bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Patients’ Protected Health Information to Solicit Hospital Funds: How did This Practice Come About?
Authors: Mahajan Uma V , Wafapoor Vahid , Mahajan Omkar A , Anderson William S
Published: June 2022

Modifications to Health Insurance Portability and Accountability Act (HIPAA) have allowed for the disclosure of patient protected health information (PHI) for the purpose of hospital fundraising. The public has recently raised ethical concerns regarding these practices. We examined the forces that brought about these HIPAA modifications. We first examined 304 comments submitted to the proposed rule for the HIPPA regulation modifications. We additionally queried the OpenSecrets repository for lobbying activity by these commenters. We found that 57 out of the 304 comments pertained specifically to fundraising practices. The majority of comments were from hospital developmental (fundraising) offices (51%, 29 of 57 comments), and the majority (96%, 24 of 25 hospital comments; 83%, 34 of 41 total comments discussing PHI disclosure) supported additional PHI disclosure. There was a paucity of comments from physician organizations (1 of 57) and patient advocates (2 of 57). The majority of lobbying dollars (95% of over $81 million) were from commenters who favored the modifications. The lack of physician and patient representation in the rule-making process likely contributed to the creation of regulations that elicit ethical concerns in physicians, and potential harm for patients.
The social vs. commercial ‘Dingpolitik’ of microlending: Mapping the glocal issue trajectory of a ‘messy object’
Authors: Lagendijk Arnoud , Simons Kim
Published: June 2022

Microlending (microcredit and microcredit) presents a complex, ‘glocal’ phenomenon meeting social concerns (poverty and community development) versus commercial interests, manifesting a myriad of practices and trends worldwide. This paper elaborates the concept of ‘issue trajectory’, enhanced by topological thinking, to understand the becoming of microlending and to consider possibilities for change. The issue trajectory maps microlending’s proliferation and divergence between 1980 and 2015, using an analytical lens drawing on a combination of the topological dimensions of mutability and mobility and Latour’s Dingpolitik. Using this lens, the study reveals how the continual grounding and proliferation of practices of microlending meet global drives towards standardization and financialization, and how this results in ‘problematization gaps’ between social and commercial aims. Through adaptation as well as confrontation, these gaps bend microlending’s issue trajectory towards new political modalities and publics, and potentially new forms of territorialization.
Investigating rural public spaces with cultural significance using morphological, cognitive and behavioural data
Authors: Bai Nan , Nourian Pirouz , Pereira Roders Ana , Bunschoten Raoul , Huang Weixin , Wang Lu
Published: June 2022

During the rural [re]vitalization process in China, national strategies required rural public spaces with cultural significance to be identified before planning decision-making. However, places identified as culturally significant by planners and visitors can differ from the ones mostly used and valued by locals. Even if there is a growing interest in integrating local perspectives and experiences in planning, studies seldom discuss and compare openly the adequacy of spatial configuration, cognition and behaviour to support it. This study took Anyi Historic Village Cluster as a case study to empirically investigate rural public spaces with three distinct, yet related approaches: (1) Morphological: spatial network centralities based on space syntax; (2) Cognitive: Lynchian village images with semi-structured interviews; (3) Behavioural: spatiotemporal occupation patterns using Wi-Fi positioning tracking. Significant places valued and used by locals and non-locals were detected with the multi-source data. Furthermore, multivariant regression models managed to characterize the relationship among different aspects of investigated rural public spaces, which also helped diagnose places of interest to prioritize in planning, demonstrating the advantage of integrating the sources of information in practice instead of studying them apart. Results can also assist rural planning on how to identify what to preserve, what to enhance, and how to develop such spaces, without overlooking the local needs or losing the rural identity.
IL-1β expression in bone marrow dendritic cells is induced by TLR2 agonists and regulates HSC function
Authors: Li Sidan , Yao Juo-Chin , Oetjen Karolyn A. , Krambs Joseph R. , Xia Jun , Zhang Jingzhu , Schmidt Amy P. , Helton Nichole M. , Fulton Robert S. , Heath Sharon E. , Turnbull Isaiah R. , Mbalaviele Gabriel , Ley Timothy J. , Walter Matthew J. , Link Daniel C.
Published: June 2022

