bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Policy, COVID-19 and Impoverished Migrants: Challenges and Prospects in Locked Down India
Authors: Sengupta Sohini , Jha Manish K.
Published: June 2020

As countries shore up existing safeguards to address the social and economic impacts of the COVID-19 pandemic, India faces a humanitarian disaster of unprecedented proportions. Ninety per cent of the Indian workforce is employed in the unorganised sector; uncounted millions work in urban areas at great distances from rural homes. When the Government of India (GOI) announced the sudden ‘lockdown’ in March to contain the spread of the pandemic, migrant informal workers were mired in a survival crisis, through income loss, hunger, destitution and persecution from authorities policing containment and fearful communities maintaining ‘social distance’. In this context, the article analyses how poverty, informality and inequality are accentuated by the COVID-19 pandemic experiences of ‘locked down’ migrant workers. The article examines the nature and scope of existing social policy, designed under changing political regimes and a fluctuating economic climate, to protect this vulnerable group and mitigate dislocation, discrimination and destitution at this moment and in future.
The 14-3-3ζ–c-Src–integrin-β3 complex is vital for platelet activation
Authors: Shen Chuanbin , Liu Ming , Xu Runjia , Wang Gan , Li June , Chen Pingguo , Ma Wenjing , Mwangi James , Lu Qiumin , Duan Zilei , Zhang Zhiye , Dahmani Fatima Zohra , Mackeigan Daniel Thomas , Ni Heyu , Lai Ren
Published: June 2020

Several adaptor molecules bind to cytoplasmic tails of β-integrins and facilitate bidirectional signaling, which is critical in thrombosis and hemostasis. Interfering with integrin-adaptor interactions spatially or temporally to inhibit thrombosis without affecting hemostasis is an attractive strategy for the development of safe antithrombotic drugs. We show for the first time that the 14-3-3ζ–c-Src–integrin-β3 complex is formed during platelet activation. 14-3-3ζ–c-Src interaction is mediated by the -PIRLGLALNFSVFYYE- fragment (PE16) on the 14-3-3ζ and SH2-domain on c-Src, whereas the 14-3-3ζ–integrin-β3 interaction is mediated by the -ESKVFYLKMKGDYYRYL- fragment (EL17) on the 14-3-3ζ and -KEATSTF- fragment (KF7) on the β3-integrin cytoplasmic tail. The EL17-motif inhibitor, or KF7 peptide, interferes with the formation of the 14-3-3ζ–c-Src–integrin-β3 complex and selectively inhibits β3 outside-in signaling without affecting the integrin-fibrinogen interaction, which suppresses thrombosis without causing significant bleeding. This study characterized a previously unidentified 14-3-3ζ–c-Src–integrin-β3 complex in platelets and provided a novel strategy for the development of safe and effective antithrombotic treatments.
Lysine-specific demethylase 1A restricts ex vivo propagation of human HSCs and is a target of UM171
Authors: Subramaniam Agatheeswaran , Žemaitis Kristijonas , Talkhoncheh Mehrnaz Safaee , Yudovich David , Bäckström Alexandra , Debnath Shubhranshu , Chen Jun , Jain Mayur Vilas , Galeev Roman , Gaetani Massimiliano , Zubarev Roman A. , Larsson Jonas
Published: June 2020

Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. Here, we report that inhibition of the epigenetic regulator lysine-specific histone demethylase 1A (LSD1) induces a rapid expansion of human cord blood–derived CD34+ cells and promotes in vitro propagation of long-term repopulating HSCs by preventing differentiation. The phenotype and molecular characteristics of cells treated with LSD1 inhibitors were highly similar to cells treated with UM171, an agent promoting expansion of HSCs through undefined mechanisms and currently being tested in clinical trials. Strikingly, we found that LSD1, as well as other members of the LSD1-containing chromatin remodeling complex CoREST, is rapidly polyubiquitinated and degraded upon UM171 treatment. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 depletion of the CoREST core member, RCOR1, resulted in expansion of CD34+ cells similar to LSD1 inhibition and UM171. Taken together, LSD1 and CoREST restrict HSC expansion and are principal targets of UM171, forming a mechanistic basis for the HSC-promoting activity of UM171.
Body mass index, waist circumference, and risk of hearing loss: a meta-analysis and systematic review of observational study
Authors: Yang Jin-Rong , Hidayat Khemayanto , Chen Cai-Long , Li Yun-Hong , Xu Jia-Ying , Qin Li-Qiang
Published: June 2020

Background

Emerging evidence implicates excess weight as a potential risk factor for hearing loss. However, this association remained inconclusive. Therefore, we aimed to systematically and quantitatively review the published observational study on the association between body mass index (BMI) or waist circumference (WC) and hearing loss.

Methods

The odds ratios (ORs) or relative risks (RRs) with their 95% confidence intervals (CIs) were pooled under a random-effects model. Fourteen observational studies were eligible for the inclusion in the final analysis.

Results

In the meta-analysis of cross-sectional studies, the ORs for prevalent hearing loss were 1.10 (95% CI 0.88, 1.38) underweight, 1.14 (95% CI 0.99, 1.32) for overweight, OR 1.40 (95% CI 1.14, 1.72) for obesity, 1.14 (95% CI 1.04, 1.24) for each 5 kg/m2 increase in BMI, and 1.22 (95% CO 0.88. 1.68) for higher WC. In the meta-analysis of longitudinal studies, the RRs were 0.96 (95% CI 0.52, 1.79) for underweight, 1.15 (95% CI 1.04, 1.27) for overweight, 1.38 (95% CI 1.07, 1.79) for obesity, 1.15 (95% CI 1.01, 1.30) for each 5 kg/m2 increase in BMI, and 1.11 (95% CI 1.01, 1.22) for higher WC.

