bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial suitability evaluation of spawning reach revealing the location preference for fish producing drifting eggs
Authors: Zhou Huabin , Yu Chunxue , Xu Zhihao , Zheng Yuanhuan , Hou Xiaoshu
Published: September 2022

Hydrologic (water temperature) and hydrodynamic (water depth, flow velocity, and Froude number) factors affect fish spawning activities, and spawning grounds provide suitable hydrologic and hydrodynamic conditions for fish spawning to occur. However, locating fish spawning grounds is encumbered by uncertainty, particularly for pelagic spawners. This may be because such fish species have unique hydrologic and hydrodynamic requirements during their spawning periods, resulting in the wide-ranging approaches used to locate their spawning grounds. Accordingly, this study was designed to accurately locate fish spawning grounds through means of spatial suitability evaluation. For this experiment, the four major “Asian carp” target species were selected in the Dongta spawning reach, a tributary of the Pearl River. First, we investigated the historical information on the location of the spawning reaches. An acoustic doppler current profiler (ADCP) was used to measure topographic and hydrodynamic data of the spawning reaches during the spawning period. Then, based on the spatial clustering method, cluster analysis on spatial attributes (water depth, flow velocity, water temperature, and Froude number) was conducted on potential spawning grounds. The cluster analysis method uses k-means clustering; a method often employed to classify large amounts of data. Finally, we analyzed and evaluated the spatial suitability of spawning reaches by combining fish spawning suitability curves to obtain spatial preferences associated with fish spawning activities. Proportionally, results revealed a high suitability (>0.4) area (60.86%). Moreover, spawning suitability in curved river sections and deep pools in straight river sections were significantly higher than bifurcated sections. Furthermore, areas near the riverbanks were more suitable than mid-course sections of the river. Finally, the locations of six potential Asian carp spawning grounds were determined according to their spatial suitability. This study provides technical support to accurately locate spawning grounds for the fish that produce drifting eggs.
Quantitative three-dimensional morphological analysis supports species discrimination in complex-shaped and taxonomically challenging corals
Authors: Ramírez-Portilla Catalina , Bieger Inge M. , Belleman Robert G. , Wilke Thomas , Flot Jean-François , Baird Andrew H. , Harii Saki , Sinniger Frederic , Kaandorp Jaap A.
Published: September 2022

Morphological characters play an important role in species descriptions and are essential for a better understanding of the function, evolution and plasticity of an organism’s shape. However, in complex-shaped organisms lacking characteristic features that can be used as landmarks, quantifying morphological traits, assessing their intra- and interspecific variation, and subsequently delineating phenotypically distinct groups continue to be problematic. For such organisms, three-dimensional morphological analysis might be a promising approach to differentiate morphogroups and potentially aid the delineation of species boundaries, though identifying informative features remains a challenge. Here, we assessed the potential of 3D-based quantitative morphology to delineatea prioriand/or to discriminatea posteriorimorphogroups of complex-shaped and taxonomically challenging organisms, such as corals from the morphologically diverse genusAcropora. Using three closely related coral taxa previously delimited using other lines of evidence, we extracted a set of variables derived from triangulated polygon meshes and medial axis skeletons of the 3D models. From the resulting data set, univariate and multivariate analyses of 3D-based variables quantifying overall shape including curvature, branching, and complexity were conducted. Finally, informative feature selection was performed to assess the discriminative power of the selected variables. Results revealed significant interspecific differences in the means of a set of 3D-based variables, highlighting potentially informative characters that provide sufficient resolution to discriminate morphogroups congruent with independent species identification based on other lines of evidence. A combination of representative features, remarkably represented by curvature, yielded measures that assisted in differentiating closely related species despite the overall morphospaces overlap. This study shows that a well-justified combination of 3D-based variables can aid species discrimination in complex-shaped organisms such as corals and that feature screening and selection is useful for achieving sufficient resolution to validate species boundaries. Yet, the significant discriminative power displayed by curvature-related variables and their potential link to functional significance need to be explored further. Integrating informative morphological features with other independent lines of evidence appears therefore a promising way to advance not only taxonomy but also our understanding of morphological variation in complex-shaped organisms.
Air exposure and cell differentiation are essential for investigation of SARS-CoV-2 entry genes in human primary airway epithelial cells in vitro
Authors: Kasper Brigitte , Yue Xiaoyang , Goldmann Torsten , Gülsen Askin , Kugler Christian , Yu Xinhua , Petersen Frank
Published: September 2022

Background

In-vitro models of differentiated primary human airway epithelial cells are a valuable tool to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Through the use of these models, it has been shown that the expression of SARS-CoV-2 entry genes in human airway epithelia is influenced by various factors such as age, sex, smoking status, and pathogenic conditions. In this study, we aimed to determine the effects of cell culture conditions and donor demographic and clinical characteristics on the expression of SARS-CoV-2 entry genes including angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), cathepsin L (CTSL), and tyrosine protein kinase receptor UFO (AXL) in primary airway epithelial cells.

Methods

Eleven lung cancer patients with or without chronic obstructive pulmonary disease (COPD) or asthma were recruited. Human bronchial epithelial cells (HBEC) or small airway epithelial cells (SAEC) isolated from submerged or air-liquid interface (ALI) cultures were analyzed by quantitative real-time PCR. We also tested for correlations with clinical data.