Hematopoietic stem/progenitor cells (HSPCs) reside in localized microenvironments, or niches, in the bone marrow that provide key signals regulating their activity. A fundamental property of hematopoiesis is the ability to respond to environmental cues such as inflammation. How these cues are transmitted to HSPCs within hematopoietic niches is not well established. Here, we show that perivascular bone marrow dendritic cells (DCs) express a high basal level of Toll-like receptor-1 (TLR1) and TLR2. Systemic treatment with a TLR1/2 agonist induces HSPC expansion and mobilization. It also induces marked alterations in the bone marrow microenvironment, including a decrease in osteoblast activity and sinusoidal endothelial cell numbers. TLR1/2 agonist treatment of mice in which Myd88 is deleted specifically in DCs using Zbtb46-Cre show that the TLR1/2-induced expansion of multipotent HPSCs, but not HSPC mobilization or alterations in the bone marrow microenvironment, is dependent on TLR1/2 signaling in DCs. Interleukin-1β (IL-1β) is constitutively expressed in both murine and human DCs and is further induced after TLR1/2 stimulation. Systemic TLR1/2 agonist treatment of Il1r1−/− mice show that TLR1/2-induced HSPC expansion is dependent on IL-1β signaling. Single-cell RNA-sequencing of low-risk myelodysplastic syndrome bone marrow revealed that IL1B and TLR1 expression is increased in DCs. Collectively, these data suggest a model in which TLR1/2 stimulation of DCs induces secretion of IL-1β and other inflammatory cytokines into the perivascular niche, which in turn, regulates multipotent HSPCs. Increased DC TLR1/2 signaling may contribute to altered HSPC function in myelodysplastic syndrome by increasing local IL-1β expression.
End-point definition and trial design to advance tuberculosis vaccine development
Authors: Garcia-Basteiro Alberto L. , White Richard G. , Tait Dereck , Schmidt Alexander C. , Rangaka Molebogeng X. , Quaife Matthew , Nemes Elisa , Mogg Robin , Hill Philip C. , Harris Rebecca C. , Hanekom Willem A. , Frick Mike , Fiore-Gartland Andrew , Evans Tom , Dagnew Alemnew F. , Churchyard Gavin , Cobelens Frank , Behr Marcel A. , Hatherill Mark
Published: June 2022

Tuberculosis (TB) remains a leading infectious cause of death worldwide and the coronavirus disease 2019 pandemic has negatively impacted the global TB burden of disease indicators. If the targets of TB mortality and incidence reduction set by the international community are to be met, new more effective adult and adolescent TB vaccines are urgently needed. There are several new vaccine candidates at different stages of clinical development. Given the limited funding for vaccine development, it is crucial that trial designs are as efficient as possible. Prevention of infection (POI) approaches offer an attractive opportunity to accelerate new candidate vaccines to advance into large and expensive prevention of disease (POD) efficacy trials. However, POI approaches are limited by imperfect current tools to measureMycobacterium tuberculosisinfection end-points. POD trials need to carefully consider the type and number of microbiological tests that define TB disease and, if efficacy against subclinical (asymptomatic) TB disease is to be tested, POD trials need to explore how best to define and measure this form of TB. Prevention of recurrence trials are an alternative approach to generate proof of concept for efficacy, but optimal timing of vaccination relative to treatment must still be explored. Novel and efficient approaches to efficacy trial design, in addition to an increasing number of candidates entering phase 2–3 trials, would accelerate the long-standing quest for a new TB vaccine.
3D Cohesive Finite Element Minimum Invasive Surgery Simulation Based on Kelvin-Voigt Model
Authors: Jiang Yonghang , Song Qinghua , Luo Xichun
Published: June 2022

Minimally invasive surgery is an important technique used for cytopathological examination. Recently, multiple studies have been conducted on a three-dimensional (3D) puncture simulation model as it can reveal the internal deformation state of the tissue at the micro level. In this study, a viscoelastic constitutive equation suitable for muscle tissue was derived. Additionally, a method was developed to define the fracture characteristics of muscle tissue material during the simulation process. The fracture of the muscle tissue in contact with the puncture needle was simulated using the cohesive zone model and a 3D puncture finite element model was established to analyze the deformation of the muscle tissue. The stress nephogram and reaction force under different parameters were compared and analyzed to study the deformation of the biological soft tissue and guide the actual operation process and reduce pain.
Comprehensive study of semi-supervised learning for DNA methylation-based supervised classification of central nervous system tumors
Authors: Tran Quynh T. , Alom Md Zahangir , Orr Brent A.
Published: June 2022

Background

Precision medicine for cancer treatment relies on an accurate pathological diagnosis. The number of known tumor classes has increased rapidly, and reliance on traditional methods of histopathologic classification alone has become unfeasible. To help reduce variability, validation costs, and standardize the histopathological diagnostic process, supervised machine learning models using DNA-methylation data have been developed for tumor classification. These methods require large labeled training data sets to obtain clinically acceptable classification accuracy. While there is abundant unlabeled epigenetic data across multiple databases, labeling pathology data for machine learning models is time-consuming and resource-intensive, especially for rare tumor types. Semi-supervised learning (SSL) approaches have been used to maximize the utility of labeled and unlabeled data for classification tasks and are effectively applied in genomics. SSL methods have not yet been explored with epigenetic data nor demonstrated beneficial to central nervous system (CNS) tumor classification.

Results

This paper explores the application of semi-supervised machine learning on methylation data to improve the accuracy of supervised learning models in classifying CNS tumors. We comprehensively evaluated 11 SSL methods and developed a novel combination approach that included a self-training with editing using support vector machine (SETRED-SVM) model and an L2-penalized, multinomial logistic regression model to obtain high confidence labels from a few labeled instances. Results across eight random forest and neural net models show that the pseudo-labels derived from our SSL method can significantly increase prediction accuracy for 82 CNS tumors and 9 normal controls.