Conclusions

In summary, our findings add weight to the evidence that elevated BMI and higher WC may be positively associated with the risk of hearing loss.
Chi-miR-30b-5p inhibits dermal papilla cells proliferation by targeting CaMKIIδ gene in cashmere goat
Authors: Zhang Yuelang , Xia Sizhe , Wang Tianci , Wang Shanhe , Yuan Dan , Li Fang , Wang Xin
Published: June 2020

Background

During goat embryonic morphogenesis and postnatal initiation of hair follicle (HF) regeneration, dermal papilla (DP) cells play a vital role in hair formation. Growing evidence shows that microRNAs (miRNAs) participate in HF development and DP cell proliferation. However, the molecular mechanisms have not been thoroughly investigated.

Result

In this study, we utilized miRNA sequencing (miRNA-Seq) to identify differentially expressed miRNAs at different HF cycling stages (anagen and telogen). MiRNA-Seq has identified 411 annotated miRNAs and 130 novel miRNAs in which 29 miRNAs were up-regulated and 32 miRNAs were down-regulated in the anagen phase compared to the telogen phase. Target gene prediction and functional enrichment analysis indicated some major biological pathways related to hair cycling, such as Wnt signaling pathways, ECM-receptor interaction, VEGF signaling pathway, biosynthesis of amino acids, metabolic pathways, ribosome and oxidative phosphorylation. Also, we explored the function of chi-miR-30b-5p in regulating hair growth cycle. Similar to the HF cycling, DP cells were isolated from skin and used to investigate miRNA functions. The MTT and EdU assays showed that the viability and proliferation of DP cells were inhibited or promoted after the transfection of chi-miR-30b-5p mimic or inhibitor, respectively. Bioinformatics analysis revealed CaMKIIδ as a candidate target gene of chi-miR-30b-5p, and the dual-luciferase and western blot assay demonstrated that chi-miR-30b-5p bound to the 3’UTR of CaMKIIδ and further inhibited its translation.

Conclusion

Chi-miR-30b-5p was found to be highly expressed in the telogen than that in the anagen phase and could inhibit the proliferation of DP cells by targeting CaMKIIδ. Our study provides new information on the regulatory functions of miRNAs during HF development.
Genetic dissection of an allotetraploid interspecific CSSLs guides interspecific genetics and breeding in cotton
Authors: Zhu De , Li Ximei , Wang Zhiwei , You Chunyuan , Nie Xinhui , Sun Jie , Zhang Xianlong , Zhang Dawei , Lin Zhongxu
Published: June 2020

Background

The low genetic diversity of Upland cotton limits the potential for genetic improvement. Making full use of the genetic resources of Sea-island cotton will facilitate genetic improvement of widely cultivated Upland cotton varieties. The chromosome segments substitution lines (CSSLs) provide an ideal strategy for mapping quantitative trait loci (QTL) in interspecific hybridization.

Results

In this study, a CSSL population was developed by PCR-based markers assisted selection (MAS), derived from the crossing and backcrossing of Gossypium hirsutum (Gh) and G. barbadense (Gb), firstly. Then, by whole genome re-sequencing, 11,653,661 high-quality single nucleotide polymorphisms (SNPs) were identified which ultimately constructed 1211 recombination chromosome introgression segments from Gb. The sequencing-based physical map provided more accurate introgressions than the PCR-based markers. By exploiting CSSLs with mutant morphological traits, the genes responding for leaf shape and fuzz-less mutation in the Gb were identified. Based on a high-resolution recombination bin map to uncover genetic loci determining the phenotypic variance between Gh and Gb, 64 QTLs were identified for 14 agronomic traits with an interval length of 158 kb to 27 Mb. Surprisingly, multiple alleles of Gb showed extremely high value in enhancing cottonseed oil content (SOC).

Conclusions

This study provides guidance for studying interspecific inheritance, especially breeding researchers, for future studies using the traditional PCR-based molecular markers and high-throughput re-sequencing technology in the study of CSSLs. Available resources include candidate position for controlling cotton quality and quantitative traits, and excellent breeding materials. Collectively, our results provide insights into the genetic effects of Gb alleles on the Gh, and provide guidance for the utilization of Gb alleles in interspecific breeding.
Mining ancient microbiomes using selective enrichment of damaged DNA molecules
Authors: Weiß Clemens L. , Gansauge Marie-Theres , Aximu-Petri Ayinuer , Meyer Matthias , Burbano Hernán A.
Published: June 2020

Background

The identification of bona fide microbial taxa in microbiomes derived from ancient and historical samples is complicated by the unavoidable mixture between DNA from ante- and post-mortem microbial colonizers. One possibility to distinguish between these sources of microbial DNA is querying for the presence of age-associated degradation patterns typical of ancient DNA (aDNA). The presence of uracils, resulting from cytosine deamination, has been detected ubiquitously in aDNA retrieved from diverse sources, and used as an authentication criterion. Here, we employ a library preparation method that separates molecules that carry uracils from those that do not for a set of samples that includes Neandertal remains, herbarium specimens and archaeological plant remains.

