bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mingjing granule, a traditional Chinese medicine in the treatment of neovascular age-related macular degeneration: study protocol for a randomized controlled trial
Authors: Li Yamin , Liang Lina , Snellingen Torkel , Xu Kai , Gao Yun , Zhang Fengmei , Guo Chengwei , Zuo Tao , Liang Fengming , Yao Xiaoping , Yang Xueyan 
Published: January 2021

Abstract
Background
Neovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients.

Methods/design
This is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form.

Discussion
Based on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD.

Trial registration
Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000035990. Registered on 21 August 2020.
Phytochemical constituents and biological activities of Salvia macrosiphon Boiss.
Authors: Balaei-Kahnamoei Majid , Eftekhari Mahdieh , Ardekani Mohammad Reza Shams , Akbarzadeh Tahmineh , Saeedi Mina , Jamalifar Hossein , Safavi Maliheh , Sam Sohrab , Zhalehjoo Naghmeh , Khanavi Mahnaz 
Published: January 2021

AbstractSalvia macrosiphon Boiss. is an aromatic perennial herb belonging to the family Lamiaceae. Phytochemical studies and biological activities of this plant have been rarely documented in the literature. The current study aimed to investigate antibacterial and cytotoxic activity of different fractions of aerial parts of S. macrosiphon. Also, we tried to isolate and identify cytotoxic compounds from the plant. In this respect, the hydroalcoholic extract of the corresponding parts of the plant was fractionated into four fractions. Then, antibacterial and cytotoxic activity of each fraction were examined. It was found that the chloroform fraction had a good antibacterial activity against gram-positive and gram-negative bacteria. The most potent cytotoxicity was also obtained by the n-hexane fraction comparing with etoposide as the reference drug which was selected for the study and characterization of secondary metabolites. Accordingly, 13-epi manoyl oxide (1), 6α-hydroxy-13-epimanoyl oxide (2), 5-hydroxy-7,4'-dimethoxyflavone (3), and β-sitosterol (4) were isolated and evaluated for their cytotoxic activity. Among them, compound 1 revealed significant cytotoxicity against A549, MCF-7, and MDA-MB-231. It merits mentioning that it showed high selectivity index ratio regarding the low cytotoxic effects on Human Dermal Fibroblast which can be considered as a promising anticancer candidate.
Morphological identification of ticks and molecular detection of tick-borne pathogens from bare-nosed wombats (Vombatus ursinus)
Authors: Beard Danielle , Stannard Hayley J. , Old Julie M. 
Published: January 2021

Abstract
Background
Ticks are obligate haematophagous ectoparasites of vertebrate hosts and transmit the widest range of pathogenic organisms of any arthropod vector. Seven tick species are known to feed on bare-nosed wombats (Vombatus ursinus), in addition to the highly prevalent Sarcoptes scabiei mite which causes fatal sarcoptic mange in most bare-nosed wombat populations. Little is known about the pathogens carried by most wombat ticks or how they may impact wombats and wombat handlers.

Methods
Wombat ticks were sourced from wildlife hospitals and sanctuaries across Australia and identified to species level using taxonomic keys. Genomic DNA was extracted from a subsample, and following the amplification of the bacterial 16S rRNA gene V3–V4 hypervariable region, next-generation sequencing (NGS) on the Illumina MiSeq platform was used to assess the microbial composition.

Results
A total of 447 tick specimens were collected from 47 bare-nosed wombats between January 2019 and January 2020. Five species of ticks were identified comprising wombat tick Bothriocroton auruginans (n = 420), wallaby tick Haemaphysalis bancrofti (n = 8), bush tick Haemaphysalis longicornis (n = 3), common marsupial tick Ixodes tasmani (n = 12), and Australian paralysis tick Ixodes holocyclus (n = 4). Tick infestations ranged from one to 73 ticks per wombat. The wombat tick was the most prevalent tick species comprising 94% of the total number of samples and was present on 97.9% (46/47) of wombat hosts. NGS results revealed the 16S rRNA gene diversity profile was predominantly Proteobacteria (55.1%) followed by Firmicutes (21.9%) and Actinobacteria (18.4%). A species of Coxiella sharing closest sequence identity to Coxiella burnetii (99.07%), was detected in 72% of B. auruginans and a Rickettsiella endosymbiont dominated the bacterial profile for I. tasmani.