Conclusions

The proposed combination of semi-supervised technique and multinomial logistic regression holds the potential to leverage the abundant publicly available unlabeled methylation data effectively. Such an approach is highly beneficial in providing additional training examples, especially for scarce tumor types, to boost the prediction accuracy of supervised models.
Global leaf and root transcriptome in response to cadmium reveals tolerance mechanisms in Arundo donax L
Authors: Santoro Danilo Fabrizio , Sicilia Angelo , Testa Giorgio , Cosentino Salvatore Luciano , Lo Piero Angela Roberta
Published: June 2022

The expected increase of sustainable energy demand has shifted the attention towards bioenergy crops. Due to their know tolerance against abiotic stress and relatively low nutritional requirements, they have been proposed as election crops to be cultivated in marginal lands without disturbing the part of lands employed for agricultural purposes.Arundo donaxL. is a promising bioenergy crop whose behaviour under water and salt stress has been recently studied at transcriptomic levels. As the anthropogenic activities produced in the last years a worrying increase of cadmium contamination worldwide, the aim of our work was to decipher the global transcriptomic response ofA. donaxleaf and root in the perspective of its cultivation in contaminated soil. In our study, RNA-seq libraries yielded a total of 416 million clean reads and 10.4 Gb per sample. De novo assembly of clean reads resulted in 378,521 transcripts and 126,668 unigenes with N50 length of 1812 bp and 1555 bp, respectively. Differential gene expression analysis revealed 5,303 deregulated transcripts (3,206 up- and 2,097 down regulated) specifically observed in the Cd-treated roots compared to Cd-treated leaves. Among them, we identified genes related to “Protein biosynthesis”, “Phytohormone action”, “Nutrient uptake”, “Cell wall organisation”, “Polyamine metabolism”, “Reactive oxygen species metabolism” and “Ion membrane transport”. Globally, our results indicate that ethylene biosynthesis and the downstream signal cascade are strongly induced by cadmium stress. In accordance to ethylene role in the interaction with the ROS generation and scavenging machinery, the transcription of several genes (NADPH oxidase 1, superoxide dismutase, ascorbate peroxidase, different glutathione S-transferases and catalase) devoted to cope the oxidative stress is strongly activated. Several small signal peptides belonging toROTUNDIFOLIA,CLAVATA3, and C-TERMINALLY ENCODED PEPTIDE 1 (CEP) are also among the up-regulated genes in Cd-treated roots functioning as messenger molecules from root to shoot in order to communicate the stressful status to the upper part of the plants. Finally, the main finding of our work is that genes involved in cell wall remodelling and lignification are decisively up-regulated in giant reed roots. This probably represents a mechanism to avoid cadmium uptake which strongly supports the possibility to cultivate giant cane in contaminated soils in the perspective to reserve agricultural soil for food and feed crops.
Daphnia magna egg piRNA cluster expression profiles change as mothers age
Authors: Hearn Jack , Little Tom J.
Published: June 2022

Background

PiRNAs prevent transposable elements wreaking havoc on the germline genome. Changes in piRNA expression over the lifetime of an individual may impact on ageing through continued suppression, or release, of transposable element expression. We identified piRNA producing clusters in the genome of Daphnia magna by a combination of bioinformatic methods, and then contrasted their expression between parthenogenetically produced eggs representing maternally-deposited germline piRNAs of young (having their 1st clutch) and old (having their 5th clutch) mothers. Results from eggs were compared to cluster expression in three generations of adults.

Results

As for other arthropods, D. magna encodes long uni-directionally transcribed non-coding RNAs consisting of fragmented transposable elements which account for most piRNAs expressed. Egg tissues showed extensive differences between clutches from young mothers and those from old mothers, with 578 and 686 piRNA clusters upregulated, respectively. Most log fold-change differences for significant clusters were modest, however. When considering only highly expressed clusters, there was a bias towards 1st clutch eggs at 41 upregulated versus eight clusters in the eggs from older mothers. F0 generation differences between young and old mothers were fewer than eggs, as 179 clusters were up-regulated in young versus 170 old mothers. This dropped to 31 versus 22 piRNA clusters when comparing adults in the F1 generation, and no differences were detected in the F3 generation. Inter-generational losses of differential piRNA cluster were similar to that observed for D. magna micro-RNA expression.

Conclusions

Little overlap in differentially expressed clusters was found between adults containing mixed somatic and germline (ovary) tissues and germ-line representing eggs. A cluster encompassing a Tudor domain containing gene important in the piRNA pathway was upregulated in the eggs from old mothers. We hypothesise that regulation of this gene could form part of a feedback loop that reduces piRNA pathway activity explaining the reduced number of highly-expressed clusters in eggs from old mothers.
Integrative analysis of expression profile indicates the ECM receptor and LTP dysfunction in the glioma-related epilepsy
Authors: Wang Zhi-Bin , Qu Jian , Xie Pan , Yang Zhi-Quan , Mao Chen-Xue , Zhang Ying , He Zheng-Wen , Yang Zhuan-Yi , Mao Xiao-Yuan , Liu Zhao-Qian
Published: June 2022

Background

Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive.

Objective

To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients.

Methods

Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor.

Results

We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease’s progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance.

Conclusion

These findings can offer a fresh perspective on GRE-induced brain network changes.
The functional mechanisms of synchronizing royal jelly consumption and physical activity on rat with multiple sclerosis-like behaviors hallmarks based on bioinformatics analysis, and experimental survey
Authors: Lohrasbi Maryam , Taghian Farzaneh , Jalali Dehkordi Khosro , Hosseini Seyed Ali
Published: June 2022

Background

Natural nutrition and physical training have been defined as non-pharmacochemical complementary and alternative medicines to prevent and treat various pathogenesis. Royal jelly possesses various pharmacological properties and is an effective therapeutic supplement for halting neurodegeneration. Multiple sclerosis is a prevalent neurodegenerative disorder that manifests as a progressive neurological condition. Inflammation, hypoxia, and oxidative stress have been identified as significant hallmarks of multiple sclerosis pathology.

