bluuebunny/crossref_metadata_2025 huggingface dataset:
Working Abroad while Families at Home: Negotiating Patriarchal Role for Women in South Asia: A Case Study of Gopalganj District of Bihar, India
Authors: Mustaqeem Muskan
Published: February 2022

In recent times, South Asia has emerged as the highest emigrant sending region to the Gulf. According to the United Nations Population Division (2017) 20.3 million stocks of migrants is in the Gulf countries, among the total number of South Asian migrants were 13millions which accounted for 63.9 percent of the total number of stock of migrants in the Persian Gulf. Due to this huge outpouring of workers, the region has also emerged as the largest receiver of remittances. It is interesting to note that these South Asian migrants are generally from the strata of societies where patriarchal structures are still in their rigidities as modernity has not yet penetrated there to change the feudal mentality, especially towards assigning women’s role in society.  Patriarchy defines a limited socio-economic role for women. They undergo inflexible social processes and remain disadvantaged often affecting their rights, social status, mobility, autonomy, and decision-making capabilities.  The physical absence of their husbands, the heads of the home, and the influx of remittance have positively impacted the lives of these women as they are now able to renegotiate their social roles and responsibilities.  The process has helped to loosen the rigidities of the patriarchal structure. The objective of the research is to find out how the truancy of men has transformed and emancipated/empowered women in home countries. This study examines the literature on the socio-economic impact of male migration, and how it affects women's mobility and empowerment in left-behind families. This qualitative research evaluates women’s empowerment through one independent variable i.e., husband’s emigration, and three dependent variables, women's decision-making power, mobility, and autonomy in the absence of their husbands within the framework of gender empowerment. For the convenience of this research, 50 samples of Gulf emigrants’ families living in the Gopalgunj district of Bihar, India have been selected (Data is collected from the field through informal and conversational interviews, questionnaires, and convenience sampling is used). This research argues that a significant social transformation in gender roles has occurred due to husbands’ migration.
Impact Of Irrigation Cropping Pattern: A Case Study of Kethepalli Mandal Nalgonda District
Authors: Saidulu Yedavelli
Published: February 2022

The present study is concerned with major crops, cropping patterns, area, production, and yield of major crops in both spatial and temporal aspects, and socioeconomic change due to agriculture, both irrigated and dryland agriculture in Kethepalli Mandal are part of Nalgonda district of Telangana State, India. The study intends first to identify the major crops and the cropping patterns of the district, by Mandals as well as overtime. Upon identification, an examination and analysis of the pattern of cropping and related aspects are attempted. The interpretation of the analysis is expected to yield an understanding of the development problems of, and prospects for, the irrigated and dryland farming of the district. The present research is introductory in that it introduces a broad overview of agriculture and global development perspectives, Indian agricultural sector, Indian and Telangana agriculture, and then introduces the problem of study, the schemes by the government, the objectives, the study area, the methodology, and the conclusion.
Indo-China Border Conflict, Regional Geopolitics and Bilateral Trade
Authors: Hosain Md Sajjad
Published: February 2022

Being two giant economic players of the world, China and India experienced a disastrous border conflict in the Ladakh area of the Line of Actual Control (LAC) during April 2020, just at the beginning of the Covid-19 outbreak. This theoretical paper is an effort to identify the tentative impact of that border clash on the bilateral trade between two countries from the perspective of regional geopolitics. The author has utilized secondary information such as newspapers articles, journal articles, online sources, and economists’ opinions on this issue as well as has made some predictions based on the previous bilateral trade statistics. The author proposes that even though the border issue has become very sensitive and important for both countries regarding the geopolitical necessity, the bilateral trade scenario will not be much affected on a substantial scale on a long-term basis. The author further predicts that a likely trade conflict between the two economically promising countries will be contagious for both. Finally, the author expects this paper to be beneficial for further research attempts focusing on the geopolitical economy of bilateral trade.
COVID-19 PANDEMİSİNDE 20-64 YAŞ ARASI BİREYLERİN SAĞLIK ALGISI
Authors: ÖZTÜRK Gizem , KOLCU Merve
Published: February 2022

Bu çalışmada Covid-19 pandemisinde 20-64 yaş arası bireylerin sağlık algısını belirlemek amaçlanmıştır. Çalışmaya, İstanbul’da yaşayan ve araştırmaya katılmayı kabul eden, okuma-yazma bilen, soruları eksiksiz yanıtlayan ve 20-64 yaş arası bireyler dahil edilmiştir. Veriler; anket formu ile Sağlık Algısı Ölçeği (SAÖ) kullanılarak elde edilmiştir. Verilerin değerlendirilmesinde; bağımsız gruplarda t-testi, One-Way ANOVA testi ve Pearson Korelasyon Analizi kullanılmıştır. Çalışmaya katılan bireylerin yaş ortalaması 27.85±9.86 yıl, vücut ağırlık ortalaması 65.40±15.20 kg ve boy uzunluğu ortalaması 166.84±9.17 cm’dir. Katılımcıların; %64.9’u genel sağlık durumunun iyi olduğunu, %89.2’si kronik hastalığının olmadığını, %49.2’si pandemide fiziksel aktivite yapmadığını, %61.9’u pandemini beslenme alışkanlıklarını değiştirdiğini ifade etmiştir. Bireylerin SAÖ toplam puan ortalaması 43.80±6.30 olarak tespit edilmiş, alt boyutlarından en yüksek puan ortalamasının da 11.79±4.14 ile kontrol merkezi alt boyutuna ait olduğu sonucuna ulaşılmıştır. Genel sağlık durumu değişkenine göre kesinlik alt boyutu ile mevcut kiloyu değerlendirme değişkenine göre de sağlığın önemi alt boyutu arasında istatistiksel olarak ileri derecede anlamlı fark bulunmuştur (p=0.001). Bu araştırma sonucunda Covid-19 pandemisinde bireylerin sağlık algılarının da orta düzeyde olduğu belirlenmiştir. Covid-19 pandemisinde toplumun sağlık algısı ve sağlık davranışlarıyla ilgili daha fazla sayıda ve daha büyük örneklemli çalışmaların yapılması önerilmektedir.
ANALISIS PERAMALAN TIME SERIES UNTUK PENGELOLAAN PERMINTAAN DENGAN METODE ARIMA BOX-JENKINS (Studi Kasus di CV. TOMY BAKERY)
Authors: Maâ€™Fulloh  , Sumarsono
Published: February 2022

