bluuebunny/crossref_metadata_2025 huggingface dataset:
Recontacting non-BRCA1/2 breast cancer patients for germline CHEK2 c.1100del pathogenic variant testing: uptake and patient experiences
Authors: Velthuizen Mary E. , van der Luijt Rob B. , de Vries Beja J. , Koudijs Marco J. , Bleiker Eveline M. A. , Ausems Margreet G. E. M.
Published: January 2021

Background

CHEK2 has been recognized as a breast cancer risk gene with moderate effect. Women who have previously tested negative for a BRCA1/2 gene germline pathogenic variant may benefit from additional genetic testing for the CHEK2 c.1100del pathogenic variant. The aims of this study were: 1) to assess the uptake of an active approach by recontacting BRCA1/2-negative women for additional CHEK2 c.1100del testing on stored DNA-samples and 2) to explore patients’ experiences with this approach.

Methods

Between 2015 and 2017, women who had been tested earlier negative for BRCA1/2 germline pathogenic variants, were recontacted for additional CHEK2 c.1100del testing on stored DNA-samples, free-of-charge. They received an information letter about the CHEK2 pathogenic variant and could return an informed consent form when they opted for additional genetic testing. Those in whom the CHEK2 pathogenic variant was absent, received a letter describing this result. Those who tested positive, were invited for a personal counseling at the department of genetics. On average 21 months (range 4–27) after the genetic test result, a questionnaire was sent to all identified carriers and a control group of women who tested negative for the pathogenic variant to explore patients’ experiences with our approach.

Results

In total, 70% (N = 1666) of the N = 2377 women contacted opted for additional testing, and 66 (4%) of them proved to be carriers of the CHEK2 c.1100del pathogenic variant. Regardless of the outcome of the genetic test, women were generally satisfied with our approach and reported that the written information was sufficient to make an informed decision about the additional CHEK2 testing.

Conclusions

The uptake (70%) of our approach was considered satisfactory. Patients considered the benefits more important than the psychosocial burden. Given the rapid developments in DNA-diagnostics, our findings may support future initiatives to recontact patients about additional genetic testing when they previously tested negative for a pathogenic variant in a breast cancer gene.
A rare large duplication of MLH1 identified in Lynch syndrome
Authors: Kumar Abhishek , Paramasivam Nagarajan , Bandapalli Obul Reddy , Schlesner Matthias , Chen Tianhui , Sijmons Rolf , Dymerska Dagmara , Golebiewska Katarzyna , Kuswik Magdalena , Lubinski Jan , Hemminki Kari , Försti Asta
Published: January 2021

Background

The most frequently identified strong cancer predisposition mutations for colorectal cancer (CRC) are those in the mismatch repair (MMR) genes in Lynch syndrome. Laboratory diagnostics include testing tumors for immunohistochemical staining (IHC) of the Lynch syndrome-associated DNA MMR proteins and/or for microsatellite instability (MSI) followed by sequencing or other techniques, such as denaturing high performance liquid chromatography (DHPLC), to identify the mutation.

Methods

In an ongoing project focusing on finding Mendelian cancer syndromes we applied whole-exome/whole-genome sequencing (WES/WGS) to 19 CRC families.

Results

Three families were identified with a pathogenic/likely pathogenic germline variant in a MMR gene that had previously tested negative in DHPLC gene variant screening. All families had a history of CRC in several family members across multiple generations. Tumor analysis showed loss of the MMR protein IHC staining corresponding to the mutated genes, as well as MSI. In family A, a structural variant, a duplication of exons 4 to 13, was identified in MLH1. The duplication was predicted to lead to a frameshift at amino acid 520 and a premature stop codon at amino acid 539. In family B, a 1 base pair deletion was found in MLH1, resulting in a frameshift and a stop codon at amino acid 491. In family C, we identified a splice site variant in MSH2, which was predicted to lead loss of a splice donor site.

Conclusions

We identified altogether three pathogenic/likely pathogenic variants in the MMR genes in three of the 19 sequenced families. The MLH1 variants, a duplication of exons 4 to 13 and a frameshift variant, were novel, based on the InSiGHT and ClinVar databases; the MSH2 splice site variant was reported by a single submitter in ClinVar. As a variant class, duplications have rarely been reported in the MMR gene literature, particularly those covering several exons.
Utilising benefit-risk assessments within clinical trials—a protocol for the BRAINS project
Authors: Totton Nikki , Julious Steven , Hughes Dyfrig , Cook Jonathan , Biggs Katie , Coates Lizzie , Cook Andrew , Hewitt Catherine , Day Simon
Published: January 2021

Background

Depending on the treatment to be investigated, a clinical trial could be designed to assess objectives of superiority, equivalence or non-inferiority. The design of the study is affected by many different elements including the control treatment, the primary outcome and associated relationships.