Results

In the present study, based on artificial intelligence and bioinformatics algorithms, we marked hub genes, molecular signaling pathways, and molecular regulators such as non-coding RNAs involved in multiple sclerosis. Also, microRNAs as regulators can affect gene expression in many processes. Numerous pathomechanisms, including immunodeficiency, hypoxia, oxidative stress, neuroinflammation, and mitochondrial dysfunction, can play a significant role in the MSc pathogenesis that results in demyelination. Furthermore, we computed the binding affinity of bioactive compounds presented in Royal Jelly on macromolecules surfaces. Also, we predicted the alignment score of bioactive compounds over the pharmacophore model of candidate protein as a novel therapeutic approach. Based on the q-RT-PCR analysis, the expression of the Dnajb1/Dnajb1/Foxp1/Tnfsf14 and Hspa4 networks as well as miR-34a-5p and miR155-3p were regulated by the interaction of exercise training and 100 mg/kg Royal Jelly (ET-100RJ). Interestingly, characteristics, motor function, a proinflammatory cytokine, and demyelination were ameliorated by ET-100RJ.

Discussion

Here, we indicated that interaction between exercise training and 100 mg/kg Royal jelly had a more effect on regulating the microRNA profiles and hub genes in rats with Multiple sclerosis.
Comprehensive analysis of the MYB transcription factor gene family in Morus alba
Authors: Liu Li , Chao Nan , Yidilisi Keermula , Kang Xiaoru , Cao Xu
Published: June 2022

Background

The V-myb myeloblastosis viral oncogene homolog (MYB) family of proteins is large, containing functionally diverse transcription factors. However, MYBs in Morus are still poorly annotated and a comprehensive functional analysis of these transcription factors is lacking.

Results

In the present study, a genome-wide identification of MYBs in Morus alba was performed. In total 166 MaMYBs were identified, including 103 R2R3-MYBs and four 3R-MaMYBs. Comprehensive analyses, including the phylogenetic analysis with putative functional annotation, motif and structure analysis, gene structure organization, promoter analysis, chromosomal localization, and syntenic relationships of R2R3-MaMYBs and 3R-MaMYBs, provided primary characterization for these MaMYBs. R2R3-MaMYBs covered the subgroups reported for R2R3-MYBs in Arabidopsis and Populus, and had two Morus-specific subgroups, indicating the high retention of MYBs in Morus. Motif analysis revealed high conservative residues at the start and end of each helix and residues consisting of the third helix in R2 and R3 repeats. Thirteen intron/exon patterns (a–m) were summarized, and the intron/exon pattern of two introns with phase numbers of 0 and 2 was the prevalent pattern for R2R3-MaMYBs. Various cis-elements in promoter regions were identified, and were mainly related to light response, development, phytohormone response, and abiotic and biotic stress response and secondary metabolite production. Expression patterns of R2R3-MaMYBs in different organs showed that MaMYBs involved in secondary cell wall components and stress responsiveness were preferentially expressed in roots or stems. R2R3-MaMYBs involved in flavonoid biosynthesis and anthocyanin accumulation were identified and characterized based on functional annotation and correlation of their expression levels with anthocyanin contents.

Conclusion

Based on a comprehensive analysis, this work provided functional annotation for R2R3-MYBs and an informative reference for further functional dissection of MYBs in Morus.
The involvement of extracellular ATP in regulating the stunted growth of Arabidopsis plants by repeated wounding
Authors: Shi Zhenzhen , Wang Hanqi , Zhang Yuejing , Jia Lingyun , Pang Hailong , Feng Hanqing , Wang Xin
Published: June 2022

Background

Extracellular ATP (exATP) has been shown to act as a signal molecule for regulating growth, development, and responses of plants to the external environment.

Results

In this study, we investigated the possible involvement of exATP in regulating the stunted growth caused by repeated wounding. The present work showed that the repeated wounding caused the decreases in leaf area, fresh weight, dry weight, and root length of Arabidopsis seedlings, while the exATP level was enhanced by the repeated wounding. Repeated application of exogenous ATP had similar effects on the plant growth, as the repeated wounding. Through the comparison of p2k1-3 mutant (in which T-DNA disrupted the gene coding P2K1, as exATP receptor) and wide type (WT) plants, it was found that the mutation in P2K1 decreased the sensitivity of plant growth to the repeated wounding and exogenous ATP application. Further works showed that the ibuprofen (IBU, an inhibitor of jasmonate biosynthesis) partially rescued the wound-induced growth degradation. In comparison, the P2K1 mutation partly rescued the wound-induced growth degradation, whereas this mutation failed to do so in the wounded seedlings treated with IBU, indicating that the role of exATP in regulating the growth degradation by repeated wounding could be linked to the JA signaling pathway.