Results

In ALI cultures, the expression of AXL was significantly higher in HBEC than in SAEC. In addition, the expression of ACE2, TMPRSS2, and CTSL was significantly increased in both HBEC and SAEC differentiated under ALI conditions compared with the submerged culture. Negligible association was found between the expression of SARS-CoV-2 entry genes in SAEC and the age, sex, smoking status, and complication of COPD, asthma or hypertension of the cell donors.

Conclusion

These results demonstrate that the expression of SARS-CoV-2 entry genes in differentiated primary airway epithelial cells in-vitro is much more influenced by individual culture conditions than by specific characteristics of individual donors.
The impact and role of hepatic hydrothorax in the prognosis of patients with decompensated cirrhosis: A retrospective propensity score-matched study
Authors: Ma Bo , Shang Tianling , Huang Jianjie , Tu Zhixin , Wang Yan , Han Yujin , Wen Xiaoyu , Jin Qinglong
Published: September 2022

Background and aims

Hepatic Hydrothorax (HH) is one of the complications in patients with decompensated cirrhosis and its impact and role in the prognosis of patients with decompensated cirrhosis are not yet clear. Thus, this study aimed to determine the role of HH in patients with decompensated cirrhosis and the long-term impact on their mortality.

Materials and methods

A retrospective study analyzed 624 patients with ascites without pleural effusion in decompensated cirrhosis and 113 patients with HH. Propensity scores were calculated based on eight variables, and the HH and non-HH groups were matched in a 1:1 ratio. The effect and role of HH on the prognosis of patients with decompensated cirrhosis was analyzed using the Kaplan–Meier method and Cox proportional hazards regression model.

Results

A total of 737 patients were included. Out of 113 HH patients, 106 could be matched to 106 non-HH patients. After matching, baseline characteristics were well-balanced. The multifactorial Cox proportional hazards model indicated that hepatic encephalopathy and HH were independent risk factors affecting prognostic survival in patients with decompensated cirrhosis (P < 0.01), with risk ratios and 95% confidence intervals (CI) of 2.073 (95% CI: 1.229–3.494, P < 0.01) and 4.724 (95% CI: 3.287–6.789, P < 0.01), respectively. Prognostic survival was significantly worse in the HH group compared to patients in the non-HH group, with mortality rates of 17.9, 30.1, and 59.4% at 6 months, 1 year, and 2 years in the HH group, compared to 0.9, 3.8, and 5.6% in the non-HH group, respectively. The estimated median survival time was 21 (95% CI: 18–25) months in the HH group and 49 (95% CI: 46–52) months in the non-HH group (P < 0.001).

Conclusion

Hepatic hydrothorax is significantly associated with higher mortality in patients with decompensated cirrhosis and is a highly negligible independent decompensated event affecting their prognosis.
Anabolic-androgenic steroids for patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis
Authors: Liu Yahui , Huang Chunrong , Du Juan , Lan Gelei , Du Xueqing , Sun Yidan , Shi Guochao
Published: September 2022

Background

Testosterone deficiency is common in chronic obstructive pulmonary disease (COPD) patients. There has been a growing interest in the potential use of anabolic-androgenic steroids (AASs) in patients with COPD recently. However, whether AASs could improve their clinical outcomes remains unknown.

Methods

In order to explore the efficacy of AASs in patients with COPD, systematic search of MEDLINE, Embase, the Cochrane Library and ClinicalTrials.gov for randomized controlled trials (RCTs) of AASs for COPD published before March 17, 2022 was performed.

Results

Data were extracted from 8 articles involving 520 participants. The median number of participants per study was 39.5 and the mean follow up was 14.2 weeks. As compared to the control group, AASs therapy could significantly improve body weight (weighted mean difference (WMD), 1.38 kg; 95% CI, 0.79 to 1.97 kg), fat-free mass (WMD, 1.56 kg; 95% CI, 0.94 to 2.18 kg) and peak workload (WMD, 6.89W; 95% CI, 3.97 to 9.81W) of COPD patients, but no improvements in spirometry indicators and six-minute walking distances (WMD, 16.88 m; 95%, −3.27 to 37.04 m). Based on the available research data, it is uncertain whether AASs treatment could improve the quality of life of COPD patients.

Conclusions

Limited published evidence indicates that AASs therapy provides clinical benefits in patients with COPD. However, longer and larger studies are needed to better clarify the efficacy of AASs and draw final conclusions.
Case report: An unusual case of multisite embolism in a patient with adenovirus pneumoniae
Authors: Mao Jia-Yu , Zhao Hua , Cui Na
Published: September 2022

A 36-year-old previous healthy man presented with fever, cough, and dyspnea associated with adenovirus pneumonia. The patient developed left ventricular thrombus, pulmonary embolism and multisite embolism of undetermined etiology. Adenovirus is a rare cause of thrombotic events in immunocompetent individuals, calling for further studies for early diagnosis and management.
Altered B cell phenotype and CD27+ memory B cells are associated with clinical features and environmental exposure in Colombian systemic lupus erythematosus patients
Authors: Hurtado Carolina , Rojas-Gualdrón Diego Fernando , Urrego Rodrigo , Cashman Kevin , Vásquez-Trespalacios Elsa María , Díaz-Coronado Juan Camilo , Rojas Mauricio , Jenks Scott , Vásquez Gloria , Sanz Ignacio
Published: September 2022

Background

B lymphocytes are dysregulated in Systemic Lupus Erythematosus (SLE) including the expansion of extrafollicular B cells in patients with SLE of African American ancestry, which is associated with disease activity and nephritis. The population of Colombia has a mixture of European, Native American, and African ancestry. It is not known if Colombian patients have the same B cell distributions described previously and if they are associated with disease activity, clinical manifestations, and environmental exposures.

