention and immunotherapy for this type of HCC. Moreover, low MDH scores indicate TKI sensitivity, and a combination of targeted and immunotherapy is recommended. The nomogram constructed by iteration least absolute shrinkage and selection operator (LASSO) Cox regression analysis successfully predicted 3- or 5-year survival outcomes and mortality risks of HCC patients. In conclusion, TKI resistance model-based MDH gene signatures provide novel insight into potential mechanisms of drug resistance and heterogeneity in HCC. Integrative analysis plus a simplified decision model may aid personalized treatment and prognostic assessment among HCC patients.
Host microRNAs are decreased in pediatric solid-organ transplant recipients during EBV+ Post-transplant Lymphoproliferative Disorder
Authors: Sen Ayantika , Enriquez Jeanna , Rao Mahil , Glass Marla , Balachandran Yarl , Syed Sharjeel , Twist Clare J. , Weinberg Kenneth , Boyd Scott D. , Bernstein Daniel , Trickey Amber W. , Gratzinger Dita , Tan Brent , Lapasaran Mary Gay , Robien Mark A. , Brown Merideth , Armstrong Brian , Desai Dev , Mazariegos George , Chin Clifford , Fishbein Thomas M. , Venick Robert S. , Tekin Akin , Zimmermann Heiner , Trappe Ralf U. , Anagnostopoulos Ioannis , Esquivel Carlos O. , Martinez Olivia M. , Krams Sheri M.
Published: October 2022

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Predisposing factors include primary Epstein-Barr virus (EBV) infection, reactivation of EBV in recipient B cells, and decreased T cell immunity due to immunosuppression. In our previous studies EBV infection was demonstrated to markedly alter the expression of host B cell microRNA (miR). Specifically, miR-194 expression was uniquely suppressed in EBV+ B cell lines from PTLD patients and the 3’untranslated region of IL-10 was determined to be targeted by miR-194. Although EBV has been shown to regulate host miR expression in B cell lymphoma cell lines, the expression of miRs in the circulation of patients with EBV-associated PTLD has not been studied. The objective of this study was to determine if changes in miR expression are associated with EBV+ PTLD. In this study, we have shown that miR-194 is significantly decreased in EBV+PTLD tumors and that additional miRs, including miRs-17, 19 and 106a are also reduced in EBV+PTLD as compared to EBV-PTLD. We quantitated the levels of miRs-17, 19, 106a, 155, and 194 in the plasma and extracellular vesicles (EV; 50-70 nm as determined by nanoparticle tracking analysis) from pediatric recipients of solid organ transplants with EBV+ PTLD+ that were matched 1:2 with EBV+ PTLD- pediatric transplant recipients as part of the NIH-sponsored Clinical Trials in Organ Transplantation in Children, (CTOTC-06) study. Levels of miRs-17, 19, 106a, and 194 were reduced in the plasma and extracellular vesicles (EV) of EBV+ PTLD+ group compared to matched controls, with miRs-17 (p = 0.034; plasma), miRs-19 (p = 0.029; EV) and miR-106a (p = 0.007; plasma and EV) being significantly reduced. Similar levels of miR-155 were detected in the plasma and EV of all pediatric SOT recipients. Importantly, ~90% of the cell-free miR were contained within the EV supporting that EBV+ PTLD tumor miR are detected in the circulation and suggesting that EVs, containing miRs, may have the potential to target and regulate cells of the immune system. Further development of diagnostic, mechanistic and potential therapeutic uses of the miRs in PTLD is warranted.
Case Report: Thalidomide in the treatment of complicated central nervous system tuberculosis
Authors: Liu Ping , Li Tao , Xi Xiuhong , Pei Ning , Huang Wei , Liu Xuhui , Xia Lu , Yang Yang , Lu Shuihua
Published: October 2022

Central nervous system tuberculosis (CNSTB) is the most fatal type of tuberculosis (TB). Early administration of glucocorticoids can improve the prognosis of CNSTB patients and reduce mortality; however, some CNSTB patients do not respond well to anti-tuberculosis drugs and glucocorticoids. As an immunomodulatory drug, Thalidomide has been used under such circumstances. We retrospectively reviewed the drug to describe its clinical characteristics, efficacy, and safety in the treatment of four complicated CNSTB patients who responded well to thalidomide. Thalidomide may be an effective and well-tolerated drug for the treatment of CNSTB, and therefore requires further study.
Thermal tolerance and critical maxima examined in marine gastropods inhabiting around Karachi Nuclear Power Plant
Authors: Shaikh Wajiha , Panhwar Sher Khan , Yaqoob Nadeem
Published: October 2022