Fluktuasi permintaan yang tinggi, menjadi masalah untuk perusahaan kecil maupun besar. Hal tersebut juga terjadi pada CV. Tomy Bakery sebagai produsen roti plemben (kering dan basah). Penelitian ini bertujuan untuk melakukan analisis peramalan penjualan roti dengan model ARIMA yang tepat pada roti kering dan basah dan mengimplementasikan hasil peramalan untuk pengelolaan permintaan roti kering dan basah. Metode analisis menggunakan metode time series ARIMA Box Jenkins. Data penelitian berupa data penjualan harian produk roti kering dan basah. Hasil temuan model ARIMA pada roti kering yakni ARIMA (4,0,4), kemudian roti basah yakni ARIMA (5,1,1).  Hasil ini menunjukan penjualan roti kering saat waktu t dipengaruhi penjualan saat t-1, t-3, dan t-4 (pola permintaan siklus 4 harian). Kemudian penjualan roti basah saat t dipengaruhi penjualan saat t-1, t-2, t-3, t-4, t-5 dan t-6 (pola permintaan siklus 6 harian). Implementasi dari hasil peramalan penjualan diketahui adanya pengaruh waktu harian. Maka keputusan hari promosi yang tepat dengan harga diskon, menjadi penting untuk mengelola permintaan. Sebagai saran hari promosi untuk roti kering yakni saat hari t-2 (selasa) dan t-3 (rabu) dan atau hari t-6 (sabtu) dan t-7 (minggu). Kemudian untuk roti basah yakni saat t-4 (kamis) dan t-5 (jumat). Penerapan promosi pada hari diatas, akan bisa meratakan permintaan di sepanjang minggu. Dampaknya bisa mengurangi biaya simpan inventory pada saat peak day, juga membuat level produk dari hari ke hari akan relative sama (tidak berfluktuasi).
STRATEGI PEMASARAN DENGAN MENGGUNAKAN PENDEKATAN ANALISIS SWOT DAN BAURAN PEMASARAN (MARKETING MIX) STUDI KASUS DI PT. GRAND ZAM-ZAM
Authors: Fahmi Moch Abdurrahman Rizzal , Afiatna Fatma Ayu Nuning Farida , Muflihah Nur
Published: February 2022

Penelitian ini bertujuan untuk mengetahui perencanaan strategi pemasaran PT. Grand Zam-zam perusahaan yang bergerak di bidang jual beli lahan perumahan, dengan menggunakan metode analisis SWOT dan Bauran Pemasaran. Dengan metode tersebut peneliti berusaha untuk menyelesaikan masalah yang ada pada perusahaan PT. Grand Zam-zam yaitu tidak tercapainya target penjualan. Dari hasil uji validitas semua variabel dinyatakan valid karena rhitung > rtabel dengan rtabel = 0,2483 dan untuk hasil uji reliabilitas dinyatakan reliabel karna semua nilai alpha (Î±) variabel lebih dari 0,6. Hasil penelitian menyimpulkan bahwa strategi SWOT berada pada posisi perusahaan pada kuadran I dengan titik kordinat 1,24:1,22 yang menggunakan strategi agresif. Sehingga di sarankan kepada PT. Grand Zam-zam untuk berfokus pada strategi memanfaatkan peluang dan memaksimalkan kekuatan internal yang di miliki perusahaan.
CIRCprimerXL: Convenient and High-Throughput PCR Primer Design for Circular RNA Quantification
Authors: Vromman Marieke , Anckaert Jasper , Vandesompele Jo , Volders Pieter-Jan
Published: March 2022

