bluuebunny/crossref_metadata_2025 huggingface dataset:
PARTISIPASI MASYARAKAT DALAM PELAKSANAAN PPKM DARURAT DI KABUPATEN GARUT
Authors: Furqan Hafadh , Sinaga Theresia Febrian , Nugraha Jioanda Riza
Published: January 2022

The Covid-19 pandemic is increasing throughout Indonesia. Due to this, the handling of covid-19 is very important to do to overcome the spread of the covid-19 virus because if there is no handling of this virus it will endanger public health. As we know COVID-19 can cause mild to severe symptoms. There are about 80% of mild symptoms (runny nose, sore throat, cough, and fever) that do not require special treatment but there are also people who suffer from severe symptoms, such as with pneumonia or difficulty breathing, which usually appear gradually. One of the efforts to deal with COVID-19 is to implement the PPKM (Enforcement of Community Activity Restrictions) policy. None other than the goal is to foster public compliance with health protocols, prevent covid-19, and suppress the spread of COVID-19, so that the tourism and creative economy sector (tourism and creative economy) will bounce back and the economic sector will recover soon. Garut Regency is one of the regencies in Indonesia that also applies this PPKM regulation. This is the background of the author to examine the participation of the people of Garut Regency during the implementation of PPKM in an effort to handle COVID-19. This study aims to find out how the role of the people of Garut Regency and what changes occur during the implementation of PPKM in Garut Regency. The research method used is a literature study by elaborating research that is relevant to the concept of empowering local communities. In one related study, it was stated that community participation in the implementation of emergency PPKM in Garut Regency showed significant results. Therefore, through this program-based idea, we are able to achieve optimal implementation of emergency PPKM so as to increase the health status as high as possible.

 

Keywords: Covid-19, Community Participation, PPKM, Health protocol
BİR EĞİTİM ARAŞTIRMA HASTANESİ BİYOKİMYA LABORATUVARINDA NUMUNE RED ORANLARININ ANALİZİ
Authors: ERDEM Mukadder , KESKİN Adem , ACİ Recai
Published: January 2022

Çalışmamız, biyokimya laboratuvarında çeşitli nedenlerle saptanan numune reddini numune türlerine göre değerlendirmeyi amaçlamıştır. Bu çalışmada, bir eğitim ve araştırma hastanesinin biyokimya laboratuvarında bir yıllık süre içinde saptanan numune reddi nedenleri kategorize edildi. Bu red nedenleri arasında pıhtılı numune, hemolizli numune, yetersiz numune, fazla numune, hatalı alınmış numune, hatalı işlem, hatalı kap/tüp ve hatalı istem nedenleri bulunmaktadır. Bu red nedenleri sedimantasyon, hormon, koagülasyon, Hb A1c, biyokimya, kan gazı, idrar, hemogram numune türlerine göre analiz edildi. 1307013 numuneden 3483'ü (%0.27) reddedilmiştir. Numune red nedenleri; sedimantasyon %0.45, hormon %0.05, koagülasyon %0.54, Hb A1c %0.77, biyokimya %0.30, kan gazı %0.52, idrar %0.21 ve hemogram %0.20 olarak belirlendi. Red nedenleri arasında ilk üç sırada pıhtılı numune, yetersiz numune ve hemolizli numune yer aldı. Personelin sürekli eğitiminin yapılması, tüm personelin işbirliği içinde olması, iş yükünün üstesinden gelebilecek personel temini hayati önem taşımaktadır.
Possible Counterexample of the Riemann Hypothesis
Authors: Vega Frank
Published: January 2022

Under the assumption that the Riemann hypothesis is true, von Koch deduced the improved asymptotic formula $\theta(x) = x + O(\sqrt{x} \times \log^{2} x)$, where $\theta(x)$ is the Chebyshev function. A precise version of this was given by Schoenfeld: He found under the assumption that the Riemann hypothesis is true that $\theta(x) < x + \frac{1}{8 \times \pi} \times \sqrt{x} \times \log^{2} x$ for every $x \geq 599$. On the contrary, we prove if there exists some real number $x \geq 2$ such that $\theta(x) > x + \frac{1}{\log \log x} \times \sqrt{x} \times \log^{2} x$, then the Riemann hypothesis should be false. In this way, we show that under the assumption that the Riemann hypothesis is true, then $\theta(x) < x + \frac{1}{\log \log x} \times \sqrt{x} \times \log^{2} x$.
Case Report: Partial Response Following Nivolumab Plus Docetaxel in a Patient With EGFR Exon 20 Deletion/Insertion (p.N771delinsGF) Mutant Lung Adenocarcinoma Transdifferentiated From Squamous Cell Carcinoma
Authors: Zhu Lingling , Liu Yanyang , Gao Honglin , Liu Jiewei , Zhou Qinghua , Luo Feng
Published: January 2022

