bluuebunny/crossref_metadata_2025 huggingface dataset:
How German health insurance providers use social online networks to promote healthy lifestyles: a content analysis of Facebook® accounts
Authors: Loss Julika , von Uslar Charlotte
Published: February 2021

Background

Social networking sites such as Facebook® can contribute to health promotion and behaviour change activities, but are currently underused for this purpose. In Germany, health insurance companies are relevant public health agencies that are responsible for health promotion, primary prevention, and health education. We intended to analyse the Facebook® accounts of health insurance providers to explore the range of prevention topics addressed, identify the communication formats used, and analyse user activity stimulated by prevention-related posts.

Methods

We performed a quantitative content analysis of text and picture data on Facebook® accounts (9 months in retrospect) in a cross-sectional study design. 64/159 German health insurance providers hosted a Facebook® page, 25/64 posted ≥ 10 posts/months. Among those 25, we selected 17 health insurance companies (12 public, 5 private) for analysis. All posts were categorized according to domains in the classification system that was developed for this study, and the number of likes and comments was counted. The data were analysed using descriptive statistics.

Results

We collected 3,763 Facebook® posts, 32% of which had a focus on prevention. The frequency of prevention-related posts varied among health insurance providers (1–25 per month). The behaviours addressed most frequently were healthy nutrition, physical activity, and stress/anxiety relief, often in combination with each other. All these topics yielded a moderate user engagement (30–120 likes, 2–10 comments per post). User engagement was highest when a competition or quiz were posted (11% of posts). The predominant communication pattern was health education, often supplemented by photos or links, or information about offline events (e.g. a public run). Some providers regularly engaged in two-side communication with users, inviting tips, stories or recipes, or responding to individual comments. Still, the interactive potential offered by Facebook® was only partly exploited.

Conclusions

Those few health insurace companies that regularly post content about prevention or healthy lifestyles on their Facebook® accounts comply with suggestions given for social media communication. Still, many health insurance providers fail to actively interact with wider audiences. Whether health communication on Facebook® can actually increase health literacy and lead to behaviour changes still needs to be evaluated.
CONECT-6: a case-finding tool to identify patients with complex health needs
Authors: Hudon Catherine , Bisson Mathieu , Dubois Marie-France , Chiu Yohann , Chouinard Maud-Christine , Dubuc Nicole , Elazhary Nicolas , Sabourin Véronique , Vanasse Alain
Published: February 2021

Background

Early identification of patients with chronic conditions and complex health needs in emergency departments (ED) would enable the provision of services better suited to their needs, such as case management. A case-finding tool would ultimately support ED teams to this end and could reduce the cost of services due to avoidable ED visits and hospitalizations. The aim of this study was to develop and validate a short self-administered case-finding tool in EDs to identify patients with chronic conditions and complex health needs in an adult population.

Methods

This prospective development and initial validation study of a case-finding tool was conducted in four EDs in the province of Quebec (Canada). Adult patients with chronic conditions were approached at their third or more visit to the ED within 12 months to complete a self-administered questionnaire, which included socio-demographics, a comorbidity index, the reference standard INTERMED self-assessment, and 12 questions to develop the case-finding tool. Significant variables in bivariate analysis were included in a multivariate logistic regression analysis and a backward elimination procedure was applied. A receiver operating characteristic (ROC) curve was developed to identify the most appropriate threshold score to identify patients with complex health needs.

Results

Two hundred ninety patients participated in the study. The multivariate analysis yielded a six-question tool, COmplex NEeds Case-finding Tool – 6 (CONECT-6), which evaluates the following variables: low perceived health; limitations due to pain; unmet needs; high self-perceived complexity; low income; and poor social support. With a threshold of two or more positive answers, the sensitivity was 90% and specificity 66%. The positive and negative predictive values were 49 and 95% respectively.

Conclusions

The case-finding process is the essential characteristic of case management effectiveness. This study presents the first case-finding tool to identify adult patients with chronic conditions and complex health needs in ED.
Multiple copies of the oxytetracycline gene cluster in selected Streptomyces rimosus strains can provide significantly increased titers
Authors: Pikl Špela , Carrillo Rincón Andrés Felipe , Slemc Lucija , Goranovič Dušan , Avbelj Martina , Gjuračić Krešimir , Sucipto Hilda , Stare Katja , Baebler Špela , Šala Martin , Guo Meijin , Luzhetskyy Andriy , Petković Hrvoje , Magdevska Vasilka
Published: February 2021

Background

Natural products are a valuable source of biologically active compounds that have applications in medicine and agriculture. One disadvantage with natural products is the slow, time-consuming strain improvement regimes that are necessary to ensure sufficient quantities of target compounds for commercial production. Although great efforts have been invested in strain selection methods, many of these technologies have not been improved in decades, which might pose a serious threat to the economic and industrial viability of such important bioprocesses.