Objective

To characterize B cell phenotype in a group of Colombian Systemic Lupus Erythematosus patients with mixed ancestry and determine possible associations with disease activity, clinical manifestations, the DNA methylation status of the IFI44L gene and environmental exposures.

Materials and methods

Forty SLE patients and 17 healthy controls were recruited. Cryopreserved peripheral B lymphocytes were analyzed by multiparameter flow cytometry, and the DNA methylation status of the gene IFI44L was evaluated in resting Naive B cells (rNAV).

Results

Extrafollicular active Naive (aNAV) and Double Negative type 2, DN2 (CD27− IgD− CD21− CD11c+) B cells were expanded in severe active patients and were associated with nephritis. Patients had hypomethylation of the IFI44L gene in rNAV cells. Regarding environmental exposure, patients occupationally exposed to organic solvents had increased memory CD27+ cells (SWM).

Conclusion

aNAV and DN2 extrafollicular cells showed significant clinical associations in Colombian SLE patients, suggesting a relevant role in the disease’s pathophysiology. Hypomethylation of the IFI44L gene in resting Naive B cells suggests that epigenetic changes are established at exceedingly early stages of B cell ontogeny. Also, an alteration in SWM memory cells was observed for the first time in patients exposed to organic solvents. This opens different clinical and basic research possibilities to corroborate these findings and deepen the knowledge of the relationship between environmental exposure and SLE.
Effect of multivitamin drug on intractable dry eye symptoms
Authors: Park Se Hie , Hwang Jin Sun , Shin Young Joo
Published: September 2022

Dry eye is a disorder of tear film and ocular surface characterized by ocular discomforts. It is associated with multiple causes and sometimes intractable. We investigated the effect of oral multivitamin supplementation (MVG) on dry eyes. Tear break-up time (TBUT), fluorescein ocular surface staining score, and tear secretion Schirmer test were measured in dry eye patients refractory to conventional topical treatment. The ocular surface disease index (OSDI), visual analog pain score (VAS), and modified standardized patient evaluation of eye dryness questionnaire were analyzed. In total, 42 eyes of 42 patients were included. TBUT increased at 1 and 3 months compared to baseline (p < 0.05). OSDI decreased at 1 and 3 months compared to baseline (p < 0.05). VAS score, impact on life, and frequency of total symptoms decreased at 3 months compared to baseline (p < 0.05). Oral administration of MVG, a vitamin complex formulation, was effective in stabilizing tear stability and alleviating symptoms in patients with intractable dry eye. Thus, it may be a viable treatment option for intractable dry eye.
Comparison of rumen bacterial communities between yaks (Bos grunniens) and Qaidam cattle (Bos taurus) fed a low protein diet with different energy levels
Authors: Liu Hu , Ran Tao , Zhang Chengfu , Yang Wenzhu , Wu Xiukun , Degen Allan , Long Ruijun , Shi Zunji , Zhou Jianwei
Published: September 2022

The yak (Bos grunniens), an indigenous bovine on the Qinghai-Tibetan plateau (QTP), is reported to digest low quality forage to a greater extent and to require less protein and energy for maintenance than the introduced Qaidam cattle (Bos taurus). Ruminal bacteria play a major role in feed degradation, and therefore, we hypothesized that ruminal bacteria composition would differ between yaks and cattle, and confer an advantage to yaks for poor quality diets. To test our hypothesis, we determined the ruminal bacteria profiles, rumen fermentation parameters, and enzyme activities in these bovine species consuming a low-protein diet differing in energy level. Six castrated yaks (155 ± 5.8 kg) and 6 castrated Qaidam cattle (154 ± 8.0 kg) were used in two concurrent 4 × 4 Latin square designs with 2 additional animals of each species in each period. The animals were offered a low-protein diet of 70.4 g/kg dry matter (DM) and one of four metabolizable energy levels, namely 6.62, 8.02, 9.42, and 10.80 MJ/kg. Ruminal pH, concentrations of ammonia-N and total volatile fatty acids (VFAs), the molar proportion of acetate, and the ratio of acetate to propionate (A:P) were greater (P < 0.05), whereas the molar proportion of propionate was lesser (P = 0.043) in yaks than in cattle. With increasing dietary energy level, ruminal pH, the molar proportion of acetate and the ratio of A:P decreased linearly (P < 0.05), whereas, the concentration of total VFAs, molar proportions of propionate, butyrate, iso-butyrate, and iso-valerate and concentration of ammonia-N increased linearly (P < 0.05). The relative abundance (RA) of Firmicutes increased linearly (P < 0.01), whereas, the RA of Bacteroidetes decreased linearly (P < 0.001) with increasing energy level in both bovine species. The RAs of Prevotella and Rikenellaceae_RC9_gut_group decreased linearly (P < 0.05) with increasing energy level in both yaks and cattle. The RAs of fibrolytic (e.g., Rikenellaceae_RC9_gut_group), and H2-incorporating (e.g., Quinella) bacteria were greater (P < 0.05) in yaks than in cattle. We concluded that the two bovines differ in ruminal bacterial profiles and rumen fermentation parameters, and confer an advantage to yaks over cattle in consuming a low protein diet with differing energy level.
A new multiplex PCR for the accurate identification and differentiation of Salmonella enterica serovar Gallinarum biovars Pullorum and Gallinarum
Authors: Xiong Dan , Yuan Li , Song Li , Jiao Xinan , Pan Zhiming
Published: September 2022

