bluuebunny/crossref_metadata_2025 huggingface dataset:
The Optimal Magnitude of Government Spending: Evidence from Cambodia
Authors: Hok Leanghak , Bartha Zoltán
Published: May 2022

Scholars and policymakers have vigorously debated what the impact of government spending on economic growth is. Some current research and theoretical models suggest that the reaction of economic growth to the extension of government spending can be either positive or negative. This article intends to investigate the inverted-U shaped relationship between output growth and government spending (i.e., government fixed capital formation [GFCF] and government final consumption expenditure [GFCE]). Ordinary least squares (OLS) is employed as an approach to annual data for Cambodia obtained from 1971 to 2015. The result reveals that GFCF and GFCE have an inverted-U shaped relation with economic growth and that 5.40% and 7.23% are the optimal values of GFCF and GFCE, respectively. The labour growth rate and export growth rate contribute positively to the growth rate of output. This study indicates that the increasing level of government expenditure reduces the efficacy of government spending, and also helps Cambodia’s policymakers to control fiscal policy more efficiently.

JEL Classification: C80, E62, H50, O40
Sonographic Assessment of Renal Transplant Anastomotic Pseudoaneurysm: A Case Study
Authors: Petersen Kendra E. , Hunt Talisha M. , McMenomy Brendan P. , Prieto Mikel
Published: May 2022

Renal transplant anastomotic pseudoaneurysms (RTAPs) are a rare vascular postoperative complication. The etiology of these pseudoaneurysms is attributed to infection or surgical vessel damage. RTAPs can lead to allograft dysfunction, allograft loss, or patient mortality due to rupture or sepsis. Because of these serious complications, expedient diagnosis is imperative for initiating surgical intervention and medical management. Sonography is a useful imaging modality for diagnosing and characterizing RTAPs. The sonographic findings, although not often described in detail in the literature, are definitive and unique. This case report describes the sonographic findings of a patient 22 days post renal autotransplant, who presented with excruciating abdominal pain. Sonographic examination identified multiple classic pseudoaneurysm findings and demonstrated intrarenal and extrarenal vascular abnormalities.
Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab
Authors: Seymour John F. , Kipps Thomas J. , Eichhorst Barbara F. , D’Rozario James , Owen Carolyn J. , Assouline Sarit , Lamanna Nicole , Robak Tadeusz , de la Serna Javier , Jaeger Ulrich , Cartron Guillaume , Montillo Marco , Mellink Clemens , Chyla Brenda , Panchal Anesh , Lu Tong , Wu Jenny Q. , Jiang Yanwen , Lefebure Marcus , Boyer Michelle , Kater Arnon P.
Published: May 2022

The MURANO trial (A Study to Evaluate the Benefit of Venetoclax Plus Rituximab Compared With Bendamustine Plus Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia [CLL]; ClinicalTrials.gov identifier #NCT02005471) reported superior progression-free survival (PFS) and overall survival (OS) with venetoclax-rituximab (VenR) vs bendamustine-rituximab (BR) in relapsed/refractory (R/R) CLL. Patients were randomized to 2 years of VenR (n = 194; rituximab for the first 6 months) or 6 months of BR (n = 195). Although undetectable minimal residual disease (uMRD) was achieved more often with VenR, the long-term implications of uMRD with this fixed-duration, chemotherapy-free regimen have not been explored. We report MRD kinetics and updated outcomes with 5 years’ follow-up. Survival benefits with VenR vs BR were sustained (median PFS [95% confidence interval]: 53.6 [48.4, 57.0] vs 17.0 [15.5, 21.7] months, respectively, P < .0001; 5-year OS [95% confidence interval]: 82.1% [76.4, 87.8] vs 62.2% [54.8, 69.6], P < .0001). VenR was superior to BR, regardless of cytogenetic category. VenR-treated patients with uMRD at end of treatment (EOT; n = 83) had superior OS vs those with high-MRD+ (n = 12): 3-year post-EOT survival rates were 95.3% vs 72.9% (P = .039). In those with uMRD at EOT, median time to MRD conversion was 19.4 months. Of 47 patients with documented MRD conversion, 19 developed progressive disease (PD); median time from conversion to PD was 25.2 months. A population-based logistic growth model indicated slower MRD median doubling time post-EOT with VenR (93 days) vs BR (53 days; P = 1.2 × 10−7). No new safety signals were identified. Sustained survival, uMRD benefits, and durable responses support 2-year fixed-duration VenR treatment in R/R CLL.
Self-management in chronic lung disease: what is missing?
Authors: Kelly Carol , Heslop-Marshall Karen , Jones Steve , Roberts Nicola J.
Published: May 2022

Self-management, as a strategy to support those living with chronic respiratory conditions such as asthma and COPD, has been widely advocated in guidelines and adopted in practice. However, there can be a disconnect between the goals of patients and healthcare professionals. Goals and barriers to self-management are often compounded by the complex social, emotional and medical needs of patients. People living with chronic respiratory conditions also often have symptoms of anxiety and depression, which can impact on self-management. Self-management therefore requires patients and healthcare professionals to work together and it is essential to involve patients when designing, implementing and evaluating self-management interventions.