Results

We show that sequencing DNA libraries enriched in molecules carrying uracils effectively amplifies age associated degradation patterns in microbial mixtures of ancient and historical origin. This facilitates the discovery of authentic ancient microbial taxa in cases where degradation patterns are difficult to detect due to large sequence divergence in microbial mixtures. Additionally, the relative enrichment of taxa in the uracil enriched fraction can help to identify bona fide ancient microbial taxa that could be missed using a more targeted approach.

Conclusions

Our experiments show, that in addition to its use in enriching authentic endogenous DNA of organisms of interest, the selective enrichment of damaged DNA molecules can be a valuable tool in the discovery of ancient microbial taxa.
Interspecific analysis of diurnal gene regulation in panicoid grasses identifies known and novel regulatory motifs
Authors: Lai Xianjun , Bendix Claire , Yan Lang , Zhang Yang , Schnable James C. , Harmon Frank G.
Published: June 2020

Background

The circadian clock drives endogenous 24-h rhythms that allow organisms to adapt and prepare for predictable and repeated changes in their environment throughout the day-night (diurnal) cycle. Many components of the circadian clock in Arabidopsis thaliana have been functionally characterized, but comparatively little is known about circadian clocks in grass species including major crops like maize and sorghum.

Results

Comparative research based on protein homology and diurnal gene expression patterns suggests the function of some predicted clock components in grasses is conserved with their Arabidopsis counterparts, while others have diverged in function. Our analysis of diurnal gene expression in three panicoid grasses sorghum, maize, and foxtail millet revealed conserved and divergent evolution of expression for core circadian clock genes and for the overall transcriptome. We find that several classes of core circadian clock genes in these grasses differ in copy number compared to Arabidopsis, but mostly exhibit conservation of both protein sequence and diurnal expression pattern with the notable exception of maize paralogous genes. We predict conserved cis-regulatory motifs shared between maize, sorghum, and foxtail millet through identification of diurnal co-expression clusters for a subset of 27,196 orthologous syntenic genes. In this analysis, a Cochran–Mantel–Haenszel based method to control for background variation identified significant enrichment for both expected and novel 6–8 nucleotide motifs in the promoter regions of genes with shared diurnal regulation predicted to function in common physiological activities.

Conclusions

This study illustrates the divergence and conservation of circadian clocks and diurnal regulatory networks across syntenic orthologous genes in panacoid grass species. Further, conserved local regulatory sequences contribute to the architecture of these diurnal regulatory networks that produce conserved patterns of diurnal gene expression.
Genomic nucleotide-based distance analysis for delimiting old world monkey derived herpes simplex virus species
Authors: Kolb Aaron W. , Brandt Curtis R.
Published: June 2020

Background

Herpes simplex viruses form a genus within the alphaherpesvirus subfamily, with three identified viral species isolated from Old World monkeys (OWM);Macacine alphaherpesvirus 1(McHV-1; herpes B),Cercopithecine alphaherpesvirus 2(SA8), andPapiine alphaherpesvirus 2(PaHV-2; herpes papio). Herpes B is endemic to macaques, while PaHV-2 and SA8 appear endemic to baboons. All three viruses are genetically and antigenically similar, with SA8 and PaHV-2 thought to be avirulent in humans, while herpes B is a biosafety level 4 pathogen. Recently, next-generation sequencing (NGS) has resulted in an increased number of published OWM herpes simplex genomes, allowing an encompassing phylogenetic analysis.

Results

In this study, phylogenetic networks, in conjunction with a genome-based genetic distance cutoff method were used to examine 27 OWM monkey herpes simplex isolates. Genome-based genetic distances were calculated, resulting in distances between lion and pig-tailed simplex viruses themselves, and versus herpes B core strains that were higher than those between PaHV-2 and SA8 (approximately 14 and 10% respectively). The species distance cutoff was determined to be 8.94%, with the method recovering separate species status for PaHV-2 and SA8 and showed that lion and pig-tailed simplex viruses (vs core herpes B strains) were well over the distance species cutoff.

Conclusions

We propose designating lion and pig-tailed simplex viruses as separate, individual viral species, and that this may be the first identification of viral cryptic species.
Diverse and unique viruses discovered in the surface water of the East China Sea
Authors: Wu Shuang , Zhou Liang , Zhou Yifan , Wang Hongming , Xiao Jinzhou , Yan Shuling , Wang Yongjie
Published: June 2020

Background

Viruses are the most abundant biological entities on earth and play import roles in marine biogeochemical cycles. Here, viral communities in the surface water of the East China Sea (ECS) were collected from three representative regions of Yangshan Harbor (YSH), Gouqi Island (GQI), and the Yangtze River Estuary (YRE) and explored primarily through epifluorescence microscopy (EM), transmission electron microscopy (TEM), and metagenomics analysis.