Results

In recent years, introduction of extra copies of an entire biosynthetic pathway that encodes a target product in a single microbial host has become a technically feasible approach. However, this often results in minor to moderate increases in target titers. Strain stability and process reproducibility are the other critical factors in the industrial setting. Industrial Streptomyces rimosus strains for production of oxytetracycline are one of the most economically efficient strains ever developed, and thus these represent a very good industrial case. To evaluate the applicability of amplification of an entire gene cluster in a single host strain, we developed and evaluated various gene tools to introduce multiple copies of the entire oxytetracycline gene cluster into three different Streptomyces rimosus strains: wild-type, and medium and high oxytetracycline-producing strains. We evaluated the production levels of these engineered S. rimosus strains with extra copies of the oxytetracycline gene cluster and their stability, and the oxytetracycline gene cluster expression profiles; we also identified the chromosomal integration sites.

Conclusions

This study shows that stable and reproducible increases in target secondary metabolite titers can be achieved in wild-type and in high oxytetracycline-producing strains, which always reflects the metabolic background of each independent S. rimosus strain. Although this approach is technically very demanding and requires systematic effort, when combined with modern strain selection methods, it might constitute a very valuable approach in industrial process development.
Highly glycosylated MUC1 mediates high affinity L-selectin binding at the human endometrial surface
Authors: Francis Lewis W. , Yao Seydou N. , Powell Lydia C. , Griffiths Sean , Berquand Alexander , Piasecki Thomas , Howe William , Gazze Andrea S. , Farach-Carson Mary C. , Constantinou Pamela , Carson Daniel , Margarit Lavinia , Gonzalez Deya , Conlan R. Steven
Published: February 2021

Background

Sialyl-Lewis X/L-selectin high affinity binding interactions between transmembrane O-glycosylated mucins proteins and the embryo have been implicated in implantation processes within the human reproductive system. However, the adhesive properties of these mucins at the endometrial cell surface are difficult to resolve due to known discrepancies between in vivo models and the human reproductive system and a lack of sensitivity in current in vitro models. To overcome these limitations, an in vitro model of the human endometrial epithelial was interrogated with single molecule force spectroscopy (SMFS) to delineate the molecular configurations of mucin proteins that mediate the high affinity L-selectin binding required for human embryo implantation.

Results

This study reveals that MUC1 contributes to both the intrinsic and extrinsic adhesive properties of the HEC-1 cellular surface. High expression of MUC1 on the cell surface led to a significantly increased intrinsic adhesion force (148 pN vs. 271 pN, p < 0.001), whereas this adhesion force was significantly reduced (271 pN vs. 118 pN, p < 0.001) following siRNA mediated MUC1 ablation. Whilst high expression of MUC1 displaying elevated glycosylation led to strong extrinsic (> 400 pN) L-selectin binding at the cell surface, low expression of MUC1 with reduced glycosylation resulted in significantly less (≤200 pN) binding events.

Conclusions

An optimal level of MUC1 together with highly glycosylated decoration of the protein is critical for high affinity L-selectin binding. This study demonstrates that MUC1 contributes to cellular adhesive properties which may function to facilitate trophoblast binding to the endometrial cell surface through the L-selectin/sialyl-Lewis x adhesion system subsequent to implantation.
A multiplex real-time PCR quantitation of human herpesvirus-6, 7, 8 viruses: application in blood transfusions
Authors: Zheng Yi , Zhao Youyun , Wang Yefu , Rao Jun
Published: February 2021

Background

In recent years, fluorescent quantitative polymerase chain reaction assays for detecting viral DNA are in widespread use throughout the world. However, considering the wide distribution of new herpesvirus among the population, we constructed a method to detect HHV-6, 7, and 8 simultaneously.

Methods

The blood samples of 74 blood donors and 45 pityriasis rosea patients were collected. The recombinant plasmids containing U67, U36, and orf65 were constructed to optimize the PCR reaction system. The forward and reverse primers and probe sequences of HHV-6 were as follows: TAAATATCGATGCCGCTCTG, ACGTTCTAGCCATCTTCTTTG, CGCAAACGACAAAGCCA. The forward and reverse primers and probe sequences of HHV-7 were as follows: TTAGACATCTTACACGACAGC, CAGCTTTTCGAACTTGTCAC, TTCATCGGGTACGTCCA. The forward and reverse primers and probe sequences of HHV-8 were as follows: GCGACATATTTCCCTGATCC, CCAACTTTAAGGTGAGAGACC, CATGCGAGCCACCAG. Through the detection of housekeeping genes, DNA sequencing, and optimization of the PCR reaction system, the triple fluorescent quantitative PCR detection system was constructed. Blood samples of blood transfusion staff and pityriasis rosea patients were detected.

Results

The correlations of HHV-6, 7, and 8 between single and multiplex PCR are 0.980, 0.987, 0.965, respectively. In 74 blood donor samples, 16.2% of HHV-6 and 55% of HHV-7 were positive (viral load > 3 log10 copies/ml) according to multiplex real-time PCR. In 45 patients suspected of pityriasis rosea (PR) infection, 40% HHV-6, 73.3% positive cases are found.

Conclusion

With the safety of blood transfusion being a major concern of the public, this method will show good specificity and sensitivity in blood transfusion screening.
Using animation to teach breastfeeding physiology: a proof of concept study
Authors: Hartney Nicki , Dooley Dolores , Nagle Cate
Published: February 2021

Background

Breastfeeding provides the optimal nourishment for infant and child health and supporting mothers to breastfeed is a global health priority. Midwives are uniquely placed to provide breastfeeding education and support to the woman and it is imperative that they have a sound understanding of the physiological underpinnings of breastfeeding. However, midwifery students and some midwives continue to struggle with the complex physiology of lactation. The purpose of this study was to evaluate an instructional animation resource to teach breastfeeding physiology to student and practicing midwives. Further, this study also offers insights into how student and practicing midwives accept novel approaches to learning.

