bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurable residual disease affects allogeneic hematopoietic cell transplantation in Ph+ ALL during both CR1 and CR2
Authors: Nishiwaki Satoshi , Akahoshi Yu , Mizuta Shuichi , Shinohara Akihito , Hirabayashi Shigeki , Noguchi Yuma , Fukuda Takahiro , Uchida Naoyuki , Tanaka Masatsugu , Onizuka Makoto , Ozawa Yukiyasu , Ota Shuichi , Shiratori Souichi , Onishi Yasushi , Kanda Yoshinobu , Sawa Masashi , Tanaka Junji , Atsuta Yoshiko , Kako Shinichi
Published: January 2021

Although measurable residual disease (MRD) at the time of allogeneic hematopoietic cell transplantation (allo-HCT) has been reported to be an important prognostic factor for Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) during first complete remission (CR1), the prognostic impact of MRD is unclear during second CR (CR2). To clarify the impact of MRD for both CR1 and CR2, we analyzed data from a registry database including 1625 adult patients with Ph+ ALL who underwent first allo-HCT during either CR1 or CR2 between 2002 and 2017. Adjusted overall and leukemia-free survival rates at 4 years were 71% and 64%, respectively, for patients undergoing allo-HCT during CR1 with MRD−, 55% and 43% during CR1 with MRD+, 51% and 49% during CR2 with MRD−, and 38% and 29% during CR2 with MRD+. Although survival rates were significantly better among patients with CR1 MRD− than among patients with CR2 MRD−, no significant difference was observed in survival rate between patients with CR1 MRD+ and CR2 MRD−. Relapse rates after 4 years were 16% in patients with CR1 MRD−, 29% in CR1 MRD+, 21% in patients with CR2 MRD−, and 46% in patients with CR2 MRD+. No significant difference was identified in relapse rate between patients with CR1 MRD− and CR2 MRD−. CR2 MRD− was not a significant risk factor for relapse in multivariate analysis (hazard ratio, 1.26; 95% confidence interval, 0.69-2.29; P = .45 vs CR1 MRD−). MRD at time of allo-HCT was an important risk factor in patients with Ph+ ALL during both CR1 and CR2.
Changes in inflammatory factors in the Brown Norway rat model of food allergy
Authors: Zhu Qingling , Wang Junli , Ma Jingqiu , Sheng Xiaoyang , Li Feng
Published: January 2021

Background

The role of serum S100A8/A9 in intestinal inflammation has been confirmed, and its role in food allergy is currently being investigated.

Objective

To explore the levels of S100A8/A9 and inflammatory factors, including Toll-like receptors 4 (TLR4), Nuclear transcription factors (NF-κB) and Tumor necrosis factor α (TNF-α), in mild food allergies.

Methods

Eighty 3-week-old male Brown Norway rats were used. Forty rats were randomly assigned to the ovalbumin-sensitized experimental group, while 40 rats were assigned to the normal saline sham-sensitized control group. Body weight and length and the levels of serum ovalbumin-specific IgE (OVA-IgE), histamine, Th1-associated and Th2-associated factors, S100A8/A9 and inflammation-associated cytokines were compared.

Results

Through the evaluation of OVA-IgE level and Th1/Th2 balance in the experimental group, a successful IgE-mediated food allergy model was constructed. Compared with the control group, the experimental group had higher serum S100A8/A9 levels on days 21, 28, 35 and 42 (allP < 0.05); higher TLR4 levels on days 28, 35 and 42 (allP < 0.05); higher TNF-α levels on days 28, 35 and 42 (allP < 0.05); higher NF-κB levels on days 35 and 42 (allP < 0.05); and higher IL-1β and IL-6 levels on days 7 to 42 (allP < 0.05). Moreover, positive correlations were found between the serum levels of S100A8/A9 and inflammation-associated cytokines [TNF-α:r = 0.378,P = 0.039; IL-1β:r = 0.679,P = 0.000; IL-6:r = 0.590,P = 0.001].

Conclusion

S100A8/A9 and inflammatory-related factors, including TLR4, NF-κB, TNF-α, IL-6 and IL-1β, is closely related to food allergies. Moreover, immune and inflammatory factors interact with each other in food allergies, which may provide insight into food allergy causes and treatments.
Construction of a patient decision aid for the treatment of uncomplicated urinary tract infection in primary care
Authors: Vincent Yves-Marie , Frachon Adèle , Buffeteau Clotilde , Conort Guillaume
Published: January 2021

Background

Uncomplicated urinary tract infection (uUTI) is very common among women in primary care. The risk of developing pyelonephritis remains low after uUTI, nonetheless, empiric antibiotic therapy is frequently prescribed for symptomatic purposes. This may lead to adverse effects and antibiotic resistance. Furthermore, patients may express the will to limit the use of antibiotics. Some European countries recommend discussing a delayed prescription with the patient and developing a shared decision. The aim of this study is to create a patient decision aid (PtDA) used in primary care settings to make a shared decision between practitioners and women about whether or not to treat uUTI with antibiotics.

Methods

We followed the steps recommended by the International Patient Decision Aids Standards, with a scoping phase, a design phase (including focus groups and literature review), and an alpha-testing phase. A steering group, made of patients and physicians, met throughout the study to develop a prototype PtDA.

