bluuebunny/crossref_metadata_2025 huggingface dataset:
Coexistence of tmexCD3-toprJ1b tigecycline resistance genes with two novel blaVIM-2-carrying and blaOXA-10-carrying transposons in a Pseudomononas asiatica plasmid
Authors: Li Qin , Chen Qiao , Liang Shuang , Wang Wei , Zhang Bingying , Martín-Rodríguez Alberto J. , Liang Qinghua , Zhang Feiyang , Guo Ling , Xiong Xia , Hu Renjing , Xiang Li , Zhou Yingshun
Published: March 2023

Introduction

Tigecycline and carbapenems are considered the last line of defense against microbial infections. The co-occurrence of resistance genes conferring resistance to both tigecycline and carbapenems in Pseudomononas asiatica was not investigated.

Methods

P. asiatica A28 was isolated from hospital sewage. Antibiotic susceptibility testing showed resistance to carbapenem and tigecycline. WGS was performed to analyze the antimicrobial resistance genes and genetic characteristics. Plasmid transfer by conjugation was investigated. Plasmid fitness costs were evaluated in Pseudomonas aeruginosa transconjugants including a Galleria mellonella infection model.

Results

Meropenem and tigecycline resistant P. asiatica A28 carries a 199, 972 bp long plasmid PLA28.4 which harbors seven resistance genes. Sequence analysis showed that the 7113 bp transposon Tn7389 is made up of a class I integron without a 5’CS terminal and a complete tni module flanked by a pair of 25bp insertion repeats. Additionally, the Tn7493 transposon, 20.24 kp long, with a complete 38-bp Tn1403 IR and an incomplete 30-bp Tn1403 IR, is made up of partial skeleton of Tn1403, a class I integron harboring blaOXA-10, and a Tn5563a transposon. Moreover, one tnfxB3-tmexC3.2-tmexD3b-toprJ1b cluster was found in the plasmid and another one in the the chromosome. Furthermore, plasmid PLA28.4 could be conjugated to P. aeruginosa PAO1, with high fitness cost.

Discussion

A multidrug-resistant plasmid carrying tmexCD3-toprJ1b and two novel transposons carrying blaVIM-2 and blaOXA-10 -resistant genes was found in hospital sewage, increasing the risk of transmission of antibiotic-resistant genes. These finding highlight the necessary of controlling the development and spread of medication resistance requires continuous monitoring and management of resistant microorganisms in hospital sewage.
Impact of severe secondary tricuspid regurgitation on rest and exercise hemodynamics of patients with heart failure and a preserved left ventricular ejection fraction
Authors: Baratto Claudia , Caravita Sergio , Corbetta Giorgia , Soranna Davide , Zambon Antonella , Dewachter Céline , Gavazzoni Mara , Heilbron Francesca , Tomaselli Michele , Radu Noela , Perelli Francesco Paolo , Perego Giovanni Battista , Vachiéry Jean-Luc , Parati Gianfranco , Badano Luigi P. , Muraru Denisa
Published: March 2023

Background

Both secondary tricuspid regurgitation (STR) and heart failure with preserved ejection fraction (HFpEF) are relevant public health problems in the elderly population, presenting with potential overlaps and sharing similar risk factors. However, the impact of severe STR on hemodynamics and cardiorespiratory adaptation to exercise in HFpEF remains to be clarified.

Aim

To explore the impact of STR on exercise hemodynamics and cardiorespiratory adaptation in HFpEF.

Methods

We analyzed invasive hemodynamics and gas-exchange data obtained at rest and during exercise from HFpEF patients with severe STR (HFpEF-STR), compared with 1:1 age-, sex-, and body mass index (BMI)- matched HFpEF patients with mild or no STR (HFpEF-controls).

Results

Twelve HFpEF with atrial-STR (mean age 72 years, 92% females, BMI 28 Kg/m2) and 12 HFpEF-controls patients were analyzed. HFpEF-STR had higher (p < 0.01) right atrial pressure than HFpEF-controls both at rest (10 ± 1 vs. 5 ± 1 mmHg) and during exercise (23 ± 2 vs. 14 ± 2 mmHg). Despite higher pulmonary artery wedge pressure (PAWP) at rest in HFpEF-STR than in HFpEF-controls (17 ± 2 vs. 11 ± 2, p = 0.04), PAWP at peak exercise was no more different (28 ± 2 vs. 29 ± 2). Left ventricular transmural pressure and cardiac output (CO) increased less in HFpEF-STR than in HFpEF-controls (interaction p-value < 0.05). This latter was due to lower stroke volume (SV) values both at rest (48 ± 9 vs. 77 ± 9 mL, p < 0.05) and at peak exercise (54 ± 10 vs. 93 ± 10 mL, p < 0.05). Despite these differences, the two groups of patients laid on the same oxygen consumption isophlets because of the increased peripheral oxygen extraction in HFpEF-STR (p < 0.01). We found an inverse relationship between pulmonary vascular resistance and SV, both at rest and at peak exercise (R2 = 0.12 and 0.19, respectively).