Results

The virus-like particles (VLPs) in the surface water of the ECS were measured to be 106 to 107 VLPs/ml. Most of the isolated viral particles possessed a head-and-tail structure, but VLPs with unique morphotypes that had never before been observed in the realm of viruses were also found. The sequences related to known viruses in GenBank accounted for 21.1–22.8% of the viromic datasets from YSH, GQI, and YRE. In total, 1029 viral species were identified in the surface waters of the ECS. Among them, tailed phages turn out to make up the majority of viral communities, however a small number of Phycodnaviridae or Mimiviridae related sequences were also detected. The diversity of viruses did not appear to be a big difference among these three aquatic environments but their relative abundance was geographically variable. For example, the Pelagibacter phage HTVC010P accounted for 50.4% of the identified viral species in GQI, but only 9.1% in YSH and 11.7% in YRE. Sequences, almost identical to those of uncultured marine thaumarchaeal dsDNA viruses and magroviruses that infect Marine Group II Euryarchaeota, were confidently detected in the ECS viromes. The predominant classes of virome ORFs with functional annotations that were found were those involved in viral biogenesis. Virus-host connections, inferred from CRISPR spacer-protospacer mapping, implied newly discovered infection relationships in response to arms race between them.

Conclusions

Together, both identified viruses and unknown viral assemblages observed in this study were indicative of the complex viral community composition found in the ECS. This finding fills a major gap in the dark world of oceanic viruses of China and additionally contributes to the better understanding of global marine viral diversity, composition, and distribution.
Concurrent amplification of Zika, chikungunya, and yellow fever virus in a sylvatic focus of arboviruses in Southeastern Senegal, 2015
Authors: Diallo Diawo , Fall Gamou , Diagne Cheikh Tidiane , Gaye Alioune , Ba Yamar , Dia Ibrahima , Faye Ousmane , Diallo Mawlouth
Published: June 2020

Background

Chikungunya (CHIKV), yellow fever (YFV) and Zika (ZIKV) viruses circulate in sylvatic transmission cycles in southeastern Senegal, where they share common hosts and vectors. All three viruses undergo periodicamplifications, during which they are detected in mosquitoes and sometimes in hosts. However, little is known about their spatio-temporal patterns in years in which they undergo concurrent amplification. The aim of this study was to describe the co-amplification of ZIKV, CHIKV, and YFV, and the daily dynamics of these arboviruses and theirs vectors within villages in southeastern Senegal.

Results

Mosquitoes were collected monthly from July to December 2015. Each evening, from 6 to 9 PM, landing collections were performed by teams of 3 persons working simultaneously in 70 sites situated in forest (canopy and ground), savannah, agriculture, barren, and village (indoor and outdoor) land covers. Collections within villages were continued until 6 AM. Mosquitoes were tested for virus infection by virus isolation and RT-PCR. Seventy-five mosquito pools comprising 10 mosquito species contained at least one virus.Ae. furciferandAe. luteocephaluswere infected by all three viruses,Ae. tayloriby YFV and ZIKV, and remaining seven species by only, only YFV or only ZIKV. No single mosquito pool contained more than one virus. CHIKV was the only virus detected in all land cover classes and was found in the greatest number of sampling sites (32.9%,n = 70). The proportion of sites in which more than one virus was detected was less than 6%.Ae. aegypti formosus,Ae. furcifer,Ae. luteocephalus,Ae. minutus,Ae. vittatus, andAn. gambiaewere found within villages. These vectors were mainly active around dusk butAe. furciferwas collected until dawn. All viruses save ZIKV were detected indoors and outdoors, mainly around dusk. Virus positive pools were detected over 2, 3 and 4 months for YFV, CHIKV and ZIKV, respectively.

Conclusion

Our data indicate that the distribution of different vector species and different arboviruses vary substantially between sites, suggesting that CHIKV, YFV, and ZIKV may have different transmission cycles in Southeastern Senegal.
Two Nucleoporin98 homologous genes jointly participate in the regulation of starch degradation to repress senescence in Arabidopsis
Authors: Xiao Long , Jiang Shanshan , Huang Penghui , Chen Fulu , Wang Xu , Cheng Zhiyuan , Miao Yuchen , Liu Liangyu , Searle Iain , Liu Chunyan , Wu Xiao-Xia , Fu Yong-Fu , Chen Qingshan , Zhang Xiao-Mei
Published: June 2020

Background

Starch is synthesized during daylight for temporary storage in leaves and then degraded during the subsequent night to support plant growth and development. Impairment of starch degradation leads to stunted growth, even senescence and death. The nuclear pore complex is involved in many cellular processes, but its relationship with starch degradation has been unclear until now. We previously identified that two Nucleoporin98 genes (Nup98a and Nup98b) redundantly regulate flowering via the CONSTANS (CO)-independent pathway in Arabidopsis thaliana. The double mutant also shows severe senescence phenotypes.

Results

We find that Nucleoporin 98 participates in the regulation of sugar metabolism in leaves and is also involved in senescence regulation in Arabidopsis. We show that Nup98a and Nup98b function redundantly at different stages of starch degradation. The nup98a-1 nup98b-1 double mutant accumulates more starch, showing a severe early senescence phenotype compared to wild type plants. The expression of marker genes related to starch degradation is impaired in the nup98a-1 nup98b-1 double mutant, and marker genes of carbon starvation and senescence express their products earlier and in higher abundance than in wild type plants, suggesting that abnormalities in energy metabolism are the main cause of senescence in the double mutant. Addition of sucrose to the growth medium rescues early senescence phenotypes of the nup98a-1 nup98b-1 mutant.