The histological transformation from lung squamous cell carcinoma (LUSC) to lung adenocarcinoma (LUAD) and p. N771delinsGF mutations in EGFR exon 20 (ex20) are exceedingly rare in non–small cell lung carcinoma (NSCLC). EGFR ex20 mutations are insensitive to EGFR tyrosine kinase inhibitors in NSCLC. Here, we present a 76-year-old male smoker harboring LUAD with a novel p. N771delinsGF deletion/insertion mutation in EGFR ex20 transdifferentiating from advanced LUSC after chemoradiotherapy. The patient presented reduced hydrothorax and relieved tightness with the treatment of nivolumab plus docetaxel and carboplatin after the failure of second-line chemotherapy. The case highlights the importance of rebiopsy and molecular retesting after the progression of lung cancer and supports the idea that the combination of immune checkpoint blockade and chemotherapy may be an attractive option for patients with EGFR ex20 mutations associated with LUSC–LUAD transformation.
A Novel Potent Carrier for Unconventional Protein Export in Ustilago maydis
Authors: Philipp Magnus , Hussnaetter Kai P. , Reindl Michèle , Müntjes Kira , Feldbrügge Michael , Schipper Kerstin
Published: January 2022

Recombinant proteins are ubiquitously applied in fields like research, pharma, diagnostics or the chemical industry. To provide the full range of useful proteins, novel expression hosts need to be established for proteins that are not sufficiently produced by the standard platform organisms. Unconventional secretion in the fungal model Ustilago maydis is an attractive novel option for export of heterologous proteins without N-glycosylation using chitinase Cts1 as a carrier. Recently, a novel factor essential for unconventional Cts1 secretion termed Jps1 was identified. Here, we show that Jps1 is unconventionally secreted using a fusion to bacterial β-glucuronidase as an established reporter. Interestingly, the experiment also demonstrates that the protein functions as an alternative carrier for heterologous proteins, showing about 2-fold higher reporter activity than the Cts1 fusion in the supernatant. In addition, Jps1-mediated secretion even allowed for efficient export of functional firefly luciferase as a novel secretion target which could not be achieved with Cts1. As an application for a relevant pharmaceutical target, export of functional bi-specific synthetic nanobodies directed against the SARS-CoV2 spike protein was demonstrated. The establishment of an alternative efficient carrier thus constitutes an excellent expansion of the existing secretion platform.
Molecular Engineering of Polymyxin B for Imaging and Treatment of Bacterial Infections
Authors: Wu Minghao , He Shipeng , Tang Hua , Hu Honggang , Shi Yejiao
Published: January 2022

The emergence of multi-drug resistant bacteria and the lack of novel antibiotics to combat them have led to the revival of polymyxin B, a previously abandoned antibiotic due to its potential nephrotoxicity and neurotoxicity. To facilitate its widely clinical applications, increasing effort has been devoted to molecularly engineer polymyxin B for the targeted imaging and effective treatment of bacterial infections. Herein, the molecular engineering strategies will be summarized in this mini review, with selected recent advances for illustration. Perspective of the challenges and trends in this exciting and eagerly anticipated research area will also be provided in the end. We hope this mini review will inspire researchers from diverse fields to bring forward the next wave of exploiting molecular engineering approaches to propel the “old” polymyxin B to “new” clinical significance in combating bacterial infections.
Improved Genomic Identification, Clustering, and Serotyping of Shiga Toxin-Producing Escherichia coli Using Cluster/Serotype-Specific Gene Markers
Authors: Zhang Xiaomei , Payne Michael , Kaur Sandeep , Lan Ruiting
Published: January 2022

Shiga toxin-producing Escherichia coli (STEC) have more than 470 serotypes. The well-known STEC O157:H7 serotype is a leading cause of STEC infections in humans. However, the incidence of non-O157:H7 STEC serotypes associated with foodborne outbreaks and human infections has increased in recent years. Current detection and serotyping assays are focusing on O157 and top six (“Big six”) non-O157 STEC serogroups. In this study, we performed phylogenetic analysis of nearly 41,000 publicly available STEC genomes representing 460 different STEC serotypes and identified 19 major and 229 minor STEC clusters. STEC cluster-specific gene markers were then identified through comparative genomic analysis. We further identified serotype-specific gene markers for the top 10 most frequent non-O157:H7 STEC serotypes. The cluster or serotype specific gene markers had 99.54% accuracy and more than 97.25% specificity when tested using 38,534 STEC and 14,216 non-STEC E. coli genomes, respectively. In addition, we developed a freely available in silico serotyping pipeline named STECFinder that combined these robust gene markers with established E. coli serotype specific O and H antigen genes and stx genes for accurate identification, cluster determination and serotyping of STEC. STECFinder can assign 99.85% and 99.83% of 38,534 STEC isolates to STEC clusters using assembled genomes and Illumina reads respectively and can simultaneously predict stx subtypes and STEC serotypes. Using shotgun metagenomic sequencing reads of STEC spiked food samples from a published study, we demonstrated that STECFinder can detect the spiked STEC serotypes, accurately. The cluster/serotype-specific gene markers could also be adapted for culture independent typing, facilitating rapid STEC typing. STECFinder is available as an installable package (https://github.com/LanLab/STECFinder) and will be useful for in silico STEC cluster identification and serotyping using genome data.
Proteases as Therapeutic Targets Against the Parasitic Cnidarian Ceratonova shasta: Characterization of Molecules Key to Parasite Virulence In Salmonid Hosts
Authors: Alama-Bermejo Gema , Bartošová-Sojková Pavla , Atkinson Stephen D. , Holzer Astrid S. , Bartholomew Jerri L.
Published: January 2022

