bluuebunny/crossref_metadata_2025 huggingface dataset:
Depressive symptoms, parental stress, and attachment style in mothers and fathers two and a half years after childbirth: Are fathers as affected as mothers?
Authors: Johansson Maude , Nordström Thomas , Svensson Idor
Published: July 2020

The study aimed to determine the prevalence of depressive symptoms and whether parental stress and attachment style affected depression in mothers and fathers two and a half years after the birth of a child. The parents completed several questionnaires including the Edinburgh Postnatal Depression Scale, the Swedish Parenthood Stress Questionnaire and the Relationship Questionnaire. The prevalence rate of depressive symptoms in mothers was 14.9%, while for fathers it was 11.5%. Differences between the parents identified as depressed and those without depressive symptoms were also analysed. There were no significant differences between depressed and non-depressed parents on the secure, avoidant and fearful attachment styles. However, there was a significant difference between groups on the preoccupied subscale. The final aim was to calculate if attachment style contributed to the level of depression while accounting for the impact of parental stress. Parental stress (incompetence, social isolation and spouse relationship problems) was the best predictor for mothers’ depressive symptoms, while parental stress (social isolation and health) and the preoccupied attachment style were the best predictors for such symptoms in fathers. The findings indicated that parental stress and depressive symptoms are closely related and can explain the difficulties parents face.
An integrative review on facilitators and barriers in delivering and managing injectable therapies in chronic conditions: A part of the ACNAP project ‘injectable medicines among patients with cardiovascular conditions’
Authors: Lambrinou Ekaterini , Kyriakou Martha , Lakatamitou Ioanna , Angus Neil , Khatib Rani , Vellone Ercole , Barrowcliff Abigail , Hansen Tina Birgitte , Lee Geraldine A
Published: July 2020

Introduction:

Although preventive health and therapeutics have benefited from advances in drug development and device innovation, translating these evidence-based treatments into real-world practice remains challenging.

Aim:

The current integrative review aims to identify facilitators and barriers and perceptions in delivering and managing injectable therapies from patient perspectives.

Methods:

An integrative review was conducted in the databases of PubMed, CINAHL, PsycINFO and Cochrane. Keywords were used “Injectable therapy”, “IV therapy”, “SC therapy”, “long term injectable therapies”, “self-administered injectable therapy”, “patients”, “caregivers”, “family”, “carers”, “facilitators”, “barriers”, “perspectives”, “needs”, “expectations”, “chronic disease”, “cardiovascular disease” linked with the words “OR” and “AND”. The search was limited from January 2000 to July 2019. Inclusion and exclusion criteria were used.

Results:

Twenty studies were identified from the literature search. Studies followed qualitative, quantitative methodology and mixed methods. Facilitators included: health improvement, prevention of disease complications, taking control of their disease, effectiveness of the medication and convenience in management. Barriers included: fear of needles, insulin will cause harm, poor perception of the benefits of injectable therapies on their quality of life, inconvenience in self-management, social stigma, impact on daily living, financial barriers, lack of education. Perceptions included: ‘treatment of last resort’, ‘life becomes less flexible’, ‘injectables were punishment/restriction’, ‘personal failure of self-management’.

Conclusion:

Evidence shows how to create effective communication and shared decision-making relationships to provide best possible care to patients who need injectable therapy and support for self-management. Future research might help guide response to the fears and barriers of the patients using patients’ perspectives.
The voice of inclusion in the midst of neoliberalist noise in the Bologna Process
Authors: Kushnir Iryna
Published: July 2020

This article belongs to a limited body of scholarship concerning inclusion in the Bologna Process. The Bologna Process aims to create the European Higher Education Area with comparable higher education structures within the European Higher Education Area member states. Unlike previous research that focuses on the implementation of one of the Bologna Process inclusion-related action lines (i.e. lifelong learning, student-centred education and social dimension), this article adopts a broader lens, and investigates the evolution of the meaning of ‘inclusion’ in the key international Bologna Process policy documents. This article argues that there is still a lack of clarity around the meaning of ‘inclusion’ in the Bologna Process, and the list of underprivileged groups that the Bologna Process aims to include in higher education, is absent. This article calls for an urgent review of this problem in the Bologna Process at the European Higher Education Area ministerial conference scheduled for 2020 which will set the agenda for post-2020 work in the European Higher Education Area.
White Masculinity, Creative Desires, and Production Ideology in Video Game Development
Authors: Bulut Ergin
Published: July 2020

Game workers have a problem. They code values and ideologies into games, but they are either not aware of it or deny it. Through a constructive and critical engagement with Games of Empire, I propose the concept of “ludic religiosity” to reveal how white masculinity informs game workers’ professional discourses, technological practices, ludic desires, and imaginations. Drawing on three-year-long ethnographic research and in conversation with cultural studies, philosophy of technology, and postcolonial game studies, I revisit desiring machine and ideology, two major concepts from Games of Empire. My goal is to demonstrate the racialized and gendered discourses and practices behind game developers’ desire to produce cognitive capitalism’s “escapist” commodities and rethink ideology within white masculine production cultures. Foregrounding how racialized and gendered practices and imaginations inform the desire behind the global game industry is crucial, especially in the aftermath of Gamergate and the rise of authoritarianism.
Perceptual Representations and the Vividness of Stimulus-Triggered and Stimulus-Independent Experiences
Authors: Fazekas Peter , Nemeth Georgina , Overgaard Morten
Published: July 2020