Bensthic communities along the coastal basins are an indication of ecosystem health but highly susceptible owing to manmade activities. This study envisages thermal tolerance in sea snailsMonodonta canalifera,Nerita albicillaandTylothais savignyiinhabiting around the outfall and intake structures of Karachi Nuclear Power Plant (KANUPP). To test the adaptability and vulnerability, a lethality test protocol under controlled temperature was applied in the laboratory where they were exposed at 25, 30, 35, and 40°C, which was raised to 45°C after an acclimation period of 1 week. The critical thermal maximum (CTmax) for the three species was found to be between 39 and 42°C, whereas the lethal temperature (LT50) tests revealed that at the utmost 45°C was lethal forM. canalifera. The correlation between LT50and CTmaxima(R= 0.47,p= 0.00) and LT50and body sizes reveals that the thermal adaptability inN. albicillaandT. savignyi(R= 0.65,p= 0.00) was relatively higher than that at 45°C given in the laboratory. In addition, microscopic changes due to temperature, which appeared in the foot (adhesive part) of each species, were deduced from the histological examination. The outcomes of this study would help to underline the ecosystem health around KANUPP and highlight precautionary measures required for the newly established K2/K3 power units to safeguard habitat.
Macrobenthic community of an anthropogenically influenced mangrove associated estuary on the East coast of India: An approach for ecological assessment
Authors: Nayak Aswini , Equbal Jawed , Rout Sonali Sanghamitra , Dash Bhagyashree , Thiruchitrambalam Ganesh , Bhadury Punyasloke , Satyanarayana Behara , Raut Dipti
Published: October 2022

The Mahanadi Estuarine System (MES), with a complex network of freshwater channels, rivers, and mangroves, is a leading seaport in State Odisha on the east coast of India, but subjected to intense human activity in recent years. Such anthropic impingements are known to impact sediment-dwelling biota adversely. However, information on the macrobenthic community of the MES is not well documented yet. Therefore, the primary objectives of this study (February 2013-March 2017) were to address knowledge gaps on the macrobenthic community structure vis-à-vis local environmental conditions and to evaluate the extent of anthropogenic disturbances on macrobenthos. The results from 264 benthic grab samples (van Veen, 0.04 m2; 2 replicates × 12 GPS fixed locations × 3 seasons) revealed 73 taxa representing 64 genera and 48 families of macrobenthic fauna. The polychaetes (81.41%) and crustaceans (15.42%) were significant faunal groups that contributed mainly to the benthic population and diversity. Multivariate approaches using benthic community attributes and biotic indices (AMBI and M-AMBI) as proxy measures of environmental disturbances proved effective for appraisal. The correlations between the environmental parameters (temperature, pH, salinity) and community estimates were statistically significant. Hierarchical clustering analysis disclosed three major groups (Global R 0.70; p < 0.002) influenced by tolerant/opportunist species. The lower abundance, richness, diversity, and dominance of opportunistic species mark the signs of environmental stress. The community health status remained unbalanced, as indicated by AMBI scoring. M-AMBI analysis contributed best in differentiating areas exposed to diverse impacts and indicated polluted community health status with moderate ecological quality. Our results reiterate the effective use of macrobenthos as bioindicators for ecological status and monitoring. The findings could be utilized for future monitoring assessments, translated into valuable information, and designed into well-defined sustainable management strategies for the MES.
Microalgal lutein biosynthesis: Recent trends and challenges to enhance the lutein content in microalgal cell factories
Authors: Patel Alok , Rova Ulrika , Christakopoulos Paul , Matsakas Leonidas
Published: October 2022

Photosynthetic organisms such as eukaryotic microalgae and prokaryotic cyanobacteria synthesize a wide range of valuable chemicals. They are predicted to become efficient and renewable sources for valuable products in the future due to their high biomass synthesis using CO2 and solar energy. Microalgae are producers of several carotenoids including lutein, which is a xanthophyll carotenoid with several health advantages, including the prevention of age-related macular degeneration. Currently, it is extracted on commercial scale from marigold flower petals, however, production from plant sources is highly affected by seasonal variations, requires arable land, and has high production cost. Microalgae, on the other hand, are an ideal alternative for lutein synthesis due to their rapid growth and high biomass and lutein yield. It is, however, necessary to further improve lutein productivity, for a successful transition to commercial production. This article describes lutein biosynthesis in microalgae by using their native biochemical pathways, as well as possible target genes for genetic engineering to enhance lutein production. Understanding the processes behind lipid droplet synthesis in chloroplasts, as well as carotenoid transport across chloroplast membranes and carotenoid esterification, might lead to novel ways to boost lutein levels in microalgae.
Distribution of blue and sei whale vocalizations, and temperature - salinity characteristics from glider surveys in the Northern Chilean Patagonia mega-estuarine system
Authors: Buchan Susannah J. , Gutiérrez Laura , Baumgartner Mark F. , Stafford Kathleen M. , Ramirez Nadin , Pizarro Oscar , Cifuentes Jose
Published: October 2022

