bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Prognostic Importance of Massive Tricuspid Regurgitation in Patients Undergoing Tricuspid Annuloplasty With Concomitant Left-Sided Valve Surgery: A Study on Rheumatic Valvular Heart Disease
Authors: Chen Yan , Chan Yap-Hang , Wu Mei-Zhen , Yu Yu-Juan , Lam Yui-Ming , Sit Ko-Yung , Chan Daniel Tai-Leung , Ho Cally Ka-Lai , Ho Lai-Ming , Lau Chu-Pak , Au Wing-Kuk , Tse Hung-Fat , Yiu Kai-Hang
Published: January 2022

Background

The presence of tricuspid regurgitation (TR) is very common in patients with concomitant left-sided valve disease. Recent studies have advocated an additional grading of massive TR that is beyond severe. The present study sought to characterize the spectrum of TR in patients undergoing tricuspid annuloplasty (TA) and to evaluate the prognostic value of TR severity for post-operative outcome following TA.

Methods

A total of 176 patients who underwent TA with combined left-sided valve surgery, secondary to rheumatic valvular heart disease, were prospectively evaluated. The severity of TR was quantified by effective regurgitant orifice area (EROA) using the proximal isovelocity surface area method. Patients were categorized as having non-massive TR (EROA < 0.6 cm2) or massive TR (EROA ≥ 0.6 cm2). Adverse outcome was defined as all-cause mortality or heart failure requiring hospital admission following TA.

Results

A total of 55 (31%) patients were considered to have massive TR. Patients with massive TR had a greater right ventricular dimension but a smaller left ventricular dimension compared with those with non-massive TR. After a median follow-up of 39 months, 35 adverse events occurred. Cox-regression analysis showed that both continuous EROA and dichotomized EROA (massive vs. non-massive TR) were independently associated with adverse events even after multivariable adjustment. Further, Harrell C index demonstrated that the addition of massive TR provided better discrimination ability of a prediction model to known prognosticators following TA.

Conclusions

Massive TR is common and up to 31% of study population had massive TR. Massive TR was associated with adverse outcome in patients undergoing TA. Classification of the severity of TR by quantitative measures and identification of massive TR in patients with concomitant left-sided valve disease are essential when considering the optimal timing of corrective surgery.
Regional Characteristics of Porosity and Permeability of Dahebian Syncline Coal and Its Application
Authors: Zhao Fuping , Wei Yuanlong
Published: January 2022

In order to study the basic properties of coal seam thus to provide reference for coalbed methane (CBM) production, the porosity and permeability of coal from DH and WJZ regions of Dahebian syncline in Liupanshui Coalfield were systematically studied. The results shows that the porosity and permeability of coal samples in DH region are between 7.4–10.1% and 0.01 mD∼0.04 mD respectively. The permeability is obviously anisotropic, and it is distributed in a U-shape along bedding angle. The porosity and permeability in the WJZ region are between 12.4–24.85% and 0.3 mD–4.8 mD, but the correlation of permeability and bedding angle is not obvious. There are many primary cracks in coal matrix of WJZ region, while the coal of DH region is relatively complete. As a result, the porosity and permeability of WJZ coal samples are much higher than that of DH coal samples. With the change of confining pressure, obvious change has taken place in the permeability of coal in the two regions. When the confining pressure decreases from 2 to 8 MPa, the permeability loss rate of coal samples is close to 80%. The internal mechanism of the permeability loss is related to crack closure and plastic deformation caused by confining pressure. In contrast, the porosity and permeability of coal in WJZ region are much higher than those in DH region, which indicates that the permeability of the same coal seam in the same structural will have great differences and inhomogeneities. Therefore, the WJZ region is the preferred area, which can be included in the preferential exploitation plan of CBM. In addition, for the typical syncline gas reservoir in Liupanshui Coalfield, it is necessary to consider the block division according to the porosity and permeability indexes, and select the optimal block and give priority to development of CBM. Furthermore, we should pay attention to the difference and adaptability of CBM development in different regions.
Prevalence and Spectrum of Predisposition Genes With Germline Mutations Among Chinese Patients With Bowel Cancer
Authors: Xie Zhengyong , Ke Yongli , Chen Junyong , Li Zehang , Wang Changzheng , Chen Yuhong , Ding Hongliang , Cheng Liyang
Published: January 2022

Background: Bowel cancer is the third-most common cancer and the second leading cause of cancer-related death worldwide. Bowel cancer has a substantial hereditary component; however, additional hereditary risk factors involved in bowel cancer pathogenesis have not been systematically defined.

Materials and Methods: A total of 573 patients with bowel cancer were enrolled in the present study, of whom 93.72% had colorectal cancer (CRC). Germline mutations were integrated with somatic mutation information via utilizing target next-generation sequencing.

Results: Pathogenic/Likely Pathogenic (P/LP) germline alterations were identified in 47 (8.2%) patients with bowel cancer and the ratio of the number of these patients with family history was significantly higher in the P/LP group than that noted in the non-pathogenic (Non-P) group. Certain rare germline alterations were noted, such as those noted in the following genes: FANCD2, CDH1, and FLCN. A total of 32 patients (68.1%) had germline alterations in the DNA-damage repair (DDR) genes and homologous recombination (HR) accounted for the highest proportion of this subgroup. By comparing 573 patients with bowel cancer with reference controls (China_MAPs database), significant associations (p < 0.01) were observed between the incidence of bowel cancer and the presence of mutations in APC, ATM, MLH1, FANCD2, MSH3, MSH6, PMS1, and RAD51D. Somatic gene differential analysis revealed a marked difference in 18 genes and a significant difference was also noted in tumor mutation burden (TMB) between germline mutation carriers and non-germline mutation subjects (p < 0.001). In addition, TMB in DDR mutation groups indicated a dramatic difference compared with the non-DDR mutation group (p < 0.01). However, no statistically significant differences in TMB were noted among detailed DDR pathways for patients with bowel cancer, irrespective of the presence of germline mutations. Moreover, a significantly higher level (p < 0.0001) of mutation count was observed in the DDR group from The Cancer Genome Atlas (TCGA) database and the DDR and non-DDR alteration groups displayed various immune profiles.