In recent years, researchers from independent subfields have begun to engage with the idea that the same cortical regions that contribute to on-line perception are recruited during and underlie off-line activities such as information maintenance in working memory, mental imagery, hallucinations, dreaming, and mind wandering. Accumulating evidence suggests that in all of these cases the activity of posterior brain regions provides the contents of experiences. This article is intended to move one step further by exploring specific links between the vividness of experiences, which is a characteristic feature of consciousness regardless of its actual content, and certain properties of the content-specific neural-activity patterns. Investigating the mechanisms that underlie mental imagery and its relation to working memory and the processes responsible for mind wandering and its similarities to dreaming form two clusters of research that are in the forefront of the recent scientific study of mental phenomena, yet communication between these two clusters has been surprisingly sparse. Here our aim is to foster such information exchange by articulating a hypothesis about the fine-grained phenomenological structure determining subjective vividness and its possible neural basis that allows us to shed new light on these mental phenomena by bringing them under a common framework.
Biologics and surgical outcomes in Crohn’s disease: is there a direct relationship?
Authors: Quaresma Abel Botelho , Yamamoto Takayuki , Kotze Paulo Gustavo
Published: July 2020

Despite significant advances in medical therapy in the management of Crohn’s disease (CD), surgery is still required in a significant proportion of patients and constitutes an important tool in treatment algorithms. Recently, more options of biological agents have been made available, and most patients with CD undergoing surgical procedures have been previously exposed to this class of drugs. There is controversy in the literature as to whether anti-tumor necrosis factor (TNF) agents, anti-integrins, or anti-interleukins (ILs) have a direct relationship with increased postoperative complications.

In this narrative review, the authors summarize the most important data regarding the effect of biologics on postoperative outcomes in CD.

Most studies (with different designs) are based on the experience with anti-TNF agents, mostly with infliximab. Some studies outlined the relationship between vedolizumab and postoperative complications, and there is a lack of data with ustekinumab in this scenario. Most studies are retrospective, but few prospective data are available. A cause–effect (proof of concept) direct relationship between biologics and an increase in postoperative morbidity has not been demonstrated to date. Several confounding factors such as previous use of steroids, malnutrition, and unfavorable abdominal conditions have a definitely effect on postoperative complications in CD.

Biologics seem safe to be used in the perioperative period, but available data are still controversial. Multidisciplinary individualized decisions should be made on a case-to-case basis, adapting the surgical strategy according to risk factors involved.
Chyluria: what does the clinician need to know?
Authors: Stainer Victoria , Jones Patrick , Juliebø Siri Øvereng , Beck Rupert , Hawary Amr
Published: July 2020

Chyluria is secondary to the presence of chyle in the urine. The classical appearance on inspection is of milky white urine, which is caused by a fistulous communication between the lymphatic system and the urinary tract. Worldwide, it is most commonly associated with the parasite Wuchereria bancrofti, which is prevalent in Asia, most extensively in India but also China and Taiwan. However, in the United Kingdom, Europe and North America, where the condition is rare, non-parasitic aetiologies predominate. Chyluria is occasionally associated with other urinary tract symptoms including infection, loin pain and haematuria. It may also cause hypoproteinaemia, weight loss and cachexia. Management is based on identifying the aetiology and depends on the severity of the chyluria and presence of associated symptoms. Given its predominate symptom being urinary, cases in the West can fall under the care of the urologist. The aim of this article is to provide an overview and summary of the aetiology, assessment and management of chyluria based on the most up-to-date evidence available. This was achieved through a non-systematic review of world literature.
Pursuing effectiveness and efficiency: Data model for workforce scheduling at Alvarino
Authors: Lim Chu-Yeong , Perdana Arif , Wong Shin-Ren
Published: July 2020

This case involves actual data obtained from an interview with a partner, a manager and two associates at a firm located in Singapore, Alvarino (pseudonym). The firm is part of a global network of accountancy and business advisory firms. The network comprises of more than 100 independently owned and managed firms that straddle more than 100 geographical locations across the world. The case illustrates issues that Alvarino experienced in scheduling their staff for audit advisory engagement. As a service oriented and cost-conscious business, workforce scheduling is essential to help Alvarino’s management optimise its workforce allocation. The objective of this case is to create a data model that maps user and data requirements to optimise Alvarino’s workforce-scheduling processes.
Efficacy and safety of riociguat in combination therapy for patients with pulmonary arterial hypertension (PATENT studies)
Authors: Ghofrani Hossein‐Ardeschir , Grünig Ekkehard , Jansa Pavel , Langleben David , Rosenkranz Stephan , Preston Ioana R. , Rahaghi Franck , Sood Namita , Busse Dennis , Meier Christian , Humbert Marc
Published: July 2020

