bluuebunny/crossref_metadata_2025 huggingface dataset:
MassARRAY-based single nucleotide polymorphism analysis in breast cancer of north Indian population
Authors: Bakshi Divya , Nagpal Ashna , Sharma Varun , Sharma Indu , Shah Ruchi , Sharma Bhanu , Bhat Amrita , Verma Sonali , Bhat Gh. Rasool , Abrol Deepak , Sharma Rahul , Vaishnavi Samantha , Kumar Rakesh
Published: September 2020

Background

Breast Cancer (BC) is associated with inherited gene mutations. High throughput genotyping of BC samples has led to the identification and characterization of biomarkers for the diagnosis of BC. The most common genetic variants studied are SNPs (Single Nucleotide Polymorphisms) that determine susceptibility to an array of diseases thus serving as a potential tool for identifying the underlying causes of breast carcinogenesis.

Methods

SNP genotyping employing the Agena MassARRAY offers a robust, sensitive, cost-effective method to assess multiple SNPs and samples simultaneously. In this present study, we analyzed 15 SNPs of 14 genes in 550 samples (150 cases and 400 controls). We identified four SNPs of genes TCF21, SLC19A1, DCC, and ERCC1 showing significant association with BC in the population under study.

Results

The SNPs were rs12190287 (TCF21) having OR 1.713 (1.08–2.716 at 95% CI) p-value 0.022 (dominant), rs1051266 (SLC19A1) having OR 3.461 (2.136–5.609 at 95% CI) p-value 0.000000466 (dominant), rs2229080 (DCC) having OR 0.6867 (0.5123–0.9205 at 95% CI) p-value 0.0116 (allelic) and rs2298881 (ERCC1) having OR 0.669 (0.46–0.973 at 95% CI), p-value 0.035 (additive) respectively. The in-silico analysis was further used to fortify the above findings.

Conclusion

It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.
Association between sexual violence and unintended pregnancy among adolescent girls and young women in South Africa
Authors: Ajayi Anthony Idowu , Ezegbe Henrietta Chinelo
Published: September 2020

Background

Unintended pregnancy has dire consequences on the health and socioeconomic wellbeing of adolescent girls and young women (AGYW) (aged 15–24 years). While most studies tend to focus on lack of access to contraceptive information and services, and poverty as the main contributing factor to early-unintended pregnancies, the influence of sexual violence has received limited attention. Understanding the link between sexual violence and unintended pregnancy is critical towards developing a multifaceted intervention to reduce unintended pregnancies among AGYW in South Africa, a country with high teenage pregnancy rate. Thus, we estimated the magnitude of unintended pregnancy among AGYW and also examined the effect of sexual violence on unintended pregnancy.

Methods

Our study adopted a cross-sectional design, and data were obtained from AGYW in a South African university between June and November 2018. A final sample of 451 girls aged 17–24 years, selected using stratified sampling, were included in the analysis. We used adjusted and unadjusted logistic regression analysis to examine the effect of sexual violence on unintended pregnancy.

Results

The analysis shows that 41.9% of all respondents had experienced an unintended pregnancy, and 26.3% of those unintended pregnancies ended in abortions. Unintended pregnancy was higher among survivors of sexual violence (54.4%) compared to those who never experienced sexual abuse (34.3%). In the multivariable analysis, sexual violence was consistently and robustly associated with increased odds of having an unintended pregnancy (AOR:1.70; 95% CI: 1.08–2.68).

Conclusion

Our study found a huge magnitude of unintended pregnancy among AGYW. Sexual violence is an important predictor of unintended pregnancy in this age cohort. Thus, addressing unintended pregnancies among AGYW in South Africa requires interventions that not only increase access to contraceptive information and services but also reduce sexual violence and cater for survivors.
Smartphone and medical application use among dentists in China
Authors: Zhang Chao , Fan Lin , Chai Zhaowu , Yu Cong , Song Jinlin
Published: September 2020

Background

With the development of information technology, an increasing number of healthcare professionals are using smartphones and mobile medical applications (apps) in their clinical practice. The objective of this study was to survey the use of smartphone-based medical apps among dentists in China and determine dentists’ perceptions of such apps.

Methods

All data were collected using anonymous questionnaires. The questionnaires for this cross-sectional study were randomly sent to dentists by email, and 379 dentists responded. Dentists’ demographics and perceptions of WeChat, QQ (the most popular social media apps in China) and other medical apps were assessed; the questionnaire including questions on the purpose, frequency, daily use, and opinion of the apps they used. Questions were answered using a Likert scale (1 = strongly agree, 2 = agree, 3 = not sure, 4 = disagree, and 5 = strongly disagree).

Results

A total of 379 valid responses were received; the respondents had a median age of 33.6 years old (63.3% female). All subjects (100%) owned a smartphone, and all of them installed and used WeChat or QQ in their clinical practice. Only 76% of subjects installed medical apps (other than WeChat and QQ) on their smartphones. Male dentists were more likely to install medical apps than female dentists (p < 0.05). With increasing age, the percentage of dentists who installed medical apps decreased (p < 0.001). The frequency and daily use were higher for WeChat and QQ than for medical apps. Medical apps were positively perceived, with dentists reporting that they recommend these medical apps to their peers (Likert score: 1.67 ± 0.68).