Northern Chilean Patagonia is a mega-estuarine system where oceanic waters mix with freshwater inputs in the coastal fjords, channels and gulfs. The aim of this study was to examine the distribution of blue and sei whales with respect to oceanographic conditions of the study area from the estuarine inner sea to the outer ocean. Ocean gliders were used, mounted with a hydrophone to determine acoustic presence of whales (Southeast Pacific and Antarctic blue whale song calls, and blue whales D-calls; sei whale downsweeps and upsweeps), and a temperature and salinity instrument. Four glider deployments were carried out in April 2018 and April-June 2019 navigating a total of 2817 kilometers during 2110 hours. To examine interannual variation, the average percentage of day with presence of calls was compared between years using the adjusted p-values for one-way ANOVA and descriptive statistics. To examine spatial variation between the hourly acoustic presence of blue whales and sei whales and temperature and salinity conditions, Generalized Linear Models (GLMs) were used. Salinities were higher in 2019 compared to 2018. Southeast Pacific blue whales produced song calls throughout the study area in both years, across estuarine and oceanic areas, but percentage of day with presence was higher in 2019 vs 2018. Percentage of day with presence of D-calls was similar between years, but higher in oceanic areas during both study periods. In contrast, the spatial pattern of sei whale acoustic presence was ambiguous and interannual variability was high, suggesting that sei whales preferred estuarine areas in 2018 and oceanic areas in 2019. We discuss possible explanations for observed acoustic presence in relation to foraging behavior and prey distribution.
Assessing the patchiness of early life stage of a fish stock (Gadus morhua) and its contribution to the stock recruitment
Authors: Dupont Nicolas , Vikebø Frode B. , Langangen Øystein
Published: October 2022

Patchiness, defined as spatial heterogeneity in distribution of organisms, is a common phenomenon in zooplankton including ichtyoplankton. In heterogeneous landscapes, depending on the scale of prey and predatory distributions, individuals in patches may experience distinct differences in the survival rate compared to individuals distributed more homogeneously outside patches. In this study, we focused on drifting eggs and larvae of Northeast Arctic (NEA) cod, one of the largest exploited fish stock in the world. The eggs and larvae are largely distributed along the north-western coast of Norway and northern Russia. We ask to what degree individuals are located in patches contribute to the species recruitment. For this purpose, we developed a patch recognition method to detect the existence of patches in particle tracking simulations using a connected-component labeling algorithm. We then assessed the contribution of individuals in detected patches to the total recruitment. Our results showed that depending on year, day of year, and resolution scale for detection of patches, recruits present in patches can vary between 0.6% and 38.7% with an average of 20.4% of total recruitment. The percentage decreased with increasing day of year in the drifting season but increased with decreasing patch resolution scale, down to the finest investigated scale of 8 km. On the basis of these results, we advise field recruitment studies of NEA cod to at least resolve an 8-km spatial scale to capture effects of spatial heterogeneity in the survival rate on the species recruitment.
Testing the hypoxia tolerance and hypoxic performance of fishes: A two-tier screening approach
Authors: Zhang Yangfan , Farrell Anthony P.
Published: October 2022

With regional hypoxic episodes in the world’s oceans becoming more severe and more frequent, a valuable management need will be a screening protocol to characterize the full diversity of hypoxic robustness among fishes (defined here as their tolerance and performance). Yet, high-throughput screening protocols to deal with the almost 33,000 fish species have the potential to trade off convenience with the information depth normally provided with comprehensive but more time-consuming phenotyping protocols. As a solution, we propose a two-tier testing approach, one that combines a simple, rapid, cost-effective, and well-established hypoxia challenge test (a measure of hypoxic tolerance) with an individual-based hypoxic performance test that defines maximum aerobic capacity over a wide range of ambient water oxygen levels (a hypoxic performance curve). The later test would be performed on selected indicator species identified from the tolerance screening test. Here we describe the two methodological approaches for this two-tier approach using some existing data to illustrate the potential for their applications in marine science.
Variation in the attached community structure and function of artificial habitats during ecological succession: A case study of the artificial reef area in Bailong Pearl Bay, China
Authors: Li Ruolin , Guo Yu , Zhang Ankai , Zhang Shuo , Zhang Hui , Qin Chuanxin
Published: October 2022

With the continuous development of ports, ship transportation, resource extraction and artificial habitat deployment, an increasing number of artificial structures have created new usable spaces for marine organisms, and the biological communities living on their surfaces have undergone ecological succession. However, related studies have ignored ecological functions, interspecific relationships, and stability in different successional stages. Based on traditional taxonomy, this study applied functional diversity, niche overlap and niche breadth indexes to compare the attached organisms on artificial reefs (ARs) with different construction times in Bailong Pearl Bay, Fangchenggang City, Guangxi Zhuang Autonomous Region, China. The change trends of richness, habitat resource supply, resource utilization degree and efficiency, and interspecific relationships during the succession process were analysed. The results indicated that richness increased with functional diversity. While the number of species increased, the attached organisms showed different functional characteristics, and the number of species with identical traits decreased. The attached community in the later stage of development had a higher degree of utilization of ecological space, more comprehensive and efficient utilization of effective resources, a stronger degree of complementarity of organismal niches, and weaker interspecific competition. In the early stage of the developmental process, the attached community was affected by more environmental factors and had very significant correlations with those factors. The combination of the niche overlap index and the niche breadth index indicated that the resource supply supporting the survival and development of the attached organisms on the ARs with earlier construction times may be greater. The decrease in the number of biomarkers, the similarity of biomarkers belonging to the same family, and the similarity of dominance alternation all indicated that during the process of long-term development and community succession, the organisms attached to the various parts of the ARs tended to become more similar.
Multi-dietary tracer approach reveals little overlap in foraging ecology between seasonally sympatric ringed and harp seals in the high Arctic
Authors: Desforges Jean-Pierre , Kohlbach Doreen , Carlyle Cody G. , Michel Christine , Loseto Lisa L. , Rosenberg Bruno , Yurkowski David J. , Ferguson Steven H.
Published: October 2022