Many patients with pulmonary arterial hypertension do not achieve treatment goals with monotherapy, and therefore combination therapy is becoming the standard of care. The soluble guanylate cyclase stimulator riociguat is licensed for the treatment of pulmonary arterial hypertension; here we present findings from patients who were receiving combined riociguat plus endothelin receptor antagonists or non‐intravenous prostanoids in the randomized, placebo‐controlled PATENT‐1 study and its open‐label extension (PATENT‐2). Moreover, we include new data from patients receiving early sequential combination therapy (three to six months of endothelin receptor antagonist treatment) or long‐term background endothelin receptor antagonist therapy (>6 months). Patients were randomized to riociguat 2.5 mg–maximum (N = 131 pretreated patients) and placebo (N = 60 pretreated patients). Riociguat improved 6‐min walking distance (PATENT‐1 primary endpoint), functional capacity, and hemodynamics after 12 weeks in pretreated patients. The placebo‐corrected changes in 6‐min walking distance were +24 m in endothelin receptor antagonist‐pretreated patients and +106 m in the small group of prostanoid‐pretreated patients. In the early sequential combination and long‐term background endothelin receptor antagonist groups, the placebo‐corrected changes in 6‐min walking distance were +65 m (95% CI: 17 to 113 m) and +13 m (95% CI: –8 to 33 m), respectively. In conclusion, these data suggest that early sequential combination of an endothelin receptor antagonist plus riociguat is a feasible treatment option. Both early sequential therapy and long‐term background endothelin receptor antagonist plus riociguat were well tolerated in the PATENT studies.
Effect of persistent opium consumption after surgery on the long-term outcomes of surgical revascularisation
Authors: Masoudkabir Farzad , Yavari Negin , Pashang Mina , Sadeghian Saeed , Jalali Arash , Poorhosseini Hamidreza , Tafti Seyed Hossein Ahmadi , Bagheri Jamshid , Abbasi Kiomars , Omran Abbas Salehi , Mansourian Soheil , Momtahan Shahram , Mortazavi Seyedeh Hamideh , Karimi Abbasali
Published: July 2020

Background

A wrong traditional belief persists among people that opium consumption beneficially affects cardiovascular disease and its risk factors. However, no evidence exists regarding the effect of opium consumption or cessation on the long-term risk of major adverse cardio-cerebrovascular events after coronary artery bypass grafting. We therefore aimed to evaluate the effect of persistent opium consumption after surgery on the long-term outcomes of coronary artery bypass grafting.

Methods

The study population consisted of 28,691 patients (20,924 men, mean age 60.9 years), who underwent coronary artery bypass grafting between 2007 and 2016 at our centre. The patients were stratified into three groups according to the status of opium consumption: never opium consumers (n = 23,619), persistent postoperative opium consumers (n = 3636) and enduring postoperative opium withdrawal (n = 1436). Study endpoints were 5-year mortality and 5-year major adverse cardio-cerebrovascular events, comprising all-cause mortality, acute coronary syndrome, cerebrovascular accident and revascularisation.

Results

After surgery, 3636 patients continued opium consumption, while 1436 patients persistently avoided opium use. The multivariable survival analysis demonstrated that persistent post-coronary artery bypass grafting opium consumption increased 5-year mortality and 5-year major adverse cardio-cerebrovascular events by 28% (hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.06–1.54; P = 0.009) and 25% (HR 1.25, 95% CI 1.13–1.40; P < 0.0001), respectively. It also increased the 5-year risk of acute coronary syndrome by 34% (sub-distribution HR 1.34, 95% CI 1.16–1.55; P < 0.0001).

Conclusions

The present data suggest that persistent post-coronary artery bypass grafting opium consumption may significantly increase mortality, major adverse cardio-cerebrovascular events and acute coronary syndrome in the long term. Future studies are needed to confirm our findings.
Linked Double-Row Equivalent Arthroscopic Rotator Cuff Repair Leads to Significantly Improved Patient Outcomes
Authors: Endo Atsushi , Hoogervorst Paul , Safranek Conrad , Sochacki Kyle R. , Safran Marc R. , Sherman Seth L. , Donahue Joseph
Published: July 2020

Background:

Biomechanical studies have demonstrated that arthroscopic rotator cuff repair using a linked double-row equivalent construct results in significantly higher load to failure compared with conventional transosseous-equivalent constructs.

Purpose:

To determine the patient-reported outcomes (PROs), reoperation rates, and complication rates after linked double-row equivalent rotator cuff repair for full-thickness rotator cuff tears.

Study Design:

Case series; Level of evidence, 4.

Methods:

Consecutive patients who underwent linked double-row equivalent arthroscopic rotator cuff repair with minimum 2-year follow-up were included. The primary outcome was the American Shoulder and Elbow Surgeons (ASES) score at final follow-up. Secondary outcomes included the Simple Shoulder Test (SST), shortened Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, visual analog scale (VAS), reoperations, and complications. Clinical relevance was defined by the minimally clinically important difference (MCID). Comparisons on an individual level that exceeded MCID (individual-level scores) were deemed clinically relevant. Comparisons between preoperative and postoperative scores were completed using the Student t test. All P values were reported with significance set at P < .05.