Conclusion

Medical apps were perceived to have a positive impact on clinical practice, education and patient care in dentistry by providing relevant medical information. However, there will still be much room for improvement in the future.
The influence of patient race on the use of diagnostic imaging in United States emergency departments: data from the National Hospital Ambulatory Medical Care survey
Authors: Ross Andrew B. , Kalia Vivek , Chan Brian Y. , Li Geng
Published: September 2020

Background

An established body of literature has shown evidence of implicit bias in the health care system on the basis of patient race and ethnicity that contributes to well documented disparities in outcomes. However, little is known about the influence of patient race and ethnicity on the decision to order diagnostic radiology exams in the acute care setting. This study examines the role of patient race and ethnicity on the likelihood of diagnostic imaging exams being ordered during United States emergency department encounters.

Methods

Publicly available data from the National Hospital Ambulatory Medical Care Survey Emergency Department sample for the years 2006–2016 was compiled. The proportion of patient encounters where diagnostic imaging was ordered was tabulated by race/ethnicity, sub-divided by imaging modality. A multivariable logistic regression model was used to evaluate the influence of patient race/ethnicity on the ordering of diagnostic imaging controlling for other patient and hospital characteristics. Survey weighting variables were used to formulate national-level estimates.

Results

Using the weighted data, an average of 131,558,553 patient encounters were included each year for the 11-year study period. Imaging was used at 46% of all visits although this varied significantly by patient race and ethnicity with white patients receiving medical imaging at 49% of visits and non-white patients at 41% of visits (p < 0.001). This effect persisted in the controlled regression model and across all imaging modalities with the exception of ultrasound. Other factors with a significant influence on imaging use included patient age, gender, insurance status, number of co-morbidities, hospital setting (urban vs non-urban) and hospital region. There was no evidence to suggest that the disparate use of imaging by patient race and ethnicity changed over the 11-year study time period.

Conclusion

The likelihood that a diagnostic imaging exam will be ordered during United States emergency department encounters differs significantly by patient race and ethnicity even when controlling for other patient and hospital characteristics. Further work must be done to understand and mitigate what may represent systematic bias and ensure equitable use of health care resources.
Malignant transformation and genetic alterations are uncoupled in early colorectal cancer progression
Authors: Mamlouk Soulafa , Simon Tincy , Tomás Laura , Wedge David C. , Arnold Alexander , Menne Andrea , Horst David , Capper David , Morkel Markus , Posada David , Sers Christine , Bläker Hendrik
Published: September 2020

Background

Colorectal cancer (CRC) development is generally accepted as a sequential process, with genetic mutations determining phenotypic tumor progression. However, matching genetic profiles with histological transition requires the analyses of temporal samples from the same patient at key stages of progression.

Results

Here, we compared the genetic profiles of 34 early carcinomas with their respective adenomatous precursors to assess timing and heterogeneity of driver alterations accompanying the switch from benign adenoma to malignant carcinoma. In almost half of the cases, driver mutations specific to the carcinoma stage were not observed. In samples where carcinoma-specific alterations were present, TP53 mutations and chromosome 20 copy gains commonly accompanied the switch from adenomatous tissue to carcinoma. Remarkably, 40% and 50% of high-grade adenomas shared TP53 mutations and chromosome 20 gains, respectively, with their matched carcinomas. In addition, multi-regional analyses revealed greater heterogeneity of driver mutations in adenomas compared to their matched carcinomas.

Conclusion

Genetic alterations in TP53 and chromosome 20 occur at the earliest histological stage in colorectal carcinomas (pTis and pT1). However, high-grade adenomas can share these alterations despite their histological distinction. Based on the well-defined sequence of CRC development, we suggest that the timing of genetic changes during neoplastic progression is frequently uncoupled from histological progression.
24-h variations of blood serum metabolites in high yielding dairy cows and calves
Authors: Hussein Hussein Awad , Thurmann Jan-Peter , Staufenbiel Rudolf
Published: September 2020

Background

Blood profile testing is commonly used to monitor herd health status, diagnose disorders, and predict the risk of diseases in cows and calves, with subsequent optimization the production of dairy herds. By understanding the physiological ranges of serum metabolites relative to age, lactation stage, and the sampling time in healthy cows and calves, the dairy practitioners can accurately diagnose abnormalities with a blood test. The effect of sampling time on the variation of serum metabolites within 24 h were evaluated in 83 cattle. All animals were originated from a dairy herd, where the animals, based on their ages and lactation stages, were classified into eight groups. The blood samples were collected from each animal every 4 h within a day.

Results

The time of sampling within the day showed significant influences on the serum concentrations of glucose, β-hydroxybutyric acid (BHBA) and urea. BHBA was the most metabolite that showed day variation among cows’ groups. Furthermore, the concentrations of total cholesterol were the most stable metabolite in all groups. The mean values of albumin, total proteins, glucose, non-esterified fatty acids (NEFA), BHBA, total cholesterol, total bilirubin, urea, and creatinine revealed significant variations among the different studied groups.