Conclusions

Severe STR complicating HFpEF impairs SV and CO reserve, leading to pulmonary vascular de-recruitment and relative left heart underfilling, undermining the typical HFpEF pathophysiology.
Field test and numerical simulation of ground settlement in super shallow buried station excavation supported by transverse pipe roof
Authors: Wang Jun , Li Xun , Wu Shengzhi , He Zhiwei , Wei Yuanjin
Published: March 2023

The pipe roof is an effective means to control the surface settlement during the construction of the super-shallow buried subway station. The transverse pipe roof method can not only reduce the construction work surface, but also improve the construction efficiency by multi-stage flow construction. Based on the transfer station project of the Olympic Sports Center of Jinan Rail Transit Line 3, the ground settlement law caused by the excavation of ultra-shallow buried subway station under the action of transverse pipe roof is analyzed through field measurement. The mechanism of pipe roof controlling ground settlement and the influence of steel pipe spacing and steel pipe length on the bearing mechanism of pipe roof are analyzed by numerical simulation. The following conclusions are drawn. 1) The surface settlement curve caused by the excavation of the small pilot tunnel in the lateral direction of the station is a wavy U-shaped, and the surface settlement curve becomes a smooth U-shaped after the soil is broken. In the longitudinal direction of the station, the surface settlement is jagged, and the surface settlement above the pipe roof is less than the surface settlement between the pipe roofs. 2) After soil excavation, pipe roof can bear the load of surrounding rock and restrain the settlement of soil above, and soil arch effect is formed between pipes to restrain the relaxation of soil between pipes. With the increase of the spacing of the steel pipe, the height of the soil arch increases. After exceeding a certain spacing, the micro-soil arching effect disappears and the surface settlement increases. 3) The length and stiffness of pipe roof will affect the bearing capacity of pipe roof and there is an upper limit. When it exceeds the upper limit, increasing the length or stiffness of pipe roof has little effect on the control effect of ground settlement. The research can provide reference for shallow buried excavation station and other projects.
A practical analytical model for performance prediction in unconventional gas reservoir
Authors: Qiu Kaixuan
Published: March 2023

Ninety percentage of newly proven natural gas reservoirs of China are mainly unconventional resources, which can be typically developed by multi-stage fracturing horizontal well technology. Two regions typically occur near each fracture after hydraulic fracturing, in which the lower permeability region is considered as the storage source and the higher permeability region as the flow channel. The existed analytical models so far are mainly derived by Laplace transforming. In this paper, an improved practical analytical solution is derived for unconventional gas reservoirs bypassing the Laplace transform and numerical inversion. Through solving material balance equation and adopting the integration, a rate vs. pseudo-time solution in real-time domain can be directly obtained. Five numerical cases are created to verify the accuracy of the proposed analytical solution and the ratio of regular/irregular region pore volume is also proved to be derived reversely by the output parameters, which is significant for the field engineers to evaluate the effect of hydraulic fracturing. Moreover, a field example of a multi-fractured horizontal well in a tight gas reservoir is provided for demonstrate application.
Influence of image reconstruction kernel on computed tomography-based finite element analysis in the clinical opportunistic screening of osteoporosis—A preliminary result
Authors: Jiang Chenyu , Jin Dan , Ni Ming , Zhang Yan , Yuan Huishu
Published: March 2023

Purpose

This study aimed to evaluate the difference in vertebral mechanical properties estimated by finite element analysis (FEA) with different computed tomography (CT) reconstruction kernels and evaluate their accuracy in the screening and classification of osteoporosis.

Methods

There were 31 patients enrolled retrospectively from the quantitative CT database of our hospital, uniformly covering the range from osteoporosis to normal. All subjects’ CT raw data were reconstructed both with a smooth standard convolution kernel (B40f) and a sharpening bone convolution kernel (B70f), and FEA was performed on L1 of each subject based on two reconstructed images to obtain vertebral estimated strength and stiffness. The trabecular volumetric bone mineral density (vBMD) of the same vertebral body was also measured. FEA measurements between two kernels and their accuracy for osteoporosis screening were compared.

Results

The vertebral stiffness and strength measured in FEA-B40f were significantly lower compared with those of FEA-B70f (12.0%, p = 0.000 and 10.7%, p = 0.000, respectively). The correlation coefficient between FEA-B70F and vBMD was slightly higher than that of FEA-B40F in both vertebral strength and stiffness (strength: r2-B40f = 0.21, p = 0.009 vs. r2-B70f = 0.27, p = 0.003; stiffness: r2-B40f = 0.37, p = 0.002 vs. r2-B70f = 0.45, p=0.000). The receiver operator characteristic curve showed little difference in the classification of osteoporosis between FEA-B40f and FEA-B70f.

Conclusion

Two kernels both seemed to be applicable to the opportunistic screening of osteoporosis by CT-FEA despite variance in FE-estimated bone strength and bone stiffness. A protocol for CT acquisition and FEA is still required to guarantee the reproducibility of clinical use.
High IgG4 serum concentration is associated with active Graves orbitopathy
Authors: Olejarz Michał , Szczepanek-Parulska Ewelina , Ostałowska-Klockiewicz Anna , Antosik Patrycja , Sawicka-Gutaj Nadia , Helak-Łapaj Celina , Stopa Marcin , Ruchala Marek
Published: March 2023

Background

The aim of the study was to evaluate the differences in clinical profile, laboratory parameters, and ophthalmological signs, and symptoms between patients with high IgG4 Graves orbitopathy and patients with normal IgG4 Graves orbitopathy.

Methods

This was a prospective observational study. We recruited adult patients with Graves Orbitopathy(GO) referred to our clinic for further diagnostics and treatment. Eventually, 60 patients with GO were enrolled in the study. All patients underwent ophthalmological assessment, magnetic resonance imaging (MRI) of the orbits, and laboratory tests, including IgG4 serum concentration measurement. High IgG4 GO was diagnosed if the IgG4 concentration exceeded 135 mg/dl. We used both the clinical activity score (CAS) and magnetic resonance imaging (MRI) to assess the activity of GO. Eventually, active GO was defined according to MRI results.