The rapid rate of climate change in the Arctic is causing broad-scale changes to the physical environment and biological communities. Characterizing the foraging ecology and habitat use of Arctic marine top predators of high ecological and cultural significance is essential to our understanding of their vulnerability to ecosystem change, especially when there is potential for dietary resource competition in spatially co-occurring species. We therefore undertook this study to explore dietary resource competition between seasonally sympatric ringed seals (Pusa hispida) and harp seals (Pagophilus groenlandicus) in Mittimatalik (previously known as Pond Inlet), Nunavut, Canadian Arctic. We used bulk stable isotopes (δ13C and δ15N), fatty acid-specific carbon isotopes (δ13C), fatty acid profiles, and diatom lipid biomarkers in a multi-tracer framework to track carbon and trophic pathways in liver and muscle of both seal species. Altogether, the dietary tracers showed little overlap in the diet between ringed seals and harp seals when they co-occurred in the open-water season in northwest Baffin Bay. Though a high dependence on sea ice-derived carbon sources for both species was found, dietary tracers suggested that ringed seals relied to a far greater extent on sympagic carbon sources (~80% vs. 50% for harp seals) and a greater extent of benthic/coastal prey species compared to the more pelagic feeding harp seals. Ringed seal samples were available year-round, and analyses revealed a clear seasonal pattern of foraging on sympagic and benthic prey during ice-covered months of the year and shifting to greater reliance on pelagic prey during the summer open-water season. Overall, ringed seals may be more vulnerable to changes in sea-ice dynamics in the rapidly changing Arctic than harp seals, though it remains difficult to predict future dietary plasticity and competition between co-occurring top predators in an increasingly ice-free Arctic with a changing prey community.
The quest for ghost gear in the German Baltic Sea: A team effort between WWF, divers, fisherfolk, and public authorities
Authors: Stolte Andrea , Dederer Gabriele , Lamp Jochen , Fenn Crayton , Lee Mareen , Frank Wolfgang , Howe Christian , Günther Michael , Vesper Heike , Werner Stefanie
Published: October 2022

In this pilot project, World Wild Fund for Nature (WWF) Germany works together with regional divers, fisherfolk and public authorities to reduce the impact of lost fishing gear in the Baltic Sea. If not removed, ghost gear poses a threat to the marine environment and wildlife including seabirds, seals, harbour porpoises and fish. Over decades to centuries, lost fishing nets and ropes shed microplastic fibres into the marine environment. Removing this hazard reduces both the risk of entanglement as well as the contamination of the marine foodweb through ingestion of microplastics and associated chemicals. Identifying lost fishing gear in the marine environment poses one of the largest challenges impeding mitigation through gear retrieval operations. Lost gear can be drifting on the surface, in the water column, or can be sunken to the seafloor as a result of material composition, fouling, and entanglement. In the Baltic Sea, ghost gear is located on the seafloor and not visible during visual surface surveys from vessels. Identifying an efficient search methodology was therefore a key aspect of WWF’s ghost gear project. After trials with different search and retrieval methodologies, WWF Germany found sonar search technology to be the most efficient technique to locate lost gear on the seafloor. Sound waves avoid the limitations faced by divers or visual cameras in low-visibility environments, and a substantially larger area can be covered. In contrast to diving teams focussing on wreck retrievals, the many nets lost on the seafloor remain unnoticed by divers under most circumstances. A combination of sonar search providing exact GPS positions of suspect ghost gear, diver verification through the WWF Ghostdiver App, point-on retrievals with fishing vessels, and manual sorting for waste management provides an efficient methodology for long-term political implementation of regular lost gear retrieval campaigns.
Bending waves localized along the edge of a semi-infinite piezoelectric plate with orthogonal symmetry
Authors: Nie Guoquan , Lei Zhenyu , Liu Jinxi , Zhang Lele
Published: October 2022

We study the propagation of bending waves along the free edge of a semi-infinite piezoelectric plate within the framework of two-variable refined plate theory (TVPT, a high-order plate theory), Reissner-Mindlin refined plate theory (RMPT, a first-order plate theory), and the classical plate theory (CPT). The piezoelectric plate has macroscopic symmetry of orthogonal mm2 The governing equations are derived using Hamilton principle. The dispersion relations for electrically open and shorted boundary conditions at the free edge are obtained analytically. The difference in dispersion property between the three plate theories is analyzed. The numerical results show that the dispersion curves predicted by TVPT and RMPT are similar and have small difference over the complete frequency range, which means both the two theories are valid for the analysis of edge waves in a piezoelectric plate. But the wave velocity calculated by CPT is much larger than the two theories above and is no longer valid for high frequency and thick plate. The electrical boundary condition at the free edge has an insignificant effect on phase velocity and group velocity which can be ignored for the analysis of edge waves in a piezoelectric plate governed by bending deformation. The velocity of bending edge waves in a semi-infinite piezoelectric plate is positively related to that of Rayleigh surface wave in a traction-free piezoelectric half-space. The edge wave velocity can be enhanced when the piezoelectric plate is considered as one with weaker anisotropy.
Gastrointestinal symptoms have a minor impact on autism spectrum disorder and associations with gut microbiota and short-chain fatty acids
Authors: Deng Wenlin , Wang Siqi , Li Fang , Wang Fang , Xing Yi Pei , Li Yongchun , Lv Ying , Ke Haoran , Li Zitong , Lv Pin Jing , Hao Hu , Chen Ye , Xiao Xin
Published: October 2022