Conclusion: Chinese patients with bowel cancer exhibited a distinct spectrum of germline variants, with distinct molecular characteristics such as TMB and DDR. Furthermore, the information on somatic mutations obtained from TCGA database indicated that a deeper understanding of the interactions among DDR and immune cells would be useful to further investigate the role of DDR in bowel cancer.
Assessment of Heterozygosity and Genome-Wide Analysis of Heterozygosity Regions in Two Duroc Pig Populations
Authors: Ruan Donglin , Yang Jie , Zhuang Zhanwei , Ding Rongrong , Huang Jinyan , Quan Jianping , Gu Ting , Hong Linjun , Zheng Enqin , Li Zicong , Cai Gengyuan , Wang Xiaopeng , Wu Zhenfang
Published: January 2022

Heterozygosity can effectively reflect the diverse models of population structure and demographic history. However, the genomic distribution of heterozygotes and the correlation between regions of heterozygosity (runs of heterozygosity, ROHet) and phenotypes are largely understudied in livestock. The objective of this study was to identify ROHet in the Duroc pig genome, and investigate the relationships between ROHet and eight important economic traits. Here, we genotyped 3,770 American Duroc (S21) and 2,096 Canadian Duroc (S22) pigs using 50 K single nucleotide polymorphism array to analyze heterozygosity. A total of 145,010 and 84,396 ROHets were characterized for S21 and S22 populations, respectively. ROHet segments were mostly enriched in 1–2 Mb length classification (75.48% in S21 and 72.25% in S22). The average genome length covered by ROHet was 66.53 ± 12.20 Mb in S21 and 73.32 ± 13.77 Mb in S22 pigs. Additionally, we detected 20 and 13 ROHet islands in S21 and S22 pigs. Genes in these genomic regions were mainly involved in the biological processes of immunity and reproduction. Finally, the genome-wide ROHet-phenotypes association analysis revealed that 130 ROHets of S21 and 84 ROHets of S22 were significantly associated with eight economic traits. Among the candidate genes in the significant ROHet regions, 16 genes related to growth, metabolism, and meat quality were considered as candidate genes for important economic traits of pigs. This work preliminarily explores the effect of heterozygosity-rich regions in the pig genome on production performance and provides new insights for subsequent research on pig genetic improvement.
The Scope of Pathogenic ABCA4 Mutations Targetable by CRISPR DNA Base Editing Systems—A Systematic Review
Authors: Piotter Elena , McClements Michelle E. , MacLaren Robert E.
Published: January 2022

Stargardt macular dystrophy (STGD1) is the most common form of inherited childhood blindness worldwide and for which no current treatments exist. It is an autosomal recessive disease caused by mutations in ABCA4. To date, a variety of gene supplementation approaches have been tested to create a therapy, with some reaching clinical trials. New technologies, such as CRISPR-Cas based editing systems, provide an exciting frontier for addressing genetic disease by allowing targeted DNA or RNA base editing of pathogenic mutations. ABCA4 has ∼1,200 known pathogenic mutations, of which ∼63% are transition mutations amenable to this editing technology. In this report, we screened the known “pathogenic” and “likely pathogenic” mutations in ABCA4 from available data in gnomAD, Leiden Open Variation Database (LOVD), and ClinVar for potential PAM sites of relevant base editors, including Streptococcus pyogenes Cas (SpCas), Staphylococcus aureus Cas (SaCas), and the KKH variant of SaCas (Sa-KKH). Overall, of the mutations screened, 53% (ClinVar), 71% (LOVD), and 71% (gnomAD), were editable, pathogenic transition mutations, of which 35–47% had “ideal” PAM sites. Of these mutations, 16–20% occur within a range of multiple PAM sites, enabling a variety of editing strategies. Further, in relevant patient data looking at three cohorts from Germany, Denmark, and China, we find that 44–76% of patients, depending on the presence of complex alleles, have at least one transition mutation with a nearby SaCas, SpCas, or Sa-KKH PAM site, which would allow for potential DNA base editing as a treatment strategy. Given the complexity of the genetic landscape of Stargardt, these findings provide a clearer understanding of the potential for DNA base editing approaches to be applied as ABCA4 gene therapy strategies.
RNA-Binding Protein IGF2BP1 Associated With Prognosis and Immunotherapy Response in Lung Adenocarcinoma
Authors: Liu JinFeng , Li Zhi , Cheang Iokfai , Li Jinghang , Zhou Chunlei
Published: January 2022