Conclusions

In conclusion, these results indicate that exATP could be a regulator for the stunted growth of plants by repeated wounding.
Acute medical missions by helicopter medical service (HEMS) to municipalities with different approach for primary care physicians
Authors: Nystøyl Dag Ståle , Østerås Øyvind , Hunskaar Steinar , Zakariassen Erik
Published: June 2022

Background

The prehospital emergency system in Norway involves out-of-hours (OOH) services with on-call physicians. Helicopter emergency medical service (HEMS) are used in cases of severe illness or trauma that require rapid transport and/or an anesthesiologist’s services. In recent years, on-call primary care physicians have been less available for call-outs in Norway, and HEMS may be requested for missions that could be adequately handled by on-call physicians. Here, we investigated how different availability of an on-call physician to attend emergency patients at site (call-out) impacted requests and use of HEMS.

Methods

Our analysis included all acute medical missions in an urban and nearby rural OOH district, which had different approach regarding physician call-outs from the OOH service. For this prospective observational study, we used data from both HEMS and the OOH service from November 1st 2017 until November 30th 2018. Standard descriptive statistical analyses were used.

Results

The rates of acute medical missions in the urban and rural OOH districts were similar (30 and 29 per 1000 inhabitants per year, respectively). The rate of HEMS requests was significantly higher in the rural OOH district than in the urban district (2.4 vs. 1.7 per 1000 inhabitants per year, respectively). Cardiac arrest and trauma were the major symptom categories in more than one half of the HEMS-attended patients, in both districts. Chest pain was the most frequent reason for an OOH call-out in the rural OOH district (21.1%). An estimated NACA score of 5–7 was found in 47.7% of HEMS patients from the urban district, in 40.0% of HEMS patients from the rural OOH district (p = 0.44), and 12.8% of patients attended by an on-call physician in the rural OOH district (p < 0.001). Advanced interventions were provided by an anesthesiologist to one-third of the patients attended by HEMS, of whom a majority had an NACA score of ≥ 5.

Conclusions

HEMS use did not differ between the two compared areas, but the rate of HEMS requests was significantly higher in the rural OOH district. The threshold for HEMS use seems to be independent of on-call primary care physician involvement.
Medicines use before and after comprehensive medicines review among residents of long-term care facilities: a retrospective cohort study
Authors: Sluggett Janet K. , Caughey Gillian E. , Air Tracy , Moldovan Max , Lang Catherine , Martin Grant , Carter Stephen R. , Jackson Shane , Stafford Andrew C. , Wesselingh Steve L. , Inacio Maria C.
Published: June 2022

Background

Residential Medication Management Review (RMMR) is a subsidized comprehensive medicines review program for individuals in Australian residential aged care facilities (RACFs). This study examined weekly trends in medicines use in the four months before and after an RMMR and among a comparison group of residents who did not receive an RMMR.

Methods

This retrospective cohort study included individuals aged 65 to 105 years who first entered permanent care between 1/1/2012 and 31/12/2016 in South Australia, Victoria, or New South Wales, and were taking at least one medicine. Individuals with an RMMR within 12 months of RACF entry were classified into one of three groups: (i) RMMR within 0 to 3 months, (ii) 3 to 6 months, or (iii) within 6 to 12 months of RACF entry. Individuals without RMMRs were included in the comparison group. Weekly trends in the number of defined daily doses per 1000 days were determined in the four months before and after the RMMR (or assigned index date in the comparison group) for 14 medicine classes.

Results

113909 individuals from 1979 RACFs were included, of whom 55021 received an RMMR. Across all three periods examined, decreased use of statins and proton pump inhibitors was observed post-RMMR in comparison to those without RMMRs. Decreases in calcium channel blockers, benzodiazepines/zopiclone, and antidepressants were observed following RMMR provision in the 3–6 and 6–12 months after RACF entry. Negligible changes in antipsychotic use were also observed following an RMMR in the 6–12 months after RACF entry by comparison to those without RMMRs. No changes in use of opioids, ACE inhibitors/sartans, beta blockers, loop diuretics, oral anticoagulants, or medicines for osteoporosis, diabetes or the cognitive symptoms of dementia were observed post-RMMR.

Conclusions

For six of the 14 medicine classes investigated, modest changes in weekly trends in use were observed after the provision of an RMMR in the 6–12 months after RACF entry compared to those without RMMRs. Findings suggest that activities such as medicines reconciliation may be prioritized when an RMMR is provided on RACF entry, with deprescribing more likely after an RMMR the longer a resident has been in the RACF.
Novel mitochondrial alanyl-tRNA synthetase 2 (AARS2) heterozygous mutations in a Chinese patient with adult-onset leukoencephalopathy
Authors: Fan Yan , Han Jinming , Yang Yanyan , Chen Tuanzhi
Published: June 2022

Background

Missense mutations in the mitochondrial alanyl-tRNA synthetase 2 (AARS2) gene are clinically associated with infantile mitochondrial cardiomyopathy or adult-onset leukoencephalopathy with early ovarian failure. To date, approximately 40 cases have been reported related toAARS2mutations, while its genetic and phenotypic spectrum remains to be defined.

Case presentation

We identified a 24-year-old Chinese female patient with adult-onset leukoencephalopathy carrying novel compound heterozygous pathogenic mutations in theAARS2gene (c.718C > T and c.1040 + 1G > A) using a whole-exome sequencing approach.