Results

The information included in the PtDA is the definition of uUTI, information on the options, their benefits, risks, and consequences, based on a review of the literature. The results of the focus group made possible to determine the patient’s values and preferences to consider in decision-making, including: the discomfort felt, the impact on daily life, patients’ perceptions of antibiotics, and the position relative to the risk of adverse effect. The choices in presentation, organisation and design are the result of the work of the steering group, improved by feedback from alpha testing. We confirmed the need for shared decision-making and the equipoise in this situation.

Conclusions

We developed a PtDA to be used in primary care for sharing decision on the use of antibiotic in uUTI. It needs to be validated in a beta-testing phase, with complementary advice from peers, and then tested in a clinical study comparing its use with the systematic prescription approach.
Combined pattern of childhood psycho-behavioral characteristics in patients with schizophrenia: a retrospective study in Japan
Authors: Hamasaki Yukiko , Nakayama Takao , Hikida Takatoshi , Murai Toshiya
Published: January 2021

Background

Although epidemiological and genetic studies have provided scientific evidence that places schizophrenia into the framework of early neurodevelopmental disorders, the psycho-behavioral characteristics of children that later go on to develop schizophrenia have not been sufficiently clarified. This study aimed to retrospectively identify characteristics specific to patients with schizophrenia during childhood via their guardians’ reporting of these characteristics.

Methods

Participants included 54 outpatients with schizophrenia in their twenties who fulfilled DSM-IV-TR criteria. Additionally, 192 normal healthy subjects participated as sex- and age-matched controls. The guardians of all participants were recruited to rate participants’ childhood characteristics from 6 to 8 years of age on a modified version of the Child Behavior Checklist (CBCL), which was used as a retrospective assessment questionnaire. Using t-tests, logistic regression, and Receiver Operating Characteristic (ROC) curve analysis, we estimated the psycho-behavioral characteristics specific to schizophrenia during childhood. Using the obtained logistic regression model, we prototyped a risk-predicting algorithm based on the CBCL scores.

Results

Among the eight CBCL subscale t-scores, “withdrawn” (p = 0.002), “thought problems” (p = 0.001), and “lack of aggressive behavior” (p = 0.002) were each significantly associated with the later diagnosis of schizophrenia, although none of these mean scores were in the clinical range at the time of childhood. The algorithm of the logistic regression model, based on eight CBCL subscales, had an area under the ROC curve of 82.8% (95% CI: 76–89%), which indicated that this algorithm’s prediction of late development of schizophrenia has moderate accuracy.

Conclusions

The results suggest that according to guardian reports, participants showed psycho-behavioral characteristics during childhood, different to those of healthy controls, which could be predictive of the later development of schizophrenia. Our newly developed algorithm is available to use in future studies to further test its validity.
Prevalence of depression symptoms and associated sociodemographic and clinical correlates among Syrian refugees in Lebanon
Authors: Naal Hady , Nabulsi Dana , El Arnaout Nour , Abdouni Lina , Dimassi Hani , Harb Ranime , Saleh Shadi
Published: January 2021

Background

Since the outbreak of the Syrian war in 2011, close to 6 million Syrian refugees have escaped to Syria’s neighbouring countries, including Lebanon. Evidence suggests rising levels of mental health disorders among Syrian refugee populations. Yet, to the best of our knowledge, large-scale studies addressing the mental health of adult Syrian refugees in Lebanon are lacking. We examined the prevalence of depression symptoms, which represent a common and debilitating mental health disorder among Syrian refugee populations in Lebanon, along with their sociodemographic and clinical correlates.

Methods

A cross-sectional survey design was conducted as part of a collaborative project-“Sijilli”- led by the Global Health Institute at the American University of Beirut (Beirut, Lebanon) across 4 informal tented settlements for refugees (Beirut, Bekaa, North, South) in Lebanon among adult Syrian refugees (≥18), over a period extending from 2018 to 2020. The survey inquired about participants’ sociodemographic and clinical characteristics, and screened participants for symptoms of depression through sequential methodology using the Patient Health Questionnaire (PHQ-2 and PHQ-9).

Results

A total of 3255 adult Syrian refugees were enrolled in the study. Of those refugees, 46.73% (n = 1521) screened positive on the PHQ-2 and were therefore eligible to complete the PHQ-9. In the entire sample (n = 3255), the prevalence of moderate to severe depression symptoms (PHQ-2 ≥ 2 and then PHQ-9 ≥ 10) was 22% (n = 706). Further analyses indicate that being ≥45 years of age (OR 1.61, 95% CI 1.13–2.30), a woman (OR 1.34, 95% CI 1.06–1.70), widowed (OR 2.88, 95% CI 1.31–6.32), reporting a neurological (OR 1.73, 95% CI 1.15–2.60) or a mental health condition (OR 3.98, 95% CI 1.76–8.97) are major risk factors for depression.