Patient preferences are clearly important and goal setting needs an individual, flexible and responsive approach from healthcare professionals, which aligns to a more personalised approach to management of treatable traits and the burden of disease. To achieve these goals, healthcare professionals need education to support patients in self-management and behaviour change. This approach should lead to shared decision-making and partnership working that puts the patient right at the centre of their care.
ERS International Congress 2021: highlights from the Pulmonary Vascular Diseases Assembly
Authors: Lichtblau Mona , Piccari Lucilla , Ramjug Sheila , Bokan Aleksandar , Lechartier Benoit , Jutant Etienne-Marie , Barata Margarida , Garcia Agustin Roberto , Howard Luke S. , Adir Yochai , Delcroix Marion , Jara-Palomares Luis , Bertoletti Laurent , Sitbon Olivier , Ulrich Silvia , Vonk Noordegraaf Anton
Published: May 2022

This article aims to summarise the latest research presented at the virtual 2021 European Respiratory Society (ERS) International Congress in the field of pulmonary vascular disease. In light of the current guidelines and proceedings, knowledge gaps are addressed and the newest findings of the various forms of pulmonary hypertension as well as key points on pulmonary embolism are discussed.

Despite the comprehensive coverage of the guidelines for pulmonary embolism at previous conferences, discussions about controversies in the diagnosis and treatment of this condition in specific cases were debated and are addressed in the first section of this article.

We then report on an interesting pro–con debate about the current classification of pulmonary hypertension.

We further report on presentations on Group 3 pulmonary hypertension, with research exploring pathogenesis, phenotyping, diagnosis and treatment; important contributions on the diagnosis of post-capillary pulmonary hypertension are also included.

Finally, we summarise the latest evidence presented on pulmonary vascular disease and COVID-19 and a statement on the new imaging guidelines for pulmonary vascular disease from the Fleischner Society.
ERS International Congress 2021: highlights from the Epidemiology and Environment Assembly
Authors: Bosch de Basea Magda , Belachew Abate Bekele , Jankowski Mateusz , Meteran Howraman , Dumas Orianne
Published: May 2022

In this article, early career members of the Epidemiology and Environment Assembly of the European Respiratory Society (ERS) summarise a selection of four sessions from the Society's 2021 virtual congress. The topics covered focus on chronic respiratory disease epidemiology, the health effects of tobacco and nicotine, and the respiratory health impact of environmental exposures and climate change. While the burden of chronic respiratory diseases such as COPD is expected to increase in the next decades, research on modifiable risk factors remains key. The tobacco and nicotine research presented here focuses on recent evolutions in cigarette alternatives, including vaping and the use of heated tobacco products, and changes in behaviours related to the coronavirus disease 2019 pandemic. The 2021 World Health Organization air quality guidelines were also a major topic of the congress. Despite their benefits, challenges remain in driving and implementing environmental health policies to take into account the respiratory effects observed at very low air pollution concentrations, as well as the impact of climate change on environmental exposures.
Development of a phenotype ontology for autism spectrum disorder by natural language processing on electronic health records
Authors: Zhao Mengge , Havrilla James , Peng Jacqueline , Drye Madison , Fecher Maddie , Guthrie Whitney , Tunc Birkan , Schultz Robert , Wang Kai , Zhou Yunyun
Published: May 2022

Background

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by restricted, repetitive behavior, and impaired social communication and interactions. However, significant challenges remain in diagnosing and subtyping ASD due in part to the lack of a validated, standardized vocabulary to characterize clinical phenotypic presentation of ASD. Although the human phenotype ontology (HPO) plays an important role in delineating nuanced phenotypes for rare genetic diseases, it is inadequate to capture characteristic of behavioral and psychiatric phenotypes for individuals with ASD. There is a clear need, therefore, for a well-established phenotype terminology set that can assist in characterization of ASD phenotypes from patients’ clinical narratives.

Methods

To address this challenge, we used natural language processing (NLP) techniques to identify and curate ASD phenotypic terms from high-quality unstructured clinical notes in the electronic health record (EHR) on 8499 individuals with ASD, 8177 individuals with non-ASD psychiatric disorders, and 8482 individuals without a documented psychiatric disorder. We further performed dimensional reduction clustering analysis to subgroup individuals with ASD, using nonnegative matrix factorization method.

Results

Through a note-processing pipeline that includes several steps of state-of-the-art NLP approaches, we identified 3336 ASD terms linking to 1943 unique medical concepts, which represents among the largest ASD terminology set to date. The extracted ASD terms were further organized in a formal ontology structure similar to the HPO. Clustering analysis showed that these terms could be used in a diagnostic pipeline to differentiate individuals with ASD from individuals with other psychiatric disorders.

Conclusion

Our ASD phenotype ontology can assist clinicians and researchers in characterizing individuals with ASD, facilitating automated diagnosis, and subtyping individuals with ASD to facilitate personalized therapeutic decision-making.
Transcriptome analysis reveals fluid shear stress (FSS) and atherosclerosis pathway as a candidate molecular mechanism of short-term low salinity stress tolerance in abalone
Authors: Boamah Grace Afumwaa , Huang Zekun , Shen Yawei , Lu Yisha , Wang Zhixuan , Su Ying , Xu Changan , Luo Xuan , Ke Caihuan , You Weiwei
Published: May 2022

Background

Transcriptome sequencing is an effective tool to reveal the essential genes and pathways underlying countless biotic and abiotic stress adaptation mechanisms. Although severely challenged by diverse environmental conditions, the Pacific abalone Haliotis discus hannai remains a high-value aquaculture mollusk and a Chinese predominantly cultured abalone species. Salinity is one of such environmental factors whose fluctuation could significantly affect the abalone’s cellular and molecular immune responses and result in high mortality and reduced growth rate during prolonged exposure. Meanwhile, hybrids have shown superiority in tolerating diverse environmental stresses over their purebred counterparts and have gained admiration in the Chinese abalone aquaculture industry.