Children with autism spectrum disorder (ASD) experience gastrointestinal (GI) issues more frequently and severely than children who are typically developing (TD). The connections between gastrointestinal problems, microbiota, and short-chain fatty acids (SCFAs) in ASD are still being debated. We enrolled 90 children, 45 of whom were diagnosed with ASD, and examined the impact of GI disorders on ASD. The six-item GI Severity Index questionnaire was used to evaluate gastrointestinal symptoms, while the Social Responsiveness Scale was used to evaluate autism symptoms. Further, the Children’s Sleep Habits Questionnaire and the Children’s Eating Behavior Questionnaire are used to assess sleep and eating disorders in children. We assessed fecal microbiota by 16S rRNA gene sequencing, and SCFA concentrations by gas chromatography/mass spectrometry. The results revealed that children with ASD exhibited a high rate of gastrointestinal issues (78%), as well as higher rates of social impairment and poor sleeping habits, compared to TD children. However, GI disturbances have a minor impact on autism. In addition, the levels of propionic acid, butyric acid, and valeric acid were significantly higher in the ASD group. Besides, the ASD, TD, and GI subgroups possessed distinct microbiome profiles. These findings suggest that gastrointestinal disturbances have no discernible effect on the core symptoms of autism. Although autism may not cause an increase in GI symptoms directly, alterations in metabolites, such as SCFAs, may cause GI symptoms.
A novel detection method for the pathogenic Aeromonas hydrophila expressing aerA gene and/or hlyA gene based on dualplex RAA and CRISPR/Cas12a
Authors: Lin Ziqin , Lu Jinfang , Wu Sihong , Lin Xi , Zheng Laibao , Lou Yongliang , Xiao Xingxing
Published: October 2022

Aeromonas hydrophila is an emerging waterborne and foodborne pathogen with pathogenicity to humans and warm water fishes, which severely threatens human health, food safety and aquaculture. A novel method for the rapid, accurate, and sensitive detection of pathogenic A. hydrophila is still needed to reduce the impact on human health and aquaculture. In this work, we developed a rapid, accurate, sensitive, and visual detection method (dRAA-CRISPR/Cas12a), without elaborate instruments, integrating the dualplex recombinase-assisted amplification (dRAA) assay and CRISPR/Cas12a system to detect pathogenic A. hydrophila expressing aerA and/or hlyA virulence genes. The dRAA-CRISPR/Cas12a method has high sensitivity, which can rapidly detect (about 45 min) A. hydrophila with the limit of detection in 2 copies of genomic DNA per reaction, and has high specificity for three pathogenic A. hydrophila strains (aerA+hlyA−, aerA−hlyA+, and aerA+hlyA+). Moreover, dRAA-CRISPR/Cas12a method shows satisfactory practicability in the analysis of the spiked human blood and stool and fish samples. These results demonstrate that our developed pathogenic A. hydrophila detection method, dRAA-CRISPR/Cas12a, is a promising potential method for the early diagnosis of human A. hydrophila infection and on-site detection of A. hydrophila in food and aquaculture.
Artificial intelligence methods enhance the discovery of RNA interactions
Authors: Pepe G , Appierdo R , Carrino C , Ballesio F , Helmer-Citterich M , Gherardini PF
Published: October 2022

Understanding how RNAs interact with proteins, RNAs, or other molecules remains a challenge of main interest in biology, given the importance of these complexes in both normal and pathological cellular processes. Since experimental datasets are starting to be available for hundreds of functional interactions between RNAs and other biomolecules, several machine learning and deep learning algorithms have been proposed for predicting RNA-RNA or RNA-protein interactions. However, most of these approaches were evaluated on a single dataset, making performance comparisons difficult. With this review, we aim to summarize recent computational methods, developed in this broad research area, highlighting feature encoding and machine learning strategies adopted. Given the magnitude of the effect that dataset size and quality have on performance, we explored the characteristics of these datasets. Additionally, we discuss multiple approaches to generate datasets of negative examples for training. Finally, we describe the best-performing methods to predict interactions between proteins and specific classes of RNA molecules, such as circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), and methods to predict RNA-RNA or RNA-RBP interactions independently of the RNA type.
Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis
Authors: Yuan Mengqin , Hu Xue , Yao Lichao , Liu Pingji , Jiang Yingan , Li Lanjuan
Published: October 2022