Conclusions
A new host record for H. longicornis is the bare-nosed wombat. One adult male and two engorged adult female specimens were found on an adult male wombat from Coolagolite in New South Wales, and more specimens should be collected to confirm this host record. The most prevalent tick found on bare-nosed wombats was B. auruginans, confirming previous records. Analysis of alpha-diversity showed high variability across both sample locations and instars, similar to previous studies. The detection of various Proteobacteria in this study highlights the high bacterial diversity in native Australian ticks.

Graphical Abstract
Dissection of the gut microbiota in mothers and children with chronic Trichuris trichiura infection in Pemba Island, Tanzania
Authors: Chen Hongliang , Mozzicafreddo Matteo , Pierella Elisa , Carletti Vanessa , Piersanti Angela , Ali Said M. , Ame Shaali M. , Wang Chunfeng , Miceli Cristina 
Published: January 2021

Abstract
Background
Soil-transmitted helminthiases are important neglected tropical diseases that result in a notably high number of disability-adjusted life years worldwide. Characterizing the interactions between the human intestinal microbiome and helminths is of interest in the development of alternative treatments that do not rely on chemotherapeutics and do not lead to drug resistance.

Methods
We recruited and obtained fecal samples from 32 pairs of mothers and children on Pemba Island and monitored their intestinal microbiota using 16S rRNA gene sequencing.

Results
We observed that microbial changes occur in the gut microbiota of infected mothers and children. Some short-chain fatty acid (SCFA)-producing bacteria and carbohydrate-degrading bacteria exhibited lower abundance in the infected individuals. Potentially pathogenic Campylobacter and proinflammatory Methanobrevibacter in infected mothers and opportunistic Enterococcus in infected children exhibited greater abundance.

Conclusions
Our findings could reveal the microbiota profiling in T. trichiura-infected individuals, indicate the potential roles of key microbiota in the host and aid to the development of novel strategies to control T. trichiura infection.

Graphical Abstract
Rbm10 facilitates heterochromatin assembly via the Clr6 HDAC complex
Authors: Weigt Martina , Gao Qingsong , Ban Hyoju , He Haijin , Mastrobuoni Guido , Kempa Stefan , Chen Wei , Li Fei 
Published: January 2021

AbstractSplicing factors have recently been shown to be involved in heterochromatin formation, but their role in controlling heterochromatin structure and function remains poorly understood. In this study, we identified a fission yeast homologue of human splicing factor RBM10, which has been linked to TARP syndrome. Overexpression of Rbm10 in fission yeast leads to strong global intron retention. Rbm10 also interacts with splicing factors in a pattern resembling that of human RBM10, suggesting that the function of Rbm10 as a splicing regulator is conserved. Surprisingly, our deep-sequencing data showed that deletion of Rbm10 caused only minor effect on genome-wide gene expression and splicing. However, the mutant displays severe heterochromatin defects. Further analyses indicated that the heterochromatin defects in the mutant did not result from mis-splicing of heterochromatin factors. Our proteomic data revealed that Rbm10 associates with the histone deacetylase Clr6 complex and chromatin remodelers known to be important for heterochromatin silencing. Deletion of Rbm10 results in significant reduction of Clr6 in heterochromatin. Our work together with previous findings further suggests that different splicing subunits may play distinct roles in heterochromatin regulation.
Low levels of PCSK9 are associated with remission in patients with rheumatoid arthritis treated with anti-TNF-α: potential underlying mechanisms
Authors: Frostegård Johan , Ahmed Sabbir , Hafström Ingiäld , Ajeganova Sofia , Rahman Mizanur 
Published: January 2021