The objective of this study was to investigate the molecular and cellular mechanisms of low salinity adaptation in abalone. Therefore, this study used transcriptome analysis of the gill tissues and flow cytometric analysis of hemolymph of H. discus hannai (DD) and interspecific hybrid H. discus hannai ♀ x H. fulgens ♂ (DF) during low salinity exposure. Also, the survival and growth rate of the species under various salinities were assessed.

Results

The transcriptome data revealed that the differentially expressed genes (DEGs) were significantly enriched on the fluid shear stress and atherosclerosis (FSS) pathway. Meanwhile, the expression profiles of some essential genes involved in this pathway suggest that abalone significantly up-regulated calmodulin-4 (CaM-4) and heat-shock protein90 (HSP90), and significantly down-regulated tumor necrosis factor (TNF), bone morphogenetic protein-4 (BMP-4), and nuclear factor kappa B (NF-kB).

Also, the hybrid DF showed significantly higher and sustained expression of CaM and HSP90, significantly higher phagocytosis, significantly lower hemocyte mortality, and significantly higher survival at low salinity, suggesting a more active molecular and hemocyte-mediated immune response and a more efficient capacity to tolerate low salinity than DD.

Conclusions

Our study argues that the abalone CaM gene might be necessary to maintain ion equilibrium while HSP90 can offset the adverse changes caused by low salinity, thereby preventing damage to gill epithelial cells (ECs).

The data reveal a potential molecular mechanism by which abalone responds to low salinity and confirms that hybridization could be a method for breeding more stress-resilient aquatic species.
Parents’ experiences caring for children with acute otitis media: a qualitative analysis
Authors: Lee Matthew C. , Kavalieratos Dio , Alberty Anastasia , Groff Destin , Haralam Mary Ann , Shaikh Nader
Published: May 2022

Background

Little is known regarding parents’ experiences caring for children with acute otitis media (AOM). This study aimed to explore parents’ experiences caring for their child with AOM, identifying symptoms they observed, their thoughts and feelings about those symptoms, how they managed the episode, and what factors caused them to seek medical evaluation.

Methods

From October 2019 to February 2020, we conducted 24 semi-structured cross-sectional interviews with parents of children 3 to 36 months of age with AOM diagnosed at primary care offices associated with the Children’s Hospital of Pittsburgh regarding (1) symptoms and behaviors that led parents to believe their child might have AOM; (2) symptoms that were most bothersome to parent and child; (3) what parents did in response to these symptoms; (4) motivations for seeking clinical care; and (5) parents’ expectations regarding AOM resolution. Data were analyzed using template analysis, resulting in a hybrid inductive/deductive analytic process.

Results

We interviewed 24 parents within 72 h of diagnosis of AOM. Parents frequently believed ear tugging was the symptom most indicative of AOM, despite its presence in only half of the children in this sample. Parents consistently sought medical care when their child had an elevated temperature or lack of sleep, or when symptoms worsened or were unresponsive to home remedies. Parents of children with history of recurrent AOM had less difficulty identifying symptoms of AOM than parents of children with their first ear infection.

Conclusions

Our findings provide insight into symptoms of AOM that cause parents concern and motivate the use of healthcare services. Parents differed in their abilities to observe and report symptoms of AOM. Thus, when interviewing parents who are concerned their preverbal child has AOM, rather than focusing on ear tugging and fever alone, providers should ascertain all unusual behaviors observed by the parent.
Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn’s disease
Authors: Logan Michael , MacKinder Mary , Clark Clare Martha , Kountouri Aikaterini , Jere Mwansa , Ijaz Umer Zeeshan , Hansen Richard , McGrogan Paraic , Russell Richard K. , Gerasimidis Konstantinos
Published: May 2022

Background

There is a clinical need to develop biomarkers of small bowel damage in coeliac disease and Crohn’s disease. This study evaluated intestinal fatty acid binding protein (iFABP), a potential biomarker of small bowel damage, in children with coeliac disease and Crohn’s disease.

Methods

The concentration iFABP was measured in plasma and urine of children with ulcerative colitis, coeliac disease, and Crohn’s disease at diagnosis and from the latter two groups after treatment with gluten free diet (GFD) or exclusive enteral nutrition (EEN), respectively. Healthy children (Controls) were also recruited.