Results:

A total of 42 shoulders in 41 consecutive patients were included in this study (21 male patients [51.2%]; mean age, 64.5 ± 11.9 years; mean follow-up, 29.7 ± 4.5 months). All patients (100%) completed the minimum 2-year follow-up. The rotator cuff tear measured on average 15.2 ± 8.9 mm in the coronal plane and 14.6 ± 9.8 mm in the sagittal plane. The ASES score improved significantly from 35.5 ± 18.2 preoperatively to 93.4 ± 10.6 postoperatively ( P < .001). The QuickDASH ( P < .001), SST ( P < .001), and VAS ( P < .001) scores also significantly improved after surgery. All patients (42/42 shoulders; 100%) achieved clinically relevant improvement (met or exceeded MCID) on ASES and SST scores postoperatively. There were no postoperative complications (0.0%) or reoperations (0.0%) at final follow-up.

Conclusion:

Arthroscopic repair of full-thickness rotator cuff tears with the linked double-row equivalent construct results in statistically significant and clinically relevant improvements in PRO scores with low complication rates (0.0%) and reoperation rates (0.0%) at short-term follow-up.
Searching for the Fetal Alcohol Behavioral Phenotype
Authors: Koren Gideon , Ornoy Asher
Published: July 2020

This narrative review presents the emerging published evidence on the existence of a phenotypic behavior in children with fetal alcohol spectrum behavior. Such a phenotype, exhibiting high sensitivity, specificity, and predictive values, may assist clinicians and families in identifying children who often miss some of the information needed for full diagnosis, but who may benefit from these screening tools in mobilizing help to these youngsters and their families.
Pediatric Hepatoblastoma: What the Sonographer Needs to Know for the Sonographic Evaluation of Complications After Treatment and After Liver Transplantation
Authors: Grice Amanda , Tennermann Nikki , Hagi Ramla , Ward Valerie L.
Published: July 2020

Hepatoblastoma (HB) is a common primary pediatric liver tumor, and its typical presentation is a palpable, nontender abdominal mass that is detected through sonographic imaging. The current treatment standard for HB includes chemotherapy followed by liver resection or transplantation. Throughout the management of HB, high-quality sonographic images inform diagnosis, treatment interventions, and detection of surgical treatment complications. It is important that sonographers be familiar with the presentation and complications of HB on imaging examinations. The authors review sonographic detection, evaluation of HB at presentation, and common complications after liver resection and transplantation.
QTL Mapping and Candidate Gene Analysis for Alkali Tolerance in Japonica Rice at the bud Stage Based on Linkage Mapping and Genome-Wide Association Study
Authors: Li Xianwei , Zheng Hongliang , Wu Wenshen , Liu Hualong , Wang Jingguo , Jia Yan , Li Jiaming , Yang Luomiao , Lei Lei , Zou Detang , Zhao Hongwei
Published: July 2020

Background

Salinity-alkalinity stress is one of the major factors limiting rice production. Damage caused by alkaline salt stress is more severe than that caused by neutral salt stress. Alkali tolerance at the bud stage in rice directly affects seedling survival and final yield when using the direct seeding cultivation model. However, genetic resources (QTLs and genes) for rice breeders to improve alkali tolerance are limited. In this study, we combined linkage mapping and a genome-wide association study (GWAS) to analyze the genetic structure of this trait in japonica rice at the bud stage.

Results

A population of 184 recombinant inbred lines (RILs) was utilized to map quantitative trait loci (QTLs) for the root length under control condition (RL), alkaline stress (ARL) and relative root length (RRL) at the bud stage. A major QTL related to alkali tolerance at the rice bud stage, qAT11, was detected on chromosome 11. Interestingly, a GWAS identified a lead SNP (Chr_21,999,659) in qAT11 that was significantly associated with alkaline tolerance. After filtering by linkage disequilibrium (LD), haplotype analysis, quantitative real-time PCR, we obtained three candidate genes (LOC_Os11g37300, LOC_Os11g37320 and LOC_Os11g37390). In addition, we performed phenotype verification on the CRISPR/Cas9 mutant of LOC_Os11g37390.

Conclusion

Based on these results, LOC_Os11g37300, LOC_Os11g37320 and LOC_Os11g37390 were the candidate genes contributing to alkaline tolerance in japonica rice. This study provides resources for breeding aimed at improving rice responses to alkalinity stress.
Incorporating representation learning and multihead attention to improve biomedical cross-sentence n-ary relation extraction
Authors: Zhao Di , Wang Jian , Zhang Yijia , Wang Xin , Lin Hongfei , Yang Zhihao
Published: July 2020

Background

Most biomedical information extraction focuses on binary relations within single sentences. However, extracting n-ary relations that span multiple sentences is in huge demand. At present, in the cross-sentence n-ary relation extraction task, the mainstream method not only relies heavily on syntactic parsing but also ignores prior knowledge.

Results

In this paper, we propose a novel cross-sentence n-ary relation extraction method that utilizes the multihead attention and knowledge representation that is learned from the knowledge graph. Our model is built on self-attention, which can directly capture the relations between two words regardless of their syntactic relation. In addition, our method makes use of entity and relation information from the knowledge base to impose assistance while predicting the relation. Experiments on n-ary relation extraction show that combining context and knowledge representations can significantly improve the n-ary relation extraction performance. Meanwhile, we achieve comparable results with state-of-the-art methods.