In some studies, there could be more than one outcome of interest. In these situations, benefit-risk methodologies could be used to assess the outcomes simultaneously and consider the trade-off between the benefits against the risks of a treatment.

Benefit-risk is used within the regulatory industry but seldom included within publicly funded clinical trials within the UK. This project aims to gain an expert consensus on how to select the appropriate trial design (e.g. superiority) and when to consider including benefit-risk methods.

Methods

The project will consist of four work packages:

A web-based survey to elicit current experiences and opinions,

A rapid literature review to assess any current recommendations,

A two-day consensus workshop to gain agreement on the recommendations, and

Production of a guidance document.

Discussion

The aim of the project is to provide a guideline for clinical researchers, grant funding bodies and reviewers for grant bodies for how to select the most appropriate trial design and when it is appropriate to consider using benefit-risk methods. The focus of the guideline will be on publicly funded trials however, the vision is that the work will be applicable across research settings and we will connect with other organisations and committees as appropriate.
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

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

Salvia 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

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

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

Splicing 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

Background

Proprotein 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).

Methods

PCSK9-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.

Results

A 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.

Conclusions

Low 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

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.
Correction to: Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts
Authors: Filice Dominic , Dhahri Wahiba , Solan Joell L. , Lampe Paul D. , Steele Erin , Milani Nikita , Van Biber Benjamin , Zhu Wei-Zhong , Valdman Tamilla Sadikov , Romagnuolo Rocco , Otero-Cruz José David , Hauch Kip D. , Kay Matthew W. , Sarvazyan Narine , Laflamme Michael A.
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
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

In 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

In 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

Five 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

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

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

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)
Bioceramic hydroxyapatite-based scaffold with a porous structure using honeycomb as a natural polymeric Porogen for bone tissue engineering
Authors: Sari Mona , Hening Puspa , Chotimah  , Ana Ika Dewi , Yusuf Yusril
Published: January 2021

Background

The application of bioceramic hydroxyapatite (HA) derived from materials high in calcium to tissue engineering has been of concern, namely scaffold. Scaffold pores allow for cell mobility metabolic processes, and delivery of oxygen and nutrients by blood vessel. Thus, pore architecture affects cell seeding efficiency, cell viability, migration, morphology, cell proliferation, cell differentiation, angiogenesis, mechanical strength of scaffolds, and, eventually, bone formation. Therefore, to improve the efficacy of bone regeneration, several important parameters of the pore architecture of scaffolds must be carefully controlled, including pore size, geometry, orientation, uniformity, interconnectivity, and porosity, which are interrelated and whose coordination affects the effectiveness of bone tissue engineering. The honeycomb (HCB) as natural polymeric porogen is used to pore forming agent of scaffolds. It is unique for fully interconnected and oriented pores of uniform size and high mechanical strength in the direction of the pores. The aim of this study was therefore to evaluate the effect of HCB concentration on macropore structure of the scaffolds.

Methods

Bioceramic hydroxyapatite (HA) was synthesized from abalone mussel shells (
Halioitis asinina
) using a precipitation method, and HA-based scaffolds were fabricated with honeycomb (HCB) as the porogen agent. Pore structure engineering was successfully carried out using HCB at concentrations of 10, 20, and 30 wt%.

Results

The Energy Dispersive X-Ray Spectroscopy (EDS) analysis revealed that the Ca/P molar ratio of HA was 1.67 (the stoichiometric ratio of HA). The Fourier Transform Infrared Spectroscopy (FTIR) spectra results for porous HA-based scaffolds and synthesized HA showed that no chemical decomposition occurred in the HA-based scaffold fabrication process. The porosity of the scaffold tended to increase when higher concentrations of HCB were added. XRD data show that the HCB was completely degraded from the scaffold material. The cell metabolic activity and morphology of the HA + HCB 30 wt% scaffold enable it to facilitate the attachment of MC3T3E1 cells on its surface.