Conclusions

A certain suitable time of blood sample collection cannot be recommended. However, care shall be taken for the time of sampling for measurements of glucose, NEFA, BHBA and urea, otherwise the comparative values of these metabolites at different sampling time points may differ significantly from each other’s, without a disease cause. It may be recommended, for metabolic assessment of dairy herds, classification the subjects into different groups based on lactation stages and ages of animals.
In vivo characterization of the activities of novel cyclodipeptide oxidases: new tools for increasing chemical diversity of bioproduced 2,5-diketopiperazines in Escherichia coli
Authors: Le Chevalier Fabien , Correia Isabelle , Matheron Lucrèce , Babin Morgan , Moutiez Mireille , Canu Nicolas , Gondry Muriel , Lequin Olivier , Belin Pascal
Published: September 2020

Background

Cyclodipeptide oxidases (CDOs) are enzymes involved in the biosynthesis of 2,5-diketopiperazines, a class of naturally occurring compounds with a large range of pharmaceutical activities. CDOs belong to cyclodipeptide synthase (CDPS)-dependent pathways, in which they play an early role in the chemical diversification of cyclodipeptides by introducing Cα-Cβ dehydrogenations. Although the activities of more than 100 CDPSs have been determined, the activities of only a few CDOs have been characterized. Furthermore, the assessment of the CDO activities on chemically-synthesized cyclodipeptides has shown these enzymes to be relatively promiscuous, making them interesting tools for cyclodipeptide chemical diversification. The purpose of this study is to provide the first completely microbial toolkit for the efficient bioproduction of a variety of dehydrogenated 2,5-diketopiperazines.

Results

We mined genomes for CDOs encoded in biosynthetic gene clusters of CDPS-dependent pathways and selected several for characterization. We co-expressed each with their associated CDPS in the pathway using Escherichia coli as a chassis and showed that the cyclodipeptides and the dehydrogenated derivatives were produced in the culture supernatants. We determined the biological activities of the six novel CDOs by solving the chemical structures of the biologically produced dehydrogenated cyclodipeptides. Then, we assessed the six novel CDOs plus two previously characterized CDOs in combinatorial engineering experiments in E. coli. We co-expressed each of the eight CDOs with each of 18 CDPSs selected for the diversity of cyclodipeptides they synthesize. We detected more than 50 dehydrogenated cyclodipeptides and determined the best CDPS/CDO combinations to optimize the production of 23.

Conclusions

Our study establishes the usefulness of CDPS and CDO for the bioproduction of dehydrogenated cyclodipeptides. It constitutes the first step toward the bioproduction of more complex and diverse 2,5-diketopiperazines.
Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer
Authors: Liao Qi , Chen Linbo , Zhang Ning , Xi Yang , Hu Shiyun , Ng Derry Minyao , Ahmed Fatma Yislam Hadi , Zhao Guofang , Fan Xiaoxiang , Xie Yangyang , Dai Xiaoyu , Jin Yanping , Ge Jiaxin , Dong Changzheng , Zhang Xinjun , Guo Junming
Published: September 2020

Background

KLF5is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers.KLF5functions as a transcription factor and regulates the diverse protein-coding genes (PCGs) in colorectal cancer (CRC). However, the long non-coding RNAs (lncRNAs) regulated byKLF5in CRC are currently unknown.

Methods

In this study, we first designed a computational pipeline to determine the PCG and lncRNA targets ofKLF5in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors ofKLF5were then searched for through bioinformatics analysis. We also constructed a regulatory network forKLF5and annotated its functions. Finally, one of theKLF5lncRNA targets,SNHG12, was selected to further explore its expression pattern and functions in CRC.

Results

We were able to identify 19 lncRNA targets ofKLF5and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factorsARandHSF1as the regulatory co-factors ofKLF5through bioinformatics analysis. Then, through the analysis of the regulatory network, we found thatKLF5may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, theSNHG12up-regulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates thatSNHG12may play a critical part in CRC tumorigenesis and progression. Additionally, expression ofSNHG12was found to be down-regulated in CRC cell lines whenKLF5expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels ofSNHG12andKLF5, further alluding to their regulatory relationship.

Conclusions

In conclusion, the network analysis ofKLF5targets indicates thatSNHG12may be a significant lncRNA in CRC.
Population estimation and harm reduction among people who inject drugs in Addis Ababa, Ethiopia
Authors: Deyessa Negussie , Senbete Bekele , Abdo Aman , Mundia Bernard M.
Published: September 2020

Background

Injecting drug use is known to contribute significantly to the spread of the HIV epidemic in many parts of the developing world. Due to the hidden nature and stigma of the problem, it is difficult to study using routine surveys. Therefore, this study aims to estimate the number of people who inject drugs in Addis Ababa, Ethiopia, and to describe the epidemiological and social situation related to HIV among people who inject drugs.

Methods

The study used rapid assessment methods, followed by combined methods of estimating populations, using nomination and multiplier methods. The combined methods used two datasets: the first includes the proportion of people who use services within a year as a multiplier, and the second, a count of the list of people with a problem who used the specific service within a year as a benchmark. The rapid assessment incorporated different qualitative tools to elicit information related to injectable drugs, using existing data sources, in-depth interviews, and focus group discussions.