Conclusions

We explored a novel method for cross-sentence n-ary relation extraction. Unlike previous approaches, our methods operate directly on the sequence and learn how to model the internal structures of sentences. In addition, we introduce the knowledge representations learned from the knowledge graph into the cross-sentence n-ary relation extraction. Experiments based on knowledge representation learning show that entities and relations can be extracted in the knowledge graph, and coding this knowledge can provide consistent benefits.
Novel ECHS1 mutations in Leigh syndrome identified by whole-exome sequencing in five Chinese families: case report
Authors: Sun Dan , Liu Zhimei , Liu Yongchu , Wu Miaojuan , Fang Fang , Deng Xianbo , Liu Zhisheng , Song Liang , Murayama Kei , Zhang Chunhua , Zhu Yuanyuan
Published: July 2020

Background

Short-chain enoyl-CoA hydratase deficiency (ECHS1D), also known as ECHS1 deficiency, is a rare inborn metabolic disorder with clinical presentations characterized by Leigh syndrome (LS). Thirty-four different pathogenic mutations have been identified from over 40 patients to date.

Case presentation

Here, we report five Chinese patients with clinical syndromes typified as LS. Despite different initial symptoms, all patients presented developmental regression, dystonia, common radiological features such as symmetrical bilateral brain abnormalities, and similar metabolic results such as elevated plasma lactate and 2,3-dihydroxy-2-methylbutyrate. Utilizing whole-exome sequencing (WES), we identified eight distinct variants in ECHS1, with six novel variants, and the remaining two variants have been previously reported. Interestingly, one of the six novel variants, c.463G > A (p.Gly155Ser), was detected in three patients from unrelated families, suggesting a potential founder effect already described for a few mutations in LS. Incorporating both genetic analysis and medical results, including magnetic resonance imaging (MRI), electroencephalography (EEG), and biochemical testing, our study enriched the mutation spectrum of the ECHS1 gene and confirmed the phenotypic presentations of LS.

Conclusions

The severity of ECHS1 deficiency seems to vary. It was affected by both genetics and external environmental factors that lead to increased metabolism. Our study enriched the mutation spectrum of the ECHS1 gene, confirmed the phenotypic presentations, and highlighted the importance of the valine catabolic pathway in Leigh syndrome. Further studies are required to examine the potential founder mutation c.463G > A (p.Gly155Ser) and the role of ECHS1 in relevant pathways.
Developing a competency profile for newly graduated registered nurses in South Africa
Authors: Rabie Gerhard Hendrik , Rabie Tinda , Dinkelmann Monica
Published: July 2020

Background

Newly graduated registered nurses experience various challenges when entering the clinical practice environment. Typical challenges include lack of specific knowledge, skills and attitude competencies which is aggravated further by factors such as transition problems, workloads, lack of confidence and independence which potentially causes poor quality care. The aim of the study was to develop a competency profile for newly graudated registered nures, based on the perceptions of both nurse educators and final-year nursing students regarding the knowledge, skills and attitudes needed to deliver quality patient care in South Africa.

Methods

A qualitative descriptive design was used. Semi-structured individual interviews were conducted with 42 participants consisting of 23 nurse educators and 19 final-year nursing students at three nursing education institutions. The interviews were guided by an interview guide that examined three predetermined themes: knowledge, skills and attitudes as competencies to deliver quality patient care. Data were processed using thematic analysis.

Results

The predetermined theme knowledge, was broken down into themes: theoretical knowledge, holistic care, cultural diversity and code of conduct, with its relating sub-themes. The predetermined theme skills delivered the following themes: interpersonal, management, administrative, practical and personal skills with its sub-themes. Attitudes unpacked into the following themes: being positive, caring, humble, friendly, empathetic, life-long learning, going the extra mile, compassionate, having passion, approachable, sensitive, helpful, and non-judgemental.

Conclusions

Rich, in-depth knowledge, skills and attitudes were identified to develop a competency profile that may assist newly graduated registered nurses when entering the clinical practice environment to deliver quality patient care.
Circulating vaccine-derived poliovirus: a menace to the end game of polio eradication
Authors: Ming Long Chiau , Hussain Zahid , Yeoh Siang Fei , Koh David , Lee Kah Seng
Published: July 2020

The World Health Organisation Western Pacific Region countries were declared free of polio in 2000 until a polio outbreak involving 305 cases occurred in Indonesia in 2006. It was not until 2014 that the World Health Organisation South East Asia region was officially declared polio-free again. However, in February 2019, the Global Polio Eradication Initiative announced a new circulating vaccine-derived poliovirus outbreak in the Papua province of Indonesia. To make matter worse, the outbreak responses were tardy and led to transmission among migrating communities to other cities. The pressing regional issues of polio outbreak caused by circulating vaccine-derived poliovirus and use of oral polio vaccine have not been well presented. Our letter highlighted the suboptimal outbreak responses as well as the necessity of cross-border vaccination to curb continued poliovirus transmission.
Can levosimendan reduce ECMO weaning failure in cardiogenic shock?: a cohort study with propensity score analysis
Authors: Guilherme Enrique , Jacquet-Lagrèze Matthias , Pozzi Matteo , Achana Felix , Armoiry Xavier , Fellahi Jean-Luc
Published: July 2020

Background

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used over the last decade in patients with refractory cardiogenic shock. ECMO weaning can, however, be challenging and lead to circulatory failure and death. Recent data suggest a potential benefit of levosimendan for ECMO weaning. We sought to further investigate whether the use of levosimendan could decrease the rate of ECMO weaning failure in adult patients with refractory cardiogenic shock.