Salmonella enterica serovar Gallinarum biovars Gallinarum and Pullorum cause severe chicken salmonellosis, a disease associated with high mortality and morbidity among chickens worldwide. The conventional serotyping and biochemical reactions have been used to identify Salmonella serovars. However, the conventional methods are complicated, time-consuming, laborious, and expensive. Furthermore, it is challenging to distinguish S. Gallinarum and S. Pullorum via biochemical assays and serotyping because of their antigenic similarity. Although various PCR methods were established, a PCR protocol to detect and discriminate S. Gallinarum and S. Pullorum simultaneously is lacking. Herein, a one-step multiplex PCR method was established for the accurate identification and discrimination of S. Pullorum and S. Gallinarum. Three specific genes were used for the multiplex PCR method, with the I137_14445 and ybgL genes being the key targets to identify and differentiate S. Gallinarum and S. Pullorum, and stn being included as a reference gene for the Salmonella genus. In silico analysis showed that the I137_14445 gene is present in all Salmonella serovars, except for S. Gallinarum, and could therefore be used for the identification of S. Gallinarum. A 68-bp sequence deficiency in ybgL was found only in S. Pullorum compared to other Salmonella serovars, and this could therefore be used for the specific identification of S. Pullorum. The developed PCR assay was able to distinguish S. Gallinarum and S. Pullorum among 75 various Salmonella strains and 43 various non-Salmonella pathogens with excellent specificity. The detection limit for the genomic DNA of S. Gallinarum and S. Pullorum was 21.4 pg./μL, and the detectable limit for bacterial cells was 100 CFU. The developed PCR method was used for the analysis of Salmonella isolates in a chicken farm. This PCR system successfully discriminated S. Gallinarum and S. Pullorum from other different Salmonella serovars. The PCR results were confirmed by the conventional serotyping method. The newly established multiplex PCR is a simple, accurate, and cost-effective method for the timely identification and differentiation of S. Pullorum and S. Gallinarum.
First determination of DNA virus and some additional bacteria from Melophagus ovinus (sheep ked) in Tibet, China
Authors: Liu Yong-Hong , Ma Yi-Min , Tian Hong-Ou , Yang Bo , Han Wen-Xiong , Zhao Wei-Hong , Chai Hai-Liang , Zhang Zhan-Sheng , Wang Li-Feng , Chen Lei , Xing Yu , Ding Yu-Lin , Zhao Li
Published: September 2022

Melophagus ovinus (sheep ked) is one of the common ectoparasites in sheep. In addition to causing direct damage to the host through biting and sucking blood, sheep ked is a potential vector of helminths, protozoa, bacteria, and viruses. Sheep M. ovinus samples from three regions in Tibet were selected for DNA extraction. The 16S rDNA V3-V4 hypervariable region was amplified, after genomic DNA fragmentation, Illumina Hiseq libraries were constructed. The 16S rRNA sequencing and viral metagenomics sequencing were separately conducted on the Illumina Novaseq 6000 platform and molecular biology software and platforms were employed to analyze the sequencing data. Illumina PE250 sequencing results demonstrated that the dominant bacteria phylum in M. ovinus from Tibet, China was Proteobacteria, where 29 bacteria genera were annotated. The dominant bacterial genera were Bartonella, Wolbachia, and Arsenophonus; Bartonella chomelii, Wolbachia spp., and Arsenophonus spp. were the dominant bacterial species in M. ovinus from Tibet, China. We also detected Kluyvera intermedia, Corynebacterium maris DSM 45190, Planomicrobium okeanokoites, and Rhodococcus erythropolis, of which the relative abundance of Kluyvera intermedia was high. Illumina Hiseq sequencing results demonstrated that 4 virus orders were detected in M. ovinus from Tibet, China, and 3 samples were annotated into 29 families, 30 families, and 28 families of viruses, respectively. Virus families related to vertebrates and insects mainly included Mimiviridae, Marseilleviridae, Poxviridae, Ascoviridae, Iridoviridae, Baculoviridae, Hytrosaviridae, Nudiviridae, Polydnaviridae, Adomaviridae, Asfarviridae, Hepeviridae, Herpesviridae, and Retroviridae; at the species level, the relative abundance of Tupanvirus_soda_lake, Klosneuvirus_KNV1, and Indivirus_ILV1 was higher. African swine fever virus and many poxviruses from the family Poxviridae were detected, albeit their relative abundance was low. The dominant bacterial phylum of M. ovinus from Tibet, China was Proteobacteria, and the dominant bacterial genera were Bartonella, Wolbachia, and Arsenophonus, where 23 out of 29 annotated bacteria genera were first reported in M. ovinus. Kluyvera intermedia, Corynebacterium maris DSM 45190, Planomicrobium okeanokoites, and Rhodococcus erythropolis were detected for the first time. All DNA viruses detected in this study have been reported in M. ovinus for the first time.
Systematic pan-cancer analysis on the expression and role of regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene 12
Authors: Hu Kai , Yu Huomei , Liu Shiyan , Liao Deyu , Zhang Yan
Published: September 2022