Results

138 children were recruited. Plasma but not urinary iFABP was higher in patients with newly diagnosed coeliac disease than Controls (median [Q1, Q3] coeliac disease: 2104 pg/mL 1493, 2457] vs Controls: 938 pg/mL [616, 1140], p = 0.001). Plasma or urinary iFABP did not differ between patients with coeliac on GFD and Controls. Baseline iFABP in plasma decreased by 6 months on GFD (6mo GFD: 1238 pg/mL [952, 1618], p = 0.045). By 12 months this effect was lost, at which point 25% of patients with coeliac disease had detectable gluten in faeces, whilst tissue transglutaminase IgA antibodies (TGA) continued to decrease. At diagnosis, patients with Crohn’s disease had higher plasma iFABP levels than Controls (EEN Start: 1339 pg/mL [895, 1969] vs Controls: 938 pg/mL [616, 1140], p = 0.008). iFABP did not differ according to Crohn’s disease phenotype. Induction treatment with EEN tended to decrease (p = 0.072) iFABP in plasma which was no longer different to Controls (EEN End: 1114 pg/mL [689, 1400] vs Controls: 938 pg/mL [616, 1140], p = 0.164). Plasma or urinary iFABP did not differ in patients with ulcerative colitis from Controls (plasma iFABP, ulcerative colitis: 1309 pg/mL [1005, 1458] vs Controls: 938 pg/mL [616, 1140], p = 0.301; urinary iFABP ulcerative colitis: 38 pg/mg [29, 81] vs Controls: 53 pg/mg [27, 109], p = 0.605).

Conclusions

Plasma, but not urinary iFABP is a candidate biomarker with better fidelity in monitoring compliance during GFD than TGA. The role of plasma iFABP in Crohn’s disease is promising but warrants further investigation.

Trial registration: Clinical Trials.gov, NCT02341248. Registered on 19/01/2015.
Clinical analysis on diagnostic accuracy of Bosch Vivalytic SARS-CoV-2 point-of-care test and evaluation of cycle threshold at admission for COVID-19 risk assessment
Authors: Heger Lukas Andreas , Elsen Nils , Rieder Marina , Gauchel Nadine , Sommerwerck Urte , Bode Christoph , Duerschmied Daniel , Oette Mark , Ahrens Ingo
Published: May 2022

Background

Point-of-care (POC) polymerase chain reaction (PCR) tests have the ability to improve testing efficiency in the Coronavirus disease 2019 (COVID-19) pandemic. However, real-world data on POC tests is scarce.

Objective

To evaluate the efficiency of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) POC test in a clinical setting and examine the prognostic value of cycle threshold (CT) on admission on the length of hospital stay (LOS) in COVID-19 patients.

Methods

Patients hospitalised between January and May 2021 were included in this prospective cohort study. Patients’ nasopharyngeal swabs were tested for SARS-CoV-2 with Allplex™2019-nCoV (Seegene Inc.) real-time (RT) PCR assay as gold standard as well as a novel POC test (Bosch Vivalytic SARS-CoV-2 [Bosch]) and the SARS-CoV-2 Rapid Antigen Test (Roche) accordingly. Clinical sensitivity and specificity as well as inter- and intra-assay variability were analyzed.

Results

120 patients met the inclusion criteria with 46 (38%) having a definite COVID-19 diagnosis by RT-PCR. Bosch Vivalytic SARS-CoV-2 POC had a sensitivity of 88% and specificity of 96%. The inter- and intra- assay variability was below 15%. The CT value at baseline was lower in patients with LOS ≥ 10 days when compared to patients with LOS < 10 days (27.82 (± 4.648) vs. 36.2 (25.9–39.18); p = 0.0191). There was a negative correlation of CT at admission and LOS (r[44]s = − 0.31; p = 0.038) but only age was associated with the probability of an increased LOS in a multiple logistic regression analysis (OR 1.105 [95% CI, 1.03–1.19]; p = 0.006).

Conclusion

Our data indicate that POC testing with Bosch Vivalytic SARS-CoV-2 is a valid strategy to identify COVID-19 patients and decrease turnaround time to definite COVID-19 diagnosis. Also, our data suggest that age at admission possibly with CT value as a combined parameter could be a promising tool for risk assessment of increased length of hospital stay and severity of disease in COVID-19 patients.
Smartphones for musculoskeletal research – hype or hope? Lessons from a decennium of mHealth studies
Authors: Beukenhorst Anna L. , Druce Katie L. , De Cock Diederik
Published: May 2022

Background

Smartphones provide opportunities for musculoskeletal research: they are integrated in participants’ daily lives and can be used to collect patient-reported outcomes as well as sensor data from large groups of people. As the field of research with smartphones and smartwatches matures, it has transpired that some of the advantages of this modern technology are in fact double-edged swords.

Body

In this narrative review, we illustrate the advantages of using smartphones for data collection with 18 studies from various musculoskeletal domains. We critically appraised existing literature, debunking some myths around the advantages of smartphones: the myth that smartphone studies automatically enable high engagement, that they reach more representative samples, that they cost little, and that sensor data is objective. We provide a nuanced view of evidence in these areas and discuss strategies to increase engagement, to reach representative samples, to reduce costs and to avoid potential sources of subjectivity in analysing sensor data.

Conclusion

If smartphone studies are designed without awareness of the challenges inherent to smartphone use, they may fail or may provide biased results. Keeping participants of smartphone studies engaged longitudinally is a major challenge. Based on prior research, we provide 6 actions by researchers to increase engagement. Smartphone studies often have participants that are younger, have higher incomes and high digital literacy. We provide advice for reaching more representative participant groups, and for ensuring that study conclusions are not plagued by bias resulting from unrepresentative sampling. Costs associated with app development and testing, data storage and analysis, and tech support are substantial, even if studies use a ‘bring your own device’-policy. Exchange of information on costs, collective app development and usage of open-source tools would help the musculoskeletal community reduce costs of smartphone studies. In general, transparency and wider adoption of best practices would help bringing smartphone studies to the next level. Then, the community can focus on specific challenges of smartphones in musculoskeletal contexts, such as symptom-related barriers to using smartphones for research, validating algorithms in patient populations with reduced functional ability, digitising validated questionnaires, and methods to reliably quantify pain, quality of life and fatigue.
Predictors of blood glucose change and microvascular complications of type 2 diabetes mellitus patients in Felege Hiwot and Debre Markos referral hospital, North West Ethiopia
Authors: Shita Nigusie Gashaye , Isayu Ashagrie Sharew
Published: May 2022

Background

Microvascular complications lead to disability, dependency, and accelerated morbidity and mortality. This study aimed to identify predictors of blood glucose change and time to microvascular complications among patients with type 2 diabetes.