N6-methyladenosine (m6A) is the most common modification in eukaryotic RNAs and plays a vital role in the tumorigenesis and metastasis of various cancers. However, a comprehensive study of m6A methylation regulators in lung adenocarcinoma (LUAD) is still lacking. The present study aimed to systematically explore the role of m6A methylation regulators in LUAD. RNA sequencing data of 20 m6A methylation regulators and clinical data of LUAD patients were downloaded from The Cancer Genome Atlas (TCGA) database. The prognosis value of m6A methylation regulators in LUAD was evaluated using the Gene Expression Profiling Interactive Analysis (GEPIA) and PrognoScan database. The correlation between IGF2BP1 and immune infiltrates in LUAD was investigated via CIBERSORT and Tumor Immune Estimation Resource (TIMER). A total of 15 m6A modification regulators were significantly abnormally expressed in LUAD tissues. Survival analysis revealed that four genes (HNRNPC, HNRNPA2B1, IGF2BP1, and IGF2BP3) were significantly associated with poor prognosis in LUAD. Multivariate Cox regression analysis showed that only IGF2BP1 was an independent predictor of LUAD after adjusting common clinical parameters. The mutation rates of m6A modification regulators in LUAD were less than 10%. Further analysis revealed that IGF2BP1 expression was significantly correlated with immune infiltration, the expression of immune checkpoints, and tumor mutational burden (TMB) in LUAD. Our findings suggest that IGF2BP1 is an independent predictor and related to immunotherapy response in LUAD, which maybe a potential novel biomarker for LUAD prognosis and the status of tumor immunity.
Integration of Single-Cell RNA Sequencing and Bulk RNA Sequencing Data to Establish and Validate a Prognostic Model for Patients With Lung Adenocarcinoma
Authors: Jiang Aimin , Wang Jingjing , Liu Na , Zheng Xiaoqiang , Li Yimeng , Ma Yuyan , Zheng Haoran , Chen Xue , Fan Chaoxin , Zhang Rui , Fu Xiao , Yao Yu
Published: January 2022

Background: Lung adenocarcinoma (LUAD) remains a lethal disease worldwide, with numerous studies exploring its potential prognostic markers using traditional RNA sequencing (RNA-seq) data. However, it cannot detect the exact cellular and molecular changes in tumor cells. This study aimed to construct a prognostic model for LUAD using single-cell RNA-seq (scRNA-seq) and traditional RNA-seq data.

Methods: Bulk RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) database. LUAD scRNA-seq data were acquired from Gene Expression Omnibus (GEO) database. The uniform manifold approximation and projection (UMAP) was used for dimensionality reduction and cluster identification. Weighted Gene Correlation Network Analysis (WGCNA) was utilized to identify key modules and differentially expressed genes (DEGs). The non-negative Matrix Factorization (NMF) algorithm was used to identify different subtypes based on DEGs. The Cox regression analysis was used to develop the prognostic model. The characteristics of mutation landscape, immune status, and immune checkpoint inhibitors (ICIs) related genes between different risk groups were also investigated.

Results: scRNA-seq data of four samples were integrated to identify 13 clusters and 9cell types. After applying differential analysis, NK cells, bladder epithelial cells, and bronchial epithelial cells were identified as significant cell types. Overall, 329 DEGs were selected for prognostic model construction through differential analysis and WGCNA. Besides, NMF identified two clusters based on DEGs in the TCGA cohort, with distinct prognosis and immune characteristics being observed. We developed a prognostic model based on the expression levels of six DEGs. A higher risk score was significantly correlated with poor survival outcomes but was associated with a more frequent TP53 mutation rate, higher tumor mutation burden (TMB), and up-regulation of PD-L1. Two independent external validation cohorts were also adopted to verify our results, with consistent results observed in them.

Conclusion: This study constructed and validated a prognostic model for LUAD by integrating 10× scRNA-seq and bulk RNA-seq data. Besides, we observed two distinct subtypes in this population, with different prognosis and immune characteristics.
T-Cell Repertoire Characteristics of Asymptomatic and Re-Detectable Positive COVID-19 Patients
Authors: Li Yizhe , Hu Jian , Wang Yongsi , Liu Dongdong , Shi Yaling , Zhang Jiaqi , Liu Yuntao , Lin Dongzi , Lin Jing , Hu Wei , He Haolan , Wang Wei , Fan Wentao , Li Linlin , Wang Dawei , Wang Kejian , Xu Jianhua
Published: January 2022

The prevention of the COVID-19 pandemic is highly complicated by the prevalence of asymptomatic and recurrent infection. Many previous immunological studies have focused on symptomatic and convalescent patients, while the immune responses in asymptomatic patients and re-detectable positive cases remain unclear. Here we comprehensively analyzed the peripheral T-cell receptor (TCR) repertoire of 54 COVID-19 patients in different courses, including asymptomatic, symptomatic, convalescent, and re-detectable positive cases. We identified a set of V–J gene combinations characterizing the upward immune responses through asymptomatic and symptomatic courses. Furthermore, some of these V–J combinations could be awakened in the re-detectable positive cases, which may help predict the risk of recurrent infection. Therefore, TCR repertoire examination has the potential to strengthen the clinical surveillance and the immunotherapy development for COVID-19.
An Update on Human Papilloma Virus Vaccines: History, Types, Protection, and Efficacy
Authors: Yousefi Zahra , Aria Hamid , Ghaedrahmati Farhoodeh , Bakhtiari Tahereh , Azizi Mahdieh , Bastan Reza , Hosseini Reza , Eskandari Nahid
Published: January 2022

Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. Early prevention with HPV vaccination is a safe and effective method against this disease. HPV vaccines provided more protection against several oncogenic HPV strains. Three prophylactic HPV vaccines have been approved to target high-risk HPV types and protect against HPV-related disorders. These existing vaccines are based on the recombinant DNA technology and purified L1 protein that is assembled to form HPV empty shells. The prophylactic vaccines are highly immunogenic and can induce production of specific neutralizing antibodies. However, therapeutic vaccines are different from these prophylactic vaccines. They induced cell-mediated immunity against transformed cells, instead of neutralizing antibodies. The second generation of prophylactic HPV vaccines, made from alternative viral components using cost-effective production strategies, is undergoing clinical evaluation. The purpose of this review is to provide a complete and up-to-date review of the types of HPV vaccines and the efficiency of each of them for readers.
Genome-Wide Association Study of Ustekinumab Response in Psoriasis
Authors: Connell William T. , Hong Julie , Liao Wilson
Published: January 2022

