bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naturally Nasal-esophageal Fiberscope in COVID-19&nbsp;Pandemic - Prevent Sneezing Without Anesthesia
Authors: Tsunoda Koichi , Hentona Ko , Yoshiharu Yamanobe 
Published: April 2021

Abstract
Background: We are laryngologists, to observe natural phonatory and swallowing functions, in every clinical examination with trans-nasal laryngeal fiberscope (TNLF), before the observation, we use epinephrine to enlarge and smoothen inside common nasal meatus (bottom of nostril), then insert wet swab inside the nose, like a swab culture in nasopharynx. In particular current COVID-19 pandemic situation, this careful technique prevents any complications even nasal bleeding, painfulness, and inducing sneezing. Here we introduce our routine to observe esophageal movement in swallowing in natural setting (sitting position) without anesthesia.Case presentation: A case was 70-year-old female who complained something stuck esophagus or strange sensation below the larynx and pharynx. After enlarge and smoothen inside common nasal meatus we insert the TNLF (slim type ⌀29mm fiberscope, VNL8-J10, PENTAX Medical, Tokyo, Japan.) in a same way. Then observe the phonatory and swallowing movement of vocal folds. To get natural movements we had never used any anesthesia. There was no pathological condition in the pyriform sinus, we asked a patient to swallow the fiberscope. At that timing we push the TNLF and insert the tip a bit deeper simultaneously with swallowing, which make the fiberscope easily enter the esophagus like the insertion of nasogastric tube. Then asked the patient to swallow sip of water or saliva, the lumen of esophagus cleared and enlarged. This makes to observe esophagus easily without any air supply. The esophagus is completely normal except glycogenic acanthosis with tone enhancement scan. Conclusions: The advance point of this examination is easily able to perform in sitting position without anesthesia, also takes only a minute and minimum invasive to observe the physiologically natural swallowing. It is also possible without anesthesia until esophagogastric junction using with a thin type flexible bronchoscopy. In the future, diameter of gastric fiberscope even with narrow band imaging (NBI) function might be gradually getting thinner. Before that time every physician should know this technique. Just insert along the bottom of nose.
Southern Ocean convection shutdown controls potential for long-term climate warming by greenhouse gases
Authors: Gjermundsen Ada , Nummelin Aleksi , Olivié D. , Bentsen Mats , Seland Øyvind , Schulz Michael 
Published: April 2021

Abstract
The effective climate sensitivity (EffCS) estimates the equilibrium near-surface temperature increase due to an doubling of the atmospheric carbon dioxide concentration, and is a widely used metric to characterise potential global warming. Cloud feedback, with considerable contribution from marine boundary layer clouds over the Southern Ocean (SO), has been identified as the main source to the spread and the increase in EffCS in the Earth System Models participating in phase 6 of the Coupled Model Intercomparison Project (CMIP6).

We trace the difference in EffCS between the Community Earth System Model (CESM2, EffCS of 5.3K) and the Norwegian Earth System model (NorESM2; EffCS of 2.5K), to SO circulation response. NorESM2 stores more heat at depth than CESM2, which delays the SO surface warming, SO cloud response, and ultimately the global surface warming by centuries in comparison to CESM2. The link between SO and EffCS is seen across 41 CMIP6 models; those with a low EffCS exhibit substantial deep SO warming. The observed slow surface but fast subsurface SO warming supports the notion of SO control over EffCS.
Integrating transcriptome and proteome analysis to determine the lignin synthesis pathway involved in Panax notoginseng in fungal stress
Authors: Yang Qian , Li Jianbin , Xiao Lin , Peng Jiani , Sun Jialing , cui xiuming 
Published: April 2021