Proteases and their inhibitors play critical roles in host-parasite interactions and in the outcomes of infections. Ceratonova shasta is a myxozoan pathogen that causes enteronecrosis in economically important salmonids from the Pacific Northwest of North America. This cnidarian parasite has host-specific genotypes with varying virulence, making it a powerful system to decipher virulence mechanisms in myxozoans. Using C. shasta genome and transcriptome, we identified four proteases of different catalytic types: cathepsin D (aspartic), cathepsin L and Z-like (cysteine) and aminopeptidase-N (metallo); and a stefin (cysteine protease inhibitor), which implied involvement in virulence and hence represent target molecules for the development of therapeutic strategies. We characterized, annotated and modelled their 3D protein structure using bioinformatics and computational tools. We quantified their expression in C. shasta genotype 0 (low virulence, no mortality) and IIR (high virulence and mortality) in rainbow trout Oncorhynchus mykiss, to demonstrate that there are major differences between the genotypes during infection and parasite development. High proliferation of genotype IIR was associated with high expression of the cathepsin D and the stefin, likely correlated with high nutrient demands and to regulate cell metabolism, with upregulation preceding massive proliferation and systemic dispersion. In contrast, upregulation of the cathepsin L and Z-like cysteine proteases may have roles in host immune evasion in genotype 0 infections, which are associated with low proliferation, low inflammation and non-destructive development. In contrast to the other proteases, C. shasta aminopeptidase-N appears to have a prominent role in nematocyst formation in both genotypes, but only during sporogenesis. Homology searches of C. shasta proteases against other myxozoan transcriptomes revealed a high abundance of cathepsin L and aminopeptidase homologs suggesting common gene requirements across species. Our study identified molecules of potential therapeutic significance for aquaculture and serves as a baseline for future research aimed at functional characterisation of these targets.
Incidence of Arterial Hypertension in People With Periodontitis and Characterization of the Oral and Subgingival Microbiome: A Study Protocol
Authors: Martínez-García Mireya , Castrejón-Pérez Roberto Carlos , Rodríguez-Hernández Adriana Patricia , Sandoval-Motta Santiago , Vallejo Maite , Borges-Yáñez Socorro Aída , Hernández-Lemus Enrique
Published: January 2022

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. High blood pressure in particular, continues to increase throughout the global population at an increasingly fast pace. The relationship between arterial hypertension and periodontitis has been recently discussed in the context of its origins and implications. Particularly relevant is the role of the periodontal microbiome linked to persistent local and systemic inflammation, along with other risk factors and social determinants of health. The present protocol will investigate/assess the association between periodontal disease and its microbiome on the onset of hypertension, within a cohort from Mexico City. One thousand two hundred twelve participants will be studied during a 60-month period. Studies will include analysis of periodontal conditions, sampling and sequencing of the salivary and subgingival microbiome, interviews on nutritional and lifestyle habits, social determinants of health, blood pressure and anthropometric measurements. Statistical associations and several classic epidemiology and machine learning approaches will be performed to analyze the data. Implications for the generation of public policy—by early public health interventions or epidemiological surveillance approaches—and for the population empowerment—via the establishment of primary prevention recommendations, highlighting the relationship between oral and cardiovascular health—will be considered. This latter set of interventions will be supported by a carefully planned science communication and health promotion strategy. This study has been registered and approved by the Research and Ethics Committee of the School of Dentistry, Universidad Nacional Autónoma de México (CIE/0308/05/2019) and the National Institute of Genomic Medicine (CEI/2020/12). The umbrella cohort was approved by the Institutional Bioethics Committee of the National Institute of Cardiology-Ignacio Chavez (INC-ICh) under code 13-802.
Sodium-Glucose Co-transporter-2 Inhibitor of Dapagliflozin Attenuates Myocardial Ischemia/Reperfusion Injury by Limiting NLRP3 Inflammasome Activation and Modulating Autophagy
Authors: Yu Yong-Wei , Que Jia-Qun , Liu Shuai , Huang Kai-Yu , Qian Lu , Weng Ying-Bei , Rong Fang-Ning , Wang Lei , Zhou Ying-Ying , Xue Yang-Jing , Ji Kang-Ting
Published: January 2022

Background: The sodium-glucose co-transporter-2 (SGLT-2) inhibitor dapagliflozin improves cardiovascular outcomes in patients with type 2 diabetes in a manner that is partially independent of its hypoglycemic effect. These observations suggest that it may exert a cardioprotective effect by another mechanism. This study explored the effects of dapagliflozin on myocardial ischemia/reperfusion injury in a mouse model.

Materials and Methods: For the in vivo I/R studies, mice received 40 mg/kg/d dapagliflozin, starting 7 days before I/R. Evans Blue/TTC double-staining was used to determine the infarct size. Serum levels of cTnI, CK-MB, and LDH were measured. Inflammation, autophagy protein expression, and caspase-1 activity changes were measured at the protein level. Primary cardiomyocytes were used to investigate the direct effect of dapagliflozin on cardiomyocytes and to verify whether they have the same effect as observed in in vivo experiments.