Regulator of chromatin condensation 1 (RCC1) is the major guanine nucleotide exchange factor of RAN GTPase, which plays a key role in various biological processes such as cell cycle and DNA damage repair. Small nucleolar RNA host gene 3 (SNHG3) and small nucleolar RNA host gene12 are long-stranded non-coding RNAs (lncRNAs) and are located on chromatin very close to the sequence of Regulator of chromatin condensation 1. Many studies have shown that they are aberrantly expressed in tumor tissues and can affect the proliferation and viability of cancer cells. Although the effects of Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 on cellular activity have been reported, respectively, their overall analysis on the pan-cancer level has not been performed. Here, we performed a comprehensive analysis of Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 in 33 cancers through the Cancer Genome Atlas and Gene Expression Database. The results showed that Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 were highly expressed in a variety of tumor tissues compared to normal tissues. The expression of Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 in BRCA, LGG and LIHC was associated with TP53 mutations. In addition, Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 expression was closely associated with the prognosis of patients with multiple tumors. Immunocorrelation analysis indicated that Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 showed a correlation with multiple immune cell infiltration. The results of enrichment analysis suggested that Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 was involved in the regulation of cell cycle, apoptosis and other pathways. We found that these effects were mainly mediated by Regulator of chromatin condensation 1, while the trend of small nucleolar RNA host gene 3/small nucleolar RNA host gene12 regulation was also consistent with regulator of chromatin condensation 1. The important role played by Regulator of chromatin condensation 1 in tumor diseases was further corroborated by the study of adjacent lncRNAs.These findings provide new and comprehensive insights into the role of Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 in tumor development and show their potential as clinical monitoring and therapy.
Relative binding free energy calculations with transformato: A molecular dynamics engine-independent tool
Authors: Karwounopoulos Johannes , Wieder Marcus , Boresch Stefan
Published: September 2022

We present the software package transformato for the setup of large-scale relative binding free energy calculations. Transformato is written in Python as an open source project (https://github.com/wiederm/transformato); in contrast to comparable tools, it is not closely tied to a particular molecular dynamics engine to carry out the underlying simulations. Instead of alchemically transforming a ligand L1 directly into another L2, the two ligands are mutated to a common core. Thus, while dummy atoms are required at intermediate states, in particular at the common core state, none are present at the physical endstates. To validate the method, we calculated 76 relative binding free energy differences ΔΔGL1→L2bind for five protein–ligand systems. The overall root mean squared error to experimental binding free energies is 1.17 kcal/mol with a Pearson correlation coefficient of 0.73. For selected cases, we checked that the relative binding free energy differences between pairs of ligands do not depend on the choice of the intermediate common core structure. Additionally, we report results with and without hydrogen mass reweighting. The code currently supports OpenMM, CHARMM, and CHARMM/OpenMM directly. Since the program logic to choose and construct alchemical transformation paths is separated from the generation of input and topology/parameter files, extending transformato to support additional molecular dynamics engines is straightforward.
In silico design of refined ferritin-SARS-CoV-2 glyco-RBD nanoparticle vaccine
Authors: Masoomi Nomandan Seyedeh Zeinab , Azimzadeh Irani Maryam , Hosseini Seyed Masoud
Published: September 2022

With the onset of Coronavirus disease 2019 (COVID-19) pandemic, all attention was drawn to finding solutions to cure the coronavirus disease. Among all vaccination strategies, the nanoparticle vaccine has been shown to stimulate the immune system and provide optimal immunity to the virus in a single dose. Ferritin is a reliable self-assembled nanoparticle platform for vaccine production that has already been used in experimental studies. Furthermore, glycosylation plays a crucial role in the design of antibodies and vaccines and is an essential element in developing effective subunit vaccines. In this computational study, ferritin nanoparticles and glycosylation, which are two unique facets of vaccine design, were used to model improved nanoparticle vaccines for the first time. In this regard, molecular modeling and molecular dynamics simulation were carried out to construct three atomistic models of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD)-ferritin nanoparticle vaccine, including unglycosylated, glycosylated, and modified with additional O-glycans at the ferritin–RBD interface. It was shown that the ferritin–RBD complex becomes more stable when glycans are added to the ferritin–RBD interface and optimal performance of this nanoparticle can be achieved. If validated experimentally, these findings could improve the design of nanoparticles against all microbial infections.
Multimodal ultrasound fusion network for differentiating between benign and malignant solid renal tumors
Authors: Zhu Dongmei , Li Junyu , Li Yan , Wu Ji , Zhu Lin , Li Jian , Wang Zimo , Xu Jinfeng , Dong Fajin , Cheng Jun
Published: September 2022

Objective: We aim to establish a deep learning model called multimodal ultrasound fusion network (MUF-Net) based on gray-scale and contrast-enhanced ultrasound (CEUS) images for classifying benign and malignant solid renal tumors automatically and to compare the model’s performance with the assessments by radiologists with different levels of experience.