Circular RNA (circRNA) is a class of endogenous non-coding RNA characterized by a back-splice junction (BSJ). In general, large-scale circRNA BSJ detection is performed based on RNA sequencing data, followed by the selection and validation of circRNAs of interest using RT-qPCR with circRNA-specific PCR primers. Such a primer pair is convergent and functional on the circRNA template but divergent and non-functional on the linear host gene. Although a few circRNA primer design pipelines have been published, none of them offer large-scale, easy-to-use circRNA primer design. Other limitations are that these tools generally do not take into account assay specificity, secondary structures, and SNPs in the primer annealing regions. Furthermore, these tools are limited to circRNA primer design for humans (no other organisms possible), and no wet-lab validation is demonstrated. Here, we present CIRCprimerXL, a circRNA RT-qPCR assay design pipeline based on the primer design framework primerXL. CIRCprimerXL takes a circRNA BSJ position as input, and designs BSJ-spanning primers using Primer3. The user can choose to use the unspliced or spliced circRNA sequence as template. Prior to primer design, sequence regions with secondary structures and common SNPs are flagged. Next, the primers are filtered based on predicted specificity and the absence of secondary structures of the amplicon to select a suitable primer pair. Our tool is both available as a user-friendly web tool and as a stand-alone pipeline based on Docker and Nextflow, allowing users to run the pipeline on a wide range of computer infrastructures. The CIRCprimerXL Nextflow pipeline can be used to design circRNA primers for any species by providing the appropriate reference genome. The CIRCprimerXL web tool supports circRNA primer design for human, mouse, rat, zebrafish, Xenopus tropicalis, and C. elegans. The design process can easily be scaled up for the qPCR assay design of tens of thousands of circRNAs within a couple of hours. We show how CIRCprimerXL has been successfully used to design qPCR assays for over 15,000 human circRNAs of which 20 were empirically validated. CIRCprimerXL software, documentation, and test data can be found at: https://github.com/OncoRNALab/CIRCprimerXL. CIRCprimerXL is also implemented as a webtool at: https://circprimerxl.cmgg.be.
Evaluation of Platelet-Rich Plasma Therapy for Peripheral Nerve Regeneration: A Critical Review of Literature
Authors: Wang Sulong , Liu Xilin , Wang Yueshu
Published: March 2022

Peripheral nerve injury (PNI) is a common disease in clinic, and the regeneration process of peripheral nerve tissue is slow, and patients with PNI often suffer from the loss of nerve function. At present, related research on the mechanism of peripheral nerve regeneration has become a hot spot, and scholars are also seeking a method that can accelerate the regeneration of peripheral nerve. Platelet-rich plasma (PRP) is a platelet concentrate extracted from autologous blood by centrifugation, which is a kind of bioactive substance. High concentration of platelets can release a variety of growth factors after activation, and can promote the proliferation and differentiation of tissue cells, which can accelerate the process of tissue regeneration. The application of PRP comes from the body, there is no immune rejection reaction, it can promote tissue regeneration with less cost, it is,therefore, widely used in various clinical fields. At present, there are relatively few studies on the application of PRP to peripheral nerve regeneration. This article summarizes the literature in recent years to illustrate the effect of PRP on peripheral nerve regeneration from mechanism to clinical application, and prospects for the application of PRP to peripheral nerve.
High-Efficiency Flexible Organic Photovoltaics and Thermoelectricities Based on Thionyl Chloride Treated PEDOT:PSS Electrodes
Authors: Wan Juanyong , Fan Xi , Li Yunfei , Li Pengcheng , Zhang Ting , Hui Kwun Nam , Huang Huihui , Kang Kai , Qian Lei
Published: March 2022

Conducting polymers have received tremendous attentions owing to their great potentials to harvest both luminous and thermal energies. Here, we reported a flexible transparent electrode of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with highly electrical conductivity and raised Seebeck coefficient via thionyl chloride treatments. The comprehensive studies of optical, electrical, morphological, structural, and thermoelectrical properties, work function, and stability of the PEDOT:PSS transparent electrodes were systematically evaluated and described. On the basis of the PEDOT:PSS transparent electrodes, the resultant flexible organic solar cells yielded a high power conversion efficiency of 15.12%; meanwhile, the flexible thermoelectricities exhibited the raised power factor of 115.9 μW m−1 K−2, which outperformed the four kinds of rigid thermoelectricities with conventional acid and base treatments.
Machine Learning for Electrocardiographic Features to Identify Left Atrial Enlargement in Young Adults: CHIEF Heart Study
Authors: Hsu Chu-Yu , Liu Pang-Yen , Liu Shu-Hsin , Kwon Younghoon , Lavie Carl J. , Lin Gen-Min
Published: March 2022

Background

Left atrial enlargement (LAE) is associated with cardiovascular events. Machine learning for ECG parameters to predict LAE has been performed in middle- and old-aged individuals but has not been performed in young adults.

Methods

In a sample of 2,206 male adults aged 17–43 years, three machine learning classifiers, multilayer perceptron (MLP), logistic regression (LR), and support vector machine (SVM) for 26 ECG features with or without 6 biological features (age, body height, body weight, waist circumference, and systolic and diastolic blood pressure) were compared with the P wave duration of lead II, the traditional ECG criterion for LAE. The definition of LAE is based on an echocardiographic left atrial dimension > 4 cm in the parasternal long axis window.

Results

The greatest area under the receiver operating characteristic curve is present in machine learning of the SVM for ECG only (77.87%) and of the MLP for all biological and ECG features (81.01%), both of which are superior to the P wave duration (62.19%). If the sensitivity is fixed to 70–75%, the specificity of the SVM for ECG only is up to 72.4%, and that of the MLP for all biological and ECG features is increased to 81.1%, both of which are higher than 48.8% by the P wave duration.