Methods

We performed an observational single-center cohort study. All patients undergoing VA-ECMO from January 2012 to December 2018 were eligible and divided into two groups: group levosimendan and group control (without levosimendan). The primary endpoint was VA-ECMO weaning failure defined as death during VA-ECMO treatment or within 24 h after VA-ECMO removal. Secondary outcomes were mortality at day 28 and at 6 months. The two groups were compared after propensity score matching. P < 0.05 was considered statistically significant.

Results

Two hundred patients were analyzed (levosimendan group: n = 53 and control group: n = 147). No significant difference was found between groups on baseline characteristics except for ECMO duration, which was longer in the levosimendan group (10.6 ± 4.8 vs. 6.5 ± 4.7 days, p < 0.001). Levosimendan administration started 6.6 ± 5.4 days on average following ECMO implantation. After matching of 48 levosimendan patients to 78 control patients, the duration of ECMO was similar in both groups. The rate of weaning failure was 29.1% and 35.4% in levosimendan and control groups, respectively (OR: 0.69, 95%CI: 0.25–1.88). No significant difference was found between groups for all secondary outcomes.

Conclusion

Levosimendan did not improve the rate of successful VA-ECMO weaning in patients with refractory cardiogenic shock.

Trial registration

ClinicalTrials.gov, NCT04323709.
Development and validation of a risk factor-based system to predict short-term survival in adult hospitalized patients with COVID-19: a multicenter, retrospective, cohort study
Authors: Zhang Shuai , Guo Mengfei , Duan Limin , Wu Feng , Hu Guorong , Wang Zhihui , Huang Qi , Liao Tingting , Xu Juanjuan , Ma Yanling , Lv Zhilei , Xiao Wenjing , Zhao Zilin , Tan Xueyun , Meng Daquan , Zhang Shujing , Zhou E , Yin Zhengrong , Geng Wei , Wang Xuan , Zhang Jianchu , Chen Jianguo , Zhang Yu , Jin Yang
Published: July 2020

Background

Coronavirus disease 2019 (COVID-19) has become a public health emergency of global concern. We aimed to explore the risk factors of 14-day and 28-day mortality and develop a model for predicting 14-day and 28-day survival probability among adult hospitalized patients with COVID-19.

Methods

In this multicenter, retrospective, cohort study, we examined 828 hospitalized patients with confirmed COVID-19 hospitalized in Wuhan Union Hospital and Central Hospital of Wuhan between January 12 and February 9, 2020. Among the 828 patients, 516 and 186 consecutive patients admitted in Wuhan Union Hospital were enrolled in the training cohort and the validation cohort, respectively. A total of 126 patients hospitalized in Central Hospital of Wuhan were enrolled in a second external validation cohort. Demographic, clinical, radiographic, and laboratory measures; treatment; proximate causes of death; and 14-day and 28-day mortality are described. Patients’ data were collected by reviewing the medical records, and their 14-day and 28-day outcomes were followed up.

Results

Of the 828 patients, 146 deaths were recorded until May 18, 2020. In the training set, multivariate Cox regression indicated that older age, lactate dehydrogenase level over 360 U/L, neutrophil-to-lymphocyte ratio higher than 8.0, and direct bilirubin higher than 5.0 μmol/L were independent predictors of 28-day mortality. Nomogram scoring systems for predicting the 14-day and 28-day survival probability of patients with COVID-19 were developed and exhibited strong discrimination and calibration power in the two external validation cohorts (C-index, 0.878 and 0.839).

Conclusion

Older age, high lactate dehydrogenase level, evaluated neutrophil-to-lymphocyte ratio, and high direct bilirubin level were independent predictors of 28-day mortality in adult hospitalized patients with confirmed COVID-19. The nomogram system based on the four factors revealed good discrimination and calibration, suggesting good clinical utility.
Presence of autoantibodies in “seronegative” rheumatoid arthritis associates with classical risk factors and high disease activity
Authors: Reed Evan , Hedström Anna Karin , Hansson Monika , Mathsson-Alm Linda , Brynedal Boel , Saevarsdottir Saedis , Cornillet Martin , Jakobsson Per-Johan , Holmdahl Rikard , Skriner Karl , Serre Guy , Alfredsson Lars , Rönnelid Johan , Lundberg Karin
Published: July 2020

Background

Rheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative.

Methods

Anti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets.

Results

Autoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined “seronegative” RA, associated with worse clinical outcome.