Results

Among 60 GO patients, 15 (25%) patients had elevated IgG4 levels. Patients in the high IgG4 group had a higher prevalence of active GO by MRI than patients with normal IgG4 (100% vs. 64.44%, P=0.006). They also had a higher eosinophile count in peripheral blood, a lower bilirubin level, a more frequent lower eyelid retraction, and a lower prevalence of glaucoma. There were no statistically significant differences between the groups in CAS. Patients with active GO, had higher median IgG4 level [89.95 (55.48; 171.1) vs 43.45 (32.48; 49.68) mg/dl, P<0.001]. The receiver operating characteristic (ROC) analysis for IgG4 as a marker of active GO revealed the following results: AUC 0.848 for the cut-off value of 54.2 mg/dl, sensitivity 79.5%, specificity 87.5%, positive predictive value 94.6%, negative predictive value 59.1%.

Conclusions

We demonstrated that IgG4 is a marker of GO activity. Certain differences in the clinical profile of patients with high IgG4 GO, and normal IgG4 GO were observed. More data is needed to establish whether patients with high IgG4 GO are GO patients with particularly active disease or actually represent a distinct clinical entity related to IgG4-Related Disease.
Bidirectional Mendelian randomization study of insulin-related traits and risk of ovarian cancer
Authors: Wang Xinghao , Sun Jing , Li Jia , Cai Linkun , Chen Qian , Wang Yiling , Yang Zhenghan , Liu Wenjuan , Lv Han , Wang Zhenchang
Published: March 2023

Background

It is well known that the occurrence and development of ovarian cancer are closely related to the patient’s weight and various endocrine factors in the body.

Aim

Mendelian randomization (MR) was used to analyze the bidirectional relationship between insulin related characteristics and ovarian cancer.

Methods

The data on insulin related characteristics are from up to 5567 diabetes free patients from 10 studies, mainly including fasting insulin level, insulin secretion rate, peak insulin response, etc. For ovarian cancer, UK Biobank data just updated in 2021 was selected, of which the relevant gene data was from 199741 Europeans. Mendelian randomization method was selected, with inverse variance weighting (IVW) as the main estimation, while MR Pleiotropy, MR Egger, weighted median and other methods were used to detect the heterogeneity of data and whether there was multi validity affecting conclusions.

Results

Among all insulin related indicators (fasting insulin level, insulin secretion rate, peak insulin response), the insulin secretion rate was selected to have a causal relationship with the occurrence of ovarian cancer (IVW, P < 0.05), that is, the risk of ovarian cancer increased with the decrease of insulin secretion rate. At the same time, we tested the heterogeneity and polymorphism of this indicator, and the results were non-existent, which ensured the accuracy of the analysis results. Reverse causal analysis showed that there was no causal effect between the two (P>0.05).

Conclusion

The impairment of the insulin secretion rate has a causal effect on the risk of ovarian cancer, which was confirmed by Mendel randomization. This suggests that the human glucose metabolism cycle represented by insulin secretion plays an important role in the pathogenesis of ovarian cancer, which provides a new idea for preventing the release of ovarian cancer.
Effects of allicin on human Simpson-Golabi-Behmel syndrome cells in mediating browning phenotype
Authors: Ali Uzair , Wabitsch Martin , Tews Daniel , Colitti Monica
Published: March 2023

Introduction

Obesity is a major health problem because it is associated with increased risk of cardiovascular disease, diabetes, hypertension, and some cancers. Strategies to prevent or reduce obesity focus mainly on the possible effects of natural compounds that can induce a phenotype of browning adipocytes capable of releasing energy in the form of heat. Allicin, a bioactive component of garlic with numerous pharmacological functions, is known to stimulate energy metabolism.

Methods

In the present study, the effects of allicin on human Simpson-Golabi-Behmel Syndrome (SGBS) cells were investigated by quantifying the dynamics of lipid droplets (LDs) and mitochondria, as well as transcriptomic changes after six days of differentiation.

Results

Allicin significantly promoted the reduction in the surface area and size of LDs, leading to the formation of multilocular adipocytes, which was confirmed by the upregulation of genes related to lipolysis. The increase in the number and decrease in the mean aspect ratio of mitochondria in allicin-treated cells indicate a shift in mitochondrial dynamics toward fission. The structural results are confirmed by transcriptomic analysis showing a significant arrangement of gene expression associated with beige adipocytes, in particular increased expression of T-box transcription factor 1 (TBX1), uncoupling protein 1 (UCP1), PPARG coactivator 1 alpha (PPARGC1A), peroxisome proliferator-activated receptor alpha (PPARA), and OXPHOS-related genes. The most promising targets are nuclear genes such as retinoid X receptor alpha (RXRA), retinoid X receptor gamma (RXRG), nuclear receptor subfamily 1 group H member 3 (NR1H3), nuclear receptor subfamily 1 group H member 4 (NR1H4), PPARA, and oestrogen receptor 1 (ESR1).