Conclusions

Our findings further extend the mutational spectrum ofAARS2-related leukoencephalopathy and highlight the importance of the whole-exome sequencing in precisely diagnosing adult-onset leukoencephalopathies.
Semaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma
Authors: Jiang Jun , Lu Yuan , Zhang Fang , Pan Tao , Zhang Zhipei , Wan Yi , Ren Xinling , Zhang Rui
Published: June 2022

Background

Semaphorins have been found to play important roles in multiple malignancy-related processes. However, the role of Semaphorin 4B (SEMA4B) in lung cancer remains unclear. Here, we aimed to explore the biological functions of SEMA4B in through bioinformatic analysis, in vitro and in vivo assays. In the present study, the possible mechanism by which SEMA4B affected the tumor growth and microenvironment of lung adenocarcinoma (LUAD) were investigated.

Methods

The expression of SEMA4B in LUAD was analyzed by bioinformatic analysis and verified by the immunohistochemistry staining. The prognostic value of SEMA4B in LUAD was investigated using the Kaplan-Meier survival and Cox’s regression model. After silencing SEMA4B expression, the functions of SEMA4B in LUAD cells were investigated by in vitro experiments, including CCK-8 and plate clone formation. And the effect of SEMA4B on tumor growth and immune infiltration was explored in C57BL/6 mice tumor-bearing models.

Results

SEMA4B expression was upregulated in LUAD tissues and correlated with later pathological stages and poor prognosis of LUAD patients. Further study found that SEMA4B silencing suppressed the proliferation of lung cancer cells both in vitro and in vivo. Bioinformatic analysis showed that SEMA4B expression was correlated with the increased infiltration of myeloid-derived suppressor cells (MDSCs), T-regs and the decreased infiltration of CD8+ T cell in LUAD. Importantly, in vivo study verified that the infiltration of T-regs and MDSCs in tumor microenvironment (TME) of Xenograft tissues was decreased after SEMA4B silencing.

Conclusions

These findings demonstrated SEMA4B might play an oncogenic role in LUAD progression, and be a promising therapeutic target for lung cancer.
Comparison of relapsing polychondritis patients with and without respiratory involvement based on chest computed tomography: a retrospective cohort study
Authors: Wang Dong , Guan Lujia , Dong Xin , Zhu Xiaofan , Tong Zhaohui
Published: June 2022

Background

Relapsing polychondritis (RP) patients with tracheal cartilage involvement are different from other patients. The objective of this study was to compare the clinical features and disease patterns between a respiratory involvement subgroup and a non-respiratory involvement subgroup according to chest computed tomography.

Method

We performed a retrospective cohort study collecting RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 and August 2021.

Results

Respiratory involvement affected 59.7% of patients in our cohort. The incidence of costochondritis was more common in RP patients with respiratory involvement (p = 0.03); the incidence of inflammatory eye disease (p = 0.001) and auricular chondritis (p = 0.001) was less frequent in RP respiratory involvement patients.. Compared with the non-respiratory involvement subgroup the incidence of pulmonary infection marginally increased in the respiratory involvement subgroup (p = 0.06). Inflammatory indexes except for C-reactive protein to albumin ratio (CAR) were significantly higher in the respiratory involvement subgroup; analysis revealed no significant relationship between inflammatory indexes and pulmonary infection.

Conclusion

RP patients with respiratory involvement had a greater incidence of costochondritis and pulmonary infectionand lesser incidence of inflammatory eye diseases and auricular chondritis compared to non-respiratory involvement. Increasing inflammatory indexes suggests that patients with respiratory involvement had a higher disease activity index of RP. The difference in probability of survival was insignificant between subgroups.
Enablement and empowerment among patients participating in a supported osteoarthritis self-management programme – a prospective observational study
Authors: Åkesson Karin Sturesdotter , Sundén Anne , Stigmar Kjerstin , Fagerström Cecilia , Pawlikowska Teresa , Ekvall Hansson Eva
Published: June 2022

Background

In Sweden, core treatment for osteoarthritis is offered through a Supported Osteoarthritis Self-Management Programme (SOASP), combining education and exercise to provide patients with coping strategies in self-managing the disease. The aim was to study enablement and empowerment among patients with osteoarthritis in the hip and/or knee participating in a SOASP. An additional aim was to study the relation between the Swedish version of the Patient Enablement Instrument (PEI) and the Swedish Rheumatic Disease Empowerment Scale (SWE-RES-23).

Methods

Patients with osteoarthritis participating in a SOASP in primary health care were recruited consecutively from 2016 to 2018. The PEI (score range 0–12) was used to measure enablement and the SWE-RES-23 (score range 1–5) to measure empowerment. The instruments were answered before (SWE-RES-23) and after the SOASP (PEI, SWE-RES-23). A patient partner was incorporated in the study. Descriptive statistics, the Wilcoxon’s signed rank test, effect size (r), and the Spearman’s rho (rs) were used in the analysis.