Hepatitis B virus (HBV) infection remains the leading cause of liver fibrosis (LF) worldwide, especially in China. Identification of decisive diagnostic biomarkers for HBV-associated liver fibrosis (HBV-LF) is required to prevent chronic hepatitis B (CHB) from progressing to liver cancer and to more effectively select the best treatment strategy. We obtained 43 samples from CHB patients without LF and 81 samples from CHB patients with LF (GSE84044 dataset). Among these, 173 differentially expressed genes (DEGs) were identified. Functional analysis revealed that these DEGs predominantly participated in immune-, extracellular matrix-, and metabolism-related processes. Subsequently, we integrated four algorithms (LASSO regression, SVM-RFE, RF, and WGCNA) to determine diagnostic biomarkers for HBV-LF. These analyses and receive operating characteristic curves identified the genes for phosphatidic acid phosphatase type 2C (PPAP2C) and versican (VCAN) as potentially valuable diagnostic biomarkers for HBV-LF. Single-sample gene set enrichment analysis (ssGSEA) further confirmed the immune landscape of HBV-LF. The two diagnostic biomarkers also significantly correlated with infiltrating immune cells. The potential regulatory mechanisms of VCAN underlying the occurrence and development of HBV-LF were also analyzed. These collective findings implicate VCAN as a novel diagnostic biomarker for HBV-LF, and infiltration of immune cells may critically contribute to the occurrence and development of HBV-LF.
Distinct mRNA and protein interactomes highlight functional differentiation of major eIF4F-like complexes from Trypanosoma brucei
Authors: Bezerra Maria J. R. , Moura Danielle M. N. , Freire Eden R. , Holetz Fabiola B. , Reis Christian R. S. , Monteiro Tallyta T. S. , Pinto Adriana R. S. , Zhang Ning , Rezende Antonio M. , Pereira-Neves Antonio , Figueiredo Regina C. B. Q. , Clayton Christine , Field Mark C. , Carrington Mark , de Melo Neto Osvaldo P.
Published: October 2022

Gene expression in pathogenic protozoans of the family Trypanosomatidae has several novel features, including multiple eIF4F-like complexes involved in protein synthesis. The eukaryotic eIF4F complex, formed mainly by eIF4E and eIF4G subunits, is responsible for the canonical selection of mRNAs required for the initiation of mRNA translation. The best-known complexes implicated in translation in trypanosomatids are based on two related pairs of eIF4E and eIF4G subunits (EIF4E3/EIF4G4 and EIF4E4/EIF4G3), whose functional distinctions remain to be fully described. Here, to define interactomes associated with both complexes in Trypanosoma brucei procyclic forms, we performed parallel immunoprecipitation experiments followed by identification of proteins co-precipitated with the four tagged eIF4E and eIF4G subunits. A number of different protein partners, including RNA binding proteins and helicases, specifically co-precipitate with each complex. Highlights with the EIF4E4/EIF4G3 pair include RBP23, PABP1, EIF4AI and the CRK1 kinase. Co-precipitated partners with the EIF4E3/EIF4G4 pair are more diverse and include DRBD2, PABP2 and different zinc-finger proteins and RNA helicases. EIF4E3/EIF4G4 are essential for viability and to better define their role, we further investigated their phenotypes after knockdown. Depletion of either EIF4E3/EIF4G4 mRNAs lead to aberrant morphology with a more direct impact on events associated with cytokinesis. We also sought to identify those mRNAs differentially associated with each complex through CLIP-seq with the two eIF4E subunits. Predominant among EIF4E4-bound transcripts are those encoding ribosomal proteins, absent from those found with EIF4E3, which are generally more diverse. RNAi mediated depletion of EIF4E4, which does not affect proliferation, does not lead to changes in mRNAs or proteins associated with EIF4E3, confirming a lack of redundancy and distinct roles for the two complexes.
Combining cysteine scanning with chemical labeling to map protein-protein interactions and infer bound structure in an intrinsically disordered region
Authors: Ahmed Shahbaz , Chattopadhyay Gopinath , Manjunath Kavyashree , Bhasin Munmun , Singh Neelam , Rasool Mubashir , Das Sayan , Rana Varsha , Khan Neha , Mitra Debarghya , Asok Aparna , Singh Ramandeep , Varadarajan Raghavan
Published: October 2022

The Mycobacterium tuberculosis genome harbours nine toxin-antitoxin (TA) systems of the mazEF family. These consist of two proteins, a toxin and an antitoxin, encoded in an operon. While the toxin has a conserved fold, the antitoxins are structurally diverse and the toxin binding region is typically intrinsically disordered before binding. We describe high throughput methodology for accurate mapping of interfacial residues and apply it to three MazEF complexes. The method involves screening one partner protein against a panel of chemically masked single cysteine mutants of its interacting partner, displayed on the surface of yeast cells. Such libraries have much lower diversity than those generated by saturation mutagenesis, simplifying library generation and data analysis. Further, because of the steric bulk of the masking reagent, labeling of virtually all exposed epitope residues should result in loss of binding, and buried residues are inaccessible to the labeling reagent. The binding residues are deciphered by probing the loss of binding to the labeled cognate partner by flow cytometry. Using this methodology, we have identified the interfacial residues for MazEF3, MazEF6 and MazEF9 TA systems of M. tuberculosis. In the case of MazEF9, where a crystal structure was available, there was excellent agreement between our predictions and the crystal structure, superior to those with AlphaFold2. We also report detailed biophysical characterization of the MazEF3 and MazEF9 TA systems and measured the relative affinities between cognate and non-cognate toxin–antitoxin partners in order to probe possible cross-talk between these systems.
Exploring nanoselenium to tackle mutated SARS-CoV-2 for efficient COVID-19 management
Authors: Singh Avtar , Singh Paramjit , Kumar Rajeev , Kaushik Ajeet
Published: October 2022