Methods

A retrospective cohort study was conducted among type 2 diabetes mellitus patients enrolled between December 2014 and December 2015 at Felege Hiwot and Debre Markos Referral Hospital. A total of 318 T2DM patients were included in the study. Joint modelling of longitudinal and survival analysis was employed to identify predictors of Blood Glucose Change and Microvascular Complications in Type 2 Diabetes Mellitus Patients.

Results

The prevalence of microvascular complications in Type 2 diabetes patients was 26.3%, 95%confidence interval(CI):(21.5, 31.1). Of which, half of the patients developed a microvascular complication after 30 months from the onset of the follow-up. The significant predictors of developing microvascular complication were positive proteinurea (adjusted hazard ratio (AHR) = 1.418, 95%CI: 1.080, 1.861), Serum creatinine (AHR = 3.704, 95%CI: 1.992, 6.887), Weight (AHR = 1.058, 95%CI: 1.023, 1.094), and log fasting blood glucose(log(FBS))(AHR = 1.013, 95%CI: 1.010, 1.015). The predictors of fasting blood glucose progression were higher baseline FBS(est(estimate) = 0.002,95%CI:0.0018, 0.0022), Systolic blood pressure (SBP) (est = 0.003, 95%CI: 0.002, 0.004), diastolic blood pressure (DBP) (est = 0.002, 95%CI: 0.0002, 0.004), and age (est = 0.003, 95%CI: 0.001, 0.004).

Conclusion

The progression of the fasting blood glucose level for rural patients was faster than for urban patients. Patients having higher baseline FBS, previous hypertension history, higher SBP, higher DBP, older age, and fewer visits to the hospital have a relatively more progressive change in blood sugar levels. Patients having higher triglyceride levels, positive proteinuria, higher fasting blood sugar, higher weight, and a lesser number of hospital visits have a higher risk of developing a complication. In response to this finding, an aggressive intervention that targets to prevent microvascular complications is required.
Improving care for hypertension and diabetes in india by addition of clinical decision support system and task shifting in the national NCD program: I-TREC model of care
Authors: Jindal Devraj , Sharma Hanspria , Gupta Yashdeep , Ajay Vamadevan S. , Roy Ambuj , Sharma Rakshit , Ali Mumtaj , Jarhyan Prashant , Gupta Priti , Srinivasapura Venkateshmurthy Nikhil , Ali Mohammed K. , Narayan K M Venkat , Prabhakaran Dorairaj , Weber Mary Beth , Mohan Sailesh , Patel Shivani A. , Tandon Nikhil
Published: May 2022

Background

The growing burden of hypertension and diabetes is one of the major public health challenges being faced by the health system in India. Clinical Decision Support Systems (CDSS) that assist with tailoring evidence-based management approaches combined with task-shifting from more specialized to less specialized providers may together enhance the impact of a program. We sought to integrate a technology “CDSS” and a strategy “Task-shifting” within the Government of India’s (GoI) Non-Communicable Diseases (NCD) System under the Comprehensive Primary Health Care (CPHC) initiative to enhance the program’s impact to address the growing burden of hypertension and diabetes in India.

Methods

We developed a model of care “I-TREC” entirely calibrated for implementation within the current health system across all facility types (Primary Health Centre, Community Health Centre, and District Hospital) in a block in Shaheed Bhagat Singh (SBS) Nagar district of Punjab, India. We undertook an academic-community partnership to incorporate the combination of a CDSS with task-shifting into the GoI CPHC-NCD system, a platform that assists healthcare providers to record patient information for routine NCD care. Academic partners developed clinical algorithms, a revised clinic workflow, and provider training modules with iterative collaboration and consultation with government and technology partners to incorporate CDSS within the existing system.

Discussion

The CDSS-enabled GoI CPHC-NCD system provides evidence-based recommendations for hypertension and diabetes; threshold-based prompts to assure referral mechanism across health facilities; integrated patient database, and care coordination through workflow management and dashboard alerts. To enable efficient implementation, modifications were made in the patient workflow and the fulcrum of the use of technology shifted from physician to nurse.

Conclusion

Designed to be applicable nationwide, the I-TREC model of care is being piloted in a block in the state of Punjab, India. Learnings from I-TREC will provide a roadmap to other public health experts to integrate and adapt their interventions at the national level.

Trial registration

CTRI/2020/01/022723.
High level of heterozygous haplotype of hemoglobin in Abidjan population with mild malaria
Authors: Koui Tosséa A. Stéphane , Gnondjui Alloh Albert , Gbessi Adji Eric , Ako Ako Aristide Bérenger , Coulibaly Baba , Aka A. Delpêche , Gonedele Bi Sery E. , Toure Offiana André , Jambou Ronan
Published: May 2022

Background

Sickle cell disease (SCD) is a hemoglobin disorders that concern 300,000 newborns each year around the world. There are hemoglobin haplotypes that affect SCD clinic expression.