Methods: A retrospective study included the CEUS videos of 181 patients with solid renal tumors (81 benign and 100 malignant tumors) from June 2012 to June 2021. A total of 9794 B-mode and CEUS-mode images were cropped from the CEUS videos. The MUF-Net was proposed to combine gray-scale and CEUS images to differentiate benign and malignant solid renal tumors. In this network, two independent branches were designed to extract features from each of the two modalities, and the features were fused using adaptive weights. Finally, the network output a classification score based on the fused features. The model’s performance was evaluated using five-fold cross-validation and compared with the assessments of the two groups of radiologists with different levels of experience.

Results: For the discrimination between benign and malignant solid renal tumors, the junior radiologist group, senior radiologist group, and MUF-Net achieved accuracy of 70.6%, 75.7%, and 80.0%, sensitivity of 89.3%, 95.9%, and 80.4%, specificity of 58.7%, 62.9%, and 79.1%, and area under the receiver operating characteristic curve of 0.740 (95% confidence internal (CI): 0.70–0.75), 0.794 (95% CI: 0.72–0.83), and 0.877 (95% CI: 0.83–0.93), respectively.

Conclusion: The MUF-Net model can accurately classify benign and malignant solid renal tumors and achieve better performance than senior radiologists.

Key points: The CEUS video data contain the entire tumor microcirculation perfusion characteristics. The proposed MUF-Net based on B-mode and CEUS-mode images can accurately distinguish between benign and malignant solid renal tumors with an area under the receiver operating characteristic curve of 0.877, which surpasses senior radiologists’ assessments by a large margin.
Adamts10 controls transforming growth factor β family signaling that contributes to retinal ganglion cell development
Authors: Wareham Lauren K. , Whitener Amy E. , Wu Hang-Jing , Wu Shu-Yu , Mchaourab Hassane S. , Mortlock Douglas P. , Kuchtey Rachel W. , Kuchtey John
Published: September 2022

Although mutations in ADAMTS10 have long been known to cause autosomal recessive Weill-Marchesani Syndrome which is characterized by short stature and ocular abnormalities, more recent work has shown that certain mutations in ADAMTS10 cause glaucoma in dogs. In humans, glaucoma is the leading cause of irreversible vision loss that affects tens of millions of people world-wide. Vision loss in glaucoma is a result of neurodegeneration of retinal ganglion cells that form the inner-most layer of the retina and whose axons form the optic nerve which relays visual information to the brain. ADAMTS10 contributes to the formation of microfibrils which sequester latent transforming growth factor β (TGFβ). Among its many biological functions, TGFβ promotes the development of retinal ganglion cells and is also known to play other roles in glaucoma pathogenesis. The aim of this study was to test the hypothesis that ADAMTS10 plays a role in retinal ganglion cell development through regulation of TGFβ signaling. To this end, Adamts10 expression was targeted for reduction in zebrafish embryos carrying either a fluorescent reporter that labels retinal ganglion cells, or a fluorescent reporter of pSmad3-mediated TGFβ family signaling. Loss of adamts10 function in zebrafish embryos reduced retinal ganglion cell reporter fluorescence and prevented formation of an ordered retinal ganglion cell layer. Targeting adamts10 expression also drastically reduced constitutive TGFβ signaling in the eye. Direct inhibition of the TGFβ receptor reduced retinal ganglion cell reporter fluorescence similar to the effect of targeting adamts10 expression. These findings unveil a previously unknown role for Adamts10 in retinal ganglion cell development and suggest that the developmental role of Adamts10 is mediated by active TGFβ family signaling. In addition, our results show for the first time that Adamts10 is necessary for pSmad3-mediated constitutive TGFβ family signaling.
Impaired sequence generation: a preliminary comparison between high functioning autistic and neurotypical adults
Authors: Heleven Elien , Bylemans Tom , Ma Qianying , Baeken Chris , Baetens Kris
Published: September 2022

Earlier research demonstrated robust cerebellar involvement in sequencing, including high-level social information sequencing that requires mental state attributions, termed mentalizing. Earlier research also found cerebellar deficiencies in autism spectrum disorders (ASD) which are characterized by social difficulties. However, studies on high-level social sequencing functionality by persons with ASD are almost non-existent. In this study, we, therefore, perform a comparison between behavioral performances of high-functioning ASD and neurotypical participants on the Picture and Verbal Sequencing Tasks. In these tasks, participants are requested to put separate events (depicted in cartoon-like pictures or behavioral sentences, respectively) in their correct chronological order. To do so, some of these events require understanding of high-level social beliefs, of social routines (i.e., scripts), or nonsocial mechanical functionality. As expected, on the Picture Sequencing task, we observed longer response times for persons with ASD (in comparison with neurotypical controls) when ordering sequences requiring an understanding of social beliefs and social scripts, but not when ordering nonsocial mechanical events. This confirms our hypotheses that social sequence processing is impaired in ASD. The verbal version of this task did not reveal differences between groups. Our results are the first step toward new theoretical insights for social impairments of persons with ASD. They highlight the importance of taking into account sequence processing, and indirectly the cerebellum when investigating ASD difficulties.
More than the end: OFF response plasticity as a mnemonic signature of a sound’s behavioral salience
Authors: Anandakumar Dakshitha B. , Liu Robert C.
Published: September 2022

