bluuebunny/crossref_metadata_2025 huggingface dataset:
Immigration, Law, and (In)Justice: Coronavirus and Its Impact on Immigration
Authors: Caraballo Krystlelynn
Published: August 2020

This introduction to the International Criminal Justice Review provides a brief overview of the books reviewed in this special issue, which address multiple facets of the immigration system. Then, I provide an overview of the key immigration policy changes and legal challenges that have occurred in the midst of the coronavirus (COVID-19) pandemic between March and July 2020. This health crisis exacerbated the struggles faced by the immigrant community and exemplify the systemic barriers that impede integration.
Consensus for the Indication of a Medializing Displacement Calcaneal Osteotomy in the Treatment of Progressive Collapsing Foot Deformity
Authors: Schon Lew C. , de Cesar Netto Cesar , Day Jonathan , Deland Jonathan T. , Hintermann Beat , Johnson Jeffrey E. , Myerson Mark S. , Sangeorzan Bruce J. , Thordarson David B. , Ellis Scott J.
Published: August 2020

Recommendation:

There is evidence that the medial displacement calcaneal osteotomy (MDCO) can be effective in treating the progressive collapsing foot deformity (PCFD). This juxta-articular osteotomy of the tuberosity shifts the mechanical axis of the calcaneus from a more lateral position to a more medial position, which provides mechanical advantage in the reconstruction for this condition. This also shifts the action of the Achilles tendon medially, which minimizes the everting deforming effect and improves the inversion forces. When isolated hindfoot valgus exists with adequate talonavicular joint coverage (less than 35%-40% uncoverage) and a lack of significant forefoot supination, varus, or abduction, we recommend performing this osteotomy as an isolated bony procedure, with or without additional soft tissue procedures. The clinical goal of the hindfoot valgus correction is to achieve a clinically neutral heel, as defined by a vertical axis from the heel up the longitudinal axis of the Achilles tendon and distal aspect of the leg. The typical range when performing a MDCO, while considering the location and rotation of the osteotomy, is 7 to 15 mm of correction.

Level of Evidence:

Level V, consensus, expert opinion.
Outpatient total hip arthroplasty does not increase complications and readmissions: a meta-analysis
Authors: Bordoni Vittorio , Marelli Niccolò , Previtali Davide , Gaffurini Paolo , Filardo Giuseppe , Candrian Christian
Published: August 2020

Background:

There is no consensus about the safety of outpatient total hip arthroplasty (THA). Therefore, the purpose of this meta-analysis was to quantitatively evaluate and compare outpatient and inpatient THA studies in terms of complication and readmission rates.

Methods:

A systematic search of the literature was performed on 26 July 2019 on PubMed, Web of Science, Cochrane library, and on the grey literature databases. The papers thus collected were used for a meta-analysis comparing outpatient and inpatient THA in terms of complication and readmission rates. Risk of bias and quality of evidence were defined according to Cochrane guidelines. The PRISMA guidelines were used to determine which papers to include in this study.

Results:

The literature search resulted in 2317 articles; of these, 8 articles were used for the meta-analysis. A total of 66,971 patients were included, of which 1428 were THA outpatients. The overall complication rate for outpatient THAs was 3.0%, while inpatient THAs had an overall complication rate of 4.7%. The readmission rate was 1.4% in outpatient THAs and 3.0% in inpatient THAs. Only 6 studies reported the number of deaths, which ranged from 0% to 0.01%. The included studies present a moderate risk of bias and, according to GRADE guidelines, the level of evidence for complications and readmissions is very low.

Conclusions:

This meta-analysis documented that outpatient THA is a feasible approach since it does not increase complications or readmissions with respect to inpatient THA, but the available studies present a moderate risk of bias and the quality of evidence of these findings is very low. Future high-level studies are needed to confirm results and indications for outpatient THA.
From Plugging the Dam to Fueling the Firing: Platelets Breach the Barrier to Seize the Brain
Authors: Nguyen Susan , Santhakumar Viji
Published: August 2020

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Four-Corner Arthrodesis Using a Dedicated Dorsal Circular Plate
Authors: Corain Massimo , Sartore Roberta , Laterza Mara , Zanotti Filippo , Pozza Paolo , Adani Roberto
Published: August 2020

Background:

Scaphoid excision and 4-corner fusion is a standard procedure for advanced carpal collapse. The purpose of this study was to evaluate its effectiveness using a specific designed locking plate of the latest generation.

Methods:

Between October 2012 and December 2015, 12 patients underwent this procedure using the Flower (KLS Martin Group, Tuttlingen, Germany) circular locking plate. The surgical technique is standardized. Three patients were affected by a scapholunate advanced collapse and 9 patients by a scaphoid nonunion advanced collapse. All patients underwent a computed tomographic scan to study the real achievement of the fusion.

Results:

Only 2 patients did not show complete fusion. All the patients with successful fusion returned to previous work and manual activities.