Methods

A cross-sectional survey design using both quantitative and qualitative approaches was employed in this proof of concept study. The setting was online with midwifery students recruited from Deakin University and registered midwives recruited from the Australian College of Midwives membership. Snowball sampling was also employed to recruit midwives through professional networks of the research team. The quantitative part of this study included a structured online questionnaire for midwives and midwifery students and descriptive statistics were used to present the quantitative data. The qualitative data were collected from open-ended questions on the questionnaire and a deductive approach was used for analysing the data.

Results

This proof of concept study collected data from 110 participants and provides evidence for the use of animation as an effective pedagogical tool to explain complex concepts. The animated instructional resource was viewed favourably by both the midwifery students and practicing midwives.

Conclusions

The findings from this study, support the pedagogical advantages of animated instructional resources for teaching complex physiology. Further, educators should be encouraged and feel confident to develop and use animation technology as both an engaging and effective teaching resource especially for complex concepts.
Heritable gene editing using FT mobile guide RNAs and DNA viruses
Authors: Lei Jianfeng , Dai Peihong , Li Yue , Zhang Wanqi , Zhou Guantong , Liu Chao , Liu Xiaodong
Published: February 2021

Background

The virus-induced genome editing (VIGE) system can be used to quickly identify gene functions and generate knock-out libraries as an alternative to the virus-induced gene silencing (VIGS). Although plant virus-mediated VIGE has been shown to have great application prospects, edited genes cannot be transferred to the next generations using this system, as viruses cannot enter into shoot apical meristem (SAM) in plants.

Results

We developed a novel cotton leaf crumple virus (CLCrV)-mediated VIGE system designed to target BRI1, GL2, PDS genes, and GUS transgene in A. thaliana by transforming Cas9 overexpression (Cas9-OE) A. thaliana. Given the deficiency of the VIGE system, ProYao::Cas9 and Pro35S::Cas9 A. thaliana were transformed by fusing 102 bp FT mRNAs with sgRNAs so as to explore the function of Flowering Locus T (FT) gene in delivering sgRNAs into SAM, thus avoiding tissue culture and stably acquiring heritable mutant offspring. Our results showed that sgRNAs fused with FT mRNA at the 5′ end (FT strategy) effectively enabled gene editing in infected plants and allowed the acquisition of mutations heritable by the next generation, with an efficiency of 4.35–8.79%. In addition, gene-edited offspring by FT-sgRNAs did not contain any components of the CLCrV genome.

Conclusions

FT strategy can be used to acquire heritable mutant offspring avoiding tissue culture and stable transformation based on the CLCrV-mediated VIGE system in A. thaliana.
Evaluation of muscle volume and degeneration after total hip arthroplasty: a comparison of the posterolateral approach and the anterolateral supine approach
Authors: Ukai Taku , Ebihara Goro , Omura Haruka , Watanabe Masahiko
Published: February 2021

Background

Muscle strength around the hip after total hip arthroplasty (THA) is crucial for preventing dislocation and limping. This study aimed to assess and compare muscle volume and degeneration after THA using the posterolateral (PL) and anterolateral (AL) approaches.

Methods

Sixty-four hips in 64 patients who underwent primary THA were retrospectively analyzed. Patients were segregated into the PL group (35 hips) and AL group (29 hips) for evaluating pre- and postoperative muscle volumes and degeneration around the hip. Computed tomography (CT) examinations were performed preoperatively and 6 months post THA. The muscle volume and Hounsfield units (HU) of the gluteus maximus (G-max), gluteus medius (G-med), tensor fasciae latae, internal obturator muscle, and external obturator muscle were measured.

Results

In the PL group, the postoperative muscle volume of the G-max significantly increased than the preoperative muscle volume. In contrast, the postoperative muscle volume of the internal obturator muscle was significantly lower than the preoperative muscle volume. The postoperative HU of the internal and external obturator muscles were significantly lower than the preoperative HU. In the AL group, the postoperative muscle volumes of the G-max, G-med, and tensor fasciae latae significantly increased than their preoperative muscle volumes. The postoperative HU of the G-med and tensor fasciae latae were significantly higher than the preoperative HU values.

Conclusion

The PL approach can lead to degeneration of the internal and external obturator. The AL approach is more beneficial for recovering the G-med, tensor fasciae latae, and internal obturator muscle than the PL approach.
Synovial fluid IL-1β appears useful for the diagnosis of chronic periprosthetic joint infection
Authors: Wang Hai , Qin Leilei , Wang Jiawei , Huang Wei
Published: February 2021

Purpose

The purpose of this study was to investigate the role of synovial fluid interleukin (IL)-1β in diagnosing chronic periprosthetic joint infection (PJI) and to identify the optimal threshold of synovial fluid IL-1β for differentiating chronic PJI from aseptic failure after knee and hip arthroplasties.