Abstract
Background Plants are constantly threatened by various pathogens in a challenging environment. Altemaria panax Whetzel is a destructive pathogen that affects many plants, including Panax notoginseng, and significantly reduces the yield and product quality of Panax notoginseng. It is not clear how Panax notoginseng responds to pathogen infection.Methods Using the advanced advantages of transcriptome and proteomics technology, we studied the response of Panax notoginseng to Altemaria panax stress.Results Compared with the control, fungal infection caused significant changes in the Panax notoginseng transcriptome and proteome. Specifically, a total of 136,100 transcripts and 4,468 proteins were identified. The integration of transcriptome and proteome profiles revealed many candidate transcripts/proteins, which may be involved in lignin synthesis during the activation of defense responses by Panax notoginseng. Many genes and proteins are induced or inhibited by fungi. Among them, the expression levels of genes PAL, 4CL, COMT, CAD and POX in the lignin synthesis pathway are significantly increased, which indicates that the fungus activates the defense response of Panax notoginseng.Conclusions As far as we know, this is the first time that transcriptome and proteome analysis have been combined to study the response of Panax notoginseng to disease. This study provides a wide range of new information about the transcriptome, proteome and their correlation of Panax notoginseng in response to fungal stress. The analysis of this resource allows us to examine the mechanisms of transcription and protein diversification, which expands the knowledge of the complexities of the transcriptome and proteome in traditional Chinese medicines.
Over-representation of MEF-2 isoforms (A/C) is associated with HTLV-1-induced acute ATLL and their recruitment to 3’LTR facilitates HBZ expression from the antisense promoter via interactions with Menin and Jun D
Authors: Madugula Kiran , Joseph Julie , Teixeira Vanessa , Ginwala Rashida , Demarino Catherine , Kashanchi Fatah , Rushing Amanda , Lemasson Isabelle , Wilson Sydney , Sales Dominc , Harhaj Edward , Janakiram Murali , Ye B. Hilda , Khan Zafar K , Jain Pooja 
Published: April 2021

Abstract
Background. HTLV-1 is a complex human retrovirus and an etiologic agent causing a malignant and intractable T-cell neoplasia termed Adult T-cell leukemia and lymphoma (ATLL). Patients suffering from ATLL present with poor prognoses and a dearth of treatment options warranting a continuous need to develop novel therapeutic targets. In contrast to the HTLV-1 transactivator protein Tax, HTLV-1 bZIP protein (HBZ) maintains its expression in ATLL cells. The HBZ gene is encoded from the antisense strand of the provirus and is not under the transcriptional control of the 5’ long terminal repeat (LTR) unlike other viral genes such as Tax. Few modifications have been reported in the 3’LTR, which regulates HBZ expression. Herein, we delineate the activities of a transcription factor MEF (Myocyte enhancer factor)-2 at both 5’ and 3’LTRs in the context of ATLL progression and maintenance. Results. In this study, we report that two MEF isoforms (2A and 2C) are highly overexpressed in acute ATLL patients from North America. These isoforms are recruited to the viral promoters at both the 5’ and 3’LTRs. Their knockdown by shRNAs resulted in the downregulation of Tax and HBZ expression as well as a significant decrease in proliferation and cell cycle arrest in ATLL cells. Similarly, chemical inhibition of MEF proteins by MC1568 (a selective Class IIa HDAC inhibitor) resulted in the cytotoxicity of ATLL cells in vitro as well as reduction of proviral load and viral gene expression in vivo. At the molecular level, high enrichment of MEF-2C occurred at the 3’LTR along with cofactors Menin, Jun D, and Sp1/Sp3 thus providing a novel mechanism of regulation at the antisense promoter of HTLV-1. Conclusions. This study establishes MEF-2 as critical players in ATLL, which interacts with Tax and HBZ at their respective promoters highlighting a novel mechanism of regulation at the 3’LTR involving Jun D and Menin. MEF signaling represent a potential target for therapeutic intervention.
Estimating the impact of Tiny Targets in reducing the incidence of gambiense sleeping sickness in the North West Uganda focus
Authors: Bessell Paul , Esterhuizen Johan , Lehane Mike , Longbottom Joshua , Mugenyi Albert , Selby Richard , Tirados Inaki , Torr Steve J , Waiswa Charles , Wamboga Charles , Hope Andrew 
Published: April 2021