Conclusions

Our results provide evidence for a novel role of the nuclear pore complex in energy metabolism related to growth and development, in which Nup98 functions in starch degradation to control growth regulation in Arabidopsis.
Efficacy and safety outcomes in novel oral anticoagulants versus vitamin-K antagonist on post-TAVI patients: a meta-analysis
Authors: Liang Hongbin , He Qiyu , Zhang Qiuxia , Liu Xuewei , Cui Kai , Chen Guojun , Xiu Jiancheng
Published: June 2020

Background

Transcatheter aortic valve implantation (TAVI) has been a favored option for the patient who suffered from symptomatic aortic stenosis. However, the efficacy and safety outcomes in novel oral anticoagulants (NOACs) versus Vitamin-K antagonist (VKA) for post-TAVI patients are still controversial. This meta-analysis aims at comparing the clinical outcome and safety of NOACs and VKA in the patients after receiving TAVI.

Method

We searched literature articles in all reachable databases, and observational study as well as randomized controlled trial would be included in order to perform a comprehensive analysis. All-cause mortality, major or life-threatening bleeding, disabling or nondisabling stroke were main pooled outcome measures. Subgroup analysis and meta-regression were adopted to explore heterogeneity. Assessment of bias was performed under the suggestion of Cochrane’s Collaboration Tool.

Results

We collected 3841 non-duplicate citations from PubMed, Embase, Cochrane and ClinicalTrials.gov, and eventually 7 studies were included for this meta-analysis. As a result, VKA showed priority against NOACs in the field of anti-thromboembolism (4435 participants, RR:1.44, 95% CI: 1.05 to 1.99, I2 = 0%,P = 0.02).

Conclusion

With corroborative analysis of severe complications, VKA is shown to be more protective on post-TAVI patients in disabling or nondisabling stroke scenario but not in mortality or bleeding event.
Efficacy and safety of intracoronary prourokinase during percutaneous coronary intervention in treating ST-segment elevation myocardial infarction patients: a randomized, controlled study
Authors: Wu Yanqiang , Fu Xianghua , Feng Qiang , Gu Xinshun , Hao Guozhen , Fan Weize , Jiang Yunfa
Published: June 2020

Background

Prourokinase is a single-chain plasminogen activator presenting with fewer hemorrhagic complications and reduced reocclusion rate compared with the conventional fibrinolytic agents in patients with coronary artery disease. However, prourokinase intracoronary injection during PCI for treating patients with ST-segment elevation myocardial infarction (STEMI) is rarely investigated. Therefore, this study aimed to evaluate the efficacy and safety of intracoronary prourokinase during the percutaneous coronary intervention (PCI) in treating STEMI patients.

Methods

Fifty STEMI patients who underwent primary PCI were consecutively enrolled and randomly assigned to intracoronary prourokinase group (N = 25) or control group (N = 25). During the primary PCI procedure, patients in the intracoronary prourokinase group received 10 ml prourokinase injection, while patients in control group received 10 ml saline injection as control. The primary endpoints were coronary physiological indexes, the secondary endpoints were angiographic assessments, myocardial infarct size/reperfusion assessment, cardiac function evaluations, major adverse coronary events (MACEs) and hemorrhagic complications. All patients were followed up for 3 months.

Results

Post PCI, the index of microcirculatory resistance (IMR) was decreased in intracoronary prourokinase group than that in control group (34.56 ± 7.48 vs. 49.00 ± 8.98, P < 0.001), while no difference of coronary flow reserve (CFR) (2.01 ± 0.32 vs. 1.88 ± 0.23, P = 0.267) or fractional flow reserve (FFR) (0.89 ± 0.05 vs. 0.87 ± 0.04, P = 0.121) was found between the two groups. The thrombolysis in myocardial infarction myocardial perfusion grade (TMPG) (P = 0.024), peak values of creatine kinase (CK) (P = 0.028), CK isoenzyme-MB (CK-MB) (P = 0.016), cardiac troponin I (cTnI) (P = 0.032) and complete ST-segment resolution (STR) (P = 0.005) were better in intracoronary prourokinase group compared with control group. At 3-months post PCI, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were higher, while left ventricular end-diastolic diameter (LVEDd) was lower in intracoronary prourokinase group compared with control group (all P < 0.05). There was no difference in hemorrhagic complication or total MACE between the two groups.

Conclusion

Intracoronary prourokinase during PCI is more efficient and equally tolerant compared with PCI alone in treating STEMI patients.

Trial registration

Chinese Clinical Trial Registry ChiCTR1800016207. Prospectively registered.
Effects of gastric sleeve surgery on the serum levels of GH, IGF-1 and IGF-binding protein 2 in healthy obese patients
Authors: Al-Regaiey Khalid , Alshubrami Suad , Al-Beeshi Ibrahim , Alnasser Torki , Alwabel Abdulnasser , Al-Beladi Hassan , Al-Tujjar Omar , Alnasser Abdulrahman , Alfadda Assim A. , Iqbal Muhammad
Published: June 2020

Background

Bariatric surgery is an effective treatment for severe obesity. It also ameliorates diabetes independently of weight loss through mechanisms that are not fully understood. In this study, we investigated the levels of GH, IGF-1 and IGF-binding protein 2 (IGFBP-2) after gastric sleeve surgery in healthy obese individuals.

Method

This study was conducted in 33 obese (BMI > 38.3) healthy male subjects aged 25 to 50 years undergoing sleeve gastrectomy. GH, IGF-1 and IGFBP-2 levels were evaluated by ELISA at baseline and 6–12 months after surgery. Other parameters, such as glucose, BMI, insulin, HOMA-IR and lipid profile, were also investigated.