Conclusions

“Seronegative” RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2−/IgM RF− patients with a high need for active treatment.
A note on the impact of late diagnosis on HIV/AIDS dynamics: a mathematical modelling approach
Authors: Mushanyu J.
Published: July 2020

Objectives:

The global incidence of HIV infection is not significantly decreasing, especially in sub-Saharan African countries. Though there is availability and accessibility of free HIV services, people are not being diagnosed early for HIV, and hence HIV-related mortality remains significantly high. We formulate a mathematical model for the spread of HIV using non linear ordinary differential equations in order to investigate the impact of late diagnosis of HIV on the spread of HIV.

Results:

The results suggest the need to encourage early initiation into HIV treatment as well as promoting HIV self-testing programs that enable more undiagnosed people to know their HIV status in order to curtail the continued spread of HIV.
Identification of potential blood biomarkers for early diagnosis of Alzheimer’s disease through RNA sequencing analysis
Authors: Shigemizu Daichi , Mori Taiki , Akiyama Shintaro , Higaki Sayuri , Watanabe Hiroshi , Sakurai Takashi , Niida Shumpei , Ozaki Kouichi
Published: July 2020

Background

With demographic shifts toward older populations, the number of people with dementia is steadily increasing. Alzheimer’s disease (AD) is the most common cause of dementia, and no curative treatment is available. The current best strategy is to delay disease progression and to practice early intervention to reduce the number of patients that ultimately develop AD. Therefore, promising novel biomarkers for early diagnosis are urgently required.

Methods

To identify blood-based biomarkers for early diagnosis of AD, we performed RNA sequencing (RNA-seq) analysis of 610 blood samples, representing 271 patients with AD, 91 cognitively normal (CN) adults, and 248 subjects with mild cognitive impairment (MCI). We first estimated cell-type proportions among AD, MCI, and CN samples from the bulk RNA-seq data using CIBERSORT and then examined the differentially expressed genes (DEGs) between AD and CN samples. To gain further insight into the biological functions of the DEGs, we performed gene set enrichment analysis (GSEA) and network-based meta-analysis.

Results

In the cell-type distribution analysis, we found a significant association between the proportion of neutrophils and AD prognosis at a false discovery rate (FDR) < 0.05. Furthermore, a similar trend emerged in the results of routine blood tests from a large number of samples (n = 3,099: AD, 1,605; MCI, 994; CN, 500). In addition, GSEA and network-based meta-analysis based on DEGs between AD and CN samples revealed functional modules and important hub genes associated with the pathogenesis of AD. The risk prediction model constructed by using the proportion of neutrophils and the most important hub genes (EEF2 and RPL7) achieved a high AUC of 0.878 in a validation cohort; when further applied to a prospective cohort, the model achieved a high accuracy of 0.727.

Conclusions

Our model was demonstrated to be effective in prospective AD risk prediction. These findings indicate the discovery of potential biomarkers for early diagnosis of AD, and their further improvement may lead to future practical clinical use.
Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration
Authors: Asgari Negin , Bagheri Fatemeh , Eslaminejad Mohamadreza Baghaban , Ghanian Mohammad Hossein , Sayahpour Forogh Azam , Ghafari Amir Mohammad
Published: July 2020

Background

Regeneration of articular cartilage poses a tremendous challenge due to its limited self-repair capability and inflammation at the damaged site. To generate the desired structures that mimic the structure of native tissue, microtissues with repeated functional units such as cell aggregates have been developed. Multicellular aggregates of mesenchymal stem cells (MSCs) can be used as microscale building blocks of cartilage due to their potential for cell-cell contact, cell proliferation, and differentiation.

Methods

Chondrogenic microtissues were developed through incorporation of kartogenin-releasing poly (lactic-co-glycolic acid) (PLGA) microparticles (KGN-MP) within the MSC aggregates. The chondrogenic potential of KGN-MP treated MSC aggregates was proven in vitro by studying the chondrogenic markers at the RNA level and histological analysis. In order to address the inflammatory responses at the defect site, the microtissues were delivered in vivo via an injectable, anti-inflammatory hydrogel that contained gelatin methacryloyl (GelMA) loaded with curcumin (Cur).

Results

The KGN-MPs were fabricated to support MSCs during cartilage differentiation. According to real-time RT-PCR analysis, the presence of KGN in the aggregates led to the expression of cartilage markers by the MSCs. Both toluidine blue (TB) and safranin O (SO) staining demonstrated homogeneous glycosaminoglycan production throughout the KGN-MP incorporated MSC aggregates. The curcumin treatment efficiently reduced the expressions of hypertrophy markers by MSCs in vitro. The in vivo results showed that implantation of chondrogenic microtissues (KGN-MP incorporated MSC aggregates) using the curcumin loaded GelMA hydrogel resulted in cartilage tissue regeneration that had characteristic features close to the natural hyaline cartilage according to observational and histological results.

Conclusions

The use of this novel construct that contained chondrogenic cell blocks and curcumin is highly desired for cartilage regeneration.