Conclusion

Our study suggests that an estimated one in four Syrian refugees in Lebanon shows moderate to severe depression symptoms, and our findings have important public health and clinical implications on refugee health. There is a need to enhance screening efforts, to improve access and referral to mental health services, and to improve post-migration factors among Syrian refugees in Lebanon.
The comparative efficacies of intravenous administration and intra-articular injection of tranexamic acid during anterior cruciate ligament reconstruction for reducing postoperative hemarthrosis: a prospective randomized study
Authors: Ma Rui , Wu Mengjun , Li Yongwei , Wang Jialin , Wang Wei , Yang Pei , Wang Kunzheng
Published: January 2021

Background

Hemarthrosis after anterior cruciate ligament (ACL) reconstruction can create many adverse joint effects. Tranexamic acid (TXA) can be used to minimize hemarthrosis and associated pain after ACL reconstruction. We aimed to compare the efficacies of intravenous (IV) administration and intra-articular (IA) injection of TXA during ACL reconstruction for reducing postoperative hemarthrosis.

Methods

A total of 120 patients who underwent arthroscopic ACL reconstruction were included in this prospective and randomized study. All patients were randomized into three groups: IV group, IA group and placebo group. Patients in the IV group received intravenously administered TXA (15 mg/kg in 100 mL of saline solution) 10 min before tourniquet release; patients in the IA group received intra-articular TXA (15 mg/kg in 100 mL of saline solution) injected via the drainage tube; and patients in the placebo group received an equivalent volume of normal saline administered into the knee joint cavity and intravenously. Drainage tubes were removed 24 h after surgery, and all enrolled patients experienced a 4-week follow-up period. The drain output volume, visual analogue scale (VAS) score, patellar circumference, hemarthrosis grade and Lysholm score of all patients were recorded.

Results

Both the IV group and the IA group had significantly lower drain output volumes at day 1, lower VAS scores at weeks 1 and 2, smaller patellar circumferences at weeks 1 and 2, and lower hemarthrosis grades at weeks 1 and 2 than the placebo group (p < 0.05). There were no significant differences in drain output volume, VAS score, patellar circumference or hemarthrosis grade between the IV group and the IA group at any time point (p > 0.05). No obvious differences in Lysholm score were observed between any pair of groups at week 4 (p > 0.05)). Neither infection nor deep vein thrombosis occurred in any group.

Conclusions

Both intravenous administration and intra-articular injection can reduce intra-articular hemarthrosis, joint pain and swelling during ACL reconstruction. No significant difference in the efficacies of reducing hemarthrosis, joint pain and swelling was found between intravenous administration and intra-articular injection.

Trial registration

The study was registered by the Chinese Clinical Trial Registry (The comparative efficacies of intravenous administration and intra-articular injection of tranexamic acid during anterior cruciate ligament reconstruction; ChiCTR-INR-17012217; August 1, 2017).
Home hospitalization for palliative cancer care: factors associated with unplanned hospital admissions and death in hospital
Authors: Gamblin Vincent , Prod’homme Chloé , Lecoeuvre Adrien , Bimbai André -Michel , Luu Joël , Hazard Pierre-Alexandre , Da Silva Arlette , Villet Stéphanie , Le Deley Marie-Cécile , Penel Nicolas
Published: January 2021

Background

Home hospitalization at the end of life can sometimes be perturbed by unplanned hospital admissions (UHAs, defined as any admission that is not part of a preplanned care procedure), which increase the likelihood of death in hospital. The objectives were to describe the occurrence and causes of UHAs in cancer patients receiving end-of-life care at home, and to identify factors associated with UHAs and death in hospital.

Methods

A retrospective, single-center study (performed at a regional cancer center in the city of Lille, northern France) of advanced cancer patients discharged to home hospitalization between January 2014 and December 2017. We estimated the incidence of UHA over time using Kaplan-Meier method and Kalbfleish and Prentice method. We investigated factors associated with the risk UHA in cause-specific Cox models. We evaluated factors associated with death in hospital in logistic regressions.

Results

One hundred and forty-two patients were included in the study. Eighty-two patients (57.7 %) experienced one or more UHAs, a high proportion of which occurred within 1 month after discharge to home. Most UHAs were related to physical symptoms and were initiated by the patient’s family physician. A post-discharge palliative care consultation was associated with a significantly lower incidence of UHAs. Sixty-five patients (47.8 % of the deaths) died in hospital. In a multivariate analysis, living alone and the presence of one or more children at home were associated with death in hospital.

Conclusions

More than 40 % of cancer patients receiving end of life home hospitalization were not readmitted to hospital, reflecting the effectiveness of this type of palliative care setting. However, over half of the UHAs were due to an acute intercurrent event. Our results suggest that more efforts should be focused on anticipating these events at home – primarily via better upstream coordination between hospital physicians and family physicians.
Text classification models for the automatic detection of nonmedical prescription medication use from social media
Authors: Al-Garadi Mohammed Ali , Yang Yuan-Chi , Cai Haitao , Ruan Yucheng , O’Connor Karen , Graciela Gonzalez-Hernandez , Perrone Jeanmarie , Sarker Abeed
Published: January 2021

Background

Prescription medication (PM) misuse/abuse has emerged as a national crisis in the United States, and social media has been suggested as a potential resource for performing active monitoring. However, automating a social media-based monitoring system is challenging—requiring advanced natural language processing (NLP) and machine learning methods. In this paper, we describe the development and evaluation of automatic text classification models for detecting self-reports of PM abuse from Twitter.