Heterogeneous genetic and environmental factors contribute to the psoriasis phenotype, resulting in a wide range of patient response to targeted therapies. Here, we investigate genetic factors associated with response to the IL-12/23 inhibitor ustekinumab in psoriasis. To date, only HLA-C*06:02 has been consistently reported to associate with ustekinumab response in psoriasis. Genome-wide association testing was performed on the continuous outcome of percent change in Psoriasis Area Severity Index (PASI) at 12 weeks of ustekinumab therapy relative to baseline. A total of 439 European ancestry individuals with psoriasis were included [mean age, 46.6 years; 277 men (63.1%)]. 310 (70.6%) of the participants comprised the discovery cohort and the remaining 129 (29.4%) individuals comprised the validation cohort. Chromosome 4 variant rs35569429 was significantly associated with ustekinumab response at 12 weeks at a genome-wide significant level in the discovery cohort and replicated in the validation cohort. Of psoriasis subjects with at least one copy of the deletion allele of rs35569429, 44% achieved PASI75 (75% improvement in PASI from baseline) at week 12 of ustekinumab treatment, while for subjects without the deletion allele, 75% achieved PASI75 at week 12. We found that differences in treatment response increased when rs35569429 was considered alongside HLA-C*06:02. Psoriasis patients with the deletion allele of rs35569429 who were HLA-C*06:02 negative had a PASI75 response rate of 35% at week 12, while those without the deletion allele who were HLA-C*06:02 positive had a PASI75 response rate of 82% at week 12. Through GWAS, we identified a novel SNP that is potentially associated with response to ustekinumab in psoriasis.
The Impact of Esophageal Oncological Surgery on Perioperative Immune Function; Implications for Adjuvant Immune Checkpoint Inhibition
Authors: Donlon Noel E. , Davern Maria , Sheppard Andrew D. , O’Connell Fiona , Dunne Margaret R. , Hayes Conall , Mylod Eimear , Ramjit Sinead , Temperley Hugo , Mac Lean Michael , Cotter Gillian , Bhardwaj Anshul , Butler Christine , Conroy Melissa J. , O’Sullivan Jacintha , Ravi Narayanasamy , Donohoe Claire L. , Reynolds John V. , Lysaght Joanne
Published: January 2022

Background

Immune checkpoint inhibitors (ICIs) are being investigated for their role as an adjunct in the multimodal treatment of esophageal adenocarcinoma (EAC). The most effective time to incorporate ICIs remains unknown. Our study profiles systemic anti-tumor immunity perioperatively to help inform the optimal timing of ICIs into current standards of care for EAC patients.

Methods

Systemic immunity in 11 EAC patients was phenotyped immediately prior to esophagectomy (POD-0) and post-operatively (POD)-1, 3, 7 and week 6. Longitudinal serological profiling was conducted by ELISA. The frequency of circulating lymphocytes, activation status, immune checkpoint expression and damage-associated molecular patterns was assessed by flow cytometry.

Results

The frequency of naïve T-cells significantly increased in circulation post-esophagectomy from POD-0 to POD-7 (p<0.01) with a significant decrease in effector memory T-cells by POD7 followed by a subsequent increase by week 6 (p<0.05). A significant increase in activated circulating CD27+ T-cells was observed from POD-0 to POD-7 (p<0.05). The percentage of PD-1+ and CTLA-4+ T-cells peaked on POD-1 and was significantly decreased by week 6 (p<0.01). There was a significant increase in soluble PD-1, PD-L2, TIGIT and LAG-3 from POD-3 to week 6 (p<0.01). Increased checkpoint expression correlated with those who developed metastatic disease early in their postoperative course. Th1 cytokines and co-stimulatory factors decreased significantly in the immediate post-operative setting, with a reduction in IFN-γ, IL-12p40, IL-1RA, CD28, CD40L and TNF-α. A simultaneous increase was observed in Th2 cytokines in the immediate post-operative setting, with a significant increase in IL-4, IL-10, IL-16 and MCP-1 before returning to preoperative levels at week 6.

Conclusion

Our study highlights the prevailing Th2-like immunophenotype post-surgery. Therefore, shifting the balance in favour of a Th1-like phenotype would offer a potent therapeutic approach to promote cancer regression and prevent recurrence in the adjuvant setting and could potentially propagate anti-tumour immune responses perioperatively if administered in the immediate neoadjuvant setting. Consequently, this body of work paves the way for further studies and appropriate trial design is needed to further interrogate and validate the use of ICI in the multimodal treatment of locally advanced disease in the neoadjuvant and adjuvant setting.
Decreased Expression of Programmed Death Ligand-L1 by Seven in Absentia Homolog 2 in Cholangiocarcinoma Enhances T-Cell–Mediated Antitumor Activity
Authors: Zheng Hao , Zheng Wen-juan , Wang Zhen-guang , Tao Yuan-ping , Huang Zhi-ping , Yang Le , Ouyang Liu , Duan Zhi-qing , Zhang Yi-nuo , Chen Bo-ning , Xiang Dai-min , Jin Gang , Fang Lu , Zhou Fan , Liang Bo
Published: January 2022