Result: A high dose of dapagliflozin significantly reduced infarct size and decreased the serum levels of cTnI, CK-MB, and LDH. Dapagliflozin also reduced serum levels of IL-1β, reduced expression of myocardial inflammation-related proteins, and inhibited cardiac caspase-1 activity. The treatment restored autophagy flux and promoted the degradation of autophagosomes. Relief of inflammation relied on autophagosome phagocytosis of NLRP3 and autophagosome clearance after lysosome improvement. 10 μM dapagliflozin reduced intracellular Ca2+ and Na+ in primary cardiomyocytes, and increasing NHE1 and NCX expression mitigated dapagliflozin effects on autophagy.

Conclusion: Dapagliflozin protects against myocardial ischemia/reperfusion injury independently of its hypoglycemic effect. High-dose dapagliflozin pretreatment might limit NLRP3 inflammasome activation and mediate its selective autophagy. Dapagliflozin directly acts on cardiomyocytes through NHE1/NCX.
The Effects of Gender Signals and Performance in Online Product Reviews
Authors: Sikdar Sandipan , Sachdeva Rachneet , Wachs Johannes , Lemmerich Florian , Strohmaier Markus
Published: January 2022

This work quantifies the effects of signaling gender through gender specific user names, on the success of reviews written on the popularamazon.comshopping platform. Highly rated reviews play an important role in e-commerce since they are prominently displayed next to products. Differences in reviews, perceived—consciously or unconsciously—with respect to gender signals, can lead to crucial biases in determining what content and perspectives are represented among top reviews. To investigate this, we extract signals of author gender from user names to select reviews where the author’s likely gender can be inferred. Using reviews authored by these gender-signaling authors, we train a deep learning classifier to quantify the gendered writing style (i.e.,gendered performance) of reviews written by authors who do not send clear gender signalsviatheir user name. We contrast the effects of gender signaling and performance on the review helpfulness ratings using matching experiments. This is aimed at understanding if an advantage is to be gained by (not) signaling one’s gender when posting reviews. While we find no general trend that gendered signals or performances influence overall review success, we find strong context-specific effects. For example, reviews in product categories such as Electronics or Computers are perceived as less helpful when authors signal that they are likely woman, but are received as more helpful in categories such as Beauty or Clothing. In addition to these interesting findings, we believe this general chain of tools could be deployed across various social media platforms.
Quantitative Assessment of Temporal Changes in Subaqueous Hydrothermal Activity in Active Crater Lakes During Unrest Based on a Time-Series of Lake Water Chemistry
Authors: Terada Akihiko , Yaguchi Muga , Ohba Takeshi
Published: January 2022

Regular sampling of lake water has been performed at many volcanoes to assess the state of volcanic activity. However, it is not clear whether the absolute concentrations or, instead, rate of changes in concentrations are more suitable for such assessments. In this study, we show that temporal changes in concentrations of an element in lake water are described by a simple differential equation, assuming changes in lake volume and chemical processes are negligible. The time constants (63% response time for changes in the chemical concentration in lake water) have a wide range varying between 20 and 1,000 days for the studied volcanoes in Japan, meaning it takes a long time to assess volcanic activity based on the absolute concentration of an element. In order to assess the volcanic activity in a shorter time period, based on a time-series of lake element concentration data, we developed a numerical model to calculate temporal changes in the steady-state concentration, which is proportional to the elemental concentrations of the bulk hydrothermal fluid injected from subaqueous fumaroles and hot springs. We applied our method to Yugama crater lake at Kusatsu–Shirane volcano, Japan, and quantitatively evaluated temporal changes in the hydrothermal input from 1964 to 2020. As a result, we detected changes in the Cl concentrations of the bulk hydrothermal input that were associated with unrest including the phreatic eruption in 1976 and earthquake swarms in 1989–1992 and 2014–2020. The future concentration in the lake water can be predicted from the most recent steady-state concentrations. Comparing the predicted concentration curve with the concentration obtained from lake water samples, it is possible to quickly assess whether the concentration of the bulk hydrothermal input has increased/decreased or remained constant.
Engineering Bilayer AlOx /YAlOx Dielectric Stacks for Hysteresis-Free Switching in Solution-Processed Metal-Oxide Thin-Film Transistors
Authors: Bolat Sami , Agiannis Evangelos , Yang Shih-Chi , Futscher Moritz H. , Aribia Abdesselam , Shorubalko Ivan , Romanyuk Yaroslav E.
Published: January 2022

Solution processing and low-temperature annealing (T < 300°C) of the precursor compounds promise low-cost manufacturing for future applications of flexible oxide electronics. However, thermal budget reduction comes at the expense of increased charge trapping residuals in the dielectric layers, which result in hysteretic switching of transistors. This work reports on a novel bilayer dielectric scheme combining aluminum oxide (AlOx) as a positive charge trapping insulator and yttrium aluminum oxide (YAlOx) as a negative charge trapping dielectric to obtain hysteresis free switching in the solution-processed metal-oxide thin-film transistors. Devices were processed at a thermal budget of 250°C, without an encapsulation layer. The presence of H+ and OH− in the AlOx were found responsible for the hysteresis in the switching, which was suppressed successfully with the thickness optimization of the YAlOx in the dielectric stack. Fabricated devices yield ON/OFF ratios of 106, sub-pA level gate leakage currents, a subthreshold swing of 150 mV/decade, and field-effect mobility of 1.5 cm2/V-sec.
Gut Microbial Signatures for Glycemic Responses of GLP-1 Receptor Agonists in Type 2 Diabetic Patients: A Pilot Study
Authors: Tsai Chih-Yiu , Lu Hsiu-Chen , Chou Yu-Hsien , Liu Po-Yu , Chen Hsin-Yun , Huang Meng-Chuan , Lin Chia-Hung , Tsai Chi-Neu
Published: January 2022

Backgrounds

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) is probably one of more effective antidiabetic agents in treatment of type 2 diabetes mellitus (T2D). However, the heterogenicity in responses to GLP-1 RA may be potentially related to gut microbiota, although no human evidence has been published. This pilot study aims to identify microbial signatures associated with glycemic responses to GLP-1 RA.