Methods

We experimented with state-of-the-art bi-directional transformer-based language models, which utilize tweet-level representations that enable transfer learning (e.g., BERT, RoBERTa, XLNet, AlBERT, and DistilBERT), proposed fusion-based approaches, and compared the developed models with several traditional machine learning, including deep learning, approaches. Using a public dataset, we evaluated the performances of the classifiers on their abilities to classify the non-majority “abuse/misuse” class.

Results

Our proposed fusion-based model performs significantly better than the best traditional model (F1-score [95% CI]: 0.67 [0.64–0.69] vs. 0.45 [0.42–0.48]). We illustrate, via experimentation using varying training set sizes, that the transformer-based models are more stable and require less annotated data compared to the other models. The significant improvements achieved by our best-performing classification model over past approaches makes it suitable for automated continuous monitoring of nonmedical PM use from Twitter.

Conclusions

BERT, BERT-like and fusion-based models outperform traditional machine learning and deep learning models, achieving substantial improvements over many years of past research on the topic of prescription medication misuse/abuse classification from social media, which had been shown to be a complex task due to the unique ways in which information about nonmedical use is presented. Several challenges associated with the lack of context and the nature of social media language need to be overcome to further improve BERT and BERT-like models. These experimental driven challenges are represented as potential future research directions.
Lack of drug-induced post-retrieval amnesia for auditory fear memories in rats
Authors: Luyten Laura , Schnell Anna Elisabeth , Schroyens Natalie , Beckers Tom
Published: January 2021

Background

Long-term memory formation is generally assumed to involve the permanent storage of recently acquired memories, making them relatively insensitive to disruption, a process referred to as memory consolidation. However, when retrieved under specific circumstances, consolidated fear memories are thought to return to a labile state, thereby opening a window for modification (e.g., attenuation) of the memory. Several interventions during a critical time frame after this destabilization seem to be able to alter the retrieved memory, for example by pharmacologically interfering with the restabilization process, either by direct protein synthesis inhibition or indirectly, using drugs that can be safely administered in patients (e.g., propranolol). Here, we find that, contrary to expectations, systemic pharmacological manipulations in auditory fear-conditioned rats do not lead to drug-induced post-retrieval amnesia.

Results

In a series of well-powered auditory fear conditioning experiments (four with propranolol, 10 mg/kg, two with rapamycin, 20–40 mg/kg, one with anisomycin, 150 mg/kg and cycloheximide, 1.5 mg/kg), we found no evidence for reduced cued fear memory expression during a drug-free test in adult male Sprague-Dawley rats that had previously received a systemic drug injection upon retrieval of the tone fear memory. All experiments used standard fear conditioning and reactivation procedures with freezing as the behavioral read-out (conceptual or exact replications of published reports) and common pharmacological agents. Additional tests confirmed that the applied drug doses and administration routes were effective in inducing their conventional effects on expression of fear (propranolol, acutely), body weight (rapamycin, anisomycin, cycloheximide), and consolidation of extinction memories (cycloheximide).

Conclusions

In contrast with previously published studies, we did not find evidence for drug-induced post-retrieval amnesia, underlining that this effect, as well as its clinical applicability, may be considerably more constrained and less readily reproduced than what the current literature would suggest.
A systematic assessment of the association between frequently prescribed medicines and the risk of common cancers: a series of nested case-control studies
Authors: McDowell R. D. , Hughes C. , Murchie P. , Cardwell C.
Published: January 2021

Background

Studies systematically screening medications have successfully identified prescription medicines associated with cancer risk. However, adjustment for confounding factors in these studies has been limited. We therefore investigated the association between frequently prescribed medicines and the risk of common cancers adjusting for a range of confounders.

Methods

A series of nested case-control studies were undertaken using the Primary Care Clinical Informatics Unit Research (PCCIUR) database containing general practice (GP) records from Scotland. Cancer cases at 22 cancer sites, diagnosed between 1999 and 2011, were identified from GP records and matched with up to five controls (based on age, gender, GP practice and date of registration). Odds ratios (OR) and 95% confidence intervals (CI) comparing any versus no prescriptions for each of the most commonly prescribed medicines, identified from prescription records, were calculated using conditional logistic regression, adjusting for comorbidities. Additional analyses adjusted for smoking use. An association was considered a signal based upon the magnitude of its adjusted OR, p-value and evidence of an exposure-response relationship. Supplementary analyses were undertaken comparing 6 or more prescriptions versus less than 6 for each medicine.

Results

Overall, 62,109 cases and 276,580 controls were included in the analyses and a total of 5622 medication-cancer associations were studied across the 22 cancer sites. After adjusting for comorbidities 2060 medicine-cancer associations for any prescription had adjusted ORs greater than 1.25 (or less than 0.8), 214 had a corresponding p-value less than or equal to 0.01 and 118 had evidence of an exposure-dose relationship hence meeting the criteria for a signal. Seventy-seven signals were identified after additionally adjusting for smoking. Based upon an exposure of 6 or more prescriptions, there were 118 signals after adjusting for comorbidities and 82 after additionally adjusting for smoking.