N6-methyladenosine (m6A) has been reported as an important mechanism of post-transcriptional regulation. Programmed death ligand 1 (PD-L1) is a primary immune inhibitory molecule expressed on tumor cells that promotes immune evasion. In addition, seven in absentia homolog 2 (Siah2), a RING E3 ubiquitin ligase, has been involved in tumorigenesis and cancer progression. However, the role of m6A-METTL14-Siah2-PD-L1 axis in immunotherapy remains to be elucidated. In this study, we showed that METTL14, a component of the m6A methyltransferase complex, induced Siah2 expression in cholangiocarcinoma (CCA). METTL14 was shown to enrich m6A modifications in the 3’UTR region of the Siah2 mRNA, thereby promoting its degradation in an YTHDF2-dependent manner. Furthermore, co-immunoprecipitation experiments demonstrated that Siah2 interacted with PD-L1 by promoting its K63-linked ubiquitination. We also observed that in vitro and in vivo Siah2 knockdown inhibited T cells expansion and cytotoxicity by sustaining tumor cell PD-L1 expression. The METTL14-Siah2-PD-L1–regulating axis was further confirmed in human CCA specimens. Analysis of specimens from patients receiving anti-PD1 immunotherapy suggested that tumors with low Siah2 levels were more sensitive to anti-PD1 immunotherapy. Taken together, our results evidenced a new regulatory mechanism of Siah2 by METTL14-induced mRNA epigenetic modification and the potential role of Siah2 in cancer immunotherapy.
Combined Use of eDNA Metabarcoding and Bottom Trawling for the Assessment of Fish Biodiversity in the Zhoushan Sea
Authors: Zhou Shan , Fan Chenrong , Xia Haoming , Zhang Jian , Yang Wei , Ji Dengjie , Wang Lei , Chen Li , Liu Nannan
Published: January 2022

With the increase in fishing intensity and the intensification of marine pollution, the fishery resources in the Zhoushan Sea are seriously degraded, and the difficulty of censusing fish diversity hampers effective management in marine fishes. Environmental DNA metabarcoding and bottom trawl methods were used to determine the ability of the methods to distinguish fish assemblages in the Zhoushan Sea. The species composition and diversity of the Zhoushan Sea were assessed via high-throughput sequencing analysis of eDNA coupled with bottom trawl fishery survey data, after which the two methods were compared. eDNA screening identified 38.2% more fish species than bottom trawls. Combining these two methods, 33 orders, 65 families, and 130 species of fishes were identified. Perciformes and Clupeiformes, the most abundant orders in the catch, represented 31.5 and 10.0% of the total fish abundance, respectively. The results of ANOSIM and redundancy analyses indicated that the fish community structure varied significantly between summer and winter, however depth and temperature being the main environmental factors influencing fish distribution. The biodiversity index was higher in summer than in winter. Thus, our work provides more detailed seasonal data on biodiversity in the Zhoushan Sea, which is essential for the long-term management and conservation of coastal biodiversity. Compared with traditional survey methods, eDNA determination is highly sensitive, accurate, cost-efficient, and suitable for fish diversity studies in relevant sea areas. Although this approach cannot completely replace traditional methods, our findings demonstrate that it provides a reliable complementary method for assessing fish diversity in marine ecosystems.
Water Masses Variability in Inner Kongsfjorden (Svalbard) During 2010–2020
Authors: De Rovere Francesco , Langone Leonardo , Schroeder Katrin , Miserocchi Stefano , Giglio Federico , Aliani Stefano , Chiggiato Jacopo
Published: January 2022

Kongsfjorden is an Arctic fjord located in the Svalbard archipelago. Its hydrography is influenced by the warm and saline Atlantic Water (AW) in the West Spitsbergen Current and the cold and fresh Polar Water circulating on the shelf. We assess the so-called atlantification of Kongsfjorden in the 2010–2020 decade by inspecting modifications in water properties and water masses variability through moored data and summer CTD surveys. Atlantification in this fjord has emerged as an increasing temperature and salinity, resulting from enhanced advection of Atlantic waters from the West Spitsbergen Current. The water column in inner Kongsfjorden warmed by 0.13°C/yr at 35 m and 0.06°C/yr at 85 m depth from 2010 to 2020, while salinity increased by 0.3 PSU. Depth-averaged temperatures have increased by 0.26°C/yr in the warmest months of the year, whereas they appear relatively stable in the coldest months. Both temperature and salinity present a linear regression change point in January 2017, with latter years featuring decreasing values. Highly diluted AW is found at the beginning of the decade, which give way to more and more pure AW in latter years, culminating in extensive intrusions in 2016 and 2017 determining the warmest and saltiest conditions over the decade in inner Kongsfjorden. Observations in the 2010–2020 decade confirm that Kongsfjorden has transitioned to an Atlantic-type fjord, featuring depleted sea ice conditions and rather regular shallow intrusions of AW in summer and frequently also in winter. Although single intrusions of AW are associated with dynamical events on the shelf, we found that the long-term temperature evolution in the inner Kongsfjord is consistent with the meridional temperature transport of the West Spitsbergen Current. The AW current flowing northward from lower latitudes along the western Svalbard archipelago thus has profoundly driven local conditions in the inner fjord in this decade.
Investigation of Correlations Between Optical Coherence Tomography Biomarkers and Visual Acuity in X-Linked Retinoschisis
Authors: Lin Zhanjie , Zang Siwen , Maman Lawali Dan Jouma Amadou , Xiao Yu , Zeng Xiaomin , Yu Honghua , Hu Yijun
Published: January 2022

Purpose

To investigate the imaging biomarkers of spectral-domain optical coherence tomography (SD-OCT) and their correlations with age and best-corrected visual acuity (BCVA) in patients with X-linked retinoschisis (XLRS).