Methods

Our goal was to identify the hemoglobin’s haplotypes among individuals with mild malaria independently of SCD status in Côte d’Ivoire. To determine these haplotypes, specific restriction enzyme (RE) is used after PCR amplification with each primer. According to the digestion of PCR product by RE, five hemoglobin’s haplotypes are found in the world.

Results

In Côte d’Ivoire, no study has yet deeply described the distribution of haplotypes. Four different “classical” haplotypes of hemoglobin were detected: Benin (56.5%), Bantou (28.5%), Senegal (4%), Cameroun (1%); and 10% of atypical profiles. Heterozygous haplotype (69%) were more frequent than homozygous haplotype (31%).

Conclusions

In this preliminary study, we note a high prevalence of atypical and heterozygous haplotype. Benin haplotype that is associated with severity of SCD was most predominant in our studied population.
NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway
Authors: Wang Wei , Liang Xiaolong , Liu Xin , Bai Jiaxiang , Zhang Wei , Li Wenming , Wang Tianhao , Li Meng , Wu Zerui , Chen Liang , Yang Huilin , Gu Ye , Tao Yunxia , Zhou Jun , Wang Huaiyu , Geng Dechun
Published: May 2022

Periprosthetic osteolysis (PPO) triggered by wear particles is the most severe complication of total joint replacement (TJR) surgeries, representing the major cause of implant failure, which is public health concern worldwide. Previous studies have confirmed the specialized role of osteoclast-induced progressive bone destruction in the progression of PPO. Additionally, the reactive oxygen species (ROS) induced by wear particles can promote excessive osteoclastogenesis and bone resorption. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), a cellular enzyme, is considered to be responsible for the production of ROS and the formation of mature osteoclasts. However, NOX4 involvement in PPO has not yet been elucidated. Therefore, we investigated the mechanism by which NOX4 regulates osteoclast differentiation and the therapeutic effects on titanium nanoparticle-induced bone destruction. We found that NOX4 blockade suppressed osteoclastogenesis and enhanced the scavenging of intracellular ROS. Our rescue experiment revealed that nuclear factor-erythroid 2-related factor 2 (Nrf2) silencing reversed the effects of NOX4 blockade on ROS production and osteoclast differentiation. In addition, we found increased expression levels of NOX4 in PPO tissues, while NOX4 inhibition in vivo exerted protective effects on titanium nanoparticle-induced osteolysis through antiosteoclastic and antioxidant effects. Collectively, these findings suggested that NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway and that NOX4 blockade may be an attractive therapeutic approach for preventing PPO.

Graphical Abstract
Serum proteome alterations during conventional and extracorporeal resuscitation in pigs
Authors: Bernhard Patrick , Bretthauer Berit Amelie , Brixius Sam Joé , Bügener Hannah , Groh Johannes Elias , Scherer Christian , Damjanovic Domagoj , Haberstroh Jörg , Trummer Georg , Benk Christoph , Beyersdorf Friedhelm , Schilling Oliver , Pooth Jan-Steffen
Published: May 2022

Background

Only a small number of patients survive an out-of-hospital cardiac arrest (CA) and can be discharged from hospital alive with a large percentage of these patients retaining neurological impairments. In recent years, extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a beneficial strategy to optimize cardiac arrest treatment. However, ECPR is still associated with various complications. To reduce these problems, a profound understanding of the underlying mechanisms is required. This study aims to investigate the effects of CA, conventional cardiopulmonary resuscitation (CPR) and ECPR using a whole-body reperfusion protocol (controlled and automated reperfusion of the whole body—CARL) on the serum proteome profiles in a pig model of refractory CA.

Methods

N = 7 pigs underwent 5 min of untreated CA followed by 30 min CPR and 120 min perfusion with CARL. Blood samples for proteomic analysis were drawn at baseline, after CPR and at the end of the CARL period. Following albumin-depletion, proteomic analysis was performed using liquid chromatography–tandem mass spectrometry.

Results

N = 21 serum samples were measured resulting in the identification and quantification of 308–360 proteins per sample and 388 unique proteins in total. The three serum proteome profiles at the investigated time points clustered individually and segregated almost completely when considering a 90% confidence interval. Differential expression analysis showed significant abundance changes in 27 proteins between baseline and after CPR and in 9 proteins after CARL compared to CPR. Significant findings were further validated through a co-abundance cluster analysis corroborating the observed abundance changes.

Conclusions

The presented data highlight the impact of systemic ischemia and reperfusion on the entire serum proteome during resuscitation with a special focus on changes regarding haemolysis, coagulation, inflammation, and cell-death processes. Generally, the observed changes contribute to post-ischemic complications. Better understanding of the underlying mechanisms during CA and resuscitation may help to limit these complications and improve therapeutic options.
Strategies for utilisation management of hospital services: a systematic review of interventions
Authors: Doshmangir Leila , Khabiri Roghayeh , Jabbari Hossein , Arab-Zozani Morteza , Kakemam Edris , Gordeev Vladimir Sergeevich
Published: May 2022

Background

To achieve efficiency and high quality in health systems, the appropriate use of hospital services is essential. We identified the initiatives intended to manage adult hospital services and reduce unnecessary hospital use among the general adult population.