Conclusion

HCB 30 wt% is the best concentration to fabricate the scaffold corresponding to the criteria for pores structure, crystallographic properties, chemical decomposition process and cell viability for bone tissue engineering.
Comparison of modern high-speed vitrectomy systems and the advantages of using dual-bladed probes
Authors: Oravecz R. , Uthoff D. , Schrage N. , Dutescu R. M.
Published: January 2021

Purpose

This study analyzes the efficiency of different vitrectomy systems and compares single with double-bladed cutters.

Methods

The systems EVA™ (DORC), Constellation® Vision System (ALCON), megaTRON S4HPS (Geuder) and Stellaris® PC (Bausch and Lomb) were used. We chose 20G and 23G probes, since not all systems had switched to a smaller G at the time the study was conducted in 2016. Cut rates were varied in increments of 1000 cuts/min from 500 cpm to the system’s maximum and vacuum pressures were varied in increments of 100 mmHg, from 100 to 600 mmHg up to the individual system’s maximum. In this study water, egg white, Pluronic®−F127 gel and isolated porcine vitreous were used as models of human vitreous. The vitrectomy efficiency was calculated from the aspirated mass (g) within 30 s. The aperture of the different vitrectomy probes was filmed with a high-speed camera.

Results

The area under the curve analysis showed differences in efficiency between vitrectomy systems. For water, a reverse relationship between the aspirated mass and cut rate was shown. By contrast, for most systems aspirated egg white and porcine vitreous showed a non-linear increase or decrease for 4000 cpm and above. For all vitreous surrogates, EVA™’s double-bladed probe aspirated significantly (p < 0.001) more vitreous than its mono-bladed probe. Video recordings showed less vitreous traction for double- in contrast to single-bladed probes.

Conclusion

We can demonstrate differences in the efficiency of vitrectomy depending on the vitrectomy system used. Double-bladed probes were more efficient and probably safer than single-bladed probes.
Repellency and insecticidal properties of seed oil of Jatropha curcas L. against American cockroach, Periplaneta americana L.
Authors: Ubulom Peace Mayen Edwin , Yaro Clement Ameh , Udoh Unyime-Abasi Philip
Published: January 2021

Background

This study evaluated the effect of Jatropha curcas seed oil against adult American cockroach, Periplaneta americana, a mechanical disease vector, using three bioassay methods to determine the repellent activity, contact and fumigant toxicity. This involved the use of J. curcas oil solution (diluted with acetone (20%)) and J. curcas pure oil. For repellency test, concentrations 0.30, 0.60 and 0.90% v/v were used for the oil solution while 1.0 and 2.0 ml concentrations were used for the pure oil. All test groups were exposed for 15 min. Contact toxicity test involved the use of 0.30, 0.60, 0.90, 1.20 and 1.50% v/v concentrations for the oil solution while 1 and 2 ml concentrations were used for the pure oil. Exposure period for all test groups was 24–120 h. For the fumigant test, 0.15% v/v and 0.5 ml concentrations were used for the oil solution and pure oil groups respectively; exposure period for the test groups was 24–120 h. All test and the control groups had ten cockroaches (P. americana) per group with four replicates.

Results

Repellency was higher in test groups treated with pure J. curcas oil than in groups treated with the oil solution with repellency of 70–100% and 60–100% respectively after 15 min exposure period. For the contact test, a higher mortality rate was observed with the oil solution than the pure oil. Mortality was lower for 1 ml of pure oil with 20% at 24 h and 40% at 120 h than 2 ml of pure oil with 30% mortality at 24 h and 50% mortality at 120 h. A 100% mortality was recorded in the highest concentration (1.50% v/v) at 120 h. Fumigation test with 0.15% v/v of oil solution resulted in 20% mortality at 120 h while fumigation test with 0.5 ml of J. curcas pure oil resulted in 60% mortality at 120 h.

Conclusion

J. curcas seed oil possesses repellent and insecticidal properties against P. americana . Thus, the menace caused by this mechanical disease vector could be reduced using J. curcas seed oil.
Efficacy of the parasitoid, Trichogrammatoidea bactrae Nagaraja (Hymenoptera: Trichogrammatidae) on the cotton leafworm, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae) egg masses
Authors: Mohamed Hend O.
Published: January 2021

Background

The Egyptian cotton leafworm, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae) is one of the major insect pests, causing a significant damage on different cultivated agricultural crops. Developing an alternative non-chemical tool, an effective and environmentally friendly method to suppress pest's infestation is essentially needed. Therefore, biological control by releasing the egg parasitoids could be the most promising tool for integrated pest management.