Discussion

Transcriptomic data and the network pharmacology-based approach revealed that genes and potential targets of allicin are involved in ligand-activated transcription factor activity, intracellular receptor signalling, regulation of cold-induced thermogenesis, and positive regulation of lipid metabolism. The present study highlights the potential role of allicin in triggering browning in human SGBS cells by affecting the LD dynamics, mitochondrial morphology, and expression of brown marker genes. Understanding the potential targets through which allicin promotes this effect may reveal the underlying signalling pathways and support these findings.
Start-up and shut-down strategies of DR-based hybrid DC converter for offshore wind power transmission system
Authors: Fang Zixi , Yang Renxin , Han Kun , Cai Xu , Hong Bo , Liu Lulu
Published: March 2023

The diode rectifier (DR) based hybrid dc converter can significantly increase the economy of the offshore wind power transmission system comparing with the traditional modular multilevel converter (MMC). However, the start-up and shut-down methods of this hybrid dc converter are not studied. In this paper, the start-up and shut-down strategies of the hybrid dc converter are proposed. The start-up process can be divided into two stages: uncontrollable precharging stage and controllable precharging stage. In the uncontrollable precharging stage, the calculation method of the precharging current is given and the design method of the current limiting resistor is presented. In the controllable precharging stage, a circulating current control strategy is proposed to balance the inner energy of the converter and charge the submodule capacitors to the rated value. Besides, the corresponding shut-down strategy is also introduced. Simulation results based on MATLAB/Simulink and hardware-in-the-loop experiment results based on the RT-LAB are provided to support the proposed strategies. The proposed start-up and shut-down strategies can charge and discharge the submodules of the hybrid DC converter safely and cheaply.
Identification and frequency analysis of drought–flood abrupt alternation events using a daily-scale standardized weighted average of the precipitation index
Authors: Zhou Wan , Liu Dedi , Zhang Jiayu , Jiang Sainan , Xing Shuying , Wang Junde , Cheng Yufei , Chen Nana
Published: March 2023

Drought–flood abrupt alternation (DFAA), which is defined as the rapid transition between drought and flood in a short period, amplifies the negative impacts of individual drought or flood. DFAA is divided into drought to flood (DTF) and flood to drought (FTD) according to the sequences of drought and flood. Previous studies of identifying DFAA events have mostly been conducted over a long timescale (e.g., over a month), leading to inaccurate identification or omissions of DFAA events. In addition, frequency analysis of DTF and FTD events, which is vital for the design of hydraulic structures and water supply systems, has rarely been studied. This study establishes an identification method for DFAA events based on a daily-scale standardized weighted average of the precipitation index (SWAP) and conducts frequency analysis of DTF and FTD events based on copula theory. The Han River Basin (HRB), China, a crucial area for water resource management, was selected as the study area. Our findings disclose that DFAA events occurred less frequently with larger intensities and durations between 1961 and 2020. The temporal trends of DTF and FTD events varied similarly, while the number of DTF events were less than that of FTD events, indicating that FTD is the main performance of DFAA in HRB. In addition, the identification processes of DFAA events at the Wuhan station were analyzed in detail and proved that SWAP is an effective index for capturing the change of precipitation and accurately depicting the occurrences of droughts and floods. Furthermore, drought intensity (DI) and flood intensity (FI) were selected for bivariate frequency analysis. An OR case was defined as DI ≥ di or FI ≥ fi, while an AND case was defined as DI ≥ di and FI ≥ fi. The results of frequency analysis showed that joint return periods (JRPs) of DFAA events under the OR case are basically equal in three sub-basins, meaning a similar occurrence of probability of drought–flood disaster. JRPs under the AND case increased from the upper and middle basins to the lower basin as a whole, indicating the decreasing risk of abrupt drought–flood transitions. Overall, this study may have potential value in the early warning and mitigation of DFAA disaster.
Construction of a fatty acid metabolism-related gene signature for predicting prognosis and immune response in breast cancer
Authors: Qian Li , Liu Yi-Fei , Lu Shu-Min , Yang Juan-Juan , Miao Hua-Jie , He Xin , Huang Hua , Zhang Jian-Guo
Published: March 2023

Background: Breast cancer has the highest incidence among malignant tumors in women, and its prevalence ranks first in global cancer morbidity.

Aim: This study aimed to explore the feasibility of a prognostic model for patients with breast cancer based on the differential expression of genes related to fatty acid metabolism.

Methods: The mRNA expression matrix of breast cancer and paracancer tissues was downloaded from The Cancer Genome Atlas database. The differentially expressed genes related to fatty acid metabolism were screened in R language. The TRRUST database was used to predict transcriptional regulators related to hub genes and construct an mRNA–transcription factor interaction network. A consensus clustering approach was used to identify different fatty acid regulatory patterns. In combination with patient survival data, Lasso and multivariate Cox proportional risk regression models were used to establish polygenic prognostic models based on fatty acid metabolism. The median risk score was used to categorize patients into high- and low-risk groups. Kaplan–Meier survival curves were used to analyze the survival differences between both groups. The Cox regression analysis included risk score and clinicopathological factors to determine whether risk score was an independent risk factor. Models based on genes associated with fatty acid metabolism were evaluated using receiver operating characteristic curves. A comparison was made between risk score levels and the fatty acid metabolism-associated genes in different subtypes of breast cancer. The differential gene sets of the Kyoto Encyclopedia of Genes and Genomes for screening high- and low-risk populations were compared using a gene set enrichment analysis. Furthermore, we utilized CIBERSORT to examine the abundance of immune cells in breast cancer in different clustering models.

Results: High expression levels of ALDH1A1 and UBE2L6 prevented breast cancer, whereas high RDH16 expression levels increased its risk. Our comprehensive assessment of the association between prognostic risk scoring models and tumor microenvironment characteristics showed significant differences in the abundance of various immune cells between high- and low-risk breast cancer patients.