Methods

OCT images of 72 eyes of 39 patients with confirmed XLRS were obtained to assess imaging biomarkers, including but not limited to the automatic evaluation of foveal thickness, central subfield thickness (CST), macular volume, and the manual measurement of area of macular schisis cavity (AMS). Correlations between age/BCVA and all OCT parameters were computed as well.

Results

In this study, median age was 10.5 (8–12) years old and median BCVA was 0.90 (0.70–1.00) logarithm of the minimum angle of resolution. Macular retinoschisis was found in all affected eyes, with peripheral retinoschisis (PRS) in 34 (47.2%) eyes. Cystic cavities most frequently affected inner nuclear layer (100%) in the macula. Ellipsoid zone (EZ) defects occurred in 53 (73.6%) eyes. As for correlation, BCVA was significantly correlated with several OCT parameters, including CST, AMS, EZ defect, PRS and vitreomacular adhesion, whereas no correlation was found between age and any OCT parameter.

Conclusion

Explicable OCT imaging biomarkers such as CST, AMS, and photoreceptor defects were identified and may serve as reference parameters or potential regions of interest for future observational and interventional research design and result interpretation.
Intravenous Infusion of Lidocaine for Bowel Function Recovery After Major Colorectal Surgery: A Critical Appraisal Through Updated Meta-Analysis, Trial Sequential Analysis, Certainty of Evidence, and Meta-Regression
Authors: Chen Po-Chuan , Lai Chao-Han , Fang Ching-Ju , Lai Pei Chun , Huang Yen Ta
Published: January 2022

Background

Intravenous infusion of lidocaine (IVF-Lido) during the perioperative period is an option to accelerate bowel function recovery after major colorectal surgery. However, previous meta-analyses have shown inconsistent conclusions. Recent randomized controlled trials (RCTs) have been reported after the publication of a previous meta-analysis.

Aim

We conducted an updated and comprehensive meta-analysis to determine the effects of IVF-Lido on time to first flatus and defecation after major colorectal surgery.

Methods

We performed a systematic review according to the Preferred Reporting Items for the Systematic Reviews and Meta-Analysis Protocols 2020 guideline. Only RCTs were included. The revised Cochrane risk-of-bias tool was chosen for appraisal. Meta-analysis with meta-regression and trial sequential analysis was carried out. The Doi plot was presented to evaluate publication bias. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology was executed to evaluate the certainty of evidence (CoE).

Results

Thirteen RCTs with 696 participants were enrolled. IVF-Lido significantly decreased the time to first flatus [mean difference (MD) = −6.03 h; 95% confidence interval (CI): (−8.80, −3.26)] and first defecation [MD = −10.49 h; 95% CI: (−15.58, −5.41)]. Trial sequential analysis yielded identical results and ampleness of required information sizes. No obviousness in publication bias was detected, and the CoE in GRADE was low in both outcomes. Meta-regression showed that a significantly shorter time to the first defecation was associated with studies with more improvement in pain control in comparison of two groups and better-improved analgesia in the control group.

Conclusions

We discretionarily suggest the use of IVF-Lido on postoperative bowel function recovery following major colorectal surgery. Beyond the analgesic effects, IVF-Lido might have additional benefits when postoperative pain relief has already been achieved. Considering the high heterogeneity in this updated meta-analysis, more RCTs are needed.

Systematic Review Registration

https://inplasy.com/inplasy-2020-7-0023/, INPLASY [202070023].
Systematic Review and Meta-Analysis of COVID-19 Vaccination Acceptance
Authors: Norhayati Mohd Noor , Che Yusof Ruhana , Azman Yacob Mohd
Published: January 2022

Introduction

Vaccination is an essential intervention to curb the coronavirus disease 2019 (COVID-19) pandemic. This review aimed to estimate the pooled proportion of COVID-19 vaccine acceptance worldwide.

Methods

A systematic search of the MEDLINE (PubMed) database using “COVID-19,” “vaccine” and “acceptance” to obtain original research articles published between 2020 and July 2021. Only studies with full text and that were published in English were included. The Joanna Briggs Institute meta-analysis was used to assess the data quality. The meta-analysis was performed using generic inverse variance with a random-effects model using the Review Manager software.

Results

A total of 172 studies across 50 countries worldwide were included. Subgroup analyses were performed with regard to vaccine acceptance, regions, population, gender, vaccine effectiveness, and survey time. The pooled proportion of COVID-19 vaccine acceptance was 61% (95% CI: 59, 64). It was higher in Southeast Asia, among healthcare workers, in males, for vaccines with 95% effectiveness, and during the first survey.

Conclusion

COVID-19 vaccine acceptance needs to be increased to achieve herd immunity to protect the population from the disease. It is crucial to enhance public awareness of COVID-19 vaccination and improve access to vaccines.