Results

This study was designed to evaluate the efficacy of the egg parasitoid, Trichogrammatoidea bactrae Nagaraja (Hymenoptera: Trichogrammatidae) as a bio-control agent against S. littoralis egg masses with different physical characteristics (number of egg layer and degree of scale density) in a no-choice and choice tests, under laboratory conditions. Also, the parasitoids’ fitness in terms of parasitism percentage, developmental period, adults’ emergence percentage, female offspring percentage, and longevity were investigated. The results revealed that T. bactrae wasps had a great ability to parasitize S. littoralis egg masses, but with different rates, related to their layers and scales’ thickness in both tests. The highest parasitism percentage was observed on one-layer eggs, followed by two layers. However, 3-layer eggs were the least preferable one. High numbers of adult emergencies (> 80%) were observed in all tested egg masses, except in the case of 3 layers with high scales. Furthermore, female-biased sex ratios were noticed at all examined eggs, with only the exception of high-scaly eggs with a single layer that recorded the lowest rate (≤ 45%). Besides, the survival of adult female parasitoids was not significantly affected in both tests.

Conclusions

T. bactrae could be used as a bio-control agent against S. littoralis egg masses with different physical characteristics based on the achieved results.
The quality of online consumer health information at the intersection of complementary and alternative medicine and arthritis
Authors: Ng Jeremy Y. , Vacca Alexandra , Jain Tanya
Published: January 2021

Background

Complementary and alternative medicine (CAM) use is prevalent among patients living with arthritis. Such patients often seek information online, for the purpose of gaining a second opinion to their healthcare provider or even self-medication. Little is known about the quality of web-based consumer health information at the intersection of CAM and arthritis; thus, investigating the quality of websites containing this information was the purpose of this study.

Methods

Four unique search terms were searched on Google across four English-speaking countries. We assessed the first 20 results of each search, including them if they contained CAM consumer health information for the treatment and/or management of arthritis. Eligible websites were assessed in duplicate using the DISCERN instrument, which consists of 16-items designed to assess quality.

Results

Of total of 320 webpages, 239 were duplicates, and a total of 38 unique websites were deemed eligible and assessed using the DISCERN instrument. The mean summed  DISCERN scores across all websites was 55.53 (SD = 9.37). The mean score of the overall quality of each website was 3.71 (SD = 0.63), thus the majority of websites are ranked as slightly above ‘fair’ quality.

Conclusion

Eligible websites generally received scores better than ‘moderate’ in terms of overall quality. Several shortcomings included a lack of transparency surrounding references used and underreporting of risks associated with treatment options. These results suggest that health providers should be vigilant of the variable quality of information their patients may be accessing online and educate them on how to identify high quality resources.
Abdominal symptoms during Sjogren’s syndrome: a pilot study
Authors: Parreau Simon , Jacques Jérémie , Dumonteil Stéphanie , Palat Sylvain. , Geyl Sophie , Gondran Guillaume , Bezanahary Holy , Liozon Eric , Azaïs Julie , Colombie Stéphanie , Jauberteau Marie-Odile , Loustaud-Ratti Véronique , Ly Kim-Heang , Fauchais Anne-Laure
Published: January 2021

Background

Abdominal symptoms in patients with primary Sjögren syndrome (pSS) are poorly documented. The objective of the study was to describe the abdominal symptoms of patients with pSS and to assess their association with characteristics of the disease.

Methods

One hundred and fifty patients with pSS were evaluated using a composite global symptom score for abdominal symptoms and their severity. Data concerning the clinical and biological characteristics of pSS and abdominal disorders were also collected.

Results

Of the patients with pSS, 95% suffered from abdominal symptoms (median global symptom score 7.5 ± 5.5 points out of 30). More than half of the patients experienced abdominal tension (68%), upper abdominal pain (54%), abdominal discomfort (58%) and/or constipation (54%). Regarding the pSS activity, in relation to European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index score items, general and central nervous system involvement wereassociated with a high global symptom score. The EULAR Sjogren Syndrome Patient Reported Index (ESSPRI) symptom score was positively correlated with the global symptom score (p < 0.01). Multivariate analysis showed a significant association between a high global symptom score and SSA seronegativity, gastroparesis, and ESSPRI score (p < 0.01 for each).