Results

The study estimated a total of 4068; with 95% CI (3196, 5207) people who inject drugs (PWIDs) in Addis Ababa. The study found people who inject drugs were young in age, male, with a lower educational status, unmarried, and living in small clerical business. People who inject drugs and participated in the study were more likely to use additional substances like alcohol, khat, and cannabis. The most common form of injectable drug used was heroin, and most of the people who inject drugs reported sharing syringes and needles. A high proportion of study subjects also disclosed having positive test results for HIV, hepatitis B, and C.

Conclusion

The population size of people who inject drugs in Addis Ababa is high. Lack of service in harm reduction in the city has made PWIDs vulnerable and at higher risk for HIV/AIDs and hepatitis B and C. Therefore, responsible bodies must start implementing the essential harm reduction strategies given by the World Health Organization.
Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1
Authors: Yin Ping , Bai Yu , Wang Zhuo , Sun Yu , Gao Jian , Na Lei , Zhang Zhongbo , Wang Wei , Zhao Chenghai
Published: September 2020

Mesenchymal-like stemness is characterized by epithelial-mesenchymal transition (EMT). Breast cancer (BC) cell mesenchymal-like stemness is responsible for distal lung metastasis. Interrogation of databases showed that Fzd7 was closely associated with a panel of mesenchymal-related genes and a panel of stemness-related genes. Fzd7 knockdown in mesenchymal-like MDA-MB-231 and Hs578T cells reduced expression of Vimentin, Slug and Zeb1, induced an epithelial-like morphology, inhibited cell motility, impaired mammosphere formation and decreased Lgr5+ subpopulation. In contrast, Fzd7 overexpression in MCF7 cells resulted in opposite changes. Fzd7 knockdown delayed xenograft tumor formation, suppressed tumor growth, and impaired lung metastasis. Mechanistically, Fzd7 combined with Wnt5a/b and modulated expression of phosphorylated Stat3 (p-STAT3), Smad3 and Yes-associated protein 1 (Yap1). Moreover, Fzd7-Wnt5b modulated expression of collagen, type VI, alpha 1 (Col6a1). Both Wnt5b knockdown and Col6a1 knockdown disrupted BC cell mesenchymal phenotype and stemness. Taken together, Fzd7 contributes to BC cell EMT and stemness, inducing tumorigenesis and metastasis, mainly through a non-canonical Wnt5b pathway. Col6a1 is implicated in Fzd7-Wnt5b signaling, and mediates Fzd7-Wnt5b -induced mesenchymal-like stemness.
Non-classical 1p36 deletion in a patient with Duane retraction syndrome: case report and literature review
Authors: Yokoyama Emiy , Villarroel Camilo E. , Diaz Sinhué , Del Castillo Victoria , Pérez-Vera Patricia , Salas Consuelo , Gómez Samuel , Barreda Reneé , Molina Bertha , Frias Sara
Published: September 2020

Background

Monosomy of 1p36 is considered the most common terminal microdeletion syndrome. It is characterized by intellectual disability, growth retardation, seizures, congenital anomalies, and distinctive facial features that are absent when the deletion is proximal, beyond the 1p36.32 region. In patients with proximal deletions, little is known about the associated phenotype, since only a few cases have been reported in the literature. Ocular manifestations in patients with classical 1p36 monosomy are frequent and include strabismus, myopia, hypermetropia, and nystagmus. However, as of today only one patient with 1p36 deletion and Duane retraction syndrome (DRS) has been reported.

Case presentation

We describe a patient with intellectual disability, facial dysmorphism, and bilateral Duane retraction syndrome (DRS) type 1. Array CGH showed a 7.2 Mb de novo deletion from 1p36.31 to 1p36.21.

Discussion

Our patient displayed DRS, which is not part of the classical phenotype and is not a common clinical feature in 1p36 deletion syndrome; we hypothesized that this could be associated with the overlapping deletion between the distal and proximal 1p36 regions. DRS is one of the Congenital Cranial Dysinnervation Disorders, and a genetic basis for the syndrome has been extensively reported. The HES3 gene is located at 1p36.31 and could be associated with oculomotor alterations, including DRS, since this gene is involved in the development of the 3rd cranial nerve and the 6th cranial nerve’s nucleus. We propose that oculomotor anomalies, including DRS, could be related to proximal 1p36 deletion, warranting a detailed ophthalmologic evaluation of these patients.
Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: statistical analysis plan for the Getting it Right: Addressing Shoulder Pain (GRASP) 2 × 2 factorial multicentre randomised controlled trial
Authors: Marian Ioana R. , Hopewell Sally , Keene David J. , Cureton Lucy , Lamb Sarah E. , Dutton Susan J.
Published: September 2020

Background

The Getting it Right: Addressing Shoulder Pain (GRASP) trial assesses the clinical and cost-effectiveness of individually tailored, progressive exercise compared with best practice advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. This article describes the statistical analysis plan for the GRASP randomised controlled trial.