Conclusions: By assessing fatty acid metabolism patterns, we gained a better understanding of the infiltration characteristics of the tumor microenvironment. Our findings are valuable for prognosis prediction and treatment of patients with breast cancer based on their clinicopathological characteristics.
Case report: Novel TBX5-related pathogenic mechanism of Holt–Oram syndrome
Authors: Lang Yuheng , Zheng Yue , Qi Bingcai , Zheng Weifeng , Zhao Chengxiu , Zhai Hu , Wang Gang , Luo Zhiqiang , Li Tong
Published: March 2023

Introduction: Holt–Oram syndrome (HOS) is a rare genetic disorder characterized by upper limb abnormalities, congenital heart defects, and/or conduction abnormalities. Sequence alteration of T-box transcription factor 5 (TBX5) is correlated with the incidence of HOS.

Case description: We present the case of a 24-year-old female with upper limb alterations (congenital dysplasia in the wrist and elbow joints) and an anomalous left main trunk arising from the right coronary sinus. The patient inherited a base T (reference C) at rs883079 from her mother and base C (reference T) at rs10850326 from her father, both of which belong to the 3′-untranslated region (UTR) of the TBX5 gene; no alterations in TBX5 expression or single-nucleotide polymorphisms (SNPs) in other exon areas were found. We explored the effects of TBX5 on cardiomyocytes using the HL-1 cell line and TBX5-knockdown cells.

Discussion: Quantitative polymerase chain reaction analysis demonstrated that TEKT2, TEKT4, and SPTB expression decreased after TBX5 knockdown, while chromatin immunoprecipitation analysis further revealed that TBX5 binds to the TEKT2, TEKT4, and SPTB promoter regions to promote gene transcription. Our findings support a novel TBX5-related pathogenic mechanism in HOS.
“From molecular to clinic”: The pivotal role of CDC42 in pathophysiology of human papilloma virus related cancers and a correlated sensitivity of afatinib
Authors: Wei Erdong , Li Jiahua , Anand Philipp , French Lars E. , Wattad Adam , Clanner-Engelshofen Benjamin , Reinholz Markus
Published: March 2023

Background

Human papilloma virus (HPV)-related cancers are global health challenge. Insufficient comprehension of these cancers has impeded the development of novel therapeutic interventions. Bioinformatics empowered us to investigate these cancers from new entry points.

Methods

DNA methylation data of cervical squamous cell carcinoma (CESC) and anal squamous cell carcinoma (ASCC) were analyzed to identify the significantly altered pathways. Through analyses integrated with RNA sequencing data of genes in these pathways, genes with strongest correlation to the TNM staging of CESC was identified and their correlations with overall survival in patients were assessed. To find a potential promising drug, correlation analysis of gene expression levels and compound sensitivity was performed. In vitro experiments were conducted to validate these findings. We further performed molecular docking experiments to explain our findings.

Results

Significantly altered pathways included immune, HPV infection, oxidative stress, ferroptosis and necroptosis. 10 hub genes in these pathways (PSMD11, RB1, SAE1, TAF15, TFDP1, CORO1C, JOSD1, CDC42, KPNA2 and NUP62) were identified, in which only CDC42 high expression was statistically significantly correlated with overall survival (Hazard Ratio: 1.6, P = 0.045). Afatinib was then screened out to be tested. In vitro experiments exhibited that the expression level of CDC42 was upregulated in HaCaT/A431 cells transfected with HPV E6 and E7, and the inhibitory effect of afatinib on proliferation was enhanced after transfection. CDC42-GTPase-effector interface-EGFR-afatinib was found to be a stable complex with a highest ZDOCK score of 1264.017.

Conclusion

We identified CDC42 as a pivotal gene in the pathophysiology of HPV-related cancers. The upregulation of CDC42 could be a signal for afatinib treatment and the mechanism in which may be an increased affinity of EGFR to afatinib, inferred from a high stability in the quaternary complex of CDC42-GTPase-effector interface-EGFR-afatinib.
Assessing the viability of estimating baleen whale abundance from tourist vessels
Authors: Henderson Angus Fleetwood , Hindell Mark Andrew , Wotherspoon Simon , Biuw Martin , Lea Mary-Anne , Kelly Nat , Lowther Andrew Damon
Published: March 2023

Many populations of southern hemisphere baleen whales are recovering and are again becoming dominant consumers in the Southern Ocean. Key to understanding the present and future role of baleen whales in Southern Ocean ecosystems is determining their abundance on foraging grounds. Distance sampling is the standard method for estimating baleen whale abundance but requires specific logistic requirements which are rarely achieved in the remote Southern Ocean. We explore the potential use of tourist vessel-based sampling as a cost-effective solution for conducting distance sampling surveys for baleen whales in the Southern Ocean. We used a dataset of tourist vessel locations from the southwest Atlantic sector of the Southern Ocean and published knowledge from Southern Ocean sighting surveys to determine the number of tourist vessel voyages required for robust abundance estimates. Second, we simulated the abundance and distributions of four baleen whale species for the study area and sampled them with both standardized line transect surveys and non-standardized tourist vessel-based surveys, then compared modeled abundance and distributions from each survey to the original simulation. For the southwest Atlantic, we show that 12-22 tourist vessel voyages are likely required to estimate abundance for humpback and fin whales, with relative estimates for blue, sei, Antarctic minke, and southern right whales. Second, we show tourist vessel-based surveys outperformed standardized line transect surveys at reproducing simulated baleen whale abundances and distribution. These analyses suggest tourist vessel-based surveys are a viable method for estimating baleen whale abundance in remote regions. For the southwest Atlantic, the relatively cost-effective nature of tourist vessel-based survey and regularity of tourist vessel voyages could allow for annual and intra-annual estimates of abundance, a fundamental improvement on current methods, which may capture spatiotemporal trends in baleen whale movements on forging grounds. Comparative modeling of sampling methods provided insights into the behavior of general additive model-based abundance modeling, contributing to the development of detailed guidelines of best practices for these approaches. Through successful engagement with tourist company partners, this method has the potential to characterize abundance across a variety of marine species and spaces globally, and deliver high-quality scientific outcomes relevant to management organizations.
Using deep leaning models to detect ophthalmic diseases: A comparative study
Authors: Li Zhixi , Guo Xinxing , Zhang Jian , Liu Xing , Chang Robert , He Mingguang
Published: March 2023

Purpose

The aim of this study was to prospectively quantify the level of agreement among the deep learning system, non-physician graders, and general ophthalmologists with different levels of clinical experience in detecting referable diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy.