Conclusions

The majority of patients with pSS suffered abdominal symptoms. There is currently no therapeutic recommendation because of the lack of information on the underlying pathophysiological mechanisms.

Trial registration

NCT03157011. Date of registration: July 17, 2017.
Why ability point estimates can be pointless: a primer on using skill measures from large-scale assessments in secondary analyses
Authors: Lechner Clemens M. , Bhaktha Nivedita , Groskurth Katharina , Bluemke Matthias
Published: January 2021

Measures of cognitive or socio-emotional skills from large-scale assessments surveys (LSAS) are often based on advanced statistical models and scoring techniques unfamiliar to applied researchers. Consequently, applied researchers working with data from LSAS may be uncertain about the assumptions and computational details of these statistical models and scoring techniques and about how to best incorporate the resulting skill measures in secondary analyses. The present paper is intended as a primer for applied researchers. After a brief introduction to the key properties of skill assessments, we give an overview over the three principal methods with which secondary analysts can incorporate skill measures from LSAS in their analyses: (1) as test scores (i.e., point estimates of individual ability), (2) through structural equation modeling (SEM), and (3) in the form of plausible values (PVs). We discuss the advantages and disadvantages of each method based on three criteria: fallibility (i.e., control for measurement error and unbiasedness), usability (i.e., ease of use in secondary analyses), and immutability (i.e., consistency of test scores, PVs, or measurement model parameters across different analyses and analysts). We show that although none of the methods are optimal under all criteria, methods that result in a single point estimate of each respondent’s ability (i.e., all types of “test scores”) are rarely optimal for research purposes. Instead, approaches that avoid or correct for measurement error—especially PV methodology—stand out as the method of choice. We conclude with practical recommendations for secondary analysts and data-producing organizations.
Growth differentiation factor 15: an emerging diagnostic biomarker of liver fibrosis in chronic hepatitis C patients
Authors: Abou Zaghla Heba M. Adel , El Sebai Aziza Ahmed , Ahmed Ossama Ashraf , Ahmed Ayat Fawzy , Saab Azza Abdel Rahman
Published: January 2021

Background

Chronic liver disease and cirrhosis are of the major health concern worldwide. Assessment of liver fibrosis is necessary to determine disease severity and prognosis at the time of presentation to determine suitable treatment. Liver biopsy is considered as standard golden method in diagnosis of liver fibrosis. However, this procedure is invasive; thus, multiple laboratory and radiologic tests are used to help determination of the degree of fibrosis. Growth differentiation factor 15 (GDF-15) is a pleiotropic cytokine involved in regulating inflammatory and apoptotic pathways. It is suggested that GDF-15 plays an important role in pathogenesis of liver fibrosis. In this study, we aimed to evaluate efficiency of growth differentiation factor 15 in diagnosing liver fibrosis. The study was a case-control study conducted on 55 chronic HCV patients recruited from hepatitis C virus clinic at Faculty of Medicine Ain Shams Research Institute (MASRI), and 30 healthy subjects age- and sex-matched. The patients were classified into three subgroups according to the degree of liver fibrosis assessed by fibro-scan. Serum concentration of GDF-15 was determined by enzyme-linked immunosorbent assay.

Results

Our results revealed a highly significant statistical rise in GDF-15 levels among studied chronic HCV patients with liver fibrosis when compared to the control group (p < 0.01). Furthermore, there was a significant positive correlation between the degree of fibrosis assessed by fibro-scan and GDF-15 serum levels. Levels of GDF-15 were significantly higher in patients with mild degree of fibrosis (patients’ subgroup І) when compared with the controls’ group (p < 0.01) suggesting the role of this marker in early detection of liver fibrosis. A statistically significant increase in serum GDF-15 levels was noticed among patients with advanced fibrosis “subgroup ІІІ” compared to those with mild fibrosis “subgroup І” (p < 0.05). The diagnostic sensitivity and specificity of GDF-15 were 96.7%, 98.2%, respectively at a cut-off value of 150 ng/L for discrimination between patients’ and controls’ groups.

Conclusion

Growth differentiation factor 15 could be a potential marker of liver fibrosis especially in early detection as its levels were significantly higher in patients’ group with liver fibrosis than controls’ group and there was a significant positive correlation between the degree of liver fibrosis and GDF-15 serum levels.