Results

Systemic GH (12.32 vs. 50.97 pg/mL, p < 0.001) and IGFBP-2 levels (51.86 vs. 68.81 pg/mL, p < 0.001) were elevated after bariatric surgery. There was no change in IGF-1 level from before to after surgery. BMI (52.18 vs. 40.11, p = 0.001), insulin (19.35 vs. 8.80 mIU/L, p < 0.001) and HOMA-IR index (6.48 to 2.52, p < 0.001) were reduced after surgery. Lipid profile analysis revealed that total cholesterol (4.26 vs. 5.12 mmol/L, p < 0.001) and high-density lipoprotein (HDL) (0.90 to 1.55 mmol/L, p < 0.001) were increased, while triglycerides were decreased, after surgery (1.62 vs. 1.05 mmol/L p < 0.001). GH, IGF-1, and IGFBP-2 were not correlated with insulin or lipid parameters.

Conclusions

Our study suggests that improved circulating GH and IGFBP-2 levels may mediate the beneficial effects of gastric sleeve surgery in improving insulin sensitivity and reducing insulin demand.
Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas harboring KRAS and BRCA mutations: case report and whole exome sequencing analysis
Authors: Yang Guangjian , Yin Jiangxia , Ou Kai , Du Qiang , Ren Wenhao , Jin Yujing , Peng Liming , Yang Lin
Published: June 2020

Background

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is an extremely uncommon pancreatic neoplasm that comprises less than 1% of all exocrine pancreatic tumors. To date, cases and data from whole-exome sequencing (WES) analysis have been reported by specific studies. We report a case of pancreatic UC-OGC with a literature review, and provide novel insights into the molecular characteristics of this tumor entity.

Case presentation

A 31-year-old male presented with intermittent abdominal pain for several months, and positron emission tomography (PET) showed isolated high metabolic nodules during the pancreatic uncinate process that were likely to be malignant disease. Pathological examination after radical excision revealed UC-OGC associated with poorly differentiated adenocarcinoma at the head of the pancreas. The disease recurred 7.4 months after radical surgery. The KRAS p.G12D (c.35G > A) and somatic BRCA2 p.R2896C (c.8686C > T) mutations were detected by subsequent WES analysis. The patient showed no response to platinum-based systemic chemotherapy, and his condition quickly worsened. He finally died, with an overall survival of 1 year.

Conclusions

As an extremely uncommon tumor entity, UC-OGC is really a unique variant of conventional pancreatic ductal adenocarcinoma due to its similarities, as shown by genomic WES analysis. Clinical examination and molecular analysis by WES could further indicate potential treatment strategies for UC-OGC.
Factors associated with health-related quality of life and burden on relatives of older people with multi-morbidity: a dyadic data study
Authors: Krevers Barbro , Ekdahl Anne , Jaarsma Tiny , Eckerblad Jeanette , Milberg Anna
Published: June 2020

Background

This study aimed to identify factors associated with health-related quality of life (HRQoL) and the burden on the relatives of older people with multi-morbidity.

Methods

A secondary analysis of baseline data from 296 dyads, including older patients with multimorbidity and their relatives, which were previously collected in a randomized study.

The analysis was conducted to select correlated independent variables to enter a final linear regression analysis of two models with different endpoints: the relatives’ HRQoL (EQ5D index) and burden (COPE index: Negative impact scale).

Results

Sixteen variables correlated with the relatives’ HRQoL, and 15 with the relatives’ burden. Both the HRQoL and burden correlated with both patient and relative variables. A high HRQoL was associated with relatives’ working/studying. A high burden was associated with caring for an older person with changed behaviour. A low burden was associated with the relatives’ high scores on positive values of caring, quality of support and HRQoL.

Conclusion

Older persons and their relatives should be considered as a unit in the development of support of older people in order to increase the health and quality of life of both groups. To support and protect relatives from a high burden, potential measures could include improving the relative’s HRQoL and strengthening their ability to find positive values in care and strengthening reliable and good support from others. The relatives’ HRQoL explained the variation in the burden. However, the burden did not explain the variation in the HRQoL, which suggests that the relatives’ HRQoL is not so readily affected by their burden, whereas the relatives’ HRQoL can influence their burden. The variables used in the regression analyses where chosen to reflect important aspects of the relatives’ and older persons’ situations. The final models explained 38% of the variation in the relatives’ burden but only 10% of the variation in their HRQoL. This could be important to consider when choosing outcome assessments in future studies.
A mixed-methods investigation of women’s experiences seeking pregnancy-related online nutrition information
Authors: Snyder Alexandra , Neufeld Hannah Tait , Forbes Laura
Published: June 2020

Background

The objective of this study was to describe women’s processes for finding pregnancy-related nutrition information, their experiences seeking this information online and their ideas for improving internet sources of this information.

Methods

In total, 97 pregnant women completed an online quantitative questionnaire and 10 primiparous pregnant women completed semi-structured telephone interviews. Questionnaires and interviews asked participants to describe sources of pregnancy-related nutrition information; time of seeking; processes of searching online; experiences searching online; ideas for improving information found online. Survey data were analyzed using descriptive statistics and Chi square tests; interview data were analyzed using thematic analysis.

Results

Nearly all (96%) survey participants sought nutrition information online. Information was most commonly sought during the first trimester of pregnancy. Motivators for using the internet included convenience and lack of support from health care providers. Barriers to using online information included lack of trust, difficulty finding information and worry. Women adapted the information they found online to meet their needs and reported making positive changes to their diets.