Methods

Between January 2019 and December 2019, we prospectively included patients scheduled to have a revision surgery for chronic PJI or aseptic failure after total joint arthroplasty. Then, synovial IL-1β was additionally measured along with routine preoperative diagnostic serum and synovial biomarkers. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker to determine diagnostic efficacy.

Results

Of the 93 patients included, their demographic data were not found to be statistically significant. The median synovial IL-1β levels were significantly higher in the chronic PJI group than in the aseptic group (894.73 pg/mL vs. 34.49 pg/mL, P<0.01). The AUC for synovial fluid IL-1β was 0.991, which was higher than serum ESR (0.627) and CRP (0.712). The optimal threshold value for detecting chronic PJI of synovial IL-1β was 312.7 pg/mL, with a sensitivity of 97.3% and a specificity of 94.64%. And the combined measurement of synovial fluid IL-1β and synovial fluid PMN% can led to a specificity of 1, and a negative predictive value (NPV) of 1.

Conclusions

The present study demonstrated that synovial fluid IL-1β is a valuable biomarker for detection of chronic PJI. The combination of synovial fluid IL-1β and PMN% led to an improvement in specificity compared with evaluation of each single index.

Trial registration

This study was prospectively registered on the Chinese Clinical Trial Registry (a non-profit organization, established according to both the WHO International Clinical Trials Register Platform Standard and Ottawa Group Standard), and the registering number was ChiCTR1800020440. Registered on December 29, 2018.
Epidemiology of systemic sclerosis: a multi-database population-based study in Tuscany (Italy)
Authors:   the Rare Diseases Working Group, Coi Alessio , Barsotti Simone , Santoro Michele , Almerigogna Fabio , Bargagli Elena , Caproni Marzia , Emmi Giacomo , Frediani Bruno , Guiducci Serena , Matucci Cerinic Marco , Mosca Marta , Parronchi Paola , Prediletto Renato , Selvi Enrico , Simonini Gabriele , Tavoni Antonio Gaetano , Bianchi Fabrizio , Pierini Anna
Published: February 2021

Background

Systemic Sclerosis (SSc) is a chronic autoimmune disease with a complex pathogenesis that includes vascular injury, abnormal immune activation, and tissue fibrosis. We provided a complete epidemiological characterization of SSc in the Tuscany region (Italy), considering prevalence and incidence, survival, comorbidities and drug prescriptions, by using a multi-database population-based approach. Cases of SSc diagnosed between 1st January 2003 and 31st December 2017 among residents in Tuscany were collected from the population-based Rare Diseases Registry of Tuscany. All cases were linked to regional health and demographic databases to obtain information about vital statistics, principal causes of hospitalization, complications and comorbidities, and drug prescriptions.

Results

The prevalence of SSc in Tuscany population resulted to be 22.2 per 100,000, with the highest prevalence observed for the cases aged ≥ 65 years (33.2 per 100,000, CI 95% 29.6–37.3). In females, SSc was predominant (86.7% on the total) with an overall sex ratio F/M of 6.5. Nevertheless, males presented a more severe disease, with a lower survival and significant differences in respiratory complications and metabolic comorbidities. Complications and comorbidities such as pulmonary involvement (HR = 1.66, CI 95% 1.17–2.35), congestive heart failure (HR = 2.76, CI 95% 1.80–4.25), subarachnoid and intracerebral haemorrhage (HR = 2.33, CI 95% 1.21–4.48) and malignant neoplasms (HR = 1.63, CI 95% 1.06–2.52), were significantly associated to a lower survival, also after adjustment for age, sex and other SSc-related complications. Disease-modifying antirheumatic drugs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors were the drugs with the more increasing prevalence of use in the 2008–2017 period.

Conclusions

The multi-database approach is important in the investigation of rare diseases where it is often difficult to provide accurate epidemiological indicators. A population-based registry can be exploited in synergy with health databases, to provide evidence related to disease outcomes and therapies and to assess the burden of disease, relying on a large cohort of cases. Building an integrated archive of data from multiple databases linking a cohort of patients to their comorbidities, clinical outcomes and survival, is important both in terms of treatment and prevention.
Deletion of Socs3 in LysM+ cells and Cx3cr1 resulted in age-dependent development of retinal microgliopathy
Authors: Du Xuan , Penalva Rosana , Little Karis , Kissenpfennig Adrien , Chen Mei , Xu Heping
Published: February 2021

Background

We generated a mouse model of primary microglial dysfunction by deleting two negative immune regulatory genes,Cx3cr1andSocs3(in LysM+cells). This study aimed to understand how primary microglial dysfunction impacts retinal neurons during aging.

Methods

TheLysMCre-Socs3fl/flCx3cr1gfp/gfpdouble knockout (DKO),LysMCre-Socs3fl/fl,Cx3cr1gfp/gfpandSocs3fl/flmice were maintained up to 12 months. Eyes were collected and processed for immunohistochemistry of IBA-1, cone arrestin, secretagogin, PKCα and GABA. Brain microglia from DKO and WT mice were stimulated with LPS + IFN-γ or IL-4. The expression of TNF-α, IL-1β, IL-6, iNOS, IL-12p40, IL-23p19, CCL2, CCL5, CXCL2, IL-10, CD206 and Arg1 were examined by qRT-PCR and protein production was measured by Luminex assay. Retinal explants from C57BL/6 J mice were co-cultured with microglia from DKO or WT mice for 24 h, after which the number of cone arrestin+cells in retinal flatmount were quantified.