AbstractBackgroundProprotein convertase subtilisin kexin 9 (PCSK9) targets the LDL-receptor (LDLR) which raises LDL-levels. In addition, PCSK9 has proinflammatory immunological effects. Here, we investigate the role of PCSK9 in relation to the inflammatory activity in patients with rheumatoid arthritis (RA).MethodsPCSK9-levels were determined at baseline by ELISA in 160 patients with RA not previously treated with biologics. The patients started anti-TNF-α (adalimumab, infliximab, or etanercept) treatment and were followed-up for 1 year. Disease activity was determined by DAS28.Effects of PCSK9 on cytokine production from macrophages of healthy individuals and synoviocytes from RA patients and inhibition by anti-PCSK9 antibodies were studied in supernatants by ELISA.ResultsA significantly lower level of PCSK9 at baseline,p = 0.035, was observed in patients who reached remission within 1 year, defined as DAS28 < 2.6, compared to those not in remission. At 12 months of TNF-α antagonist treatment, the mean DAS28 was reduced but was significantly greater in patients with highest quartile PCSK9 (Q4) compared to those at lowest PCSK9 (Q1) in both crude (p = 0.01) and adjusted analysis (p = 0.004).In vitro, PCSK9 induced TNF-alpha and IL-1beta in macrophages and monocyte chemoattractant protein-1 (MCP1) in synoviocytes. These effects were inhibited by anti-PCSK9 antibodies.ConclusionsLow levels of PCSK9 at baseline are associated with being DAS28-responder to anti-TNF-α treatment in RA. An underlying cause could be that PCSK9 stimulates the production of proinflammatory cytokines from macrophages and synoviocytes, effects inhibited by anti-PCSK9 antibodies. PCSK9 could thus play an immunological role in RA.
Genetic diversity of Giardia isolates from patients in Chandigarh region: India
Authors: Thakur Shabnam , Kaur Upninder , Sehgal Rakesh 
Published: January 2021

Abstract
Objective
The aim of study was to characterize Giardia isolates genetically among patients in Chandigarh region, India. For this, nested PCR targeting fragment of the glutamate dehydrogenase (GLUD1 earlier named as GDH) gene was used. Phylogenetic analysis was done by constructing neighbor-joining tree made out of the nucleotide sequences of G. intestinalis isolates obtained in this study and with the known sequences published in GenBank.

Results
Out of 40 samples, GLUD1 gene was amplified in 33 samples (82.5%). The product of GLUD1 gene was successfully sequenced only in 32 samples. In these samples, assemblage B was found in 27 (84.37%) samples whereas 5 (15.6%) samples had assemblage A. Among assemblage B most of them were of BIII. Therefore, genotyping of Giardia would be helpful in conducting epidemiological studies.
Stability analysis of initial value problem of pantograph-type implicit fractional differential equations with impulsive conditions
Authors: Ali Arshad , Mahariq Ibrahim , Shah Kamal , Abdeljawad Thabet , Al-Sheikh Bahaa 
Published: January 2021

AbstractIn this paper, we study an initial value problem for a class of impulsive implicit-type fractional differential equations (FDEs) with proportional delay terms. Schaefer’s fixed point theorem and Banach’s contraction principle are the key tools in obtaining the required results. We apply our results to a numerical problem for demonstration purpose.
A fixed point approach to the solution of singular fractional differential equations with integral boundary conditions
Authors: Chandran Kalaivani , Gopalan Kalpana , Zubair Sumaiya Tasneem , Abdeljawad Thabet 
Published: January 2021

AbstractIn this article, we first demonstrate a fixed point result under certain contraction in the setting of controlledb-Branciari metric type spaces.Thereafter, we specifically consider a following boundary value problem (BVP) for a singular fractional differential equation of order α:$$ \begin{aligned} &{}^{c}D^{\alpha }v(t) + h \bigl(t,v(t) \bigr) = 0,\quad 0< t< 1, \\ &v''(0) = v'''(0) = 0, \\ &v'(0) = v(1) = \beta \int _{0}^{1} v(s) \,ds, \end{aligned} $$Dαcv(t)+h(t,v(t))=0,0<t<1,v″(0)=v‴(0)=0,v′(0)=v(1)=β∫01v(s)ds,where$3<\alpha <4$3<α<4,$0<\beta <2$0<β<2,${}^{c}D^{\alpha }$Dαcis the Caputo fractional derivative andhmay be singular at$v = 0$v=0.Eventually, we investigate the existence and uniqueness of solutions of the aforementioned boundary value problem of orderαvia a fixed point problem of an integral operator.
Anti-bacterial effect of phytoconstituents isolated from Alimatis rhizoma
Authors: Li Chengfu , Yan Wei , Cui Enji , Zheng Changji 
Published: January 2021