Systematic Review Registration

PROSPERO 2021, identifier CRD42021268645.
The Sinorhizobium meliloti Nitrogen Stress Response Changes Radically in the Face of Concurrent Phosphate Stress
Authors: Hagberg Kelly L. , Price Jason P. , Yurgel Svetlana N. , Kahn Michael L.
Published: January 2022

Expression of hundreds of S. meliloti genes changed more than two-fold in response to either nitrogen or phosphate limitation. When these two stresses were applied together, stress responsive gene expression shifted dramatically. In particular, the nitrogen stress response in the presence of phosphate stress had only 30 of about 350 genes in common with the 280 genes that responded to nitrogen stress with adequate phosphate. Expression of sRNAs was also altered in response to these stresses. 82% of genes that responded to nitrogen stress also responded to phosphate stress, including 20 sRNAs. A subset of these sRNAs is known to be chaperoned by the RNA binding protein, Hfq. Hfq had previously been shown to influence about a third of the genes that responded to both nitrogen and phosphate stresses. Phosphate limitation influenced changes in gene expression more than nitrogen limitation and, when both stresses were present, phosphate stress sometimes reversed the direction of some of the changes induced by nitrogen stress. These nutrient stress responses are therefore context dependent.
Perspective: Simple State Communities to Study Microbial Interactions: Examples and Future Directions
Authors: Sarkar Soumyadev , Ward Kaitlyn , Kamke Abigail , Ran Qinghong , Feehan Brandi , Richie Tanner , Reese Nicholas , Lee Sonny T. M.
Published: January 2022

Microbial interactions in natural environments are intricately complex. High numbers and rich diversity of microorganisms, along with compositional heterogeneities complicate the cause. It is essential to simplify these complex communities to understand the microbial interactions. We proposed a concept of “simple state community,” which represents a subset of microbes and/or microbial functions of the original population that is necessary to build a stable community. By combining microbial culturing and high-throughput sequencing, we can better understand microbe-microbe and microbe-host interactions. To support our proposed model, we used carbon-based and nitrogen-based media to capture the simple state communities. We used 16S rRNA amplicon sequencing and assigned taxonomic identity to the bacterial populations before and after simple state communities. We showed that simple state communities were a subset of the original microbial communities at both phyla and genera level. We further used shotgun metagenomics to gain insights into the functional potential of the assembled simple state communities. Our proposed model supported the goal of simplifying the complex communities across diverse systems to provide opportunity to facilitate comprehension of both the structure and function of the subset communities. Further applications of the concept include the high-throughput screening of simple state communities using the BIOLOG®system and continuous culturing (Chemostat). This concept has the potential to test diverse experimental hypotheses in simplified microbial communities, and further extend that knowledge to answer the overarching questions at a more holistic level.
Acid Tolerant and Acidophilic Microalgae: An Underexplored World of Biotechnological Opportunities
Authors: Abiusi Fabian , Trompetter Egbert , Pollio Antonino , Wijffels Rene H. , Janssen Marcel
Published: January 2022

Despite their large number and diversity, microalgae from only four genera are currently cultivated at large-scale. Three of those share common characteristics: they are cultivated mainly autotrophically and are extremophiles or tolerate “extreme conditions.” Extreme growth conditions aid in preventing contamination and predation of microalgae, therefore facilitating outdoor cultivation. In search for new extremophilic algae suitable for large-scale production, we investigated six microalgal strains able to grow at pH below 3 and belonging to four genera; Stichococcus bacillaris ACUF158, Chlamydomonas acidophila SAG 2045, and Chlamydomonas pitschmannii ACUF238, Viridiella fridericiana ACUF035 and Galdieria sulphuraria ACUF064 and ACUF074. All strains were cultivated autotrophically at light intensity of 100 and 300 μmol m−2 s−1 and pH between 1.9 and 2.9. The autotrophic biomass productivities were compared with one of the most productive microalgae, Chlorella sorokiniana SAG 211-8K, grown at pH 6.8. The acid tolerant strains have their autotrophic biomass productivities reported for the first time. Mixotrophic and heterotrophic properties were investigated when possible. Five of the tested strains displayed autotrophic biomass productivities 10–39% lower than Chlorella sorokiniana but comparable with other commercially relevant neutrophilic microalgae, indicating the potential of these microalgae for autotrophic biomass production under acidic growth conditions. Two acid tolerant species, S. bacillaris and C. acidophila were able to grow mixotrophically with glucose. Chlamydomonas acidophila and the two Galdieria strains were also cultivated heterotrophically with glucose at various temperatures. Chlamydomonas acidophila failed to grow at 37°C, while G. sulphuraria ACUF64 showed a temperature optimum of 37°C and G. sulphuraria ACUF74 of 42°C. For each strain, the biomass yield on glucose decreased when cultivated above their optimal temperature. The possible biotechnological applications of our findings will be addressed.
Performance Analysis of Machine Learning and Deep Learning Architectures on Early Stroke Detection Using Carotid Artery Ultrasound Images
Authors: Latha S. , Muthu P. , Lai Khin Wee , Khalil Azira , Dhanalakshmi Samiappan
Published: January 2022

Atherosclerotic plaque deposit in the carotid artery is used as an early estimate to identify the presence of cardiovascular diseases. Ultrasound images of the carotid artery are used to provide the extent of stenosis by examining the intima-media thickness and plaque diameter. A total of 361 images were classified using machine learning and deep learning approaches to recognize whether the person is symptomatic or asymptomatic. CART decision tree, random forest, and logistic regression machine learning algorithms, convolutional neural network (CNN), Mobilenet, and Capsulenet deep learning algorithms were applied in 202 normal images and 159 images with carotid plaque. Random forest provided a competitive accuracy of 91.41% and Capsulenet transfer learning approach gave 96.7% accuracy in classifying the carotid artery ultrasound image database.
Measuring and Modeling the Effect of Audio on Human Focus in Everyday Environments Using Brain-Computer Interface Technology
Authors: Haruvi Aia , Kopito Ronen , Brande-Eilat Noa , Kalev Shai , Kay Eitan , Furman Daniel
Published: January 2022