Despite ongoing public health measures and increasing vaccination rates, deaths and disease severity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new emergent variants continue to threaten the health of people around the world. Therefore, there is an urgent need to develop novel strategies for research, diagnosis, treatment, and government policies to combat the variant strains of SARS-CoV-2. Since the state-of-the-art COVID-19 pandemic, the role of selenium in dealing with COVID-19 disease has been widely discussed due to its importance as an essential micronutrient. This review aims at providing all antiviral activities of nanoselenium (Nano-Se) ever explored using different methods in the literature. We systematically summarize the studied antiviral activities of Nano-Se required to project it as an efficient antiviral system as a function of shape, size, and synthesis method. The outcomes of this article not only introduce Nano-Se to the scientific community but also motivate scholars to adopt Nano-Se to tackle any serious virus such as mutated SARS-CoV-2 to achieve an effective antiviral activity in a desired manner.
The efficacy and safety of Chinese herbal medicine as an add-on therapy for amyotrophic lateral sclerosis: An updated systematic review and meta-analysis of randomized controlled trials
Authors: Liao Yingdi , He Sijin , Liu Duo , Gu Lihua , Chen Qigang , Yang Shuang , Li Daiying
Published: October 2022

Background

Amyotrophic lateral sclerosis (ALS) has attracted widespread attention because of its unknown pathogenesis, rapid progression, and life-threatening and incurable characteristics. A series of complementary therapies, including Chinese herbal medicine (CHM), is available for use in the clinic and has been the focus of much research. However, it is unclear as to whether supplementary CHM relieves disease symptoms or extends life span; thus, we conducted this updated meta-analysis to validate the efficacy and safety of this practice.

Methods

We searched six electronic databases for randomized controlled trials involving CHM and patients with ALS that were published up to April 2022. Two researchers independently screened the literature, assessed the risk of bias for each trial, and then extracted data. The methodological quality of the included trials was assessed using the Cochrane risk of bias tool, and a pooled data analysis was performed using RevMan 5.3.

Results

A total of 14 trials led to the publication of 15 articles featuring 1,141 participants during the study period; the articles were included in the systematic review. In terms of increasing ALS functional rating scale (ALSFRS) scores, CHM was superior to the placebo after 3 months of treatment [mean difference (MD):0.7; 95% CI:0.43 to 0.98; P < 0.01] and to riluzole after 4 weeks of treatment (MD: 2.87; 95% CI: 0.81 to 4.93; P < 0.05), and it was superior to conventional medicine (CM) alone when used as an add-on therapy after 8 weeks of treatment (MD: 3.5; 95% CI: 0.51 to 6.49; P < 0.05). The change in the modified Norris score (m-Norris) from baseline to the end of more than 3 months of treatment was significantly different when compared between the CHM plus CM group and the CM alone group (MD: 2.09; 95% CI: 0.62 to 3.55; P < 0.01). In addition, CHM had a significantly better effect on increase in clinical effective rate (RR: 1.54; 95% CI: 1.23 to 1.92; P < 0.01) and improvement in forced vital capacity (MD: 7.26; 95% CI: 2.92 to 11.6; P < 0.01). However, there was no significant difference between the CHM therapy and CM in terms of improving life quality (MD: 5.13; 95% CI: −7.04 to 17.31; P = 0.41) and decreasing mortality (RR: 0.41; 95% CI: 0.04 to 4.21; P = 0.46).

Conclusion

The analysis suggested that the short-term adjunct use of CHM could improve the ALSFRS score and clinical effect with a good safety profile when compared with the placebo or riluzole alone. However, future research should be centered on the long-term efficacy of patient-oriented outcomes.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=323047, identifier: CRD42022323047.
Retinal nerve fiber layer in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
Authors: Wong Bryan M. , Hudson Christopher , Snook Emily , Tayyari Faryan , Jung Hyejung , Binns Malcolm A. , Samet Saba , Cheng Richard W. , Balian Carmen , Mandelcorn Efrem D. , Margolin Edward , Finger Elizabeth , Black Sandra E. , Tang-Wai David F. , Zinman Lorne , Tan Brian , Lou Wendy , Masellis Mario , Abrahao Agessandro , Frank Andrew , Beaton Derek , Sunderland Kelly M. , Arnott Stephen R. ,   ONDRI Investigators, Tartaglia Maria Carmela , Hatch Wendy V.
Published: October 2022

Purpose

Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect in vivo. This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate in vivo the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia).

Study design

Prospective, multi-centre, observational study.

Materials and methods

pRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness.

Results

A significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (n = 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (n = 9 eyes; mean difference = 15.46 μm, SE = 6.98, p = 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness.