Materials and Methods

Microbial compositions of 52 patients with T2D receiving GLP-1 RA were determined by 16S rRNA amplicon sequencing. Bacterial biodiversity was compared between responders versus non-responders. Pearson’s correlation and random forest tree algorithm were used to identify microbial features of glycemic responses in T2D patients and multivariable linear regression models were used to validate clinical relevance.

Results

Beta diversity significantly differed between GLP-1 RA responders (n = 34) and non-responders (n = 18) (ADONIS, P = 0.004). The top 17 features associated with glycohemoglobin reduction had a 0.96 diagnostic ability, based on area under the ROC curve: Bacteroides dorei and Roseburia inulinivorans, the two microbes having immunomodulation effects, along with Lachnoclostridium sp. and Butyricicoccus sp., were positively correlated with glycemic reduction; Prevotella copri, the microbe related to insulin resistance, together with Ruminococcaceae sp., Bacteroidales sp., Eubacterium coprostanoligenes sp., Dialister succinatiphilus, Alistipes obesi, Mitsuokella spp., Butyricimonas virosa, Moryella sp., and Lactobacillus mucosae had negative correlation. Furthermore, Bacteroides dorei, Lachnoclostridium sp. and Mitsuokella multacida were significant after adjusting for baseline glycohemoglobin and C-peptide concentrations, two clinical confounders.

Conclusions

Unique gut microbial signatures are associated with glycemic responses to GLP-RA treatment and reflect degrees of dysbiosis in T2D patients.
P2Y Receptors in Bone - Anabolic, Catabolic, or Both?
Authors: Zhou Yuhan , Arredondo Hector M. , Wang Ning
Published: January 2022

P2Y receptors, including eight subtypes, are G protein-coupled receptors that can be activated by extracellular nucleotides. Nearly all P2Y receptors are expressed in bone cells, suggesting their involvements in bone physiology and pathology. However, their exact roles in bone homeostasis are not entirely clear. Therefore, this mini review summarizes new research developments regarding individual P2Y receptors and their roles in bone biology, particularly detailing those which execute both anabolic and catabolic functions. This dual function has highlighted the conundrum of pharmacologically targeting these P2Y receptors in bone-wasting diseases. Further research in finding more precise targeting strategy, such as promoting anabolic effects via combining with physical exercise, should be prioritized.
A Multi-Level Investment Demand Assessment Model for Renewable-Dominated Power System Planning
Authors: Li Xianghua , Liu Cong , Sheng Kun , Wen Bo , Xie Haodong , Zhao Wenxin , Yang Qixiong
Published: January 2022

To achieve the goal of carbon peak and carbon neutrality, the integration of diversified renewable energy will be the principal feature of the planning framework of the smart grid, and the planning direction and focus of power systems would shift to the network transmittability and flexibility enhancement. This paper presents an infrastructure investment demand assessment model based on multi-level analysis method for the renewable-dominated power system planning. First, for the load side, the composite capacity ratio is used to assess the capacity demand of power transformation infrastructure for satisfying the load growth. Then, the renewable energy permeability is adopted as the basis to assess the extensional transmittability capacity for the integration of high renewables. Furthermore, the capacity demand of flexible transmission lines for power grid flexibility enhancement is also estimated. Finally, the amount of unit investment for source-network-load infrastructure capacities can be predicted based on the least square generation adjunctive network and support vector machine (LSGAN-SVM) algorithm. The performance of the proposed model has been tested and benchmarked on a practical-sized power system to verify its effectiveness and feasibility.
Soil Organic Carbon and Geochemical Characteristics on Different Rocks and Their Significance for Carbon Cycles
Authors: Chen Qiao , Zhang Pengpeng , Hu Ziyuan , Li Sha , Zhang Yongshuai , Hu Lei , Zhou Liangyu , Lin Bin , Li Xuefeng
Published: January 2022