Results

In total, 143 patients were included in the study, 111 (78%) were women (mean age 66, SD 9.3 years). At baseline the reported median value for the SWE-RES-23 (n = 142) was 3.6 (IQR 3.3–4.0). After the educational part of the SOASP, the reported median value was 6 (IQR 3–6.5) for the PEI (n = 109) and 3.8 (IQR 3.6–4.1) for the SWE-RES-23 (n = 108). At three months follow-up (n = 116), the reported median value was 6 (IQR 4–7) for the PEI and 3.9 (IQR 3.6–4.2) for the SWE-RES-23. The SWE-RES-23 score increased between baseline and three months (p ≤ 0.000). The analysis showed a positive correlation between PEI and SWE-RES-23 after the educational part of the SOASP (rs = 0.493, p < 0.00, n = 108) and at follow-up at three months (rs = 0.507, p < 0.00, n = 116).

Conclusions

Patients reported moderate to high enablement and empowerment and an increase in empowerment after participating in a SOASP, which might indicate that the SOASP is useful to enable and empower patients at least in the short term. Since our results showed that the PEI and the SWE-RES-23 are only partly related both instruments can be of use in evaluating interventions such as the SOASP.

Trial registration

ClinicalTrials.gov. NCT02974036. First registration 28/11/2016, retrospectively registered.
Guideline-concordant utilization of magnetic resonance imaging in adults receiving chiropractic manipulative therapy vs other care for radicular low back pain: a retrospective cohort study
Authors: Trager Robert J. , Anderson Brian R. , Casselberry Regina M. , Perez Jaime A. , Dusek Jeffery A.
Published: June 2022

Background

Lumbar magnetic resonance imaging (LMRI) is often performed early in the course of care, which can be discordant with guidelines for non-serious low back pain. Our primary hypothesis was that adults receiving chiropractic spinal manipulative therapy (CSMT) for incident radicular low back pain (rLBP) would have reduced odds of early LMRI over 6-weeks’ follow-up compared to those receiving other care (a range of medical care, excluding CSMT). As a secondary hypothesis, CSMT recipients were also expected to have reduced odds of LMRI over 6-months’ and 1-years’ follow-up.

Methods

A national 84-million-patient health records database including large academic healthcare organizations (TriNetX) was queried for adults age 20–70 with rLBP newly-diagnosed between January 31, 2012 and January 31, 2022. Receipt or non-receipt of CSMT determined cohort allocation. Patients with prior lumbar imaging and serious pathology within 90 days of diagnosis were excluded. Propensity score matching controlled for variables associated with LMRI utilization (e.g., demographics). Odds ratios (ORs) of LMRI over 6-weeks’, 6-months’, and 1-years’ follow-up after rLBP diagnosis were calculated.

Results

After matching, there were 12,353 patients per cohort (mean age 50 years, 56% female), with a small but statistically significant reduction in odds of early LMRI in the CSMT compared to other care cohort over 6-weeks’ follow-up (9%, 10%, OR [95% CI] 0.88 [0.81–0.96] P = 0.0046). There was a small but statistically significant increase in odds of LMRI among patients in the CSMT relative to the other care cohort over 6-months’ (12%, 11%, OR [95% CI] 1.10 [1.02–1.19], P < 0.0174) and 1-years’ follow-up (14%, 12%, OR [95% CI] 1.21 [1.13–1.31], P < 0.0001).

Conclusions

These results suggest that patients receiving CSMT for newly-diagnosed rLBP are less likely to receive early LMRI than patients receiving other care. However, CSMT recipients have a small increase in odds of LMRI over the long-term. Both cohorts in this study had a relatively low rate of early LMRI, possibly because the data were derived from academic healthcare organizations. The relationship of these findings to other patient care outcomes and cost should be explored in a future randomized controlled trial.

Registration

Open Science Framework (https://osf.io/t9myp).
Professional identity formation of medical students: A mixed-methods study in a hierarchical and collectivist culture
Authors: Findyartini Ardi , Greviana Nadia , Felaza Estivana , Faruqi Muhammad , Zahratul Afifah Taris , Auliya Firdausy Mutiara
Published: June 2022

Background

Professional identity formation (PIF) has been recognized as an integral part of professional development in medical education. PIF is dynamic: it occurs longitudinally and requires immersion in the socialization process. Consequently, in the medical education context, it is vital to foster a nurturing learning environment that facilitates PIF.

Aim

This study assesses PIF among medical students in various stages of study and explores their perceptions of PIF, with its contributing and inhibiting factors.

Method

This mixed-methods study uses a sequential explanatory approach with undergraduate (years 2, 4, and 6) and postgraduate medical students in Indonesia. We examine the subjects by administering an adapted questionnaire on PIF. We completed a series of FGDs following questionnaire administration. Quantitative and thematic analyses were conducted sequentially.

Results & Discussion

A total of 433 respondents completed the questionnaire. There were statistically significant differences among subjects on the subscales “Recognition and internalization of professional roles” and “Self-control in professional behavior”; the more senior students had higher scores. We conducted 6 FGDs in total. The results characterize PIF as a complex, dynamic, and longitudinal journey to becoming a medical doctor that is closely related to a student’s motivation. The FGDs also highlight the importance of both internal factors (students’ values, attributes, and personal circumstances) and external factors (curriculum, the learning environment, workplace-based learning, and external expectations) for PIF in medical education.