In studying how neural populations in sensory cortex code dynamically varying stimuli to guide behavior, the role of spiking after stimuli have ended has been underappreciated. This is despite growing evidence that such activity can be tuned, experience-and context-dependent and necessary for sensory decisions that play out on a slower timescale. Here we review recent studies, focusing on the auditory modality, demonstrating that this so-called OFF activity can have a more complex temporal structure than the purely phasic firing that has often been interpreted as just marking the end of stimuli. While diverse and still incompletely understood mechanisms are likely involved in generating phasic and tonic OFF firing, more studies point to the continuing post-stimulus activity serving a short-term, stimulus-specific mnemonic function that is enhanced when the stimuli are particularly salient. We summarize these results with a conceptual model highlighting how more neurons within the auditory cortical population fire for longer duration after a sound’s termination during an active behavior and can continue to do so even while passively listening to behaviorally salient stimuli. Overall, these studies increasingly suggest that tonic auditory cortical OFF activity holds an echoic memory of specific, salient sounds to guide behavioral decisions.
Ultrasonography of abdominal muscles: Differential diagnosis of late-onset Pompe disease and myotonic dystrophy type 1
Authors: Hsieh Pei-Chen , Chang Chun-Wei , Ro Long-Sun , Huang Chin-Chang , Chi Jia-En , Kuo Hung-Chou
Published: September 2022

Introduction

Axial muscles are involved earlier and to a greater extent in late-onset Pompe disease (LOPD) than in myotonic muscular dystrophy type 1 (DM1). We aimed to evaluate abdominal muscles in LOPD compared in DM1 using muscle ultrasonography.

Methods

Patients with LOPD (n = 3), DM1 (n = 10), and age- and gender-matched healthy subjects (n = 34) were enrolled for muscle ultrasonography. Patients with LOPD and DM1 were 20 to 59 years of age with a disease duration ranging between 7 and 30 years. A multifrequency linear transducer was used to evaluate quality and thickness in the abdominal muscles and extremities.

Results

The quantitative muscle echo score revealed a higher Z score in abdominal muscles in Patients with LOPD (scores were relatively normal for the biceps and flexor digitorum groups). Patients with LOPD had significantly lower abdominal muscle thickness than patients with DM1. Abdominal muscle strength was significantly correlated with the muscle echogenicity, trunk impairment scale, and trunk control test. The extremities' sum score was correlated with the total Medical Research Council score.

Discussion

The increased quantitative muscle score in abdominal muscles, sparing the biceps and flexor digitorum groups, may offer differential diagnosis between LOPD and DM1. Ultrasound can easily access abdominal muscles and investigate muscle echogenicity and thickness. A quantitative approach using muscle echogenicity rather than muscle thickness may provide a greater correlation with trunk muscle function.
Cerebral hemodynamic changes to transcranial Doppler sonography in celiac disease: A pilot study
Authors: Fisicaro Francesco , Lanza Giuseppe , D’Agate Carmela Cinzia , Pennisi Manuela , Cantone Mariagiovanna , Pennisi Giovanni , Hadjivassiliou Marios , Bella Rita
Published: September 2022

Background

Sonographic mesenteric pattern in celiac disease (CD) suggests a hyperdynamic circulation. Despite the well-known CD-related neurological involvement, no study has systematically explored the cerebral hemodynamics to transcranial Doppler sonography.

Materials and methods

Montreal Cognitive Assessment (MoCA) and 17-item Hamilton Depression Rating Scale (HDRS) were assessed in 15 newly diagnosed subjects with CD and 15 age-, sex-, and education-matched healthy controls. Cerebral blood flow (CBF) velocities and indices of resistivity (RI) and pulsatility (PI) from the middle cerebral artery (MCA), bilaterally, and the basilar artery (BA) were recorded. We also assessed cerebral vasomotor reactivity (CVR) through the breath-holding test (BHT).

Results

Worse scores of MoCA and HDRS were found in patients compared to controls. Although patients showed higher values of CBF velocity from MCA bilaterally compared to controls, both at rest and after BHT, no comparison reached a statistical significance, whereas after BHT both RI and PI from BA were significantly higher in patients. A significant negative correlation between both indices from BA and MoCA score were also noted.