Abstract
Background Riverine species of tsetse (Glossina) transmit Trypanosoma brucei gambiense which causes Gambian human African trypanosomiasis (gHAT), a neglected tropical disease. Uganda aims to eliminate gHAT as a public health problem through detection and treatment of human cases and vector control. The latter is being achieved through the deployment of ‘Tiny Targets’, insecticide-impregnated panels of material which attract and kill tsetse. We analysed the spatial and temporal distribution of cases of gHAT in Uganda during the period 2010-2019 to assess whether Tiny Targets have had an impact on disease incidence.Methods To quantify the deployment of Tiny Targets, we mapped the rivers and their associated watersheds in the intervention area. We then categorised each of these on a 0-3 scale according to whether Tiny Targets were absent (0), present only in neighbouring watersheds (1), present in the watersheds but not all neighbours (2) or present in the watershed and all neighbours (3). We overlaid all cases that were diagnosed between 2000 and 2020 and assessed whether the probability of finding cases in a watershed changed following the deployment of targets. We also estimated the number of cases averted by tsetse control.Results We found that following the deployment of Tiny Targets in a watershed there are fewer cases of HAT (p=0.007). We estimate that during the intervention period 2012-2019 we should have expected 48 cases (95% confidence intervals = 40-57) compared to the 36 cases observed. The results are robust to a range of sensitivity analyses.Conclusions Tiny Targets have reduced the incidence of gHAT by 25% in North Western Uganda.
In Vivo Antiplasmodial Activities and Acute Toxicity Assessment of Two Plant Cocktail Extracts Commonly Used Among Southwestern Nigerians.
Authors: Omagha Rachel , Idowu E.T. , Alimba C.G. , Otubanjo A.O , Agbaje E.O. 
Published: April 2021

Abstract
Discovering and developing the desired antimalarials continue to be a necessity especially due to treatment failures, drug resistance, limited availability and affordability of pharmaceutical antimalarials, costs and logistical problems especially in poor malarious countries. This study investigated the efficacies of two plant cocktails; CtA and CtB, selected based on their traditional usage. Activities of the cocktail extracts, chloroquine and pyrimethamine against Plasmodium berghei berghei were evaluated using the suppressive, curative and prophylactic test models, after oral and intraperitoneal acute toxicity determination of the plant cocktails in accordance with Lorke method. Data was analyzed using SPSS software version 23.0 with level of significance set at P<0.05. The median lethal dose was determined to be higher than 5000 mg/kg body weight orally for both CtA and CtB; and 316.23 mg/kg body weight intraperitoneally for CtA. Each cocktail exhibited high dose dependent Plasmodium berghei berghei inhibition which was 96.95%, 99.13% in the CtA800 mg/kg, CtB800 mg/kg doses in the curative groups respectively, 96.46%, 78.62% for CtA800mg/kg, CtB800mg/kg doses in the suppressive groups respectively, and 65.05%, 88.80% for CtA800mg/kg, CtB800mg/kg doses in the prophylactic groups respectively. Throughout the observation periods, the standard drugs, chloroquine phosphate and pyrimethamine maintained higher inhibitions up to 100%. These findings demonstrate that CtA and CtB possess good antimalarial abilities and calls for their development and standardization as effective and readily available antimalarial options. The acute toxicity results obtained underscore the importance of obtaining information on toxicities of medicinal plant remedies before their administration in both humans and animals.
Anti-Markovnikov Hydro(amino)alkylation of Vinylarenes via Photoredox Catalysis
Authors: Wu Zhao , Gockel Samuel , Hull Kami 
Published: April 2021