Conclusion

Higher-level students show higher scores in some aspects of PIF, which further validates the potential use of the questionnaire to monitor PIF, a dynamic process influenced by internal and external factors. Generating awareness among medical students and encouraging reflection on their PIF stage may be crucial for PIF processes.
Serological study of CoronaVac vaccine and booster doses in Chile: immunogenicity and persistence of anti-SARS-CoV-2 spike antibodies
Authors: Vargas Leonardo , Valdivieso Nicolás , Tempio Fabián , Simon Valeska , Sauma Daniela , Valenzuela Lucía , Beltrán Caroll , Castillo-Delgado Loriana , Contreras-Benavides Ximena , Acevedo Mónica L. , Acevedo Johanna , Gonzalez Rafael I. , Valiente-Echeverría Fernando , Soto-Rifo Ricardo , Rosemblatt Mario , Lopez Mercedes , Osorio Fabiola , Bono María Rosa
Published: June 2022

Background

Chile was severely affected by COVID19 outbreaks but was also one of the first countries to start a nationwide program to vaccinate against the disease. Furthermore, Chile became one of the fastest countries to inoculate a high percentage of the target population and implemented homologous and heterologous booster schemes in late 2021 to prevent potential immunological waning. The aim of this study is to compare the immunogenicity and time course of the humoral response elicited by the CoronaVac vaccine in combination with homologous versus heterologous boosters.

Methods

We compared the immunogenicity of two doses of CoronaVac and BNT162b2 vaccines and one homologous or heterologous booster through an ELISA assay directed against the ancestral spike protein of SARS-CoV-2. Sera were collected from individuals during the vaccination schedule and throughout the implementation of homologous and heterologous booster programs in Chile.

Results

Our findings demonstrate that a two-dose vaccination scheme with CoronaVac induces lower levels of anti-SARS-CoV-2 spike antibodies than BNT162b2 in a broad age range (median age 42 years; interquartile range (IQR) 27-61). Furthermore, antibody production declines with time in individuals vaccinated with CoronaVac and less noticeably, with BNT162b2. Analysis of booster schemes revealed that individuals vaccinated with two doses of CoronaVac generate immunological memory against the SARS-CoV-2 ancestral strain, which can be re-activated with homologous or heterologous (BNT162b2 and ChAdOx1) boosters. Nevertheless, the magnitude of the antibody response with the heterologous booster regime was considerably higher (induction fold BNT162b2: 11.2x; ChAdoX1; 12.4x; CoronaVac: 6.0x) than the responses induced by the homologous scheme. Both homologous and heterologous boosters induced persistent humoral responses (median 122 days, IQR (108-133)), although heterologous boosters remained superior in activating a humoral response after 100 days.

Conclusions

Two doses of CoronaVac induces antibody titers against the SARS-CoV-2 ancestral strain which are lower in magnitude than those induced by the BNT162b2 vaccine. However, the response induced by CoronaVac can be greatly potentiated with a heterologous booster scheme with BNT162b2 or ChAdOx1 vaccines. Furthermore, the heterologous and homologous booster regimes induce a durable antibody response which does not show signs of decay 3 months after the booster dose.
Pentraxin-3 as a predictive marker of mortality in sepsis: an updated systematic review and meta-analysis
Authors: Wang Guobin , Jiang Chunyan , Fang Junjun , Li Zhitao , Cai Hongliu
Published: June 2022

Background

The purpose of this study was to clarify the prognostic value of Pentraxin-3 (PTX3) on the mortality of patients with sepsis.

Methods

Publications published up to January 2021 were retrieved from PubMed, EMBASE, and the Cochrane library. Data from eligible cohort and case–control studies were extracted for the meta-analysis. Multivariate regression analysis was used to evaluate the correlation of the outcomes with sample size and male proportion.

Results

A total of 17 studies covering 3658 sepsis patients were included. PTX3 level was significantly higher in non-survivor compared to survivor patients (SMD (95% CI): −1.06 (−1.43, −0.69), P < 0.001). Increased PTX3 level was significantly associated with mortality (HR (95% CI): 2.09 (1.55, 2.81), P < 0.001). PTX3 showed good predictive capability for mortality (AUC:ES (95% CI): 0.73 (0.70, 0.77), P < 0.001). The outcome comparing PTX3 level in non-survivors vs. survivors and the outcome of the association between PTX3 and mortality were associated with sample size but not male proportion. AUC was associated with both sample size and male proportion.

Conclusions

PTX3 level was significantly higher in non-survivor compared to survivor patients with sepsis. Elevated PTX3 level was significantly associated with mortality. Furthermore, the level of PTX3 might predict patient mortality.
Resilience is a dirty word: misunderstood, and how we can truly build it
Authors: Tan Mark Z. Y.
Published: June 2022

Resilience is ubiquitous in everyday speech, academic literature and governmental policies. Yet it seems to have taken a narrow scope in healthcare, confined to individual and psychological resilience. This short essay aims to broaden the understanding of resilience to organisational levels and calls intensivists to take active roles in fostering resilience for their staff. The article explores firstly the background and etymology of resilience. It then challenges current approaches and briefly signposts some current work in the area. Some examples of structural factors which build individual resilience are listed, followed by a call for intensivists to take active roles to build future resilience. The need for interdisciplinary, cross-sectoral and multi-level approaches is vital to build future healthcare resilience, and we intensivists must continue to be advocates for systemic change.