Conclusions

This study suggests that machine learning is a reliable method for ECG and biological features to predict LAE in young adults. The proposed MLP, LR, and SVM methods provide early detection of LAE in young adults and are helpful to take preventive action on cardiovascular diseases.
Mining-Induced Stress and Ground Pressure Behavior Characteristics in Mining a Thick Coal Seam With Hard Roofs
Authors: Zhu Zhijie , Wu Yunlong , Liang Zhuang
Published: March 2022

The hard roof of coal mines has the characteristics of high hardness, good integrity, and large layer thickness, which leads to many ground control problems. To reveal the influence of a hard roof structure on the stress performance and coal pillar stability during mining operations, the 8,104 and 8,105 working faces in the Tongxin coal mine were considered as the research object to analyze the stress behavior during the working face advance. Numerical simulation software FLAC3D was used to establish the numerical model of the longwall face under hard roof conditions. The stress distribution laws and coal pillar stability under different roof strengths were analyzed so as to explain the impacts of the hard roof on the stress distribution at the working face. The results show that during the second face proceeding, the influence zone of the front abutment pressure under hard roof conditions is 6 m wider than that under soft roof conditions, and the bearing stress at the working face is 10.4 MPa higher. At the mining position, the plastic zone of the pillar under hard roof conditions is 11 m wider than that under soft roof conditions, and the peak vertical stress is 5.13 MPa higher than that under soft roof conditions. At 25 m ahead of the working face, the plastic zone of the pillar under hard roof conditions is 6 m wider than that under soft roof conditions, and the peak vertical stress is 24.84 MPa higher than that under soft roof conditions. Additional overburden pressure produced by the uncaved hard roof increased pillar stress and plastic zones. Therefore, the hard roof is the main cause of strong ground pressure behavior in the Tongxin coal mine. Aiming at the strong mine pressure behavior, it is suggested to adopt the pre-splitting technology to reduce the influence of the hard roof on mine pressure.
Treatment Adherence to Injectable Treatments in Pediatric Growth Hormone Deficiency Compared With Injectable Treatments in Other Chronic Pediatric Conditions: A Systematic Literature Review
Authors: Gomez Roy , Ahmed S. Faisal , Maghnie Mohamad , Li Dejun , Tanaka Toshiaki , Miller Bradley S.
Published: March 2022

Background

Pediatric patients with growth hormone deficiency (GHD) are currently treated with daily injections of recombinant human growth hormone (rhGH) to promote linear growth and enable attainment of normal adult height. One of the main reasons for suboptimal growth during rhGH therapy is non-adherence to treatment. The objective of this systematic literature review was to examine the recent literature on pediatric adherence to injectable treatments for chronic conditions (focusing on rhGH) to characterize levels of adherence and identify the factors/barriers associated with adherence.

Methods

The Embase and MEDLINE databases (January 2015–October 2020) were searched to identify publications describing studies of pediatric patients (aged ≤17 years) with GHD and other chronic conditions requiring daily or weekly injectable treatments; a similar targeted search of Chinese literature was also performed. Adherence data were extracted from the included studies and summarized. Risk of bias was determined using the Cochrane Risk of Bias tool 2 or the Newcastle-Ottawa Scale.

Results

A total of 23 publications were included, with all publications except for one (multiple sclerosis) focused on pediatric GHD studies: there were two clinical trials, 18 observational studies and three survey studies. Study sample sizes ranged from 30 to 13,553 patients (median: 95 patients). The definition of adherence varied between studies and included mean adherence rate, median adherence rate, and the percentage of patients within pre-specified adherence categories. Of the publications assessing adherence to daily rhGH, 11 studies reported 12-month mean adherence rate (range: 73.3%– 95.3%) and eight studies reported median adherence (range: 91%– 99.2%). The barriers to treatment adherence identified included self-administration, increased administration frequency, age (adolescence), longer treatment duration, device design, and insufficient family education, awareness, and/or engagement. Recommendations for increasing adherence included using adherence reminder tools, increasing patient engagement/education, and improving injection device design and drug product.

Conclusions

Adherence to rhGH treatment was high (>80%) for many studies, though comparability between studies was limited given the substantial heterogeneity in the way adherence was defined, measured, and reported. To address this heterogeneity, we recommend standardizing how adherence is defined and reported and encourage the use of standardized study designs and outcome measures.
miR-218-5p Induces Interleukin-1β and Endovascular Trophoblast Differentiation by Targeting the Transforming Growth Factor β-SMAD2 Pathway
Authors: Shan Yanan , Chen Yan , Brkić Jelena , Fournier Leslie , Ma Haiying , Peng Chun
Published: March 2022

The acquisition of an endovascular trophoblast (enEVT) phenotype is essential for normal placental development and healthy pregnancy. MicroRNAs (miRNAs) are small noncoding RNAs that play critical roles in regulating gene expression. We have recently reported that miR-218-5p promotes enEVT differentiation and spiral artery remodeling in part by targeting transforming growth factor β2 (TGFβ2). We also identified IL1B, which encodes interleukin 1β (IL1β), as one of the most highly upregulated genes by miR-218-5p. In this study, we investigated how miR-218-5p regulates IL1B expression and IL1β secretion and the potential role of IL1β in enEVT differentiation. Using two cell lines derived from extravillous trophoblasts (EVTs), HTR-8/SVneo and Swan 71, we found that stable overexpression of miR-218-5p precursor, mir-218-1, or transient transfection of miR-218-5p mimic, significantly increased IL1B mRNA and IL1β protein levels in cells and conditioned media. We also showed that miR-218-5p directly interacted with SMAD2 3’UTR and reduced SMAD2 at mRNA and protein levels. Knockdown of SMAD2 induced IL1B expression and attenuated the inhibitory effect of TGFβ2 on IL1B expression. On the other hand, overexpression of SMAD2 reduced IL1β levels and blocked the stimulatory effects of miR-218-5p on IL1B expression, trophoblast migration and endothelial-like network formation. In addition, treatment of trophoblasts with IL1β induced the formation of endothelial-like networks and the expression of enEVT markers in a dose-dependent manner. These results suggest that miR-218-5p inhibits the TGFβ/SMAD2 pathway to induce IL1β and enEVT differentiation. Finally, low doses of IL1β also inhibited the expression of miR-218-5p, suggesting the existence of a negative feedback regulatory loop. Taken together, our findings suggest a novel interactive miR-218-5p/TGFβ/SMAD2/IL1β signaling nexus that regulates enEVT differentiation.
Environmental Benefits From Carbon Tax in the Chinese Carbon Market: A Roadmap to Energy Efficiency in the Post-COVID-19 Era
Authors: Wei Ran , Ayub Bakhtawer , Dagar Vishal
Published: March 2022