Abstract
Photoredox catalysis is a powerful means to generate odd-electron species under mild reaction conditions from a wide array of radical precursors. Herein, we present the application of this powerful catalytic manifold to address the hydroaminoalkylation and hydroalkylation of electronically diverse vinylarenes. Utilizing easily accessible α-silyl amine reagents, secondary and tertiary amine moieties can be installed onto monoaryl and diaryl alkenes to access valuable products, including g,g-diarylamines pharmacophores. This reaction was further extended to allow for generalized alkene hydroalkylation leveraging common alkyl radical precursors, such as organotrifluoroborate salts and carboxylic acids. Thus, under a unified system, both hydroaminoalkylation and hydroalkylation of alkenes are achieved. The substrate scope is evaluated through 54 examples, the synthetic utility of the method is demonstrated, and preliminary mechanistic insights are presented.
IL6ST–induced muscarinic receptor opens goblet cell associated antigen passages to suppress alcoholic liver disease
Authors: Karin Michael , Llorente Cristina , Bruellman Ryan , Cabré Noemí , Brea Rocío , Pell Nuria , Maccioni Luca , Alghafri Ameera , Zhou Rongrong , Gao Bei , Duan Yi , Liu Junlai , Taniguchi Koji , Newberry Rodney , Fouts Derrick , Brenner David , Starkel Peter , Schnabl Bernd 
Published: April 2021

Abstract
Alcohol consumption is the seventh leading risk factor for death worldwide 1 48 and alcoholic liver disease (ALD) is the major cause of liver transplantation in the West 2 49 . Alcohol metabolites can 50 directly damage the liver, but the gut-liver axis also plays an important role in ALD pathogenesis, 51 acting through complex and obscure mechanisms. Although alcohol intake is associated with increased intestinal permeability 3 52 , it is not clear how the intestinal immune system affects liver 53 disease. Paradoxically, we found that chronic alcohol use increases intestinal goblet cell (GC) 54 number and mucin production in patients and mice. This, however, comes with the expense of 55 GC associated antigen passages (GAPs) closure and defective delivery of luminal antigens and 56 bacteria to lamina propria (LP) antigen presenting cells (APCs). IL-6 is one of several cytokines elevated in ALD that affects the liver and the intestine 4 57 . Although IL-6 expression correlates with disease severity 5 , IL-6 also exerts barrier protective effects 6 58 . We now show that GAPs are 59 controlled by intestinal IL-6 signal transducer (IL6ST/gp130). Although mice that express constitutively active gp130 in intestinal epithelial cells (IEC; gp130 60 Act/IEC mice) have fewer GCs 7 61 , they are ALD resistant due to increased GAP formation, which enhances the generation of 62 tolerogenic LP-APCs and production of IL-22 by type-3 innate lymphoid cells (ILC3s). GAP 63 opening induces an intestinal C-type regenerating islet derived-3 (Reg3) lectin-mediated 64 antibacterial defense, reducing bacterial translocation to the liver and preventing alcoholic 65 steatohepatitis. gp130 signaling exerted its protective effects via muscarinic acetylcholine (ACh) 66 receptor 4 (mAChR4), whose GC expression was induced by IL-6. Based on these findings, we 67 developed a new therapeutic approach, administering a mAChR4 positive allosteric modulator 68 (PAM) to stimulate intestinal GAP formation, thereby increasing tolerogenic LP-APCs and Reg3 69 expression, to prevent microbial translocation and protect mice from alcoholic steatohepatitis. 70 Our results show that IL6ST signaling modulates intestinal immunity through mAChR4. GAP 71 induction by mAChR4 PAMs is a promising strategy for enhancing intestinal immune tolerance 72 and interception in ALD and other diseases linked to uncontrolled microbial translocation.
Molecular Breeding of a Novel PTGMS&nbsp;Line of Wdr for Broad-spectrum Resistance to Blast Using Pi9, Pikh, and Pi5 Genes
Authors: Liu Yi , Zhang Fenyun , Luo Xingxing , Kong Deyan , Zhang Anning , Wang Feiming , Pan Zhongquan , Wang Jiahong , Bi Junguo , Luo Lijun , Liu Guolan , Yu Xinqiao 
Published: April 2021