Methods

We systematically reviewed studies published in English using five databases (PubMed, ProQuest, Scopus, Web of Science, and MEDLINE via Ovid). We only included studies that evaluated interventions aiming to reduce the use of hospital services or emergency department, frequency of hospital admissions, length of hospital stay, or the use of diagnostic tests in a general adult population. Studies reporting no relevant outcomes or focusing on a specific patient population or children were excluded.

Results

In total, 64 articles were included in the systematic review. Nine utilisation management methods were identified: care plan, case management, care coordination, utilisation review, clinical information system, physician profiling, consultation, education, and discharge planning. Primary case management was shown to effectively reduce emergency department use. Care coordination reduced 30-day post-discharge hospital readmission or emergency department visit rates. The pre-admission review program decreased elective admissions. The physician profiling, concurrent review, and discharge planning effectively reduced the length of hospital stay. Twenty three studies that evaluated costs, reported cost savings in the hospitals.

Conclusions

Utilisation management interventions can decrease hospital use by improving the use of community-based health services and improving the quality of care by providing appropriate care at the right time and at the right level of care.
Market survey on the traditional medicine of the Lijiang area in Yunnan Province, China
Authors: Zhang Mingshuo , Li Haitao , Wang Junqi , Tang Maohong , Zhang Xiaobo , Yang Shaohua , Liu Jianqin , Li Ying , Huang Xiulan , Li Zhiyong , Huang Luqi
Published: May 2022

Background

Traditional markets are important trading places for medicinal plants, and researchers performing market surveys often engage in ethnobotanical research to record the herbal plants used locally and any related traditional knowledge. However, information on market-traded medicinal plants from traditional markets in the Lijiang area of Yunnan is not well documented. This research is an ethnobotanical survey focusing on medicinal plants traded in the traditional markets of the Lijiang area and contributes to the understanding of medicinal plants and related information used by the Naxi people.

Methods

Ethnobotanical surveys were performed for two years (2019–2020). Three traditional markets in the Lijiang area were investigated. The methods we used included literature research, participatory surveys and group discussions. The collected voucher specimens were identified using the botanical taxonomy method and were deposited in the herbarium. The data were analysed through the informant consensus factor and use frequency (UF). These medicinal plants were compared with the Information System of Chinese Rare and Endangered Plants from the Chinese Academy of Sciences. Those results were in turn compared with the Dongba Sutras and Yulong Ben Cao.

Results

A total of 277 species from 97 families were recorded, with Asteraceae providing the maximum numbers of medicinal plants. Among them, 248 species (89%) were wild plants and 266 species (92.39%) were from the local area. Root (40.43%) was the most common medicinal part. A total of 267 species (96.04%) had a UF value above 0.5. Eighty-three investigated human ailments were grouped into 16 categories. Diseases of the digestive system (166 mentions) were most frequently mentioned in this study. There were 19 species of nationally protected plants in China, including 2 species of first-level nationally protected plants and 17 species of second-level nationally protected plants. A total of 31 species of these medicinal plants can be found in the Dongba Sutra or Yulong Ben Cao.

Conclusion

We surveyed the herbal medicine in the markets covering the Lijiang area, analysing and revealing the resource composition and current market situations. The medicinal plants used by the Naxi people are diverse and are used to treat a wide spectrum of body disorders. There are many wild medicinal plants, and to ensure sustainable development, their natural protection should be strengthened. Knowledge of the medicinal plants recorded in Naxi medical classics has ethnobotanical value and should be further developed.
Quantitative analysis with load–displacement ratio measured via digital arthrometer in the diagnostic evaluation of chronic ankle instability: a cross-sectional study
Authors: Chen Yungu , Cao Shengxuan , Wang Chen , Ma Xin , Wang Xu
Published: May 2022

Background

Arthrometry has been introduced to evaluate the laxity of ankle joint in recent years. However, its role in the diagnosis of chronic ankle instability is still debatable. Therefore, we assessed the diagnostic accuracy of a digital arthrometer in terms of sensitivity and specificity.

Methods

According to the inclusion and exclusion criteria proposed by the International Ankle Consortium, we recruited 160 uninjured ankles (control group) and 153 ankles with chronic ankle instability (CAI group). Ankle laxity was quantitively measured by a validated digital arthrometer. Data of loading force and joint displacement were recorded in a continuous manner. Differences between the control and CAI groups were compared using 2-tailed independent t test. A receiver operating characteristic curve analysis was used to calculate area under a curve, sensitivity and specificity.

Results

Load–displacement curves of the two groups were depicted. Differences of joint displacement between the control and CAI groups were compared at 30, 45, 60, 75, 90, 105 and 120 N, which were all of statistical significance (all p < 0.001) with the largest effect size at 90 N. Statistical significance was found in the differences between the two groups in load–displacement ratio at 10–120 N, 10–40 N, 40–80 N and 80–120 N (all p < 0.001), with the largest effect size at 10–40 N. Load–displacement ratio at the interval of 10–40 N had the highest area under a curve (0.9226), with sensitivity and specificity of 0.804 and 0.863, respectively, when the cutoff point was 0.1582 mm/N.

Conclusion

The digital arthrometer measurement could quantitively analyze the ankle laxity with high diagnostic accuracy. The load–displacement ratio would be a reliable and promising approach for chronic ankle instability diagnosis.