Soil organic carbon (SOC) is significant for soil quality and global carbon cycles. SOC was observed to be related to soil geochemistry, and soils originating from different bedrocks have different geochemical properties, but the effect of bedrock on SOC is still undefined. Soils overlying different bedrocks in Zhenxiong County and Weixin County were sampled. Specifically, soils in the mineral horizon, which are less affected by the external environment than surface soils, are focused on to reveal the effect of bedrock on SOC. Al/Ti, Fe/Ti, and Al/Fe indicate a soil–rock successive relationship. SOC contents in the mineral horizon are 0.19–2.74% (1.24% on average), and those in the surface horizon are 1.26–4.01% (2.63% on average). SOC contents in the surface and mineral horizons of the same bedrock are significantly positively correlated, implying that the bedrock is an important factor affecting SOC. SOC in the mineral horizon is related to the first transition metal ions. Significantly, positive correlations of SOC (p < 0.01) with Co, Cu, Ti, V, and Zn, and a positive correlation (p < 0.05) with Ni were observed in the mineral horizon. Organic transition metal complexation seems to play an important role in governing SOC in the mineral horizon. That is, the complexation maintains organic carbon stability, slows down its decomposition rate, and accumulates organic carbon. The Ca–SOC positive correlation in the mineral horizon exits because Ca also can complex with organic carbon. Co, Cu, and V–SOC positive correlations (p < 0.05) were also observed, but there were no significant positive correlations (p < 0.01) in the surface horizon because surface SOC had diversified sources. An SOC evolution model influenced by the bedrock was forwarded. Thus, the different soil geochemistry originating from different bedrocks should be noticed when SOC and global carbon cycles are discussed.
How to Enhance the Green Innovation of Sports Goods? Micro- and Macro-Level Evidence From China’s Manufacturing Enterprises
Authors: Huang Chengyin , Chen Ying
Published: January 2022

This study aims to explore the driving factors of green innovation, and uses the micro- and macro-data from China’s sports goods manufacturing industries. In particularly, sports goods manufacturing enterprises are identified by the textual analysis of information disclosure, and the competitive environment faced by each enterprise is built through their unique closest rivals. Empirically, this study finds that competition and policy can promote green innovation in sports goods manufacturing industries, and industrial policy can moderate the role of product market competition in promoting green innovation. Considering the characteristics of the Chinese market, more industrial policies may intensify the competition among manufacturing enterprises, forcing such enterprises to obtain competitive advantages through innovation outcomes. It is worth noting that the association between product market competition and green innovation changes as financial constraints increase, and this may be caused by the impact of industrial policy on the interactions among enterprises. After implementing the strict environmental policy, product market competition and industrial policy can both promote green innovation. In high-polluting industries, sports goods manufacturing enterprises get more social attention and suffer from higher penalties for environmental violations, so that such enterprises will get more motivations from industrial policies to support green innovation. In addition, we also find that there is a significant inverted-U shape relationship between industrial policy and green innovation in sports goods manufacturing industries. As financial constraints increase, the non-linear relationship between product market competition and green innovation converts from a U shape relationship to an inverted-U shape relationship. Our findings can provide a better understanding of the investment of sports goods manufacturing enterprises in green innovation.
Gene-Based Therapeutics for Inherited Retinal Diseases
Authors: Fenner Beau J. , Tan Tien-En , Barathi Amutha Veluchamy , Tun Sai Bo Bo , Yeo Sia Wey , Tsai Andrew S. H. , Lee Shu Yen , Cheung Chui Ming Gemmy , Chan Choi Mun , Mehta Jodhbir S. , Teo Kelvin Y. C.
Published: January 2022

Inherited retinal diseases (IRDs) are a heterogenous group of orphan eye diseases that typically result from monogenic mutations and are considered attractive targets for gene-based therapeutics. Following the approval of an IRD gene replacement therapy for Leber’s congenital amaurosis due to RPE65 mutations, there has been an intensive international research effort to identify the optimal gene therapy approaches for a range of IRDs and many are now undergoing clinical trials. In this review we explore therapeutic challenges posed by IRDs and review current and future approaches that may be applicable to different subsets of IRD mutations. Emphasis is placed on five distinct approaches to gene-based therapy that have potential to treat the full spectrum of IRDs: 1) gene replacement using adeno-associated virus (AAV) and nonviral delivery vectors, 2) genome editing via the CRISPR/Cas9 system, 3) RNA editing by endogenous and exogenous ADAR, 4) mRNA targeting with antisense oligonucleotides for gene knockdown and splicing modification, and 5) optogenetic approaches that aim to replace the function of native retinal photoreceptors by engineering other retinal cell types to become capable of phototransduction.
Genetic Relationship Among the Kazakh People Based on Y-STR Markers Reveals Evidence of Genetic Variation Among Tribes and Zhuz
Authors: Khussainova Elmira , Kisselev Ilya , Iksan Olzhas , Bekmanov Bakhytzhan , Skvortsova Liliya , Garshin Alexander , Kuzovleva Elena , Zhaniyazov Zhassulan , Zhunussova Gulnur , Musralina Lyazzat , Kahbatkyzy Nurzhibek , Amirgaliyeva Almira , Begmanova Mamura , Seisenbayeva Akerke , Bespalova Kira , Perfilyeva Anastasia , Abylkassymova Gulnar , Farkhatuly Aldiyar , Good Sara V. , Djansugurova Leyla
Published: January 2022