Results

In 3–5 month old mice, the number of microglia in retinal ganglion cell layer (GCL) and inner plexiform layer (IPL) were comparable in all strains of mice. The DKO mice had a significantly higher number of microglia in the outer plexiform layer (OPL) but significantly lower numbers of cone arrestin+, secretagogin+and GABA+cells compared toSocs3fl/fland single KO mice. During aging, 57% of the DKO mice died before 12 months old. The 10–12 months old DKO mice had significantly higher numbers of microglia in GCL/IPL and OPL than age-matchedSocs3fl/fland single KO mice. The aged DKO mice developed retinal pigment epithelial (RPE) dysmorphology accompanied by subretinal microglial accumulation. The number of photoreceptors, bipolar cells (Secretagogin+or PKCα+) and GABA+amacrine cells was significantly lower in aged DKO mice compared to age-matchedSocs3fl/fland single KO mice. Microglia from DKO mice showed significantly higher levels of phagocytic activity and produced higher levels of TNF-α, IL-6, CCL2, CCL5, CXCL2 and CXCL10 compared to microglia fromSocs3fl/flmice. Co-culture of retinal explants with LPS + IFN-γ or IL-4 pre-treated DKO microglia significantly reduced cone photoreceptor survival.

Conclusions

TheLysMCre-Socs3fl/flCx3cr1gfp/gfpDKO mice displayed primary microglial dysfunction and developed age-related retinal microgliopathy characterized by aggragated microglial activation and multiple retinal neuronal and RPE degeneration.

Trial registration

Not applicable. The article does not contain any results from human participants.
Optimized expression of Hfq protein increases Escherichia coli growth
Authors: VO Phuong N. L. , LEE Hyang-Mi , REN Jun , NA Dokyun
Published: February 2021

Escherichia coli is a widely used platform for metabolic engineering due to its fast growth and well-established engineering techniques. However, there has been a demand for faster-growing E. coli for higher production of desired substances. Here, to increase the growth of E. coli cells, we optimized the expression level of Hfq protein, which plays an essential role in stress responses. Six variants of the hfq gene with a different ribosome binding site sequence and thereby a different expression level were constructed. When the Hfq expression level was optimized in DH5α, its growth rate was increased by 12.1% and its cell density was also increased by 4.5%. RNA-seq and network analyses revealed the upregulation of stress response genes and metabolic genes, which increases the tolerance against pH changes. When the same strategy was applied to five other E. coli strains (BL21 (DE3), JM109, TOP10, W3110, and MG1655), all their growth rates were increased by 18–94% but not all their densities were increased (− 12 − + 32%). In conclusion, the Hfq expression optimization can increase cell growth rate and probably their cell densities as well. Since the hfq gene is highly conserved across bacterial species, the same strategy could be applied to other bacterial species to construct faster-growing strains.
Potential therapeutic targets in the tumor microenvironment of hepatocellular carcinoma: reversing the protumor effect of tumor-associated macrophages
Authors: Zhou Jingyi , Wang Weiyu , Li Qi
Published: February 2021

In hepatocellular carcinoma patients, due to the microenvironmental specificity of liver, the tumor microenvironment exhibits high immunosuppression and drug resistance, resulting in excessive or insufficient responses to immunotherapy. The dynamic interactions between tumor cells and immune modulators in the TME significantly impact the occurrence and development of tumors, efficacy, and drug resistance, which can create a much more positive response to immunotherapy. Moreover, with the wide application of single-cell sequencing technology in the TME, increasing evidence shows an interaction network among cells. Sequencing results suggest that specific tumor-associated macrophages are a hub node, connecting different cell populations in the cell interaction network, and can could regulate tumor generation and antitumor immunity. This review focused on therapeutic targets that could be targeted to remodel the tumor microenvironment and reprogram the tumor-associated macrophage phenotype in hepatocellular carcinoma patients, thereby improving immunotherapeutic efficacy.
The effect of a topical combination of clonidine and pentoxifylline on post-traumatic neuropathic pain patients: study protocol for a randomized, double-blind placebo-controlled trial
Authors: Fulas Oli Abate , Laferrière André , Ware D. Mark A. , Shir Yoram , Coderre Terence J.
Published: February 2021

Background

First-line pharmacotherapy for neuropathic pain entails the use of systemic antidepressants and anticonvulsants. These drugs are not optimally effective and poorly tolerated, especially for older patients with comorbid conditions. Given the high number of such patients, there is a need for a greater repertoire of safer and more effective analgesics. Clonidine and pentoxifylline are vasodilator agents that work synergistically to enhance tissue perfusion and oxygenation. The topical administration of these drugs, individually and in combination, has shown anti-nociceptive properties in rodent models of neuropathic pain. A topically-administered combination of clonidine and pentoxifylline also effectively reduced the intensity of both spontaneous and evoked pain in healthy volunteers with experimentally-induced neuropathic pain. The next step in advancing this formulation to clinical use is the undertaking of a phase II clinical study to assess its efficacy and safety in neuropathic pain patients.