Conclusions

In this study a number of novel associations between medicine and cancer were identified which require further clinical and epidemiological investigation. The majority of medicines were not associated with an altered cancer risk and many identified signals reflected known associations between medicine and cancer.
A quantitative test of the face validity of behavior-change messages based on the Brazilian Dietary Guidelines
Authors: Khandpur Neha , Quinta Fernanda Paranhos , Jaime Patricia Constante
Published: January 2021

Background

Implementation science has scant evidence of how dietary guidelines can be developed into actionable behavior-change messages and even less evidence on their motivating potential and perceived effect on behavior. This may explain the widening gap between nutrition science and individual behavior and the low uptake of dietary recommendations by the population for which they are intended. This study aimed to: (i) assess participant receptivity and acceptance of behavior-change messages; (ii) determine if the behavior-change strategies used in the messages and the main theme they relayed influenced participant evaluation of the messages; (iii) explore if evaluations varied by participants’ stage of behavior-change; and (iv) elucidate reasons for non-compliance with the messages.

Methods

An online survey was used to test the face validity and participant receptivity of 28 behavior-change messages, among a diverse sample of 2400 adult Brazilians. Participants’ understanding of the messages, message likeability and convincingness, and the probability that participants would change behavior in accordance with the message were measured, along with reasons for non-compliance.

Results

The mean overall scores suggested that participants liked the messages, understood them, and found them convincing. As expected, the probability of complying with the messages scored lower compared to other study outcomes. Messages about shopping practices, cooking practices, and planning and organization performed better than those on other themes. Participants were more receptive to messages that included behavior-change strategies like goals, social identity, and pleasure, however, the probability of compliance was higher for messages with constructs that emphasized health and cost consequences. Participants trying to change their diet or seeking resources to support healthier dietary choices had greater engagement with and receptivity to the messages. Time and effort, and high costs associated with making healthy changes, were barriers to compliance.

Conclusions

Messages may help improve individual understanding, stimulate interest in a topic and get participants engaged, particularly if messages are goal-oriented and highlight the pleasure and collective identity of these food-related behaviors. However, messages stop short of addressing the structural, social, and economic barriers to healthy diets. These aspects will need to be targeted through legislative action for sustainable behavior change.
Optimizing the use of cesarean section in Argentina: design and methodology of a formative research for the development of interventions
Authors: Ramos Silvina , Romero Mariana , Perrotta Carla , Sguassero Yanina , Straw Cecilia , Gialdini Celina , Righetti Natalia , Betran Ana P.
Published: January 2021

Background

While cesarean section is an essential life-saving strategy for women and newborns, its current overuse constitutes a global problem. The aim of this formative research is to collect information from hospitals, health professionals and women regarding the use of cesarean section in Argentina. This article describes the methodology of the study, the characteristics of the hospitals and the profile of the participants.

Methods

This formative research is a mixed-method study that will be conducted in seven provinces of Argentina. The eligibility criteria for the hospitals are (a) use of the Perinatal Information System, (b) cesarean section rate higher than 27% in 2016, (c) ≥ 1000 deliveries per year. Quantitative and qualitative research techniques will be used for data collection and analysis. The main inquiry points are the determining factors for the use of cesarean section, the potential interventions to optimize the use of cesarean section and, in the case of women, their preferred type of delivery.

Discussion

It is expected that the findings will provide a situation diagnosis to help a context-sensitive implementation of the interventions recommended by the World Health Organization to optimize cesarean section use.

Trial registration IS002316

Plain English Summary

Cesarean section is an essential medical tool for mothers and their children, but nowadays its overuse is a problem worldwide. Our purpose is to get information from hospitals, health professionals and women about how cesarean section is used in Argentina. In this protocol we describe how we will carry out the study and the characteristics of the hospitals and participants. We will implement this study in seven provinces of Argentina, in hospitals that have more than 1,000 births each year, had a cesarean section rate higher than 27% in 2016 and use the Perinatal Information System. We will gather information using forms, surveys and interviews. We want to identify the factors that decide the use of a cesarean section, the potential interventions that can improve the use of cesarean section and, in the case of women, the type of delivery they prefer. We expect that this study will give us a diagnosis of how cesarean section is used in Argentina, and that this will help to apply the interventions that the World Health Organization recommends to optimize the use of cesarean section in our specific context.
Population genomics reveal rapid genetic differentiation in a recently invasive population of Rattus norvegicus
Authors: Chen Yi , Zhao Lei , Teng Huajing , Shi Chengmin , Liu Quansheng , Zhang Jianxu , Zhang Yaohua
Published: January 2021

Background

Invasive species bring a serious effect on local biodiversity, ecosystems, and even human health and safety. Although the genetic signatures of historical range expansions have been explored in an array of species, the genetic consequences of contemporary range expansions have received little attention, especially in mammal species. In this study, we used whole-genome sequencing to explore the rapid genetic change and introduction history of a newly invasive brown rat (Rattus norvegicus) population which invaded Xinjiang Province, China in the late 1970s.

Results

Bayesian clustering analysis, principal components analysis, and phylogenetic analysis all showed clear genetic differentiation between newly introduced and native rat populations. Reduced genetic diversity and high linkage disequilibrium suggested a severe population bottleneck in this colonization event. Results of TreeMix analyses revealed that the introduced rats were derived from an adjacent population in geographic region (Northwest China). Demographic analysis indicated that a severe bottleneck occurred in XJ population after the split off from the source population, and the divergence of XJ population might have started before the invasion of XJ. Moreover, we detected 42 protein-coding genes with allele frequency shifts throughout the genome for XJ rats and they were mainly associated with lipid metabolism and immunity, which could be seen as a prelude to future selection analyses in the novel environment of XJ.