Methods

Deep learning systems for diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy classification, with accuracy proven through internal and external validation, were established using 210,473 fundus photographs. Five trained non-physician graders and 47 general ophthalmologists from China were chosen randomly and included in the analysis. A test set of 300 fundus photographs were randomly identified from an independent dataset of 42,388 gradable images. The grading outcomes of five retinal and five glaucoma specialists were used as the reference standard that was considered achieved when ≥50% of gradings were consistent among the included specialists. The area under receiver operator characteristic curve of different groups in relation to the reference standard was used to compare agreement for referable diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy.

Results

The test set included 45 images (15.0%) with referable diabetic retinopathy, 46 (15.3%) with age-related macular degeneration, 46 (15.3%) with glaucomatous optic neuropathy, and 163 (55.4%) without these diseases. The area under receiver operator characteristic curve for non-physician graders, ophthalmologists with 3–5 years of clinical practice, ophthalmologists with 5–10 years of clinical practice, ophthalmologists with >10 years of clinical practice, and the deep learning system for referable diabetic retinopathy were 0.984, 0.964, 0.965, 0.954, and 0.990 (p = 0.415), respectively. The results for referable age-related macular degeneration were 0.912, 0.933, 0.946, 0.958, and 0.945, respectively, (p = 0.145), and 0.675, 0.862, 0.894, 0.976, and 0.994 for referable glaucomatous optic neuropathy, respectively (p < 0.001).

Conclusion

The findings of this study suggest that the accuracy of this deep learning system is comparable to that of trained non-physician graders and general ophthalmologists for referable diabetic retinopathy and age-related macular degeneration, but the deep learning system performance is better than that of trained non-physician graders for the detection of referable glaucomatous optic neuropathy.
Central retinal artery occlusion – detection score
Authors: Casagrande Maria , Steinhorst Nils Alexander , Dippel Susanne Kathrin , Kück Fabian , Grohmann Carsten , Spitzer Martin S. , Poli Sven , Feltgen Nicolas , Schultheiss Maximilian
Published: March 2023

Purpose

To investigate the sensitivity and specificity of central retinal artery occlusion (CRAO)-Detection Score in diagnosing CRAO via questionnaire and without fundoscopy.

Methods

This prospective study enrolled 176 emergency patients suffering from acute visual loss, of whom 38 were suffering from CRAO. Before conducting any examination, we administered our questionnaire containing six questions, followed by a thorough ophthalmologic examination to make the diagnosis. Statistical analysis involved a LASSO penalised multivariate logistic regression model.

Results

Our receiver operating characteristic (ROC) analysis based on a LASSO penalised multivariate logistic regression model showed an area under the curve (AUC) of 0.9 – three out of six questions were selected by LASSO. Interestingly, the unweighted ROC analysis of only two questions (Short CRAO-Detection Score) yielded similar results with an AUC of 0.88. The short CRAO-Detection Score of 2 yielded 14% (4/28) false positive patients.

Conclusion

This prospective study demonstrates that a high percentage of CRAO patients are detectable with a questionnaire. The CRAO-Detection Score might be used to triage patients suffering acute visual loss, which is important as intravenous fibrinolysis seem to be time-dependent to be effective.
Dietary protein to starch metabolizable energy ratios alter growth performance and gastrointestinal microbiota of calves
Authors: Chen Xue , Han Zhiyi , Dong Jianan , Xiao Jun , Zhao Wei , Rong Jiye , Aschalew Natnael D. , Zhang Xuefeng , Qin Guixin , Zhen Yuguo , Sun Zhe , Wang Tao
Published: March 2023