Conclusion

These treatment-naïve CD patients may show some subtle CVR changes in posterior circulation, thus possibly expanding the spectrum of pathomechanisms underlying neuroceliac disease and in particular gluten ataxia. Subclinical identification of cerebrovascular pathology in CD may help adequate prevention and early management of neurological involvement.
Associations between food-specific IgG antibodies and intestinal permeability biomarkers
Authors: Vita Alexandra Adorno , Zwickey Heather , Bradley Ryan
Published: September 2022

Increasing translational evidence suggests that intestinal permeability may be a contributing factor to systemic inflammatory events and numerous pathologies. While associations between IgE-mediated food allergies and increased intestinal permeability have been well-characterized, the relationship between IgG-mediated food sensitivities and intestinal permeability is not well-described in the literature. Thus, we tested for associations between intestinal permeability biomarkers and food-specific IgG antibodies in 111 adults, with and without gastrointestinal symptoms. All biomarkers and food-specific IgG antibodies were measured via ELISA. The intestinal permeability biomarkers anti-lipopolysaccharide (LPS) and anti-occludin IgG and IgA antibodies, but not anti-vinculin or anti-CdtB IgG antibodies, were significantly and positively associated with IgG-mediated food sensitivities. These significant relationships were attenuated by adjusting for the severity of wheat, dairy, and egg reactions. The results of this study support strong associations between titers of food-specific IgG antibodies and intestinal permeability biomarkers in adults, to the extent that the presence of multiple IgG antibodies to food, and increasing IgG food titers, can be considered indicative of increased antibodies to LPS and occludin. Notably, neither IgG titers to wheat, eggs, and dairy, nor permeability biomarkers, were increased in symptomatic participants compared to those without symptoms.
The cyclin dependent kinase inhibitor p21Cip1/Waf1 is a therapeutic target in high-risk neuroblastoma
Authors: Sorteberg Agnes Luise , Halipi Vesa , Wickström Malin , Shirazi Fard Shahrzad
Published: September 2022

Platinum-based chemotherapies such as cisplatin are used as first-line treatment for the paediatric tumour neuroblastoma. Although the majority of neuroblastoma tumours respond to therapy, there is a high fraction of high-risk neuroblastoma patients that eventually relapse with increased resistance. Here, we show that one key determinant of cisplatin sensitivity is phosphorylation of the cyclin-dependent kinase inhibitor p21Cip1/Waf1. A panel of eight neuroblastoma cell lines and a TH-MYCN mouse model were investigated for the expression of p21Cip1/Waf1 using RT-qPCR, Western blot, and immunofluorescence. This was followed by investigation of sensitivity towards cisplatin and the p21Cip1/Waf1 inhibitor UC2288. Whereas the cell lines and the mouse model showed low levels of un-phosphorylated p21Cip1/Waf1, the phosphorylated p21Cip1/Waf1 (Thr145) was highly expressed, which in the cell lines correlated to cisplatin resistance. Furthermore, the neuroblastoma cell lines showed high sensitivity to UC2288, and combination treatment with cisplatin resulted in considerably decreased cell viability and delay in regrowth in the two most resistant cell lines, SK-N-DZ and BE(2)-C. Thus, targeting p21Cip1/Waf1 can offer new treatment strategies and subsequently lead to the design of more efficient combination treatments for high-risk neuroblastoma.
Case Report: Submucosal gastroblastoma with a novel PTCH1::GLI2 gene fusion in a 58-year-old man
Authors: Chen Cuimin , Lu Junliang , Wu Huanwen
Published: September 2022

Gastroblastoma is a rare biphasic tumor of the stomach that generally presents in young patients. MALAT1-GLI1 gene fusion was considered to be the characteristic molecular alteration of this tumor in previous reports. Herein, we described a 58-year-old man with a mass mainly located in the submucosa of the stomach. Microscopic examination showed a biphasic morphology with the same immunohistochemical phenotype as gastroblastoma. Interestingly, a novel PTCH1::GLI2 fusion rather than MALAT1-GLI1 fusion was detected in the tumor by RNA-based next generation sequencing (NGS). This was the first report that demonstrated a novel PTCH1::GLI2 gene fusion in gastroblastoma, and thus expanded the molecular spectrum of this tumor. The underlying pathogenesis merits further investigation.
Mesenchymal gene expression subtyping analysis for early-stage human papillomavirus-negative head and neck squamous cell carcinoma reveals prognostic and predictive applications
Authors: Mayhew Gregory M. , Uronis Joshua M. , Hayes David Neil , Zevallos Jose P.
Published: September 2022

Patients with oral cavity squamous cell carcinoma (OCSCC) are predominantly human papillomavirus (HPV)(−), and treatment typically involves surgical resection ± neck dissection, followed by radiation ± chemotherapy. We previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we examine the clinical utility of gene expression subtyping in head and neck squamous cell carcinoma (HNSCC) and introduce potentially predictive applications in HPV(−) OCSCC. A retrospective genomic database analysis was performed including 562 HNSCC patients from MD Anderson (MDA-GSE41116) and The Cancer Genome Atlas (TCGA). Samples were assigned molecular subtypes (classical, atypical, basal, and mesenchymal) using an 88-gene classifier. HPV status was determined by gene expression. The clinical endpoint was overall survival censured at 36 months. The Kaplan–Meier plots and log-rank tests were used to investigate associations between clinical variables and survival. Of the 418 TCGA training patients who met analysis criteria, nearly 20% presented as stage I/II. Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease. This was confirmed in the MDA validation cohort. Node(−) non-mesenchymal OCSCC patients had far better survival compared to node(−) mesenchymal, and all node(+) patients had similarly poor survival. These findings suggest that the mesenchymal subtype is associated with poor survival in surgically resected, early-stage, node(−) OCSCC otherwise expected to have favorable outcomes. These findings highlight the potential value of gene expression subtyping as a pathology adjunct for prognostication and treatment decision-making in OCSCC patients.