Conclusions

This study presents the first genomic evidence on genetic differentiation which developed rapidly, and deepens the understanding of invasion history and evolutionary processes of this newly introduced rat population. This would add to our understanding of how invasive species become established and aid strategies aimed at the management of this notorious pest that have spread around the world with humans.
Identification and screening of host proteins interacting with ORFV-ORF047 protein
Authors: Chen Guohua , He Xiaobing , Jia Huaijie , Fang Yongxiang , Wang Xiaoxia , Lou Zhongzi , Yang Fan , Li Weike , Jing Zhizhong
Published: January 2021

Background

Orf virus (ORFV) is a member of the genus Parapoxvirus and family Poxviridae. The virus has a worldwide distribution and infects sheep, goats, humans, and wild animals. However, due to the complex structure of the poxvirus, the underlying mechanism of the entry and infection by ORFV remains largely unknown. ORFV ORF047 encodes a protein named L1R. Poxviral L1R serves as the receptor-binding protein and blocks virus binding and entry independently of glycosaminoglycans (GAGs). The study aimed to identify the host interaction partners of ORFV ORF047.

Methods

Yeast two-hybrid cDNA library of sheep testicular cells was applied to screen the host targets with ORF047 as the bait. ORF047 was cloned into a pBT3-N vector and expressed in the NMY51 yeast strain. Then, the expression of bait proteins was validated by Western blot analysis.

Results

Sheep SERP1and PABPC4 were identified as host target proteins of ORFV ORF047, and a Co-IP assay further verified their interaction.

Conclusions

New host cell proteins SERP1and PABPC4 were found to interact with ORFV ORF047 and might involve viral mRNA translation and replication.
Role of human Pegivirus infections in whole Plasmodium falciparum sporozoite vaccination and controlled human malaria infection in African volunteers
Authors: Tumbo Anneth-Mwasi , Schindler Tobias , Dangy Jean-Pierre , Orlova-Fink Nina , Bieri Jose Raso , Mpina Maximillian , Milando Florence A. , Juma Omar , Hamad Ali , Nyakarungu Elizabeth , Chemba Mwajuma , Mtoro Ali , Ramadhan Kamaka , Olotu Ally , Makweba Damas , Mgaya Stephen , Stuart Kenneth , Perreau Matthieu , Stapleton Jack T. , Jongo Said , Hoffman Stephen L. , Tanner Marcel , Abdulla Salim , Daubenberger Claudia
Published: January 2021

Background

Diverse vaccination outcomes and protection levels among different populations pose a serious challenge to the development of an effective malaria vaccine. Co-infections are among many factors associated with immune dysfunction and sub-optimal vaccination outcomes. Chronic, asymptomatic viral infections can contribute to the modulation of vaccine efficacy through various mechanisms. Human Pegivirus-1 (HPgV-1) persists in immune cells thereby potentially modulating immune responses. We investigated whether Pegivirus infection influences vaccine-induced responses and protection in African volunteers undergoing whole P. falciparum sporozoites-based malaria vaccination and controlled human malaria infections (CHMI).

Methods

HPgV-1 prevalence was quantified by RT-qPCR in plasma samples of 96 individuals before, post vaccination with PfSPZ Vaccine and after CHMI in cohorts from Tanzania and Equatorial Guinea. The impact of HPgV-1 infection was evaluated on (1) systemic cytokine and chemokine levels measured by Luminex, (2) PfCSP-specific antibody titers quantified by ELISA, (3) asexual blood-stage parasitemia pre-patent periods and parasite multiplication rates, (4) HPgV-1 RNA levels upon asexual blood-stage parasitemia induced by CHMI.

Results

The prevalence of HPgV-1 was 29.2% (28/96) and sequence analysis of the 5′ UTR and E2 regions revealed the predominance of genotypes 1, 2 and 5. HPgV-1 infection was associated with elevated systemic levels of IL-2 and IL-17A. Comparable vaccine-induced anti-PfCSP antibody titers, asexual blood-stage multiplication rates and pre-patent periods were observed in HPgV-1 positive and negative individuals. However, a tendency for higher protection levels was detected in the HPgV-1 positive group (62.5%) compared to the negative one (51.6%) following CHMI. HPgV-1 viremia levels were not significantly altered after CHMI.

Conclusions

HPgV-1 infection did not alter PfSPZ Vaccine elicited levels of PfCSP-specific antibody responses and parasite multiplication rates. Ongoing HPgV-1 infection appears to improve to some degree protection against CHMI in PfSPZ-vaccinated individuals. This is likely through modulation of immune system activation and systemic cytokines as higher levels of IL-2 and IL17A were observed in HPgV-1 infected individuals. CHMI is safe and well tolerated in HPgV-1 infected individuals. Identification of cell types and mechanisms of both silent and productive infection in individuals will help to unravel the biology of this widely present but largely under-researched virus.
Neuro-Muscular Dentistry: the “diamond” concept of electro-stimulation potential for stomato-gnathic and oro-dental conditions
Authors: Sandoval-Munoz Catalina P. , Haidar Ziyad S.
Published: January 2021