AbstractFive compounds including three triterpenoids and two sesquiterpenes were isolated from Alimatis rhizoma. Their chemical structures were determined to be alisol B 23-acetate (1), alisol C 23-acetate (2), alisol B (3), alismol (4) and alismoxide (5) by various spectroscopic analysis, including 1H-NMR, 13C-NMR, HMBC and MS spectra. Compounds 1–5 were evaluated for their antibacterial potential against 6 strains of bacteria including three drug-resistant bacteria (one methicillin-resistant Staphylococcus aureus strain CCARM 3506, two quinolone-resistant Staphylococcus aureus strains CCARM 3505 and CCARM 3519), two G+ bacteria (Streptococcus mutans KCTC 3289 and Staphylococcus aureus KCTC 209) and one G− bacterium (Escherichia coli KCTC 1924). Compounds 1–5 showed strong antibacterial effect against S. mutans KCTC 3289, their MIC values were 2, 64, 16, 32 and 32 μg/mL, respectively. The antibacterial activity results of compounds 1–5 against these bacteria were reported for the first time. The results indicate that Alimatis rhizoma are potential sources of new antibacterial material.
Development of acoustically isolated extracellular plasma vesicles for biomarker discovery in allogeneic hematopoietic stem cell transplantation
Authors: Lim Hooi Ching , Soneji Shamit , Pálmason Róbert , Lenhoff Stig , Laurell Thomas , Scheding Stefan 
Published: January 2021

Abstract
Background
Infection and graft-versus-host disease (GvHD) are the major causes for mortality and morbidity of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Plasma-derived extracellular vesicles (EVs) contain disease-related proteins, DNAs and RNAs, and have recently been suggested as potential biomarker candidates for transplantation complications. However, EV isolation from small plasma volumes in clinical biomarker studies using conventional methods is challenging. We therefore investigated if EVs isolated by novel automated acoustic trapping could be developed as potential biomarkers for allo-HSCT complications by performing a clinical proof-of-principle study.

Results
Plasma samples were collected from twenty consecutive patients with high-risk/relapsed hematologic malignancies undergoing allo-HSCT before transplantation and post-transplant up to 12 weeks. EVs were isolated from small plasma sample volumes (150 μl) by an automated, acoustofluidic-based particle trapping device, which utilizes a local λ/2 ultrasonic standing wave in a borosilicate glass capillary to capture plasma EVs among pre-seeded polystyrene microbeads through sound scatter interactions. We found that EVs could be reliably isolated from all plasma samples (n = 173) and that EV numbers increased more than 2-fold in the majority of patients after transplantation. Also, sufficient quantities of RNA for downstream microRNA (miRNA) analysis were obtained from all samples and EV miRNA profiles were found to differ from whole plasma profiles. As a proof of principle, expression of platelet-specific miR-142-3p in EVs was shown to correlate with platelet count kinetics after transplantation as expected. Importantly, we identified plasma EV miRNAs that were consistently positively correlated with infection and GvHD, respectively, as well as miRNAs that were consistently negatively correlated with these complications.

Conclusions
This study demonstrates that acoustic enrichment of EVs in a clinical biomarker study setting is feasible and that downstream analysis of acoustically-enriched EVs presents a promising tool for biomarker development in allo-HSCT. Certainly, these findings warrant further exploration in larger studies, which will have significant implications not only for biomarker studies in transplantation but also for the broad field of EV-based biomarker discovery.
Assessment of tissue perfusion of pancreatic cancer as potential imaging biomarker by means of Intravoxel incoherent motion MRI and CT perfusion: correlation with histological microvessel density as ground truth
Authors: Mayer Philipp , Fritz Franziska , Koell Marco , Skornitzke Stephan , Bergmann Frank , Gaida Matthias M. , Hackert Thilo , Maier-Hein Klaus , Laun Frederik B. , Kauczor Hans-Ulrich , Grenacher Lars , Klauß Miriam , Stiller Wolfram 
Published: January 2021

Abstract
Background/objectives
The aim of this study was to compare intravoxel incoherent motion (IVIM) diffusion weighted (DW) MRI and CT perfusion to assess tumor perfusion of pancreatic ductal adenocarcinoma (PDAC).