Because of China’s global responsibilities to address climate change, the country has made a commitment to limiting the growth of future emissions using policy measures, such as funding mitigation research and regulating energy efficiency requirements directly. Extensions of these policies, such as the measures to improve energy efficiency, use of carbon taxes, and changes to the mix of electricity generation in the country, are also of interest to China. This article applied a computable general equilibrium (CGE) model to examine the effects of such energy efficiency and climate change policy options in the post-COVID-19 era in the China economy. The study findings show that even modest measures can have significant effects on emissions with marginal economic impacts, given the current level of development in the China electricity generation and transportation sectors. It is estimated that a 5 RMB per ton carbon tax will reduce emissions by 4.1% and GDP by 0.27%. Emissions drop by 8.2% and GDP drops by 0.54% when energy efficiency increases by 2% across the China economy, respectively. As a final result, a 5% shift away from burning coal would reduce emissions by 9.0%, while GDP would increase by 1.3%. It has been shown that even low carbon taxes can encourage a notable cleaner energy system.
Genome-Wide Association Studies Provide Insight Into the Genetic Determination for Hyperpigmentation of the Visceral Peritoneum in Broilers
Authors: Zhou Guangyuan , Liu Tianfei , Wang Yan , Qu Hao , Shu Dingming , Jia Xinzheng , Luo Chenglong
Published: March 2022

Hyperpigmentation of the visceral peritoneum (HVP) has been becoming one of the most challenging problems in yellow-feathered chicken production, which seriously affected chicken carcass quality traits. Detecting which genes dominantly impact pigmentation in the peritoneum tissues is of great benefit to the genetic improvement of HVP. To investigate the genetic mechanism of HVP in yellow-feathered broilers, genome-wide association studies (GWASs) were conducted in the F2 generation of a cross broiler population with 395 birds. A total of 115,706 single-nucleotide polymorphisms (SNPs) of 122,415 were retained to identify quantitative trait loci (QTL) associated to HVP in chicken. The GWAS results based on the logistic mixed model (LMM) revealed that a narrow genomic location on chromosomes 1 (49.2–51.3 Mb) was significantly associated (p ≤ 4.32 × 10−7) with HVP, which contained 23 SNP makers related to 14 functional genes (MFNG, POLDIP3, POLR2F, PICK1, PDXP, SGSM3, RANGAP1, MYH9, RPL3, GALP3, LGALS1, MICALL1, ATF4, and CYP2D6). Four highly associated (p < 10−5) haplotype blocks of 0.80 kb (two SNPs), 0.06 kb (two SNPs), 0.95 kb (two SNPs), and 0.03 kb (two SNPs) were identified with two, two, four, and four distinct haplotypes, respectively. As a melanoma-associated gene, CYP2D6 were also possibly involved in the development of HVP occurring in chicken with two significant variations (rs314284996 and rs317955795) in the promoter regions. Further tests revealed that the expression of CYP2D6 was obviously higher in the visceral peritoneum tissue of chicken with HVP than that in the normal group (p < 0.05). Our results provide a novel clue to understand the genetic mechanism of HVP generation in chicken, and the mapped QTL or candidate genes might serve for genomic selection to improve carcass quality in the yellow-feathered chicken industry.
Validation of New Gene Variant Classification Methods: a Field-Test in Diagnostic Cardiogenetics
Authors: Alimohamed Mohamed Z. , Westers Helga , Vos Yvonne J. , Van der Velde K. Joeri , Sijmons Rolf H. , Van der Zwaag Paul A. , Sikkema-Raddatz Birgit , Jongbloed Jan D. H.
Published: March 2022

Background: In the molecular genetic diagnostics of Mendelian disorders, solutions are needed for the major challenge of dealing with the large number of variants of uncertain significance (VUSs) identified using next-generation sequencing (NGS). Recently, promising approaches using constraint metrics to calculate case excess scores (CE), etiological fractions (EF), and gnomAD-derived constraint scores have been reported that estimate the likelihood of rare variants in specific genes or regions that are pathogenic. Our objective is to study the usability of these constraint data into variant interpretation in a diagnostic setting, using our cardiomyopathy cohort.

Methods and Results: Patients (N = 2002) referred for clinical genetic diagnostics underwent NGS testing of 55–61 genes associated with cardiomyopathies. Previously classified likely pathogenic (LP) and pathogenic (P) variants were used to validate the use of data from CE, EF, and gnomAD constraint analyses for (re)classification of associated variant types in specific cardiomyopathy subtype-related genes. The classifications corroborated in 94% (354/378) of cases. Next, we reclassified 23 unique VUSs to LP, increasing the diagnostic yield by 1.2%. In addition, 106 unique VUSs (5.3% of patients) were prioritized for co-segregation or functional analyses.