Conclusions

The internet is a key source of prenatal nutrition information that women report using to make positive dietary changes. Women would benefit from improved access to trustworthy internet sources, increased availability of information on different diets and health conditions, and increased support from health care providers.
Diagnostic accuracy of maternal serum multiple marker screening for early detection of gestational diabetes mellitus in the absence of a gold standard test
Authors: Amini Maedeh , Kazemnejad Anoshirvan , Zayeri Farid , Montazeri Ali , Rasekhi Aliakbar , Amirian Azam , Kariman Nourossadat
Published: June 2020

Background

Gestational diabetes mellitus (GDM) is associated with adverse diabetic complications for both mother and child during pregnancy. The common Gold Standard (GS) for diagnosis of GDM is 75 g oral glucose tolerance test (OGTT) during 24–28 gestational weeks which seems a little late for any proper intervention. This study aimed to employ the Bayesian latent class models (LCMs) for estimating the early diagnostic power of combination of serum multiple marker in detecting GDM during 14–17 weeks of gestation.

Methods

Data from a sample of 523 pregnant women who participated in gestational diabetes screening tests at health centers affiliated to Shahid Beheshti University of Medical Sciences in Tehran, Iran from 2017 to 2018 were used. The beta-human chorionic gonadotropin (β-hCG), unconjugated estriol (uE3), and alfa-fetoprotein (AFP) values were extracted from case records for all participants. The Bayesian LCMs were applied for estimating sensitivity, specificity, and area under receiver operating characteristic curve (AUC) of combining the three biomarkers’ results in the absence of GS, adjusting for maternal age and body mass index.

Results

The mean (standard deviation) maternal age of the participants was 28.76 (±5.33) years. Additionally, the mean (standard deviation) BMI was 24.57 (±3.22) kg/m2. According to the Bayesian model, the cSensitivity, cSpecificity, and cAUC for the optimal composite diagnostic test were estimated as 94% (95% credible interval (CrI) [0.91–0.99]), 86% (95% CrI [0.80–0.92]), and 0.92 (95% CrI [0.87–0.98]), respectively.

Conclusions

Overall, the findings revealed that the combination of uE3, AFP, and β-hCG results might be considered as an acceptable predictor for detecting GDM with a rather high level of accuracy in the early second trimester of pregnancy without a GS.
A protocol for developing, disseminating, and implementing a core outcome set (COS) for childbirth pelvic floor trauma research
Authors: Doumouchtsis Stergios K. , Rada Maria Patricia , Pergialiotis Vasilios , Falconi Gabriele , Haddad Jorge Milhem , Betschart Cornelia
Published: June 2020

Background

More than 85% of women sustain different degrees of trauma during vaginal birth. Randomized controlled trials on childbirth pelvic floor trauma have reported a wide range of outcomes and used different outcome measures. This variation restricts effective data synthesis, impairing the ability of research to inform clinical practice. The development and use of a core outcome set (COS) for childbirth pelvic floor trauma aims to ensure consistent use of outcome measures and reporting of outcomes.

Methods

An international steering group, within CHORUS, an International Collaboration for Harmonising Outcomes, Research and Standards in Urogynaecology and Women’s Health, including academic community members, researchers, healthcare professionals, policy makers and women with childbirth pelvic floor trauma will lead the development of this COS. Relevant outcome parameters will be identified through comprehensive literature reviews. The selected outcomes will be entered into an international, multi-perspective online Delphi survey. Subsequently and based on the results of the Delphi surveys consensus will be sought on ‘core’ outcomes.

Discussion

Dissemination and implementation of the resulting COS within an international context will be supported and promoted. Embedding the COS for childbirth pelvic floor trauma within future clinical trials, systematic reviews, and clinical practice guidelines is expected to enrich opportunities for comparison of future clinical trials and allow better synthesis of outcomes, and will enhance mother and child care. The infrastructure created by developing a COS for childbirth pelvic floor trauma could be leveraged in other settings, for example, advancing research priorities and clinical practice guideline development.
Nutritional status according to the mini nutritional assessment (MNA)® as potential prognostic factor for health and treatment outcomes in patients with cancer – a systematic review
Authors: Torbahn G. , Strauss T. , Sieber C. C. , Kiesswetter E. , Volkert D.
Published: June 2020

Background

Patients with cancer have an increased risk of malnutrition which is associated with poor outcome. The Mini Nutritional Assessment (MNA®) is often used in older patients with cancer but its relation to outcome is not known.

Methods

Four databases were systematically searched for studies relating MNA-results with any reported outcome. Two reviewers screened titles/abstracts and full-texts, extracted data and rated the risk of bias (RoB) independently.

Results

We included 56 studies which varied widely in patient and study characteristics. In multivariable analyses, (risk of) malnutrition assessed by MNA significantly predicts a higher chance for mortality/poor overall survival (22/27 studies), shorter progression-free survival/time to progression (3/5 studies), treatment maintenance (5/8 studies) and (health-related) quality of life (2/2 studies), but not treatment toxicity/complications (1/7 studies) or functional status/decline in (1/3 studies). For other outcomes – length of hospital stay (2 studies), falls, fatigue and unplanned (hospital) admissions (1 study each) – no adjusted results were reported. RoB was rated as moderate to high.