Methods
In this prospective study, DW-MRI and CT perfusion were conducted in nineteen patients with PDAC on the day before surgery. IVIM analysis of DW-MRI was performed and the parameters perfusion fraction f, pseudodiffusion coefficient D*, and diffusion coefficient D were extracted for tumors, upstream, and downstream parenchyma. With a deconvolution-based analysis, the CT perfusion parameters blood flow (BF) and blood volume (BV) were estimated for tumors, upstream, and downstream parenchyma. In ten patients, intratumoral microvessel density (MVDtumor) and microvessel area (MVAtumor) were analyzed microscopically in resection specimens. Correlation coefficients between IVIM parameters, CT perfusion parameters, and histological microvessel parameters in tumors were calculated. Receiver operating characteristic (ROC) analysis was performed for differentiation of tumors and upstream parenchyma.

Results
ftumor significantly positively correlated with BFtumor (r = 0.668, p = 0.002) and BVtumor (r = 0.672, p = 0.002). There were significant positive correlations between ftumor and MVDtumor/ MVAtumor (r ≥ 0.770, p ≤ 0.009) as well as between BFtumor and MVDtumor/ MVAtumor (r ≥ 0.697, p ≤ 0.025). Correlation coefficients between ftumor and MVDtumor/ MVAtumor were not significantly different from correlation coefficients between BFtumor and MVDtumor/ MVAtumor (p ≥ 0.400). Moreover, f, BF, BV, and permeability values (PEM) showed excellent performance in distinguishing tumors from upstream parenchyma (area under the ROC curve ≥0.874).

Conclusions
The study shows that IVIM derived ftumor and CT perfusion derived BFtumor similarly reflect vascularity of PDAC and seem to be comparably applicable for the evaluation of tumor perfusion for tumor characterization and as potential quantitative imaging biomarker.

Trial registration
DRKS, DRKS00022227, Registered 26 June 2020, retrospectively registered. https://www.drks.de/drks_web/navigate.do?navigationId=trial. HTML&TRIAL_ID=DRKS00022227.
Brief psychotherapy administered by non-specialised health workers to address risky substance use in patients with multidrug-resistant tuberculosis: a feasibility and acceptability study
Authors: Calligaro Gregory L. , de Wit Zani , Cirota Jacqui , Orrell Catherine , Myers Bronwyn , Decker Sebastian , Stein Dan J. , Sorsdahl Katherine , Dawson Rodney 
Published: January 2021

Abstract
Background
Only 55% of multidrug-resistant tuberculosis (MDR-TB) cases worldwide complete treatment, with problem substance use a risk for default and treatment failure. Nevertheless, there is little research on psychotherapeutic interventions for reducing substance use amongst MDR-TB patients, in general, and on their delivery by non-specialist health workers in particular.

Objectives
To explore the feasibility and acceptability of a non-specialist health worker-delivered 4-session brief motivational interviewing and relapse prevention (MI-RP) intervention for problem substance use and to obtain preliminary data on the effects of this intervention on substance use severity, depressive symptoms, psychological distress and functional impairment at 3 months after hospital discharge.

Methods
Between December 2015 and October 2016, consenting MDR-TB patients admitted to Brewelskloof Hospital who screened at moderate to severe risk for substance-related problems on the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were enrolled, and a baseline questionnaire administered. In the 4 weeks prior to planned discharge, trained counsellors delivered the MI-RP intervention. The baseline questionnaire was re-administered 3 months post-discharge and qualitative interviews were conducted with a randomly selected sample of participants (n = 10).

Results
Sixty patients were screened: 40 (66%) met inclusion criteria of which 39 (98%) were enrolled. Of the enrolled patients, 26 (67%) completed the counselling sessions and the final assessment. Qualitative interviews revealed participants’ perceptions of the value of the intervention. From baseline to follow-up, patients reported reductions in substance use severity, symptoms of depression, distress and functional impairment.

Conclusion
In this feasibility study, participant retention in the study was moderate. We found preliminary evidence supporting the benefits of the intervention for reducing substance use and symptoms of psychological distress, supported by qualitative reports of patient experiences. Randomised studies are needed to demonstrate efficacy of this intervention before considering potential for wider implementation.

Trial registration
South African National Clinical Trials Register (DOH-27-0315-5007) on 01/04/2015 (http://www.sanctr.gov.za)