Methods/design

GRASP is a multicentre randomised controlled trial using a 2 × 2 factorial design. Adults aged ≥ 18 years with a new episode of shoulder pain related to a rotator cuff disorder, not currently receiving physiotherapy or being considered for surgery, are randomised (centralised computer-generated 1:1:1:1 allocation ratio) to one of four interventions: (1) progressive exercise (up to 6 physiotherapy sessions), (2) best practice advice (one physiotherapy session), (3) subacromial corticosteroid injection then progressive exercise and (4) subacromial corticosteroid injection then best practice advice. The primary outcome is the mean difference in Shoulder Pain and Disability Index (SPADI) total score over 12 months. Secondary outcomes are as follows: pain and function SPADI subdomains, health-related quality of life (EuroQol EQ-5D-5L), sleep disturbance, return to activity, global impression of change, health resource use, out-of-pocket expenses and work disability. Here, we describe in detail the following: sample size calculation, descriptive statistics of the primary and secondary outcomes, statistical models used for the analysis of the main outcomes, handling of missing data, planned sensitivity and subgroup analyses. This pre-specified statistical analysis plan was written and submitted without prior knowledge of the trial results.

Discussion

Publication of the statistical analysis plan for the GRASP trial aims to reduce the risk of outcome reporting bias and increase transparency of the data analysis. Any deviations or changes to the current SAP will be described and justified in the final study report and any results publications.

Trial registration

International Standard Randomised Controlled Trial Number ISRCTN16539266. Registered on 14 June 2016. EudraCT number 2016-002991-28. Registered on 12 June 2016.
Morphological identification keys for adults of sand flies (Diptera: Psychodidae) in Sri Lanka
Authors: Wijerathna Tharaka , Gunathilaka Nayana
Published: September 2020

Background

Phlebotomine sand flies are a medically important group of insects that is responsible for the transmission of leishmaniasis. Surveillance plays a major role in vector control programmes through exploring species abundance, potential entomological risk and designing appropriate control measures. In field surveillance programmes of such nature, morphological identification of vector species is of paramount importance. However, in Sri Lanka, there is no published taxonomic key available for the identification of leishmaniasis vectors.

Method

Identification keys for both male and females of the sand flies recorded in Sri Lanka were developed using morphological features. Main identification features were compared with the original observation of specimens collected from surveys and the use of published literature. Photographic illustrations of morphological features are included with the intention of making the keys user-friendly for non-taxonomists.

Results

A total of 22 sand fly species (Diptera: Psychodidae) of the genera Phlebotomus and Sergentomyia reported in Sri Lanka from 1910 to 2019 are included in the present work.

Conclusion

This simplified key, along with photographs taken from specimens would be beneficial to the health staff, entomologists and research staff who deal with leishmaniasis control programmes and vector-related studies.
Therapeutic potential of fucoidan in the reduction of hepatic pathology in murine schistosomiasis japonica
Authors: Bai Xueqi , Li Maining , Wang Xinyue , Chang Hao , Ni Yangyue , Li Chen , He Kaiyue , Wang Huiquan , Yang Yuxuan , Tian Tian , Hou Min , Ji Minjun , Xu Zhipeng
Published: September 2020

Background

Hepatic granuloma formation and fibrosis as the consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology ofSchistosoma japonicuminfection. It has been proposed that fucoidan, a sulfated polysaccharide existing naturally in brown seaweedFucus vesiculosus, plays a diversified role to perform immunomodulatory activities. However, whether fucoidan functions in the host hepatic pathology is unknown and identifying the potential mechanism that is responsible for hepatic improvement is still necessary.

Methods

We evaluated the hepatic pathology fromS. japonicum-infected mice after treatment with fucoidan. qRT-PCR and immunofluorescence were used to detect the pro- or anti-inflammatory factors and the phosphorylated p65 in the livers. In addition, flow cytometry was also performed to investigate the T cell subsets in theS. japonicum-infected mice after treatment with fucoidan, and functional molecules relatively specific to Treg cells were detectedin vitro. Furthermore, macrophages were treated with fucoidanin vitroand to detect the inflammatory cytokines.

Results

Treatment with fucoidan significantly reduced the hepatic granuloma size and fibrosis response duringS. japonicuminfection. The attenuated phospho-p65 protein levels and the mRNA levels of pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) were observed in the livers from fucoidan-treatedS. japonicum-infected mice; however, the mRNA levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased. In addition, the infiltration of Treg cells was significantly enhanced both in the livers and spleens from fucoidan-treatedS. japonicum-infected mice. Consistent with this, the mRNA levels of IL-10 and TGF-β were dramatically increased in the livers fromS. japonicum-infected mice after fucoidan treatment. Furthermore,in vitrostimulated splenocytes with fucoidan resulted in increasing Treg cells in splenocytes as well as the functional expression of CC chemokine receptor type 4 (CCR4) and CXC chemokine receptor type 5 (CXCR5) in Treg cells. Additionally, fucoidan promoted the mRNA levels of IL-4 and IL-13 in macrophages.

Conclusions

These findings suggest an important role of natural fucoidan in reducing hepatic pathology in the progress ofS. japonicuminfection with a stronger Treg response, which may reveal a new potential therapeutic strategy for hepatic disease caused by parasitic chronic infection.
Short-wave enhances mesenchymal stem cell recruitment in fracture healing by increasing HIF-1 in callus
Authors: Ye Dongmei , Chen Chen , Wang Qiwen , Zhang Qi , Li Sha , Liu Hongwei
Published: September 2020

Background

As a type of high-frequency electrotherapy, a short-wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms remain unclear.