Conclusions

MNA®-result predicts mortality/survival, cancer progression, treatment maintenance and (health-related) quality of life and did not predict adverse treatment outcomes and functional status/ decline in patients with cancer. For other outcomes results are less clear. The moderate to high RoB calls for studies with better control of potential confounders.
Opening large-conductance potassium channels selectively induced cell death of triple-negative breast cancer
Authors: Sizemore Gina , McLaughlin Sarah , Newman Mackenzie , Brundage Kathleen , Ammer Amanda , Martin Karen , Pugacheva Elena , Coad James , Mattes Malcolm D. , Yu Han-Gang
Published: June 2020

Background

Unlike other breast cancer subtypes that may be treated with a variety of hormonal or targeted therapies, there is a need to identify new, effective targets for triple-negative breast cancer (TNBC). It has recently been recognized that membrane potential is depolarized in breast cancer cells. The primary objective of the study is to explore whether hyperpolarization induced by opening potassium channels may provide a new strategy for treatment of TNBC.

Methods

Breast cancer datasets in cBioPortal for cancer genomics was used to search for ion channel gene expression. Immunoblots and immunohistochemistry were used for protein expression in culture cells and in the patient tissues. Electrophysiological patch clamp techniques were used to study properties of BK channels in culture cells. Flow cytometry and fluorescence microscope were used for cell viability and cell cycle studies. Ultrasound imaging was used to study xenograft in female NSG mice.

Results

In large datasets of breast cancer patients, we identified a gene, KCNMA1 (encoding for a voltage- and calcium-dependent large-conductance potassium channel, called BK channel), overexpressed in triple-negative breast cancer patients. Although overexpressed, 99% of channels are closed in TNBC cells. Opening BK channels hyperpolarized membrane potential, which induced cell cycle arrest in G2 phase and apoptosis via caspase-3 activation. In a TNBC cell induced xenograft model, treatment with a BK channel opener significantly slowed tumor growth without cardiac toxicity.

Conclusions

Our results support the idea that hyperpolarization induced by opening BK channel in TNBC cells can become a new strategy for development of a targeted therapy in TNBC.
Prediction of lymph node metastasis by tumor-infiltrating lymphocytes in T1 breast cancer
Authors: Takada Koji , Kashiwagi Shinichiro , Asano Yuka , Goto Wataru , Kouhashi Rika , Yabumoto Akimichi , Morisaki Tamami , Shibutani Masatsune , Takashima Tsutomu , Fujita Hisakazu , Hirakawa Kosei , Ohira Masaichi
Published: June 2020

Background

Lymph node metastasis is more likely in early-stage breast cancer with lower tumor-infiltrating lymphocyte (TIL) density. Therefore, we investigated the correlation between TILs and lymph node metastasis in cT1 breast cancer patients undergoing surgery and the usefulness of TILs in predicting sentinel lymph node metastasis (SLNM) in cT1N0M0 breast cancer.

Methods

We investigated 332 breast cancer patients who underwent surgery as the first-line treatment after preoperative diagnosis of cT1. A positive diagnosis of SLNM as an indication for axillary clearance was defined as macrometastasis in the sentinel lymph node (SLN) (macrometastasis: tumor diameter > 2 mm). Semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in primary tumor biopsy specimens prior to treatment was conducted.

Results

For SLN biopsy (SLNB), a median of 2 (range, 1–8) SLNs were pathologically evaluated. Sixty cases (19.4%) of SLNM (macrometastasis: 46, micrometastasis: 16) were observed. Metastasis was significantly greater in breast cancers with tumor diameter > 10 mm than in those with diameter ≤ 10 mm (p = 0.016). Metastasis was significantly associated with lymphatic invasion (p < 0.001). These two clinicopathological factors correlated with SLNM even in patients diagnosed with cN0 (tumor size; p = 0.017, lymphatic invasion; p = 0.002). Multivariate analysis for SLNM predictors revealed lymphatic invasion (p = 0.008, odds ratio [OR] = 2.522) and TILs (p < 0.001, OR = 0.137) as independent factors.

Conclusions

Our results suggest a correlation between lymph node metastasis and tumor immune-microenvironment in cT1 breast cancer. TIL density may be a predictor of SLNM in breast cancer without lymph node metastasis on preoperative imaging.
Heimann-Bielschowsky phenomenon and hypotropic DVD in case of monocular vision loss: a case report
Authors: Choi Hyung Jun , Chun Bo Young
Published: June 2020

Background

The Heimann-Bielschowsky phenomenon (HBP) is an underrecognized condition characterized by slow, pendular, vertical oscillations of the eye accompanying monocular vision loss. Hypotropic dissociated vertical deviation (DVD) is another rare condition induced by asymmetric visual input. This report documents a rare case of HBP with hypotropic DVD.

Case presentation

This report describes a case of a 58-year-old woman with HBP and hypotropic DVD, having suffered monocular vision loss in the left eye due to blunt trauma at the age of 10. Preoperatively, she was orthophoric at near fixation and demonstrated an intermittent, slow hypotropia of the left eye upon distance fixation that never rose above the midline. She underwent a 7 mm recession of the inferior rectus muscle in the left eye. After surgery, intermittent, downward drifts became constant vertical oscillations at both distance and near fixation.

Conclusions

This case describes the clinical manifestation of an eye movement disorder related to prolonged monocular vision loss.