Abstract
Background: The two-line method based on the photoperiod and thermo-sensitive genic male sterile (PTGMS) lines is more cost-effective, simple, and efficient than the three-line system based on cytoplasmic male-sterility (CMS). Blast and drought are the most prevalent biotic and abiotic stress factors that hamper rice production, respectively. Molecular techniques demonstrate higher efficacy in the pyramiding of disease resistance genes, providing green performance under the background of water-saving and drought-resistance rice.Results: This work employed molecular marker-assisted selection (MAS), conventional hybridization and high-intensity stress screening to integrate the broad-spectrum blast resistance genes Pi9, Pikh, and Pi5 into Huhan 1S. Subsequently a novel water-saving and drought-resistance rice (WDR) PTGMS line Huhan 74S was developed. The drought resistance of the new PTGMS line Huhan 74S was comparable to that of Huhan 1S. The artificial inoculation of 14 blast strains revealed that the resistance frequency of Huhan 74S was 85.7%. Based on the conditions of natural field induction, Huhan 74S and its hybrid combination revealed satisfactory resistance to leaf and neck blast. The identification outcomes of photo-thermal characteristics showed that the critical point of Huhan 74S fertility conversion had an average daily temperature of 23℃, and the stable sterile period in Shanghai lasted 51 days. The rice quality of Huhan 74S was grade 3 based on standards issued by the ministry. Also, both the agronomic and rice quality performances adhered to the conditions of two-line hybrid rice production.Conclusion: The newly bred PTGMS line Huhan 74S demonstrated a stable and lasting resistance to blast. Moreover, the hybrid combination showed a high yield potential and can be used in the breeding of high-yield, high-quality, disease-resistance two-line hybrid water-saving and drought-resistance rice (WDR), hence promoting sustainable rice production in China.
CRISPR/Cas-mediated non-viral genome specific targeted CAR T cells achieve high safety and efficacy in relapsed/refractory B-cell non-Hodgkin lymphoma
Authors: Huang He , Zhang Jiqin , Hu Yongxian , Yang Jiaxuan , Li Wei , Zhang Mingming , Tian Yue , Wei Guoqing , Zhang Linjie , Zhao Kui , Tan Binghe , Cui Jiazhen , Qi Yalei , Li Yi , Tian Qiliang , Wang Qingcan , Wu Yuxuan , Li Dali , Du Bing , Liu Mingyao 
Published: April 2021

Abstract
In recent years, chimeric antigen receptor (CAR) T cell therapy has shown great promise in treating hematological malignancies. However, CAR T cell therapy currently has several limitations. Here we successfully developed a two-in-one approach to generate non-viral genome specific targeted CAR T cells through CRISPR/Cas9. Based on the optimized protocol, the feasibility was preliminarily demonstrated by a preclinical study inserting an anti-CD19 CAR cassette into the AAVS1 safe harbor locus. We found that non-viral AAVS1-knockin CAR T cells behave comparably to those conventionally produced by lentivirus. Furthermore, an innovative type of anti-CD19 CAR T cells with PD1-integration was constructed and shows a superior ability to eradicate tumor cells with high PD-L1 expression. In adoptive therapy for relapsed/refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL), we observed a high rate (87.5%) of complete remission (CR) and durable responses without serious adverse events in eight patients after treatment. Notably, these enhanced CAR T cells were effective even at a low infusion dose and with a low CAR percentage, which indicated that they have higher potency. No off-target events were found in the infusion product. Single-cell RNA sequencing analysis further validated the advantage of PD1 interference that results in fewer dysfunctional CAR T cells through this treatment. Collectively, our results demonstrate the outstanding safety and efficacy of non-viral genome specific integrated CAR T cells, thus providing a revolutionary technology for CAR T cell therapy.
Reduced fecal short-chain fatty acids levels and the relationship with gut microbiota in IgA nephropathy
Authors: Chai Lingxiong , Luo Qun , Cai Kedan , Wang Kaiyue , Xu Binbin 
Published: April 2021