Conclusions: Our analysis confirms that the use of constraint metrics data can improve variant interpretation, and we, therefore, recommend using constraint scores on other cohorts and disorders and its inclusion in variant interpretation protocols.
Exploration of an XX/XY Sex Determination System and Development of PCR-Based Sex-specific Markers in Procambarus clarkii Based on Next-Generation Sequencing Data
Authors: Shen Yudong , Wang Qishuai , Wang Weimin , Li Yanhe
Published: March 2022

Many economic crustacean species have sex dimorphisms during their growth. Exploring the sex determination system and developing sex-specific molecular marker(s) are very helpful for carrying out sex control breeding, and next-generation sequencing has been used as an efficient way to explore them in recent years. In this study, first, the genetic sex determination system of P. clarkii was explored as an XX/XY system by analyzing the 2b-RAD sequencing data. Furthermore, DNA samples of male and female individuals from a P. clarkii family were pooled separately for whole-genome resequencing. Based on the data of whole-genome resequencing, the 9,163 male- and female-specific bias sites with higher feasibility were obtained based on the assumption of the XX/XY sex determination system, and four sites were selected to design the sex-specific marker primers. One efficient sex-specific marker was identified with a sex discrimination rate of 99.49% (195/196) when applied to five different geographical groups with 196 individuals. The results of this study would provide a foundation for the realization of P. clarkii sex control and could provide some reference for investigating the sex determination system and sex molecular marker(s) of other crustacean species based on next-generation sequencing data.
ALKBH5-Mediated m6A Modification of A20 Regulates Microglia Polarization in Diabetic Retinopathy
Authors: Chen Tingting , Zhu Wenhui , Wang Congyao , Dong Xia , Yu Fenfen , Su Yihua , Huang Jingwen , Huo Lijun , Wan Pengxia
Published: March 2022

Background

To investigate the role of microglia polarization in the pathogenesis of diabetic retinopathy, and study the mechanism of ALKBH5-mediated m6A modification of A20 of retinal microglia polarization.

Methods

Diabetics rats were constructed and the M1/M2 polarization of retinal microglia was determined using immunofluorescence, flow cytometry, and quantitative real-time PCR (qRT-PCR). Glucose at different concentrations was added to treat the microglia, and the polarization rate was detected. RNA sequencing was performed to identify the differentially expressed gene in glucose treated microglia, and A20 expression was confirmed by qRT-PCR and western blotting. Lentiviruses encoding shRNA for A20 or overexpressing A20 were constructed to clarify the role of A20 in microglia polarization in vitro and vivo. N6-methyladenosine (m6A) modification level and degradation rate of A20 were determined and m6A related proteins were detected.

Results

Diabetics rats showed a higher M1 polarization rate but lower M2 polarization rate of retinal microglia. With the increase of glucose concentration, microglia tend to polarize into M1 inflammatory type rather than M2 anti-inflammatory type. Shown by RNA sequencing, glucose treated microglia showed a differentially expressed gene profile, which was enriched in kinds of inflammatory categories and pathways. A20 expression was lower in microglia with glucose treatment, which was demonstrated to negatively regulate the M1 polarization. Moreover, intraocular injection of A20-overexpression lentiviruses (OE-A20) rectified the enhanced M1 retinal microglia polarization of diabetes rats. The higher m6A modification level and faster degradation rate of A20 was observed in glucose treated microglia, which was mediated by m6A demethylase ALKBH5.

Conclusion

Lower expression A20 resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m6A modification. This study may provide new perspectives on not only the pathogenesis but also the diagnosis and treatment for diabetic retinopathy.
Improved Purification of Human Granzyme A/B and Granulysin Using a Mammalian Expression System
Authors: Rasi Valerio , Hameed Owais Abdul , Matthey Patricia , Bera Sibes , Grandgenett Duane P. , Salentinig Stefan , Walch Michael , Hoft Daniel F.
Published: March 2022

Cytotoxic lymphocytes release proteins contained within the cytoplasmic cytolytic granules after recognition of infected or tumor target cells. These cytotoxic granular proteins (namely granzymes, granulysin, and perforin) are key immunological mediators within human cellular immunity. The availability of highly purified cytotoxic proteins has been fundamental for understanding their function in immunity and mechanistic involvement in sepsis and autoimmunity. Methods for recovery of native cytotoxic proteins can be problematic leading to: 1) the co-purification of additional proteins, confounding interpretation of function, and 2) low yields of highly purified proteins. Recombinant protein expression of individual cytolytic components can overcome these challenges. The use of mammalian expression systems is preferred for optimal post-translational modifications and avoidance of endotoxin contamination. Some of these proteins have been proposed for host directed human therapies (e.g. - granzyme A), or treatment of systemic infections or tumors as in granulysin. We report here a novel expression system using HEK293T cells for cost-effective purification of high yields of human granzymes (granzyme A and granzyme B) and granulysin with enhanced biological activity than previous reports. The resulting proteins are free of native contaminants, fold correctly, and remain enzymatically active. Importantly, these improvements have also led to the first purification of biologically active recombinant human granulysin in high yields from a mammalian system. This method can be used as a template for purification of many other secreted cellular proteins and may lead to advances for human medicine.
Effect of CRISPR/Cas9-Edited PD-1/PD-L1 on Tumor Immunity and Immunotherapy
Authors: Xu Yanxin , Chen Chen , Guo Yaxin , Hu Shengyun , Sun Zhenqiang
Published: March 2022

Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology implements precise programming of the human genome through RNA guidance. At present, it has been widely used in the construction of animal tumor models, the study of drug resistance regulation mechanisms, epigenetic control and innovation in cancer treatment. Tumor immunotherapy restores the normal antitumor immune response by restarting and maintaining the tumor-immune cycle. CRISPR/Cas9 technology has occupied a central position in further optimizing anti-programmed cell death 1(PD-1) tumor immunotherapy. In this review, we summarize the recent progress in exploring the regulatory mechanism of tumor immune PD-1 and programmed death ligand 1(PD-L1) based on CRISPR/Cas9 technology and its clinical application in different cancer types. In addition, CRISPR genome-wide screening identifies new drug targets and biomarkers to identify potentially sensitive populations for anti-PD-1/PD-L1 therapy and maximize antitumor effects. Finally, the strong potential and challenges of CRISPR/Cas9 for future clinical applications are discussed.
Transarterial Chemoembolization Combined With Lenvatinib Plus PD-1 Inhibitor for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study
Authors: Cai Mingyue , Huang Wensou , Huang Jingjun , Shi Wenbo , Guo Yongjian , Liang Licong , Zhou Jingwen , Lin Liteng , Cao Bihui , Chen Ye , Zhou Juan , Zhu Kangshun
Published: March 2022

Purpose

To investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus PD-1 inhibitor (TACE-L-P) versus TACE combined with lenvatinib (TACE-L) for patients with advanced hepatocellular carcinoma (HCC).

Materials and Methods

Data of advanced HCC patients treated with TACE-L-P (TACE-L-P group) or TACE-L (TACE-L group) from January 2019 to December 2020 were prospectively collected and retrospectively analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were determined.

Results

A total of 81 patients were included in this study. Among them, 41 received TACE-L-P and 40 received TACE-L. The patients in TACE-L-P group had prolonged OS (median, 16.9 vs. 12.1 months, P=0.009), longer PFS (median, 7.3 vs. 4.0 months, P=0.002) and higher objective response rate (56.1% vs. 32.5%, P=0.033) and disease control rate (85.4% vs. 62.5%, P=0.019) than those in TACE-L group. Multivariate analyses revealed that the treatment option of TACE-L, main portal vein invasion and extrahepatic metastasis were the independent risk factors for OS, while TACE-L and extrahepatic metastasis were the independent risk factors for PFS. In subgroup analyses, a superior survival benefit was achieved with TACE-L-P in patients with extrahepatic metastasis or tumor number >3 but not in those with main portal vein invasion. The incidence and severity of AEs in TACE-L-P group were comparable to those in TACE-L group (any grade, 92.7% vs. 95.0%, P=1.000; grade 3, 36.6% vs. 32.5%, P=0.699).

Conclusion

TACE-L-P significantly improved survival over TACE-L with an acceptable safety profile in advanced HCC patients, especially those with extrahepatic metastasis or tumor number >3 but without main portal vein invasion.
Role of Salinity-Induced Barrier Layer in Air-Sea Interaction During the Intensification of a Typhoon
Authors: Hong Ji-Seok , Moon Jae-Hong , Kim Taekyun , You Sung Hyup , Byun Kun-Young , Eom Hyunmin
Published: March 2022

A pronounced increase in the intensification of Typhoon Bavi in 2020 was detected when the typhoon passed over the Changjiang plume in the northern East China Sea. Using a coupled atmosphere-ocean modeling system, this study investigates the role of the plume-induced barrier layer (BL) in the air–sea interaction during the intensification of a typhoon. Simple comparative experiments with and without the river plume revealed a strong relationship between BL formation and typhoon intensification as a result of the significant surface freshening discharged from the Changjiang River. The plume-induced BL maintained a warm sea surface before the typhoon approached, thereby influencing the energy transfer at the air–sea interface. The enthalpy and moisture reaching the atmosphere were increased by approximately 20%, leading to the intensification of Typhoon Bavi and providing further support for the results observed in the best-track record. The model comparison also indicates that the salinity-induced BL led to the reduction of the typhoon-induced SST cooling by restricting the vertical diffusion between the surface and the thermocline, and consequently contributed to maintaining the typhoon intensity. This study suggests that the effect of river-induced surface freshening in a coupled atmosphere-ocean model may help in improving typhoon forecasts and may aid in mitigating against the destructive power of typhoons in the future.
Optic Nerve Ultrasound Evaluation in Idiopathic Intracranial Hypertension
Authors: De Bernardo Maddalena , Vitiello Livio , De Pascale Ilaria , Capasso Luigi , Cornetta Palmiro , Rosa Nicola
Published: March 2022