Conclusion

The finding that the temporal pRNFL in the TDP-43 group was on average 15.46 μm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.
The independent adverse prognostic significance of 1q21 gain/amplification in newly diagnosed multiple myeloma patients
Authors: You Hongying , Jin Song , Wu Chunxiao , Wang Qingqing , Yan Shuang , Yao Weiqin , Shi Xiaolan , Shang Jingjing , Yan Lingzhi , Yao Ying , Wang Jing , Wang Panfeng , Pan Jinlan , Wu Depei , Fu Chengcheng
Published: October 2022

Objective

1q21 gain/amplification (1q21+) is a common abnormal karyotype in multiple myeloma, and its proportion in Chinese patients is much higher. If 1q21+ is included as one of the poor prognostic factors, it will greatly increase the proportion of high-risk patients in newly diagnosed multiple myelome (NDMM) patients. Therefore, the poor prognostic significance of 1q21+ is still controversial. This study mainly analyzed the clinical characteristics, treatment response and prognostic significance of 1q21+ in NDMM patients.

Methods

248 NDMM patients admitted in The First Affiliated Hospital of Soochow University from September 01, 2018 to August 31, 2021 of a VRD registration study, were retrospectively analyzed. 135 cases (54.4%) had 1q21+ by CD38-sorted fluorescence in situ hybridization (FISH). The clinical characteristics, treatment response and prognosis of the general population and subgroups were analyzed, among which 153 patients were compared for the involved genes by CytoScan.

Results

Compared with negative patients, 1q21+ patients were more likely to have anemia, hypoalbuminemia, renal insufficiency, high lactate dehydrogenase and high proportion of R-ISS-III stage. The patients with 1q21+ involving CKS1B detected by Cytoscan had a higher proportion of complex karyotypes and abnormal CNVs, and all at middle-risk or high-risk groups defined by Prognostic Index. Multivariate analysis showed that 1q21+ was an independent adverse prognostic factor (PFS HR=2.358, 95%CI 1.286-4.324, P=0.006; OS HR=2.598, 95%CI 1.050-6.425, P=0.039). 1q21+ subgroup had an inferior outcome (PFS P=0.0133, OS P=0.0293). Furthermore 1q21 amplification had a shorter PFS than 1q21 gain (24 months vs not reached, P=0.0403), but the OS difference was not clinically significant. The proportion of 1q had no effects on prognosis. In addition, 1q21+ in main clone rather than subclone was an adverse factor affecting the prognosis (PFS P=0.0172, OS P=0.1260). Autologous stem cell transplantation can effectively improve the survival of 1q21+ patients (P<0.05).

Conclusion

Patients with 1q21+ have clinically significant end-stage organ damage and higher tumor burden, more likely to combine 13q14-, t(4;14), 1p32- and other cytogenetic abnormalities. 1q21+ is an independent high-risk cytogenetic factor for poor prognosis in NDMM patients, of which 4 or more copy numbers and main clone position significantly associated with prognosis results.
Evaluation of the efficacy and feasibility of concurrent weekly docetaxel-nedaplatin and hypo-fractionated radiotherapy in atypical histologic subtypes of primary and metastatic mediastinal malignancies
Authors: Meng FanJun , Ai XinLei , Wang Bin , Zhou Yin , Li Su , Wang DaQuan , Liu FangJie , Chen NaiBin , Zhou Rui , Guo JinYu , Huang XiaoYan , Yin ShaoHan , Qiu Bo , Liu Hui
Published: October 2022

Background

We aimed to evaluate the efficacy and feasibility of concurrent weekly docetaxel-nedaplatin and hypo-fractionated radiotherapy (hypo-RT) in atypical histologic subtypes of primary and metastatic mediastinal malignancies.

Methods

Fifty-four patients diagnosed with atypical primary or metastatic mediastinal malignancies were retrospectively reviewed. 30 patients received concurrent weekly docetaxel and nedaplatin and hypo-RT (CChRT group) and 24 patients had hypo-RT alone (hRT group). Overall response rate (ORR), in-field locoregional progression-free survival (LPFS) and toxicities were analyzed. The radiobiological effect was evaluated by the LQRGC/TCP model, incorporating four “R”s of radiobiology, Gompertzian tumor growth and radio-sensitizing effect of chemotherapeutic agent. The biologically effective doses (BEDs) were calculated.

Results

The median follow-up time was 29.2 months for all patients. The ORR was 86.7% in CChRT group, compared with 62.5% in hRT group (p=0.033). The 2-year in-field LPFS of CChRT and hRT group was 73.4% and 47.3%, respectively (p=0.003). There was no significant difference of any >=Grade 3 toxicities between the two groups (p=0.754). The mean total dose and mean BED by the LQRGC/TCP model in CChRT group were 58.2Gy and 72.34Gy, versus 52.6Gy and 67.25Gy in hRT group.

Conclusions

Concurrent weekly docetaxel-nedaplatin and hypo-RT achieved promising in-field LPFS and tolerable toxicities compared with hypo-RT alone in different histologic subtypes of primary and metastatic mediastinal malignancies.