Methods/design

This is a study protocol for a randomized, double-blind, placebo-controlled, phase II clinical trial with a cross-over design. It is a single-centered, 5-week study that will enroll a total of 32 patients with post-traumatic peripheral neuropathic pain. Patients will be treated topically with either a combination of clonidine and pentoxifylline or placebo for a period of 2 weeks each, in randomly assigned order across patients, with an intervening washout period of 1 week. The primary outcome measures of the study are the intensity of spontaneous pain recorded daily in a pain diary with a visual analog scale, and the degree of mechanical allodynia evoked by a brush stimulus. The secondary outcome measures of the study include scores of pain relief and change in the area of punctate hyperalgesia. This trial has been prospectively registered with ClinicalTrials.gov on November 1, 2017. ClinicalTrials.gov Identifier: NCT03342950.

Discussion

The analgesic use of topical treatment with clonidine and pentoxifylline in combination has not been investigated in post-traumatic neuropathic pain. This study could generate the first evidence for the efficacy and safety of the formulation in alleviating pain in patients with neuropathic pain. Furthermore, this trial will provide objective grounds for the investigation of other agents that enhance tissue oxygenation in the topical treatment of peripheral neuropathic pain.

Trial registration

This trial has been registered with ClinicalTrials.gov owned by NIH’s US National Library of Medicine.

ClinicalTrials.gov NCT03342950. Registered on November 1, 2017 (trial was prospectively registered).

Protocol version and identifiers

This is protocol version 5, dated June 2018. McGill University Health Center (MUHC) Reaseach Ethics Board (REB) identification number: TTNP 2018-3906.
Host–parasite interactions of rodent hosts and ectoparasite communities from different habitats in Germany
Authors: Obiegala Anna , Arnold Leonie , Pfeffer Martin , Kiefer Matthias , Kiefer Daniel , Sauter-Louis Carola , Silaghi Cornelia
Published: February 2021

Background

Small mammals are important maintenance hosts of ectoparasites as well as reservoir hosts for many arthropod-borne pathogens. In Germany, only a few studies have investigated ectoparasite communities on small mammals in their natural habitats. The aim of this study was to assess the species diversity and parameters influencing the mean intensity and prevalence of macroscopically visible ectoparasites, such as fleas, predatory mites and ticks.

Methods

A total of 779 small mammals and 3383 ticks were available from earlier investigations for the data analysis of the current study from three differently structured study sites. In addition, fleas and predatory mites were collected from the captured rodents and taxonomically identified. Regression analyses were conducted on the group (ticks/mites/fleas) and species levels using hurdle models for the abundance of ectoparasite groups and a negative binomial model for the abundance of species.

Results

Nearly 90% of the small mammals analyzed were infested with ectoparasites, with an average of 7.3 specimens per host. Hosts were infested with up to six species of ectoparasites simultaneously. In total, 12 flea, 11 mite and three tick species were detected. Ticks were more prevalent than fleas or mites, with > 80% of the hosts in urban and forest areas hosting ticks and around 60% of hosts presenting fleas, and only 20–40% of hosts presenting mites. Polyparasitism had a statistically significant influence on the prevalence of the investigated tick, mite and flea species, with odds ratios of > 1.0. Trapping location, season and host characteristics had significant influences on some—but not all—of the investigated species.

Conclusions

The diversity of flea species was unexpectedly high and higher than that reported in comparable studies, which can be explained by the differently structured habitats and regions examined in this study. Polyparasitism was a key influencing factor and had a positive effect on the prevalence and/or abundance of the predominant tick, flea and mite species occurring on small mammals. Season, trapping location, host species and sex of the host species also had an influence on the prevalence and mean intensity of certain, but not all, ectoparasite species.

Graphical Abstract
GCKR common functional polymorphisms are associated with metabolic syndrome and its components: a 10-year retrospective cohort study in Iranian adults
Authors: Zahedi Asiyeh Sadat , Akbarzadeh Mahdi , Sedaghati-Khayat Bahareh , Seyedhamzehzadeh Atefeh , Daneshpour Maryam S.
Published: February 2021

Background

Previous studies reported that common functional variants (rs780093, rs780094, and rs1260326) in the glucokinase regulator gene (GCKR) were associated with metabolic syndrome despite the simultaneous association with the favorable and unfavorable metabolic syndrome components. We decided to evaluate these findings in a cohort study with a large sample size of Iranian adult subjects, to our knowledge for the first time. We investigated the association of the GCKR variants with incident MetS in mean follow-up times for nearly 10 years.

Methods

Analysis of this retrospective cohort study was performed among 5666 participants of the Tehran Cardiometabolic Genetics Study (TCGS) at 19–88 years at baseline. Linear and logistic regression analyses were used to investigate the metabolic syndrome (JIS criteria) association and its components with rs780093, rs780094, and rs1260326 in an additive genetic model. Cox regression was carried out to peruse variants’ association with the incidence of metabolic syndrome in the TCGS cohort study.