The diet structure is very important for the growth and development of calves. This study aimed to investigate the effects of dietary protein-to-starch metabolizable energy ratios (DPSRs) on growth performance, blood index, and gastrointestinal microbiota of calves. Forty-eight Holstein bull calves were fed six dietary DPSRs including A20-35 (20% CP and 35% starch), B20-30, C20-25, D22-35, E22-30, and F22-25 at d 4 to d 60, and then changed to another six dietary DPSRs at d 61 to d 180 (A18-30, B18-27, C18-24, D20-30, E20-27, and F20-24). Twelve calves (d 60) from groups A20-35, C20-25, D22-35, and F22-25 (n = 3) and another twelve calves (d 180) from groups A18-30, C18-24, D20-30, and F20-24 (n = 3) were euthanized. The growth performance parameters were measured. Blood, ruminal fluid, and cecum digesta were collected for further analysis. Results showed heart girth gain of B18-27 was significantly higher than A18-30, C18-24, and heart girth gain (d 180) was significantly affected by protein × starch (DPSRs; p < 0.05). Blood urea nitrogen (BUN; d 60) in C20-25 was significantly higher than A20-35 and B20-30 (p < 0.05). The BUN (d 180) in D20-30 was significantly higher than A18-30 (p < 0.05). The BUN was significantly affected by protein × starch (p < 0.05) on d 60. The albumin (ALB) levels in C20-25 and C18-24 were significantly higher than that in A20-35 on d 60 and A18-30 on d 180, respectively (p < 0.05). The ALB level in D22-35 on d 60 and E20-27 on d 180 was significantly higher than that in other groups (p < 0.05). The ALB level was significantly affected by protein and starch, respectively, on d 60 (p < 0.05). In the rumen, the genera Roseburia (C20-25) and Dialister (D22-35), Prevotellaceae UCG-001 (C18-24), Erysipelotrichaceae UCG-002, and Anaerovorax (F20-24) were found in significant higher relative abundances than those in other groups (p < 0.05). In the cecum, the genera Bacteroides and Eisenbergiella (F22-25), Ruminiclostridium_1 and Candidatus Stoquefichus (A18-30), Erysipelotrichaceae UCG-004 and Tyzzerella 4 (D20-30), and Prevotellaceae UCG-003 and Klebsiella (F20-24) were found in significant higher abundances than those in other groups (p < 0.05). Collectively, these results indicated that the heart girth, BUN, ALB, and gastrointestinal microbiota responded distinctly to differing DPSRs.
Structural analysis of the housecleaning nucleoside triphosphate pyrophosphohydrolase MazG from Mycobacterium tuberculosis
Authors: Wang Sen , Gao Baocai , Chen Anke , Zhang Zhifei , Wang Sheng , Lv Liangdong , Zhao Guoping , Li Jixi
Published: March 2023

The housecleaning enzyme of Mycobacterium tuberculosis (Mtb), MazG, is a nucleoside triphosphate pyrophosphohydrolase (NTP-PPase) and can hydrolyze all canonical or non-canonical NTPs into NMPs and pyrophosphate. The Mycobacterium tuberculosis MazG (Mtb-MazG) contributes to antibiotic resistance in response to oxidative or nitrosative stress under dormancy, making it a promising target for treating TB in latent infection patients. However, the structural basis of Mtb-MazG is not clear. Here we describe the crystal structure of Mtb-MazG (1–185) at 2.7 Å resolution, composed of two similar folded spherical domains in tandem. Unlike other all-α NTP pyrophosphatases, Mtb-MazG has an N-terminal extra region composed of three α-helices and five β-strands. The second domain is global, with five α-helices located in the N-terminal domain. Gel-filtration assay and SAXS analysis show that Mtb-MazG forms an enzyme-active dimer in solution. In addition, the metal ion Mg2+ is bound with four negative-charged residues Glu119, Glu122, Glu138, and Asp141. Different truncations and site-directed mutagenesis revealed that the full-length dimeric form and the metal ion Mg2+ are indispensable for the catalytic activity of Mtb-MazG. Thus, our work provides new insights into understanding the molecular basis of Mtb-MazG.
Influence of gluconate on the retention of Eu(III), Am(III), Th(IV), Pu(IV), and U(VI) by C-S-H (C/S = 0.8)
Authors: Dettmann Sophie , Huittinen Nina M. , Jahn Nicolas , Kretzschmar Jerome , Kumke Michael U. , Kutyma Tamara , Lohmann Janik , Reich Tobias , Schmeide Katja , Shams Aldin Azzam Salim , Spittler Leon , Stietz Janina
Published: March 2023

The retention of actinides in different oxidation states (An(X), X = III, IV, VI) by a calcium-silicate-hydrate (C-S-H) phase with a Ca/Si (C/S) ratio of 0.8 was investigated in the presence of gluconate (GLU). The actinides considered were Am(III), Th(IV), Pu(IV), and U(VI). Eu(III) was investigated as chemical analogue for Am(III) and Cm(III). In addition to the ternary systems An(X)/GLU/C-S-H, also binary systems An(X)/C-S-H, GLU/C-S-H, and An(X)/GLU were studied. Complementary analytical techniques were applied to address the different specific aspects of the binary and ternary systems. Time-resolved laser-induced luminescence spectroscopy (TRLFS) was applied in combination with parallel factor analysis (PARAFAC) to identify retained species and to monitor species-selective sorption kinetics. 13C and 29Si magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy and X-ray photoelectron spectroscopy (XPS) were applied to determine the bulk structure and the composition of the C-S-H surface, respectively, in the absence and presence of GLU. The interaction of Th(IV) with GLU in different electrolytes was studied by capillary electrophoresis-inductively coupled plasma mass spectrometry (CE-ICP-MS). The influence of GLU on An(X) retention was investigated for a large concentration range up to 10−2 M. The results showed that GLU had little to no effect on the overall An(X) retention by C-S-H with C/S of 0.8, regardless of the oxidation state of the actinides. For Eu(III), the TRLFS investigations additionally implied the formation of a Eu(III)-bearing precipitate with dissolved constituents of the C-S-H phase, which becomes structurally altered by the presence of GLU. For U(VI) sorption on the C-S-H phase, only a small influence of GLU could be established in the luminescence spectroscopic investigations, and no precipitation of U(VI)-containing secondary phases could be identified.
Biochemical and antioxidant activity of wild edible fruits of the eastern Himalaya, India
Authors: Rymbai Heiplanmi , Verma Veerendra Kumar , Talang Hammylliende , Assumi S. Ruth , Devi M. Bilashini , Vanlalruati  , Sangma Rumki Heloise CH. , Biam Kamni Paia , Chanu L. Joymati , Makdoh Badapmain , Singh A. Ratankumar , Mawleiñ Joiedevivreson , Hazarika Samarendra , Mishra Vinay Kumar
Published: March 2023