Purpose

To observe the effect of Short-Wave therapy on mesenchymal stem cell (MSC) homing and relative mechanisms associated with fracture healing.

Materials and methods

For in vivo study, the effect of Short-Wave therapy to fracture healing was examined in a stabilized femur fracture model of 40 SD rats. Radiography was used to analyze the morphology and microarchitecture of the callus. Additionally, fluorescence assays were used to analyze the GFP-labeled MSC homing after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast from newborn rats simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC from rats was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot.

Results

Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Wave therapy upregulated HIF-1 and SDF-1 expression in osteoblast and its cultured medium, as well as the expression of CXCR-4, β-catenin, F-actin, and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC.

Conclusions

These results suggested that Short-Wave therapy could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.
Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats
Authors: Sun Junyi , Ding Xianfei , Liu Shaohua , Duan Xiaoguang , Liang Huoyan , Sun Tongwen
Published: September 2020

Background

We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) may ameliorate sepsis-induced acute lung injury (ALI) and change microorganism populations in the gut microbiota, such as that of Firmicutes and Bacteroidetes.

Methods

A total of 60 male adult Sprague-Dawley (SD) rats were separated into three groups: the sham control (SC) group, the sepsis induced by cecal ligation and puncture (CLP) group, and the ADMSC treatment (CLP-ADMSCs) group, in which rats underwent the CLP procedure and then received 1 × 106 ADMSCs. Rats were sacrificed 24 h after the SC or CLP procedures. To study the role of ADMSCs during ALI caused by sepsis and examine the impact of ADMSCs on the gut microbiome composition, rat lungs were histologically evaluated using hematoxylin and eosin (H&E) staining, serum levels of pro-inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA), and fecal samples were collected and analyzed using 16S rDNA sequencing.

Results

The serum levels of inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, were significantly increased in rats after the CLP procedure, but were significantly decreased in rats treated with ADMSCs. Histological evaluation of the rat lungs yielded results consistent with the changes in IL-6 levels among all groups. Treatment with ADMSCs significantly increased the diversity of the gut microbiota in rats with sepsis. The principal coordinates analysis (PCoA) results showed that there was a significant difference between the gut microbiota of the CLP-ADMSCs group and that of the CLP group. In rats with sepsis, the proportion of Escherichia–Shigella (P = 0.01) related to lipopolysaccharide production increased, and the proportion of Akkermansia (P = 0.02) related to the regulation of intestinal mucosal thickness and the maintenance of intestinal barrier function decreased. These changes in the gut microbiota break the energy balance, aggravate inflammatory reactions, reduce intestinal barrier functions, and promote the translocation of intestinal bacteria. Intervention with ADMSCs increased the proportion of beneficial bacteria, reduced the proportion of harmful bacteria, and normalized the gut microbiota.

Conclusions

Therapeutically administered ADMSCs ameliorate CLP-induced ALI and improves gut microbiota, which provides a potential therapeutic mechanism for ADMSCs in the treatment of sepsis.
Double sperm cloning (DSC) is a promising strategy in mammalian genetic engineering and stem cell research
Authors: Zhang Zhi-ping , Zhang Jun-tao , Huang Shu-cheng , He Xiu-yuan , Deng Li-xin
Published: September 2020

Embryonic stem cells (ESCs) derived from somatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSCs) are promising tools for meeting the personalized requirements of regenerative medicine. However, some obstacles need to be overcome before clinical trials can be undertaken. First, donor cells vary, and the reprogramming procedures are diverse, so standardization is a great obstacle regarding SCNT and iPSCs. Second, somatic cells derived from a patient may carry mitochondrial DNA mutations and exhibit telomere instability with aging or disease, and SCNT-ESCs and iPSCs retain the epigenetic memory or epigenetic modification errors. Third, reprogramming efficiency has remained low. Therefore, in addition to improving their success rate, other alternatives for producing ESCs should be explored. Producing androgenetic diploid embryos could be an outstanding strategy; androgenic diploid embryos are produced through double sperm cloning (DSC), in which two capacitated sperms (XY or XX, sorted by flow cytometer) are injected into a denucleated oocyte by intracytoplasmic sperm injection (ICSI) to reconstruct embryo and derive DSC-ESCs. This process could avoid some potential issues, such as mitochondrial interference, telomere shortening, and somatic epigenetic memory, all of which accompany somatic donor cells. Oocytes are naturally activated by sperm, which is unlike the artificial activation that occurs in SCNT. The procedure is simple and practical and can be easily standardized. In addition, DSC-ESCs can overcome ethical concerns and resolve immunological response matching with sperm providers. Certainly, some challenges must be faced regarding imprinted genes, epigenetics, X chromosome inactivation, and dosage compensation. In mice, DSC-ESCs have been produced and have shown excellent differentiation ability. Therefore, the many advantages of DSC make the study of this process worthwhile for regenerative medicine and animal breeding.
Predictive value of quantitative 18F-FDG-PET radiomics analysis in patients with head and neck squamous cell carcinoma
Authors: Martens Roland M. , Koopman Thomas , Noij Daniel P. , Pfaehler Elisabeth , Übelhör Caroline , Sharma Sughandi , Vergeer Marije R. , Leemans C. René , Hoekstra Otto S. , Yaqub Maqsood , Zwezerijnen Gerben J. , Heymans Martijn W. , Peeters Carel F. W. , de Bree Remco , de Graaf Pim , Castelijns Jonas A. , Boellaard Ronald
Published: September 2020

Background

Radiomics is aimed at image-based tumor phenotyping, enabling application within clinical-decision-support-systems to improve diagnostic accuracy and allow for personalized treatment. The purpose was to identify predictive 18-fluor-fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography (PET) radiomic features to predict recurrence, distant metastasis, and overall survival in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy.