Results

In the current study, we have consistently replicated the association of the GCKR SNPs with higher triglyceride and lower fasting blood sugar levels (p < 0.05) in Iranian adults. The CT genotype of the variants was associated with lower HDL-C levels. The proportional Cox adjusted model regression resulted that TT carriers of rs780094, rs780093, and rs1260326 were associated with 20%, 23%, and 21% excess risk metabolic syndrome incidence, respectively (p < 0.05).

Conclusions

Elevated triglyceride levels had the strongest association with GCKR selected variants among the metabolic syndrome components. Despite the association of these variants with decreased fasting blood sugar levels, T alleles of the variants were associated with metabolic syndrome incidence; so whether individuals are T allele carriers of the common functional variants, they have a risk factor for the future incidence of metabolic syndrome.
Characteristics of patients infected with Clostridioides difficile at a Saudi Tertiary Academic Medical Center and assessment of antibiotic duration
Authors: Alammari Khadijah M. , Thabit Abrar K.
Published: February 2021

Background

Clostridioides difficile infection (CDI) is a common hospital-associated diarrhea. Several antibiotics commonly associate with CDI; however, limited data are available on the duration of exposure prior to CDI. Moreover, studies on the characteristics of CDI patients in Saudi Arabia are limited. Therefore, this study aimed to characterize CDI patients identified over 10 years and assess antibiotic days of therapy (DOT) prior to CDI.

Methods

This was a retrospective descriptive analysis of CDI patients at a Saudi tertiary academic medical center between December 2007 and January 2018. Patients characteristics, prior exposure to known CDI risk factors, and DOT of antibiotics prior to CDI incidence were assessed.

Results

A total of 159 patients were included. Median age was 62 years. Most cases were hospital-acquired (71.1%), non-severe (44.7%), and admitted to medical wards (81.1%). Prior exposure to antibiotics and acid suppression therapy were reported with the majority (76.1 and 75.5%, respectively). The most frequently prescribed antibiotics were piperacillin/tazobactam, ceftriaxone, meropenem, and ciprofloxacin with median DOTs prior to CDI incidence of 14 days for the β-lactams and 26 days for ciprofloxacin. The distribution of DOT was significantly different for piperacillin/tazobactam in different units (P = 0.003) where its median DOT was the shortest in medical wards (11 days), and for ciprofloxacin among different severity groups (P = 0.013), where its median DOT was the shortest in severe CDI patients (11 days).

Conclusion

Most patients in this study had hospital-acquired non-severe CDI and were largely exposed to antibiotics and acid suppression therapy. Therefore, such therapies should be revised for necessity.
Fetal liver hematopoiesis: from development to delivery
Authors: Lewis Kyle , Yoshimoto Momoko , Takebe Takanori
Published: February 2021

Clinical transplants of hematopoietic stem cells (HSC) can provide a lifesaving therapy for many hematological diseases; however, therapeutic applications are hampered by donor availability. In vivo, HSC exist in a specified microenvironment called the niche. While most studies of the niche focus on those residing in the bone marrow (BM), a better understanding of the fetal liver niche during development is vital to design human pluripotent stem cell (PSC) culture and may provide valuable insights with regard to expanding HSCs ex vivo for transplantation. This review will discuss the importance of the fetal liver niche in HSC expansion, a feat that occurs during development and has great clinical potential. We will also discuss emerging approaches to generate expandable HSC in cell culture that attain more complexity in the form of cells or organoid models in combination with engineering and systems biology approaches. Overall, delivering HSC by charting developmental principles will help in the understanding of the molecular and biological interactions between HSCs and fetal liver cells for their controlled maturation and expansion.
Determinants of hospital and one-year mortality among older patients admitted to intensive care units: results from the multicentric SENIOREA cohort
Authors: Demiselle Julien , Duval Guillaume , Hamel Jean-François , Renault Anne , Bodet-Contentin Laetitia , Martin-Lefèvre Laurent , Vivier Dominique , Villers Daniel , Lefèvre Montaine , Robert René , Markowicz Philippe , Lavoué Sylvain , Courte Anne , Lebas Eddy , Chevalier Stéphanie , Annweiler Cédric , Lerolle Nicolas
Published: February 2021

Background

Improving outcomes of older patients admitted into intensive care units (ICU) is a raising concern. This study aimed at determining which geriatric and ICU parameters were associated with in-hospital and long-term mortality in this population.

Methods

We conducted a prospective multicentric observational cohort study, including patients aged 75 years and older requiring mechanical ventilation, admitted between September 2012 and December 2013 into ICU of 13 French hospitals. Comprehensive geriatric assessment at ICU admission and ICU usual parameters were registered in a standardized manner. Survival was recorded and comprehensive geriatric assessment was updated after 1 year during a dedicated home visit.

Results

501 patients were analyzed. 108 patients (21.6%) died during the hospital stay. One-year survival rate was 53.8% (IC 95% [49.2%; 58.2%]). Factors associated with increased in-hospital mortality were higher acute illness severity score, resuscitated cardiac arrest as primary ICU diagnosis, perception of anxiety and low quality of life by the proxy, and living in a chronic care facility before ICU admission. Among patients alive at hospital discharge, factors associated with increased 1-year mortality in multivariate analysis were longer duration of mechanical ventilation, all primary ICU diagnoses other than septic shock, a Katz-activities of daily living (ADL) score below 5 and living in a chronic care facility before ICU admission. Among the 163 survivors at 1 year who received a second comprehensive geriatric assessment, the ADL score (functional abilities) showed a significant but moderate decline over time, whereas the Mini-Zarit score (family burden) improved. No significant change in patients’ place of life was observed after 1 year, and quality of life was reported as happy-to-very-happy in 88% of survivors.