The goal of this study was to investigate the effect of audio listened to through headphones on subjectively reported human focus levels, and to identify through objective measures the properties that contribute most to increasing and decreasing focus in people within their regular, everyday environment. Participants (N = 62, 18–65 years) performed various tasks on a tablet computer while listening to either no audio (silence), popular audio playlists designed to increase focus (pre-recorded music arranged in a particular sequence of songs), or engineered soundscapes that were personalized to individual listeners (digital audio composed in real-time based on input parameters such as heart rate, time of day, location, etc.). Audio stimuli were delivered to participants through headphones while their brain signals were simultaneously recorded by a portable electroencephalography headband. Participants completed four 1-h long sessions at home during which different audio played continuously in the background. Using brain-computer interface technology for brain decoding and based on an individual’s self-report of their focus, we obtained individual focus levels over time and used this data to analyze the effects of various properties of the sounds contained in the audio content. We found that while participants were working, personalized soundscapes increased their focus significantly above silence (p = 0.008), while music playlists did not have a significant effect. For the young adult demographic (18–36 years), all audio tested was significantly better than silence at producing focus (p = 0.001–0.009). Personalized soundscapes increased focus the most relative to silence, but playlists of pre-recorded songs also increased focus significantly during specific time intervals. Ultimately we found it is possible to accurately predict human focus levels a priori based on physical properties of audio content. We then applied this finding to compare between music genres and revealed that classical music, engineered soundscapes, and natural sounds were the best genres for increasing focus, while pop and hip-hop were the worst. These insights can enable human and artificial intelligence composers to produce increases or decreases in listener focus with high temporal (millisecond) precision. Future research will include real-time adaptation of audio for other functional objectives beyond affecting focus, such as affecting listener enjoyment, drowsiness, stress and memory.
Longitudinal Associations of Self-Reported Visual, Hearing, and Dual Sensory Difficulties With Symptoms of Depression Among Older Adults in the United States
Authors: Killeen Olivia J. , Xiang Xiaoling , Powell Danielle , Reed Nicholas S. , Deal Jennifer A. , Swenor Bonnielin K. , Ehrlich Joshua R.
Published: January 2022

Evidence conflicts on the association between sensory difficulty and depression. Few studies have examined this association using longitudinal or population-based data. We used data from Rounds 1–9 of the nationally representative National Health and Aging Trends Study to evaluate the longitudinal association between self-reported visual, hearing, and dual sensory difficulties and clinically significant depressive symptoms. Multivariable Cox regression models were used to evaluate the hazard of incident depressive symptoms. Group-based trajectory modeling identified depressive symptom trajectories (DSTs). Multinomial logistic regression was used to examine the association between sensory status and DSTs. A total of 7,593 participants were included: 56.5% were female, 53.0% were 65–74 years old, 19.0% (95% CI 17.9–20.2%) had hearing, 5.6% (4.9–6.4%) had visual, and 3.3% (2.9–3.8%) had dual sensory difficulties at baseline. Hazard ratios for depressive symptoms in those with visual, hearing, and dual sensory difficulties were 1.25 (95% CI 1.00–1.56, p = 0.047), 0.98 (95% CI 0.82–1.18, p = 0.82), and 1.67 (95% CI 1.29–2.16, p < 0.001), respectively, relative to those without sensory difficulty. A model with four trajectory groups best fit the data. Group 1 (35.8% of the sample, 95% CI: 34.1–37.4) had persistently low risk of depressive symptoms; Group 2 (44.8%, 43.4–46.3) had low but increasing risk; Group 3 (7.1%, 6.2–8.3) had moderate risk; and Group 4 (12.4%, 11.5–13.3) had moderate to high risk that increased. Compared to those without sensory difficulties, individuals with each difficulty were significantly more likely to belong to a group other than Group 1. This study reveals associations between sensory difficulties and mental health that can inform public health interventions.
An in vivo Cell-Based Delivery Platform for Zinc Finger Artificial Transcription Factors in Pre-clinical Animal Models
Authors: Deng Peter , Halmai Julian A. N. M. , Beitnere Ulrika , Cameron David , Martinez Michele L. , Lee Charles C. , Waldo Jennifer J. , Thongphanh Krista , Adhikari Anna , Copping Nycole , Petkova Stela P. , Lee Ruth D. , Lock Samantha , Palomares Miranda , O’Geen Henriette , Carter Jasmine , Gonzalez Casiana E. , Buchanan Fiona K. B. , Anderson Johnathan D. , Fierro Fernando A. , Nolta Jan A. , Tarantal Alice F. , Silverman Jill L. , Segal David J. , Fink Kyle D.
Published: January 2022

Zinc finger (ZF), transcription activator-like effectors (TALE), and CRISPR/Cas9 therapies to regulate gene expression are becoming viable strategies to treat genetic disorders, although effective in vivo delivery systems for these proteins remain a major translational hurdle. We describe the use of a mesenchymal stem/stromal cell (MSC)-based delivery system for the secretion of a ZF protein (ZF-MSC) in transgenic mouse models and young rhesus monkeys. Secreted ZF protein from mouse ZF-MSC was detectable within the hippocampus 1 week following intracranial or cisterna magna (CM) injection. Secreted ZF activated the imprinted paternal Ube3a in a transgenic reporter mouse and ameliorated motor deficits in a Ube3a deletion Angelman Syndrome (AS) mouse. Intrathecally administered autologous rhesus MSCs were well-tolerated for 3 weeks following administration and secreted ZF protein was detectable within the cerebrospinal fluid (CSF), midbrain, and spinal cord. This approach is less invasive when compared to direct intracranial injection which requires a surgical procedure.