Methods

Between 2012 and 2018, 103 retrospectively (training cohort) and 71 consecutively included patients (validation cohort) underwent 18F-FDG-PET/CT imaging. The 434 extracted radiomic features were subjected, after redundancy filtering, to a projection resulting in outcome-independent meta-features (factors). Correlations between clinical, first-order 18F-FDG-PET parameters (e.g., SUVmean), and factors were assessed. Factors were combined with 18F-FDG-PET and clinical parameters in a multivariable survival regression and validated. A clinically applicable risk-stratification was constructed for patients’ outcome.

Results

Based on 124 retained radiomic features from 103 patients, 8 factors were constructed. Recurrence prediction was significantly most accurate by combining HPV-status, SUVmean, SUVpeak, factor 3 (histogram gradient and long-run-low-grey-level-emphasis), factor 4 (volume-difference, coarseness, and grey-level-non-uniformity), and factor 6 (histogram variation coefficient) (CI = 0.645). Distant metastasis prediction was most accurate assessing metabolic-active tumor volume (MATV)(CI = 0.627). Overall survival prediction was most accurate using HPV-status, SUVmean, SUVmax, factor 1 (least-axis-length, non-uniformity, high-dependence-of-high grey-levels), and factor 5 (aspherity, major-axis-length, inversed-compactness and, inversed-flatness) (CI = 0.764).

Conclusions

Combining HPV-status, first-order 18F-FDG-PET parameters, and complementary radiomic factors was most accurate for time-to-event prediction. Predictive phenotype-specific tumor characteristics and interactions might be captured and retained using radiomic factors, which allows for personalized risk stratification and optimizing personalized cancer care.

Trial registration

Trial NL3946 (NTR4111), local ethics commission reference: Prediction 2013.191 and 2016.498. Registered 7 August 2013, https://www.trialregister.nl/trial/3946
Ultrasonographic assessment of parasternal intercostal muscles during mechanical ventilation
Authors: Formenti Paolo , Umbrello Michele , Dres Martin , Chiumello Davide
Published: September 2020

Although mechanical ventilation is a lifesaving treatment, abundant evidence indicates that its prolonged use (1 week or more) promotes respiratory muscle weakness due to both contractile dysfunction and atrophy. Along with the diaphragm, the intercostal muscles are one of the most important groups of respiratory muscles. In recent years, muscular ultrasound has become a useful bedside tool for the clinician to identify patients with respiratory muscle dysfunction related to critical illness and/or invasive mechanical ventilation. Images obtained over the course of illness can document changes in muscle dimension and can be used to estimate changes in function. Recent evidence suggests the clinical usefulness of ultrasound imaging in the assessment of intercostal muscle function. In this narrative review, we summarize the current literature on ultrasound imaging of the parasternal intercostal muscles as used to assess the extent of muscle activation and muscle weakness and its potential impact during discontinuation of mechanical ventilation. In addition, we proposed a practical flowchart based on recent evidence and experience of our group that can be applied during the weaning phase. This approach integrates multiple predictive parameters of weaning success with respiratory muscle ultrasound.
Bacterial and viral co-infections in patients with severe SARS-CoV-2 pneumonia admitted to a French ICU
Authors: Contou Damien , Claudinon Aurore , Pajot Olivier , Micaëlo Maïté , Longuet Flandre Pascale , Dubert Marie , Cally Radj , Logre Elsa , Fraissé Megan , Mentec Hervé , Plantefève Gaëtan
Published: September 2020

Background

Data on the prevalence of bacterial and viral co-infections among patients admitted to the ICU for acute respiratory failure related to SARS-CoV-2 pneumonia are lacking. We aimed to assess the rate of bacterial and viral co-infections, as well as to report the most common micro-organisms involved in patients admitted to the ICU for severe SARS-CoV-2 pneumonia.

Patients and methods

In this monocenter retrospective study, we reviewed all the respiratory microbiological investigations performed within the first 48 h of ICU admission of COVID-19 patients (RT-PCR positive for SARS-CoV-2) admitted for acute respiratory failure.