Oro-Pharyngeal Dysphagia - or simply dysphagia - is the difficulty (persistent) in swallowing/passing food and/or liquid from the mouth to the pharynx into the esophagus and finally the stomach; a deglutition disorder (a symptom, by definition, often due to neuro-degenerative/−muscular, drug-induced or localized structural pathologies such as head and neck tumors, lesions and associated surgical and/or radiation injuries) linked to severe consequences on Quality of Life (QoL), including malnutrition, dehydration, and even sudden death. Likewise, Temporo-Mandibular Jaw and Joint disorder(s) – or simply TMD – is a multifactorial etiological condition, regularly encountered in the dental office. Whether due to malocclusion, bruxism, stress and/or trauma, TMD destabilizes the whole cranio-mandibular system structurally and functionally, via affecting mastication, teeth, supporting structures, comfort and aesthetics, and thus, QoL, again. While several treatment regimens do exist for such conditions, some of which have been standardized for use over the years, most continue to lack proper evidence-based literature support. Hence, (1) caution is to be exercised; and (2) the need for alternative therapeutic strategies is amplified, subsequently, the door for innovation is wide open. Indeed, neuromuscular electrical stimulation or “NMES”, is perhaps a fine example. Herein, we present the interested oro-dental health care provider with an up-dated revision of this therapeutic modality, its potential benefits, risks and concerns, to best handle the dysphagic patient: an intra-disciplinary approach or strategy bridging contemporary dentistry with speech and language therapy; a rather obscure and un-discovered yet critical allied health profession. A pre-clinical and clinical prospectus on employing inventive NMES-based regimens and devices to manage TMD is also highlighted.
Prediction of hypericin content in Hypericum perforatum L. in different ecological habitat using artificial neural networks
Authors: Saffariha Maryam , Jahani Ali , Jahani Reza , Latif Sajid
Published: January 2021

Background

Hypericum is an important genus in the family Hypericaceae, which includes 484 species. This genus has been grown in temperate regions and used for treating wounds, eczema and burns. The aim of this study was to predict the content of hypericin in Hypericum perforatum in varied ecological and phenological conditions of habitat using artificial neural network techniques [MLP (Multi-Layer Perceptron), RBF (Radial Basis Function) and SVM (Support Vector Machine)].

Results

According to the results, the MLP model (R2 = 0.87) had an advantage over RBF (R2 = 0.8) and SVM (R2 = 0.54) models and it was relatively accurate in predicting hypericin content in H. perforatum based on the ecological conditions of site including soil types, its characteristics and plant phenological stages of habitat. The results of sensitivity analysis revealed that phenological stages, hill aspects, total nitrogen, altitude and organic carbon are the most influential factors that have an integral effect on the content of hypericin.

Conclusions

The designed graphical user interface will help pharmacognosist, manufacturers and producers of medicinal plants and so on to run the MLP model on new data to easily discover the content of hypericin in H. perforatum by entering ecological conditions of site, soil characteristics and plant phenological stages.
Opioid use, regulation, and harms in Brazil: a comprehensive narrative overview of available data and indicators
Authors: Maia Lucas O. , Daldegan-Bueno Dimitri , Fischer Benedikt
Published: January 2021

Background

Global opioid consumption increased multifold post-2000, disproportionately in high-income countries, with severe mortality/morbidity consequences. Latin America features comparatively low opioid availability; Brazil, the region’s most populous country, makes an interesting case study concerning opioid use/harms. In this comprehensive overview, we aimed to identify and summarize medical and non-medical data and indicators of opioid availability and use, regulation/control, and harm outcomes in Brazil since 2000.

Methods

We searched multiple scientific databases to identify relevant publications and conducted additional ‘grey’ literature searches to identify other pertinent information.

Results

Despite some essential indicators, opioid-related data are limited for Brazil. Data indicate that population-level availability of prescription opioids represents only a small fraction of use in comparison to high-income countries. However, within Latin America, Brazil ranks mid-level for opioid consumption, indicating relatively moderate consumption compared to neighboring jurisdictions. Brazil has implemented restrictive regulations to opioid prescribing and is considered ‘highly restricted’ for opioid access. Codeine remains the major opioid analgesic utilized, but stronger opioids such as oxycodone are becoming more common. Professional knowledge regarding medical opioid use and effects appears limited. National surveys indicate increases in non-medical use of prescription opioids, albeit lower than observed in North America, while illicit opioids (e.g., heroin) are highly uncommon.

Conclusions

Overall population-level opioid availability and corresponding levels of opioid-related harms in Brazil remain substantially lower than rates reported for North America. However, the available surveillance and analytical data on opioid use, policy/practice, and harms in Brazil are limited and insufficient. Since existing and acute (e.g., pain-related) needs for improved opioid utilization and practice appear to be substantiated, improved indicators for and understanding of opioid use, practice, and harms in Brazil are required.
Effect of a culturally safe student placement on students' understanding of, and confidence with, providing culturally safe podiatry care
Authors: West Matthew , Sadler Sean , Hawke Fiona , Munteanu Shannon E. , Chuter Vivienne
Published: January 2021

Background

For university‐based podiatry education there are little data available documenting the delivery method and impact of Aboriginal and Torres Strait Islander health curricula or the use of, and outcomes from, immersive clinical placements generally or specific to podiatry practice. Therefore, the primary aim of this study was to evaluate the effect of undertaking clinical placement in a culturally safe podiatry service for Aboriginal and Torres Strait Islander Peoples on podiatry students' understanding of, and confidence with, providing culturally safe podiatry care.