The eastern Himalayas, one of the important hotspots of global biodiversity, have a rich diversity of wild edible fruit trees. The fruits of these tree species have been consumed by the tribal people since time immemorial. However, there is limited information available on the biochemical and antioxidant properties of the fruits. Therefore, the present investigation was undertaken to study the physico-chemical and antioxidant properties of the nine most important wild fruit trees. Among the species, Pyrus pashia had the maximum fruit weight (37.83 g), while the highest juice (43.72%) and pulp content (84.67%) were noted in Haematocarpus validus and Myrica esculenta, respectively. Maximum total soluble solids (18.27%), total sugar (11.27%), moisture content (88.39%), ascorbic acid content (63.82 mg/100 g), total carotenoids (18.47 mg/100 g), and total monomeric anthocyanin (354.04 mg/100 g) were recorded in H. validus. Docynia indica had the highest total phenolic content (19.37 mg GAE/g), while H. validus recorded the highest total flavonoids and flavanol content. The antioxidant activities of the different fruits ranged from 0.17 to 0.67 IC50 for DPPH activity and 3.59–13.82 mg AAE/g for FRAP. These fruits had attractive pigmentation of both pulp and juice and were a good potential source for the extraction of natural edible color in the food industry. The fruits also possess high market prices; Prunus nepalensis fetched $ 34.10–$ 141.5 per tree. Therefore, these fruits are rich sources of antioxidants, pigments and have a high market value for livelihood and nutritional security.
Effect of combined therapies including nutrition and physical exercise in advanced cancer patients: A pooled analysis
Authors: Storck Lena J. , Uster Alexandra , Gafner Lucia , Ruehlin Maya , Gaeumann Sabine , Gisi David , Schmocker Martina , Meffert Peter J. , Imoberdorf Reinhard , Pless Miklos , Ballmer Peter E.
Published: March 2023

Background and aims

Although many cancer patients suffer from malnutrition or cancer cachexia, there is no standard of care so far due to limited intervention trials. Pooled data from two combined trials were analyzed regarding nutritional status and survival time.

Materials and methods

Data from two trials with advanced cancer patients were included. In both trials, patients in the intervention group received at least three times nutritional counseling and supervised training sessions. Patients in the control group continued being treated according to usual care. Nutritional status was measured using BMI, body composition and handgrip strength. Survival time was analyzed using the Cox proportional hazard model with the period between the beginning of the trial and death as underlying time scale.

Results

68 men (61.8%) and 42 women (38.2%) were randomized either to the intervention (n = 56) or the control (n = 54) group. The inter-group difference for changes in BMI and body composition was not statistically significant after 3 months. Handgrip strength improved significantly from 34.4 ± 10.2 kg to 36.3 ± 9.9 kg at 3 months in the intervention compared to 33.9 ± 9.2 kg to 34.9 ± 9.1 kg in the control group (p = 0.006). The analysis of survival time showed no inter-group difference for all patients. A detailed analysis for different diagnoses showed that in patients with lung cancer, the covariates “CRP value,” “days from first diagnosis to randomization” as well as “gender” were significantly associated with survival time. Patients with higher CRP value had a shorter survival time and female patients had a shorter survival time than male patients in our analysis. In addition, patients with pancreatic cancer randomized to the control group had a 20% shorter survival time than those in the intervention group (p = 0.048).

Conclusion

The pooled analysis showed a significant improvement of handgrip strength in advanced cancer patients through the implementation of a combined therapy. Handgrip strength is of prognostic significance in hospitalized patients due to its association with mortality and morbidity. However, no improvements in further tests were detected. There is great need for further investigations examining the effect of nutritional and exercise therapy on survival time with focus on different cancer diagnoses.
The effects of camelina sativa oil and high-intensity interval training on liver function and metabolic outcomes in male type 2 diabetic rats
Authors: Kavyani Zeynab , Dehghan Parvin , Khani Mostafa , Khalafi Mousa , Rosenkranz Sara K.
Published: March 2023

Objectives

The purpose of this study was to evaluate the independent and combined effects of camelina sativa oil and high-intensity interval training (HIIT) on liver function, and metabolic outcomes in streptozotocin-induced diabetic rats.

Methods

Forty male Wistar rats were randomly assigned to five equal groups (8 per group): Normal control (NC), diabetic control (DC), diabetic + camelina sativa oil (300 mg/kg by oral gavage per day; D + CSO), diabetic + HIIT (running on a treadmill 5 days/week for 8 weeks; D + HIIT), diabetic + camelina sativa oil + HIIT (D + CSO +  HIIT).

Results

In all three intervention groups (D + CSO, D + HIIT, and D + CSO + HIIT) compared to the DC, hepatic TNF-α, MDA, and histopathology markers, decreased and hepatic PGC-1α, and PPAR-γ increased (p < 0.05). However, the effect of D + CSO was greater than D + HIIT alone. Hepatic TG decreased significantly in D + HIIT and D + CSO + HIIT compared to other groups (p < 0.001). Fasting plasma glucose in all three intervention groups (D + CSO, D + HIIT, and D + CSO + HIIT) and HOMA-IR in D + CSO and D + CSO + HIIT were decreased compared to DC (p < 0.001). Only hepatic TAC and fasting plasma insulin remained unaffected in the three diabetic groups (p < 0.001). Overall, D + CSO + HIIT had the largest effect on all outcomes.

Conclusions

At the doses and treatment duration used in the current study, combination of CSO and HIIT was beneficial for reducing liver function and metabolic outcomes other than CSO and HIIT alone.