Results

From March 13th to April 16th 2020, a total of 92 adult patients (median age: 61 years, 1st–3rd quartiles [55–70]; males: n = 73/92, 79%; baseline SOFA: 4 [3–7] and SAPS II: 31 [21–40]; invasive mechanical ventilation: n = 83/92, 90%; ICU mortality: n = 45/92, 49%) were admitted to our 40-bed ICU for acute respiratory failure due to SARS-CoV-2 pneumonia. Among them, 26 (28%) were considered as co-infected with a pathogenic bacterium at ICU admission with no co-infection related to atypical bacteria or viruses. The distribution of the 32 bacteria isolated from culture and/or respiratory PCRs was as follows: methicillin-sensitive Staphylococcus aureus (n = 10/32, 31%), Haemophilus influenzae (n = 7/32, 22%), Streptococcus pneumoniae (n = 6/32, 19%), Enterobacteriaceae (n = 5/32, 16%), Pseudomonas aeruginosa (n = 2/32, 6%), Moraxella catarrhalis (n = 1/32, 3%) and Acinetobacter baumannii (n = 1/32, 3%). Among the 24 pathogenic bacteria isolated from culture, 2 (8%) and 5 (21%) were resistant to 3rd generation cephalosporin and to amoxicillin–clavulanate combination, respectively.

Conclusions

We report on a 28% rate of bacterial co-infection at ICU admission of patients with severe SARSCoV-2 pneumonia, mostly related to Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Enterobacteriaceae. In French patients with confirmed severe SARSCoV-2 pneumonia requiring ICU admission, our results encourage the systematic administration of an empiric antibiotic monotherapy with a 3rd generation cephalosporin, with a prompt de-escalation as soon as possible. Further larger studies are needed to assess the real prevalence and the predictors of co-infection together with its prognostic impact on critically ill patients with severe SARS-CoV-2 pneumonia.
Point prevalence survey of antimicrobial use in three hospitals in North-Eastern Tanzania
Authors: Horumpende Pius G. , Mshana Stephen E. , Mouw Elise F. , Mmbaga Blandina T. , Chilongola Jaffu O. , de Mast Quirijn
Published: September 2020

Background

Antimicrobial resistance (AMR) is one of the most urgent global health threats with low-resource countries being disproportionately affected. Targeted interventions require insight in antibiotic prescription practices. A point prevalence survey (PPS) is a well-known tool to get insight in antibiotic dispensing practices in hospitals and identify areas for improvement. Here, we describe the results of a PPS performed in a tertiary, regional and district hospital in Kilimanjaro region in Tanzania.

Methods

A PPS was performed in the Kilimanjaro Christian Medical Centre (KCMC; tertiary hospital), Mawenzi (regional) and St. Joseph (district) hospital in November and December 2016. Antibiotic use in all patients admitted more than 24 h and those undergoing surgery was recorded. All clinical wards were included except the pediatrics. Data from a single ward were collected on the same day.

Results

A total of 399 patients were included in the PPS: 232 patients from KCMC, 94 from Mawenzi hospital and 73 patients from St. Joseph hospital. Overall prevalence of antibiotic use was 44.0%: 38% in KCMC, 59% in Mawenzi and 63% in St. Joseph. Ceftriaxone (n = 94, 29.8%), metronidazole (n = 79, 23.9%) and other antibiotics belonging to the penicillin class (n = 89, 28.3%) were most commonly prescribed. Antibiotics prescribed for surgical prophylaxis were continued for more than 3 days in 57% of cases.

Conclusion

Our study shows a rate of broad-spectrum antibiotic use in Tanzanian hospitals and prolonged surgical antibiotic prophylaxis being a common practice. PPS is an important tool to improve future antibiotic use in Tanzania hospitals.
Parental self-medication with antibiotics for children promotes antibiotic over-prescribing in clinical settings in China
Authors: Xu Jiayao , Wang Xiaomin , Sun Kai Sing , Lin Leesa , Zhou Xudong
Published: September 2020

Background

Self-medication with antibiotics (SMA) is one of the most dangerous inappropriate antibiotic use behaviors. This study aims to investigate the impact of parental SMA for children before a consultation on their doctor’s subsequent antibiotic prescribing behavior, including intravenous (IV) antibiotic use in the clinical setting of China.

Methods

A cross-sectional survey was conducted between June 2017 and April 2018 in three provinces of China. A total of 9526 parents with children aged 0–13 years were investigated. Data from 1275 parents who had self-medicated their children and then visited a doctor in the past month were extracted and analyzed.

Results

One-third (410) of the studied children had parental SMA before the consultation and 83.9% of them were subsequently prescribed antibiotics by doctors. Children with parental SMA were more likely to be prescribed antibiotics (aOR = 7.79, 95% CI [5.74–10.58]), including IV antibiotics (aOR = 3.05, 95% CI [2.27–4.11]), and both oral and IV antibiotics (aOR = 3.42, 95% CI [2.42–4.84]), than children without parental SMA. Parents with SMA behaviors were more likely to request antibiotics (aOR = 4.05, 95% CI [2.59–6.31]) including IV antibiotics (aOR = 2.58, 95% CI [1.40–4.76]), and be fulfilled by doctors (aOR = 3.22, 95% CI [1.20–8.63]).

Conclusions

Tailored health education for parents is required in both community and clinical settings to discourage parental SMA for children. The doctors should not prescribe unnecessary antibiotics to reinforce parents’ SMA behaviors. We recommend expanding the current IV antibiotics ban in outpatient settings of China to cover outpatient pediatrics.