Graphical abstract
Pluripotent stem cell differentiation as an emerging model to study human prostate development
Authors: Yu Yangyang , Jiang Wei
Published: July 2020

Prostate development is a complex process, and knowledge about this process is increasingly required for both basic developmental biology studies and clinical prostate cancer research, as prostate tumorigenesis can be regarded as the restoration of development in the adult prostate. Using rodent animal models, scientists have revealed that the development of the prostate is mainly mediated by androgen receptor (AR) signaling and that some other signaling pathways also play indispensable roles. However, there are still many unknowns in human prostate biology, mainly due to the limited availability of proper fetal materials. Here, we first briefly review prostate development with a focus on the AR, WNT, and BMP signaling pathways is necessary for prostate budding/BMP signaling pathways. Based on the current progress in in vitro prostatic differentiation and organoid techniques, we propose human pluripotent stem cells as an emerging model to study human prostate development.
A synergistic role of convalescent plasma and mesenchymal stem cells in the treatment of severely ill COVID-19 patients: a clinical case report
Authors: Peng Hongbing , Gong Tiefeng , Huang Xiaoying , Sun Xun , Luo Hong , Wang Weizhong , Luo Junbiao , Luo Baowei , Chen Yanhui , Wang Xingxing , Long Haifeng , Mei Hua , Li Chuang , Dai Yanni , Li Honghui
Published: July 2020

Acute respiratory distress syndrome virus-2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) infection, which causes global public health emergencies, has sped widely for more than 5 months and has the risk of long-term transmission. No effective treatment has been discovered to date. In the cases we report, the patient continued to deteriorate even after administration of antiviral drugs such as lopinavir/ritonavir, interferon-α, and ribavirin, as well as intravenous injection of meropenem, methylprednisolone, and immunoglobulin. So, we infused the patient with convalescent plasma (CP), and the absolute lymphocyte count increased the next day and returned to normal on the fourth day. Followed by intravenous infusion of mesenchymal stem cells (MSCs), bilateral infiltrates were absorbed and the pulmonary function was significantly improved. We note that the intravenous infusion of CP and MSCs for the treatment of severe COVID-19 patients may have synergistic characteristics in inhibiting cytokine storm, promoting the repair of lung injury, and recovering pulmonary function. We hope to provide a reference for the research direction of COVID-19 clinical strategies.
Human amnion mesenchymal stem cells restore spermatogenesis in mice with busulfan-induced testis toxicity by inhibiting apoptosis and oxidative stress
Authors: Qian Chunfeng , Meng Qingxia , Lu Jiafeng , Zhang Liya , Li Hong , Huang Boxian
Published: July 2020

Background

Before starting gonadotoxic therapies, cryopreservation of mature sperm has been proposed worldwide as a method for male fertility preservation and for enabling the conception of a healthy baby with assisted reproductive technology (ART); however, these technologies are not feasible for prepubertal boys and men with spermatogenic failure. Transplantation of mesenchymal stem cells has exhibited successful therapeutic benefits in restoring spermatogenesis via gonadal graft angiogenesis, transplanted cell clonogenesis, and disordered somatic compartment recovery. This study aimed to elucidate the fertility protective effects and the underlying mechanisms of human amnion mesenchymal stem cells (hAMSCs) against busulfan-induced testis toxicity.

Methods

An in vivo busulfan-induced testis toxicity mouse model and an in vitro busulfan-administered mouse Sertoli cell line were employed to evaluate the efficacy and mechanisms of hAMSC transplantation on male fertility preservation. The process of spermatogenesis was evaluated histologically, and the percentage of seminiferous tubules with vacuoles was evaluated by HE staining. Semen parameters were calculated by computer-assisted semen analysis. ELISA was employed to test the testosterone concentration and the levels of oxidative- and antioxidative-associated substances LDH, MDA, GR, SOD, GPx, and CAT. The rates of proliferation (Ki67), apoptosis (Annexin V), and ROS were measured by FACS. The fluorescence intensity of a marker of apoptosis (TUNEL) and a meiosis gene in spermatogenesis (SCP3) were detected by immunofluorescence assay. The expression of mRNA in germ cell-specific (GCS) genes (Dazl, Ddx4, and Miwi) and meiosis genes (Scp3, Cyclin A1, and Stra8) was tested by qPCR. The expression of antiapoptotic proteins (SURVIVIN and BCL2), apoptotic proteins (CASPASE3 and CASPASE9), GCS proteins (Dazl, Ddx4, and Miwi), and meiosis proteins (Scp3, Cyclin A1, and Stra8) was tested by western blotting.

Results

hAMSC transplantation following disruption by busulfan-induced testis toxicity restored spermatogenesis, elevating testosterone levels and enhancing testicular weight, size, and semen parameters in vivo. In addition, hAMSCs clearly ameliorated cell apoptosis, enhanced cell proliferation, repressed oxidative damage, and augmented oxidative defense in vivo and in vitro. Moreover, hAMSCs distinctly increased the expression of the GCS genes Dazl, Ddx4, and Miwi and the meiosis genes Scp3, Cyclin A1, and Stra8 in vivo.

Conclusions

hAMSCs might represent a promising tool for the use in regenerative medicine, as these cells can restore spermatogenesis in a busulfan-induced testis toxicity mouse model and facilitate activity in a busulfan-administered mouse Sertoli cell line by resisting apoptosis and oxidative stress.