Ethnogenesis of Kazakhs took place in Central Asia, a region of high genetic and cultural diversity. Even though archaeological and historical studies have shed some light on the formation of modern Kazakhs, the process of establishment of hierarchical socioeconomic structure in the Steppe remains contentious. In this study, we analyzed haplotype variation at 15 Y-chromosomal short-tandem-repeats obtained from 1171 individuals from 24 tribes representing the three socio-territorial subdivisions (Senior, Middle and Junior zhuz) in Kazakhstan to comprehensively characterize the patrilineal genetic architecture of the Kazakh Steppe. In total, 577 distinct haplotypes were identified belonging to one of 20 haplogroups; 16 predominant haplogroups were confirmed by SNP-genotyping. The haplogroup distribution was skewed towards C2-M217, present in all tribes at a global frequency of 51.9%. Despite signatures of spatial differences in haplotype frequencies, a Mantel test failed to detect a statistically significant correlation between genetic and geographic distance between individuals. An analysis of molecular variance found that ∼8.9% of the genetic variance among individuals was attributable to differences among zhuzes and ∼20% to differences among tribes within zhuzes. The STRUCTURE analysis of the 1164 individuals indicated the presence of 20 ancestral groups and a complex three-subclade organization of the C2-M217 haplogroup in Kazakhs, a result supported by the multidimensional scaling analysis. Additionally, while the majority of the haplotypes and tribes overlapped, a distinct cluster of the O2 haplogroup, mostly of the Naiman tribe, was observed. Thus, firstly, our analysis indicated that the majority of Kazakh tribes share deep heterogeneous patrilineal ancestries, while a smaller fraction of them are descendants of a founder paternal ancestor. Secondly, we observed a high frequency of the C2-M217 haplogroups along the southern border of Kazakhstan, broadly corresponding to both the path of the Mongolian invasion and the ancient Silk Road. Interestingly, we detected three subclades of the C2-M217 haplogroup that broadly exhibits zhuz-specific clustering. Further study of Kazakh haplotypes variation within a Central Asian context is required to untwist this complex process of ethnogenesis.
Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) up to 15 Months Post-Infection
Authors: Patterson Bruce K. , Francisco Edgar B. , Yogendra Ram , Long Emily , Pise Amruta , Rodrigues Hallison , Hall Eric , Herrera Monica , Parikh Purvi , Guevara-Coto Jose , Triche Timothy J. , Scott Paul , Hekmati Saboor , Maglinte Dennis , Chang Xaiolan , Mora-Rodríguez Rodrigo A. , Mora Javier
Published: January 2022

The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect up to 30% of all infected individuals. The underlying mechanism and source of this distinct immunologic condition three months or more after initial infection remains elusive. Here, we investigated the presence of SARS-CoV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls (P=0.002 and P=0.01, respectively). A statistically significant number of non-classical monocytes contained SARS-CoV-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. Non-classical monocytes were sorted from PASC patients using flow cytometric sorting and the SARS-CoV-2 S1 protein was confirmed by mass spectrometry. Cells from 4 out of 11 severe COVID-19 patients and 1 out of 26 PASC patients contained ddPCR+ peripheral blood mononuclear cells, however, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient. That non-classical monocytes may be a source of inflammation in PASC warrants further study.
Case Report: Multicentric Reticulohistiocytosis Associated With Posterior Mediastinal Adenosquamous Carcinoma, Antinuclear Antibody Positivity and Lupus Anticoagulant Positivity
Authors: Tang Ziyi , Wang Xiangpeng , Xia Zijing , Wang Zhongming , Zhao Yi , Liu Yi
Published: January 2022

Multicentric reticulohistiocytosis (MRH) is a rare systemic disease of non-Langerhans cell histiocytosis. A number of studies in the literature have documented that it can coexist with malignancy or autoimmune disease, making it difficult to determine the most appropriate therapy. Here, we present a case study of MRH associated with posterior mediastinal adenosquamous carcinoma along with antinuclear antibody positivity and lupus anticoagulant positivity. The patient experienced 6 months of clinical benefit after surgical resection and chemoradiotherapy of the mediastinal malignancy. This case adds to the available literature on multicentric reticulohistiocytosis associated with different types of malignancy and provides supplementary clinical data on the coexistence of this syndrome with malignancy and immune system abnormalities. To the best of our knowledge, this is the first case study describing MRH accompanied by posterior mediastinal adenosquamous carcinoma and lupus anticoagulant positivity. The unknown aetiology and polymorphic clinical presentation of MRH warrants further investigation.
HLA-DQ-Specific Recombinant Human Monoclonal Antibodies Allow for In-Depth Analysis of HLA-DQ Epitopes
Authors: Bezstarosti Suzanne , Kramer Cynthia S. M. , Franke-van Dijk Marry E. I. , Vergunst Manon , Bakker Kim H. , Uyar-Mercankaya Merve , Buchli Rico , Roelen Dave L. , de Fijter Johan W. , Claas Frans H. J. , Heidt Sebastiaan
Published: January 2022

HLA-DQ donor-specific antibodies (DSA) are the most prevalent type of DSA after renal transplantation and have been associated with eplet mismatches between donor and recipient HLA. Eplets are theoretically defined configurations of surface exposed amino acids on HLA molecules that require verification to confirm that they can be recognized by alloantibodies and are therefore clinically relevant. In this study, we isolated HLA-DQ specific memory B cells from immunized individuals by using biotinylated HLA-DQ monomers to generate 15 recombinant human HLA-DQ specific monoclonal antibodies (mAb) with six distinct specificities. Single antigen bead reactivity patterns were analyzed with HLA-EMMA to identify amino acids that were uniquely shared by the reactive HLA alleles to define functional epitopes which were mapped to known eplets. The HLA-DQB1*03:01-specific mAb LB_DQB0301_A and the HLA-DQB1*03-specific mAb LB_DQB0303_C supported the antibody-verification of eplets 45EV and 55PP respectively, while mAbs LB_DQB0402_A and LB_DQB0602_B verified eplet 55R on HLA-DQB1*04/05/06. For three mAbs, multiple uniquely shared amino acid configurations were identified, warranting further studies to define the inducing functional epitope and corresponding eplet. Our unique set of HLA-DQ specific mAbs will be further expanded and will facilitate the in-depth analysis of HLA-DQ epitopes, which is relevant for further studies of HLA-DQ alloantibody pathogenicity in transplantation.
In Silico Analyses on the Comparative Potential of Therapeutic Human Monoclonal Antibodies Against Newly Emerged SARS-CoV-2 Variants Bearing Mutant Spike Protein
Authors: Das Nabarun Chandra , Chakraborty Pritha , Bayry Jagadeesh , Mukherjee Suprabhat
Published: January 2022