Idiopathic intracranial hypertension (IIH) is a disease with a heterogeneity of possible causes, which needs to be quickly diagnosed. Ocular ultrasonography could be considered a useful tool to diagnose this condition in a fast and non-invasive way. In fact, Karl Ossoinig had already proposed this diagnostic tool in the 1970s for the evaluation of intracranial pressure changes under several pathological conditions, including idiopathic intracranial hypertension. The aim of this review is to analyze scientific articles published in the last 30 years concerning the use of ocular ultrasonography to assess optic nerve indices in patients with idiopathic intracranial hypertension. Specifically, 15 published articles found in PubMed database were included and analyzed in the present review. Our conclusion suggests that ocular ultrasonography is a reliable diagnostic technique to be utilized in all the cases of suspected raised intracranial pressure. To obtain the best possible accuracy and precision in the least invasive way, standardized A-scan seems to be the best choice.
Precipitous Increase of Bacterial CRISPR-Cas Abundance at Around 45°C
Authors: Lan Xin-Ran , Liu Zhi-Ling , Niu Deng-Ke
Published: March 2022

Although performing adaptive immunity, CRISPR-Cas systems are present in only 40% of bacterial genomes. We observed an abrupt increase of bacterial CRISPR-Cas abundance at around 45°C. Phylogenetic comparative analyses confirmed that the abundance correlates with growth temperature only at the temperature range around 45°C. From the literature, we noticed that the diversities of cellular predators (like protozoa, nematodes, and myxobacteria) have a steep decline at this temperature range. The grazing risk faced by bacteria reduces substantially at around 45°C and almost disappears above 60°C. We propose that viral lysis would become the dominating factor of bacterial mortality, and antivirus immunity has a higher priority at higher temperatures. In temperature ranges where the abundance of cellular predators does not change with temperature, the growth temperatures of bacteria would not significantly affect their CRISPR-Cas contents. The hypothesis predicts that bacteria should also be rich in CRISPR-Cas systems if they live in other extreme conditions inaccessible to grazing predators.
Epilithic Microbial Community Functionality in Deep Oligotrophic Continental Bedrock
Authors: Nuppunen-Puputti Maija , Kietäväinen Riikka , Raulio Mari , Soro Aino , Purkamo Lotta , Kukkonen Ilmo , Bomberg Malin
Published: March 2022

The deep terrestrial biosphere hosts vast sessile rock surface communities and biofilms, but thus far, mostly planktic communities have been studied. We enriched deep subsurface microbial communities on mica schist in microcosms containing bedrock groundwater from the depth of 500 m from Outokumpu, Finland. The biofilms were visualized using scanning electron microscopy, revealing numerous different microbial cell morphologies and attachment strategies on the mica schist surface, e.g., bacteria with outer membrane vesicle-like structures, hair-like extracellular extensions, and long tubular cell structures expanding over hundreds of micrometers over mica schist surfaces. Bacterial communities were analyzed with amplicon sequencing showing that Pseudomonas, Desulfosporosinus, Hydrogenophaga, and Brevundimonas genera dominated communities after 8–40 months of incubation. A total of 21 metagenome assembled genomes from sessile rock surface metagenomes identified genes involved in biofilm formation, as well as a wide variety of metabolic traits indicating a high degree of environmental adaptivity to oligotrophic environment and potential for shifting between multiple energy or carbon sources. In addition, we detected ubiquitous organic carbon oxidation and capacity for arsenate and selenate reduction within our rocky MAGs. Our results agree with the previously suggested interaction between the deep subsurface microbial communities and the rock surfaces, and that this interaction could be crucial for sustaining life in the harsh anoxic and oligotrophic deep subsurface of crystalline bedrock environment.
Molecular Characterization of Penicillin-Binding Protein2x, 2b and 1a of Streptococcus pneumoniae Causing Invasive Pneumococcal Diseases in China: A Multicenter Study
Authors: Zhou Menglan , Wang Lulu , Wang Ziran , Kudinha Timothy , Wang Yao , Xu Yingchun , Liu Zhengyin
Published: March 2022

Streptococcus pneumoniae is a common human pathogen that can cause severe invasive pneumococcal diseases (IPDs). Penicillin-binding proteins (PBPs) are the targets for β-lactam antibiotics (BLAs), which are the common empirical drugs for treatment of pneumococcal infection. This study investigated the serotype distribution and antibiotic resistance patterns of S. pneumoniae strains causing IPD in China, including exploring the association between penicillin (PEN) susceptibility and PBPs variations. A total of 300 invasive S. pneumoniae isolates were collected from 27 teaching hospitals in China (2010-2015). Serotypes were determined by Quellung reaction. Serotypes 23F and 19F were the commonest serotypes in isolates from cerebrospinal fluid (CSF), whilst serotypes 19A and 23F were most commonly seen in non-CSF specimens. Among the 300 invasive S. pneumoniae strains, only one strain (serotype 6A, MIC = 0.25 μg/ml) with PEN MIC value ≤ 0.25 μg/ml did not have any substitutions in the PBPs active sites. All the strains with PEN MIC value ≥ 0.5 μg/ml had different substitutions within PBPs active sites. Substitutions in PBP2b and PBP2x active sites were common in low-level penicillin-resistant S. pneumoniae (PRSP) strains (MIC = 0.5 μg/ml), with or without PBP1a substitution, while all strains with PEN MIC ≥ 1 μg/ml had substitutions in PBP1a active sites, accompanied by PBP2b and PBP2x active site substitutions. Based on the three PBPs substitution combinations, a high degree of diversity was observed amongst the isolates. This study provides some new insights for understanding the serology and antibiotic resistance dynamics of S. pneumoniae causing IPD in China. However, further genomic studies are needed to facilitate a comprehensive understanding of antibiotic resistance mechanisms of S. pneumoniae.