Conclusions

The mortality rate remains high among older ICU patients requiring mechanical ventilation. Factors associated with short- and long-term mortality combined geriatric and ICU criteria, which should be jointly evaluated in routine care.

Clinical trial registration NCT01679171
An analytics model for TelecoVAS customers’ basket clustering using ensemble learning approach
Authors: Vahidi Farashah Mohammadsadegh , Etebarian Akbar , Azmi Reza , Ebrahimzadeh Dastjerdi Reza
Published: February 2021

Value-Added Services at a Mobile Telecommunication company provide customers with a variety of services. Value-added services generate significant revenue annually for telecommunication companies. Providing solutions that can provide customers of a telecommunication company with relevant and engaging services has become a major challenge in this field. Numerous methods have been proposed so far to analyze customer basket and provide related services. Although these methods have many applications, they still face difficulties in improving the accuracy of bids. This paper combines the X-Means algorithm, the ensemble learning system, and the N-List structure to analyze the customer portfolio of a mobile telecommunication company and provide value-added services. The X-Means algorithm is used to determine the optimal number of clusters and clustering of customers in a mobile telecommunication company. The ensemble learning algorithm is also used to assign categories to new Elder customers, and finally to the N-List structure for customer basket analysis. By simulating the proposed method and comparing it with other methods including KNN, SVM, and deep neural networks, the accuracy improved to about 7%.
A potential subsurface cavity in the continuous ejecta deposits of the Ziwei crater discovered by the Chang’E-3 mission
Authors: Ding Chunyu , Xiao Zhiyong , Su Yan
Published: February 2021

In the radargram obtained by the high-frequency lunar penetrating radar onboard the Chang’E-3 mission, we notice a potential subsurface cavity that has a smaller permittivity compared to the surrounding materials. The two-way travel time between the top and bottom boundaries of the potential cavity is ~ 21 ns, and the entire zone is located within the continuous ejecta deposits of the Ziwei crater, which generally have similar physical properties to typical lunar regolith. We carried out numerical simulations for electromagnetic wave propagation to investigate the nature of this low-permittivity zone. Assuming different shapes for this zone, a comprehensive comparison between our model results and the observed radargram suggests that the roof of this zone is convex and slightly inclined to the south. Modeling subsurface materials with different relative permittivities suggests that the low-permittivity zone is most likely formed due to a subsurface cavity. The maximum vertical dimension of this potential cavity is ~ 3.1 m. While the continuous ejecta deposits of Ziwei crater are largely composed of pre-impact regolith, competent mare basalts were also excavated, which is evident by the abundant meter-scale boulders on the wall and rim of Ziwei crater. We infer that the subsurface cavity is supported by excavated large boulders, which were stacked during the energetic emplacement of the continuous ejecta deposits. However, the exact geometry of this cavity (e.g., the width) cannot be constrained using the single two-dimensional radar profile. This discovery indicates that large voids formed during the emplacement of impact ejecta should be abundant on the Moon, which contributes to the high bulk porosity of the lunar shallow crust, as discovered by the GRAIL mission. Our results further suggest that ground penetrating radar is capable of detecting and deciphering subsurface cavities such as lava tubes, which can be applied in future lunar and deep space explorations.
Construct validity and psychosocial correlates of the Italian version of the 21-item Medical Interview Satisfaction Scale in primary care
Authors: Balestrieri Matteo , de Girolamo Giovanni , Rucci Paola
Published: February 2021

Background

Satisfaction with the medical interview has been rarely explored in primary care outside the UK, despite evidence suggesting that a trustful doctor–patient relationship is a key ingredient to facilitate treatment adherence and relief from illness-related distress.

Aims

The aims of this study are to analyse the construct validity of the Italian version of the Medical Interview Satisfaction Scale (MISS-21) and its correlations with two outcome measures, the Inventory of Depressive Symptomatology – Self-Report and World Health Organization Quality Of Life Brief Version, in patients with mild-to-moderate depression, recruited in primary care practices.

Method

The factor structure underlying the MISS-21 was investigated with principal component analysis, and the internal consistency of the factors was evaluated with Cronbach's alpha. Network analysis was used to investigate the interrelationships among items. The importance of individual items in the network structure was determined with centrality analyses. Correlations of MISS-21 scores with changes in depression and quality of life were analysed with Spearman's correlation coefficient.

Results

The MISS-21 proved to have a robust four-dimensional factor structure. Cronbach's alpha for the factors ranged from 0.77 to 0.93, suggesting good to excellent internal consistency. The four factors identified were positively correlated with improvement in depressive symptoms and three quality-of-life domains.

Conclusions

The MISS-21 has sound psychometric properties, and comprises four factors related to clinical outcomes, which makes it suitable for clinical and research applications. The central items in the network should be considered as possible targets for quality improvement interventions in primary care.