Since the start of the pandemic, SARS-CoV-2 has already infected more than 250 million people globally, with more than five million fatal cases and huge socio-economic losses. In addition to corticosteroids, and antiviral drugs like remdesivir, various immunotherapies including monoclonal antibodies (mAbs) to S protein of SARS-CoV-2 have been investigated to treat COVID-19 patients. These mAbs were initially developed against the wild-type SARS-CoV-2; however, emergence of variant forms of SARS-CoV-2 having mutations in the spike protein in several countries including India raised serious questions on the potential use of these mAbs against SARS-CoV-2 variants. In this study, using an in silico approach, we have examined the binding abilities of eight mAbs against several SARS-CoV-2 variants of Alpha (B.1.1.7) and Delta (B.1.617.2) lineages. The structure of the Fab region of each mAb was designed in silico and subjected to molecular docking against each mutant protein. mAbs were subjected to two levels of selection based on their binding energy, stability, and conformational flexibility. Our data reveal that tixagevimab, regdanvimab, and cilgavimab can efficiently neutralize most of the SARS-CoV-2 Alpha strains while tixagevimab, bamlanivimab, and sotrovimab can form a stable complex with the Delta variants. Based on these data, we have designed, by in silico, a chimeric antibody by conjugating the CDRH3 of regdanivimab with a sotrovimab framework to combat the variants that could potentially escape from the mAb-mediated neutralization. Our finding suggests that though currently available mAbs could be used to treat COVID-19 caused by the variants of SARS-CoV-2, better results could be expected with the chimeric antibodies.
Endoplasmic Reticulum Stress-Associated Neuronal Death and Innate Immune Response in Neurological Diseases
Authors: Shi Mingming , Chai Yan , Zhang Jianning , Chen Xin
Published: January 2022

Neuronal death and inflammatory response are two common pathological hallmarks of acute central nervous system injury and chronic degenerative disorders, both of which are closely related to cognitive and motor dysfunction associated with various neurological diseases. Neurological diseases are highly heterogeneous; however, they share a common pathogenesis, that is, the aberrant accumulation of misfolded/unfolded proteins within the endoplasmic reticulum (ER). Fortunately, the cell has intrinsic quality control mechanisms to maintain the proteostasis network, such as chaperone-mediated folding and ER-associated degradation. However, when these control mechanisms fail, misfolded/unfolded proteins accumulate in the ER lumen and contribute to ER stress. ER stress has been implicated in nearly all neurological diseases. ER stress initiates the unfolded protein response to restore proteostasis, and if the damage is irreversible, it elicits intracellular cascades of death and inflammation. With the growing appreciation of a functional association between ER stress and neurological diseases and with the improved understanding of the multiple underlying molecular mechanisms, pharmacological and genetic targeting of ER stress are beginning to emerge as therapeutic approaches for neurological diseases.
The Polygenic Map of Keloid Fibroblasts Reveals Fibrosis-Associated Gene Alterations in Inflammation and Immune Responses
Authors: Li Yang , Li Min , Qu Caijie , Li Yongxi , Tang Zhanli , Zhou Zhike , Yu Zengzhao , Wang Xu , Xin Linlin , Shi Tongxin
Published: January 2022

Due to many inconsistencies in differentially expressed genes (DEGs) related to genomic expression changes during keloid formation and a lack of satisfactory prevention and treatment methods for this disease, the critical biomarkers related to inflammation and the immune response affecting keloid formation should be systematically clarified. Normal skin/keloid scar tissue-derived fibroblast genome expression data sets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases. Hub genes have a high degree of connectivity and gene function aggregation in the integration network. The hub DEGs were screened by gene-related protein–protein interactions (PPIs), and their biological processes and signaling pathways were annotated to identify critical biomarkers. Finally, eighty-one hub DEGs were selected for further analysis, and some noteworthy signaling pathways and genes were found to be closely related to keloid fibrosis. For example, IL17RA is involved in IL-17 signal transduction, TIMP2 and MMP14 activate extracellular matrix metalloproteinases, and TNC, ITGB2, and ITGA4 interact with cell surface integrins. Furthermore, changes in local immune cell activity in keloid tissue were detected by DEG expression, immune cell infiltration, and mass CyTOF analyses. The results showed that CD4+ T cells, CD8+ T cells and NK cells were abnormal in keloid tissue compared with normal skin tissue. These findings not only support the key roles of fibrosis-related pathways, immune cells and critical genes in the pathogenesis of keloids but also expand our understanding of targets that may be useful for the treatment of fibrotic diseases.