Methods

Final year University of Newcastle undergraduate podiatry students attending a culturally safe Aboriginal and Torres Strait Islander student clinic at a local hospital were purposively recruited to participate. Students completed a custom‐made and pilot‐tested cultural awareness and capability survey before and after placement. Survey domains were determined from a principle component analysis. The Wilcoxon Signed Rank test was used to compare pre‐placement scores on each domain of the survey to the post‐placements scores. Effect sizes were calculated and interpreted as small (0.1–0.29), medium (0.3–0.49), and large (≥0.5).

Results

This study recruited 58 final year University of Newcastle podiatry students to complete baseline and follow‐up surveys. For survey domain 1 (level of understanding of power relationships), domain 2 (level of understanding of the interrelationship between culture and self‐perceived health), domain 3 (level of understanding of the importance of culture in clinical practice and access to health care), and domain 4 (level of confidence with providing culturally safe care) a statistically significant (p < 0.05) increase in scores was recorded post‐placement. The effect sizes were medium to large.

Conclusion

This study demonstrated that an immersive student placement at a culturally safe podiatry clinic significantly improved students' understanding of, and confidence with, providing culturally appropriate care to Aboriginal and Torres Strait Islander Peoples. This study provides foundation evidence of the role that such placements have on developing students' cultural capability in a tertiary health care setting, and will help inform future curricula development at both educational institutions and health services, as well as form the basis for ongoing research.
Chinese herbal formula Xuefu Zhuyu for primary dysmenorrhea patients (CheruPDYS): a study protocol for a randomized placebo-controlled trial
Authors: Li Geng , Zhang Zhe , Zhou Li , Liao Shaojun , Sun Jing , Liu Yinghua , Wang Xin , Wen Zehuai
Published: January 2021

Background

Epidemiological studies have shown that young women often suffer from primary dysmenorrhea (PD) which is a common cause that affects their routine work and quality of life. Chinese herbal medicine has been widely used for PD in China. A systematic review found that Xuefu Zhuyu (XFZY) has a promising effect on PD management, yet there is a dearth of high-quality evidence in support of this claim. We want to conduct a randomized controlled trial to evaluate the efficacy and safety of XFZY for PD patients.

Methods

This is a protocol for a multicenter, randomized, placebo-controlled trial. A total of 248 participants with PD will be recruited at 6 centers and randomized into two groups—a herbal treatment group and a placebo group. The participants will receive either XFZY or placebo, three times per day, for 3 menstrual cycles, with a 12-week follow-up. The primary outcome will be the mean change in pain intensity as measured by VAS, while the change in menstrual pain duration, the change in peak pain intensity as measured by VAS, the Cox Menstrual Symptom Scale (CMSS), quality of life EQ-5D-5L, cumulative painkiller consumption, and health economics will be included as secondary outcomes. Adverse events will also be reported.

Discussion

This protocol describes a multicenter, double-blind, randomized, placebo-controlled trial that investigates the efficacy and safety of XFZY for primary dysmenorrhea. Validated evaluation tools will assess dysmenorrhea severity. We believe that this research will provide important evidence regarding the use of XFZY to treat dysmenorrhea.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900026819. Registered on 23 October 2019
Concentration of survivin in children with oligo- and polyarticular juvenile idiopathic arthritis (JIA): diagnostic and prognostic value—a single-center study
Authors: Lipinska Joanna , Kaszkowiak Marcin , Malachowska Beata , Swidrowska-Jaros Joanna , Smolewska Elzbieta
Published: January 2021

Aim

The goal of the study was to assess the diagnostic and prognostic utility of survivin in patients with juvenile idiopathic arthritis (JIA).

Methods

Seventy children with JIA—59 newly diagnosed and 11 biologically treated (46 girls and 17 boys) aged 1.5–18 years and 29 healthy children as a control group, appropriately matched in terms of sex and age, were included in the study. The disease activity was established on the basis of the JADAS-27 criteria. The concentration of survivin was assessed by an ELISA test in serum and also 18 matched synovial fluid samples collected from patients with JIA.

Results

Children with JIA were divided according to the subtype of the JIA. In 65.7% of patients, oligoarthritis was diagnosed. The largest group comprised children of low disease activity (62.9%) according to JADAS-27. The serum concentration of survivin was significantly higher in children with JIA compared to the controls (p < 0.001). The concentration of survivin was higher among patients positive for anti-cyclic citrullinated peptide autoantibodies (ACPA) (p = 0.001). In all synovial fluid samples, the concentration of survivin was higher than in matched serum (p = 0.003). Serum survivin concentration was not significantly associated with radiological damage status or active synovitis assessed by joint ultrasonography. Survivin level was not significantly associated with disease duration time or treatment with TNF-α inhibitors in DMARD’s non-responders.

Conclusions

Survivin should be considered as a biomarker of joint inflammation helpful in the diagnosis of oligo- and polyarticular JIA and probably not dependent on treatment with TNF-α inhibitors.