Abstract
Background: IgA nephropathy(IgAN)) is the common pathological type of glomerular diseases. The role of gut microbiota in mediating "gut-IgA nephropathy" has not received sufficient attention in the previous studies. The purpose of this study was to investigate the changes of fecal short-chain fatty acids(SCFAs), a metabolite of the intestinal microbiota, in patients with IgAN and its correlation with intestinal flora and clinical indicators, and to further investigate the role of the gut-renal axis in IgAN.Methods: There were 29 patients with IgAN and 29 normal control subjects recruited from January 2018 to May 2018. The fresh feces were collected. The fecal SCFAs were measured by gas chromatography/mass spectrometry and gut microbiota was analysed by16S rDNA sequences, followed by estimation of α- and β-diversity. Correlation analysis was performed using the spearman’s correlation test between SCFAs and gut microbiota. Results:The levels of acetic acid, propionic acid, butyric acid, isobutyric acid and caproic acid in the IgAN patients were significantly reduced compared with control group(P<0.05). Butyric acid(r=-0.336, P=0.010) and isobutyric acid(r=-0.298, P=0.022) were negatively correlated with urea acid; butyric acid(r=-0.316, P=0.016) was negatively correlated with urea nitrogen; caproic acid(r=-0.415,P=0.025) showed negative correlation with 24-h urine protein level.Exemplified by the results of α-diversity and β-diversity, the intestinal flora of IgAN patients was significantly different from that of the control group. Acetic acid was positively associated with c_Clostridia(r=0.357, P=0.008), o_Clostridiales(r=0.357, P=0.008) and g_Eubacterium_coprostanoligenes_group(r=0.283, P=0.036). Butyric acid was positively associated with g_Alistipes (r=0.278, P=0.040). The relative abundance of those were significantly decreased in IgAN group compared to control group.Conclusion: The levels of fecal SCFAs in the IgAN patients were reduced, and correlated with clinical parameters and gut microbiota, which may be involved in the pathogenesis of IgAN, and this finding may provide a new therapeutic approach.
Evaluation of two Plasmodium vivax sexual-stage antigens as transmission-blocking vaccine candidates
Authors: Zhang Yongzhe , Liu Fei , Zhao Yan , Yang Fan , Bai Jie , Jia Xitong , Roobsoong Wanlapa , Sattabongkot Jetsumon , Cui Liwang , Cao Yaming , Luo Enjie , Wang Meilian 
Published: April 2021

Abstract
Background: Plasmodium vivax transmission-blocking vaccines (TBVs) have received high attention. PVX_098655 (PvPH) and PVX_101120 (PvSOP26) were predicted to be potential TBV antigens based on the studies of their orthologs in Plasmodium berghei. Methods: Fragments of PvPH (amino acids 22–304) and PvSOP26 (amino acids 30–272) were expressed in the yeast expression system. The recombinant proteins were used to immunize mice to obtain the antisera. The transmission-reducing activities of these antisera were evaluated using the standard membrane feeding assay (SMFA) using Anopheles dirus mosquitoes and P. vivax clinical isolates. Results: The recombinant proteins PvPH and PvSOP26 induced robust antibody responses in mice. With SMFA, the anti-PvSOP26 sera significantly reduced oocyst densities by 92.0% and 84.1% in two parasite isolates, while the anti-PvPH sera did not show evident transmission-reducing activity. Both PvPH and PvSOP26 showed limited gene polymorphisms in the clinical P. vivax isolates. Conclusion: PvSOP26 could be a promising TBV candidate for P. vivax.