Level of evidence level II.
Impact of GERAADA score in patients with acute type A aortic dissection
Authors: Sugiyama Kayo , Watanuki Hirotaka , Tochii Masato , Futamura Yasuhiro , Kitagawa Yuka , Makino Satoshi , Ohashi Wataru , Matsuyama Katsuhiko
Published: May 2022

Background

Despite continuous developments and advances in the perioperative management of patients suffering from acute aortic dissection type A (AADA), the associated postoperative morbidity and mortality remain high and strongly depend on the preoperative clinical status. The associated postoperative mortality is still hard to predict prior to the surgical procedure. The so-called German Registry of Acute Aortic Dissection Type A (GERAADA) score uses very basic and easily retrievable parameters and was specifically designed for predicting the 30-day mortality rate in patients undergoing surgery for AADA. This study evaluated impact of the GERAADA score in the authors’ institutional results.

Methods

Among 101 acute type A aortic dissection patients treated at our hospital during August 2015–March 2021, the GERAADA was calculated individually and retrospectively. Predicted and actual mortalities were assessed, and independent predicted factors were searched. The primary endpoint was defined as comparison of GERAADA scores and early mortality, and the secondary endpoints were defined as comparison of GERAADA scores and other postoperative results, and comparison of preoperative factors and postoperative results regardless to GERAADA scores.

Results

While the overall 30-day mortality for the entire study cohort calculated by the GERAADA score was 14.3 (8.1–77.6)%, the actual mortality rate was 6%. However, the GERAADA score was significantly high in some postoperative complications and showed significant correlation with some peri- and post-operative factors. In addition, factors not belonging to GERAADA score such as time from onset to arrival at the hospital, time from onset to arrival at the operation room, spouse presence, and hemodialysis were significantly associated with 30-day mortality.

Conclusions

Although the actual mortality was lower than predicted, GERAADA score may impact on the postoperative course. In addition, it would be desirable to add parameters such as the time from onset to arrival, family background, and hemodialysis for further accuracy.
Pharmacological activities and molecular mechanisms of Pulsatilla saponins
Authors: Zhong Jinmiao , Tan Lihua , Chen Meiwan , He Chengwei
Published: May 2022

Saponins are found in a variety of higher plants and display a wide range of pharmacological activities, including expectorant, anti-inflammatory, vasoprotective and antimicrobial properties.Pulsatilla chinensis(P. chinensis,Bai Tou Weng, 白頭翁) has been used medically in China for thousands of years for the treatment of diseases caused by bacteria, and it is rich in triterpenoid saponins. In recent decades, anemoside B4 (Pulchinenoside C) is well studied since it has been used as a quality control marker forP. chinensis. At the same time, more and more other active compounds were found in the genus ofPulsatilla. In this review, we summarize the pharmacological activities ofPulsatillasaponins (PS) and discuss the cellular or molecular mechanisms that mediate their multiple activities, such as inducing cancer cell apoptosis, inhibiting tumor angiogenesis, and protecting organs via anti-inflammatory and antioxidant measures. We aim to provide comprehensive analysis and summary of research progress and future prospects in this field to facilitate further study and drug discovery of PS.
Phenotype expansion of variants affecting p38 MAPK signaling in hypospadias patients
Authors: Lin Defu , Du Huakang , Zhao Sen , Liu Bowen , Song Hongcheng , Wang Guannan , Zhang Weiping , Liang Haiyan , Liu Pei , Liu Chao , Han Wenwen , Li Zhenwu , Yang Yang , Chen Shuofan , Zhao Lina , Li Xiaoxin , Wu Zhihong ,   DISCO (Deciphering Disorders Involving Scoliosis & COmorbidities) study group, Qiu Guixing , Wu Zhihong , Zhang Terry Jianguo , Wu Nan , Wang Shengru , Liu Jiaqi , Liu Sen , Zuo Yuzhi , Liu Gang , Yu Chenxi , Liu Lian , Shao Jiashen , Zhao Sen , Yan Zihui , Zhao Hengqiang , Niu Yuchen , Li Xiaoxin , Wang Huizi , Ma Congcong , Chen Zefu , Liu Bowen , Cheng Xi , Lin Jiachen , Du Huakang , Li Yaqi , Song Shuang , Tian Weijie , Xie Zhixin , Zhao Zhengye , Zhao Lina , Zhao Zhi , Zheng Zhifa , Huang Yingzhao , Sun Ning , Wu Nan
Published: May 2022

Background

Hypospadias is a congenital anomaly of the male urogenital system. Genetics factors play an important role in its pathogenesis. To search for potential causal genes/variants for hypospadias, we performed exome sequencing in a pedigree with three patients across two generations and a cohort of 49 sporadic patients with hypospadias.

Results

A novel BRAF variant (NM_004333.6: c.362C > A) was found to co-segregate with the hypospadias phenotype in the disease pedigree. In cells overexpressing the BRAF mutant, the phosphorylation level of p38 MAPK was significantly increased as compared with the cells overexpressing the wild-type BRAF or RASopathy-related BRAF mutant. This variant further led to a reduced transcription level of the SRY gene, which is essential for the normal development of the male reproductive system. In the cohort of sporadic patients, we identified two additional variants in p38 MAPK signaling-related genes (TRIM67 and DAB2IP) potentially associated with hypospadias.

Conclusion

Our study expands the phenotypic spectrum of variants affecting p38 MAPK signaling toward the involvement of hypospadias.