Conclusions:

Four-corner arthrodesis with circular locking plate is an alternative surgical treatment for carpal arthritic collapse.
Endovascular treatment for the flow-related aneurysm originating from an anterior inferior cerebellar artery supplying the cerebellar arteriovenous malformation
Authors: Hou Kun , Xu Kan , Chen Xuan , Wang Yiheng , Li Kailing , Yu Jinlu
Published: August 2020

Background

When a flow-related aneurysm originates from an anterior inferior cerebellar artery (AICA) supplying the cerebellar arteriovenous malformation (AVM), the management becomes very complicated. Endovascular treatment (EVT) was an option, but no consensus has been achieved. Methods and materials: A retrospective investigation was performed for patients with flow-related aneurysm originating from an AICA supplying the cerebellar AVM.

Results

Ten patients, harboring 13 aneurysms, were identified. Of the 5 a1 aneurysms, 2 underwent stent assisted coiling, 2 underwent parent artery occlusion (PAO), and 1 was intact. Of the 8 a2 aneurysms, 3 underwent coiling with preservation of the AICA, 3 underwent PAO with Onyx, 1 underwent PAO with coils, and 1 was intact. Seven patients underwent partial embolization of the cerebellar AVM, 3 were intact. One patient died 6 hours postoperatively for cerebellar AVM rebleeding. During a follow-up from 6 months to 6 years, 9 patients had favorable recovery.

Conclusion

For the flow-related aneurysm originating from an AICA supplying the cerebellar AVM, the EVT depends on the specific circumstances. When the aneurysm is located at the a1 segment, coiling of the aneurysm with preservation of the parent AICA should be performed. PAO is the last resort. When the a2 aneurysm is proximal to the internal auditory artery, coiling of the aneurysm with preservation of the AICA is preferred. When the aneurysm is distal to the internal auditory artery, PAO can be safely performed.
Endovascular treatment of cerebral dural arteriovenous fistulas with SQUID 12
Authors: Lozupone Emilio , Bracco Sandra , Trombatore Pietro , Milonia Luca , D’Argento Francesco , Alexandre Andrea , Valente Iacopo , Semeraro Vittorio , Cioni Samuele , Pedicelli Alessandro
Published: August 2020

Background

Endovascular therapy with liquid embolic agents (LEAs) is the gold standard for the treatment of cerebral dural arteriovenous fistulas (cDAVFs). The aim of the study is to retrospectively evaluate effectiveness, safety, and midterm follow-up results of endovascular treatment of cDAVFs using SQUID 12.

Methods

Between June 2017 and January 2020 the authors retrospectively reviewed clinical, demographic and embolization data of 19 consecutive patients with cDAVF who underwent embolization using SQUID 12. The number of arteries catheterized for each procedure, the total amount of embolic agent, the occlusion rate, the injection time, any technical and/or clinical complications were recorded. Mid-term follow-up with DSA was reviewed.

Results

20 procedures were performed in 19 patients. A transarterial approach was accomplished in 19 procedure; a combined transvenous-transarterial approach was realized in 1 treatment. The average time of injection was 33 minutes (2–82 minutes), and the average amount of SQUID 12 was 2.8 mL (0.5–6 mL). Complete angiographic cure at the end of the procedure was achieved in 17 patients. No major periprocedural adverse events were recorded. Mid-term follow-up was achieved in 15 out of 19 patients and confirmed complete occlusion of the cDAVFs in 13/15 patients (87%); in 2 of the initially cured patients a small relapse was detected.

Conclusions

The treatment of the cDAVFs using SQUID 12 was effective and safe. The lower viscosity seems to allow an easier penetration of the agent with a high rate of complete occlusion of the cDAVFs.
The entrepreneurial leadership practices of Malaysian secondary school principals in fundraising
Authors: Ghazali Siti Sabihah , Kadir Suhaida Abdul , Krauss Steven Eric , Asimiran Soaib
Published: August 2020

The reduction of funding allocation for school operations occurs in the education administration yearly. It is a notable fact that schools around the world are facing challenges in school funding as it affects the school’s operation. As a result, the performance of school for the long term would not be a primary concern in the future. Schools in Malaysia are not exempted from this issue as it is one of the main concerns in the centralized schools of this country. Generally, as the number of schools is increasing and a corresponding decrease takes place in centralized funding, it is vital for school principals to find alternatives for fundraising. Following a growing pattern of decentralization of school policies, entrepreneurial leadership currently begins to make an appearance in the education system through the transformation it creates in schools. However, there is insufficient discussion regarding the practices of entrepreneurial leadership and the abilities of entrepreneurial leaders in centralized schools. This study aims to identify the practices performed by centralized school principals to implement entrepreneurial activities in two schools selected for this study, which consisted of two different demographic backgrounds, districts, and locations. It investigates the entrepreneurial leadership practices performed by the Malaysian school principals in fundraising activities. The roles of the school principals as entrepreneurial leaders were identified based on their peers and other school staff who gained the experience of working under those principals. The various fundraising practices of the entrepreneurial leaders of both of these schools are examined within this crucial and challenging environment, followed by a discussion of how the school administrations deal with the external parties to obtain school funding. This study contributes to the field of educational administration by analysing the current fundraising practices of entrepreneurial principals of centralized schools in Malaysia.
Infliximab, adalimumab, golimumab, vedolizumab and tofacitinib in moderate to severe ulcerative colitis: comparative cost-effectiveness study in Poland
Authors: Petryszyn Pawel , Ekk-Cierniakowski Pawel , Zurakowski Grzegorz
Published: August 2020

Background:

Current management of ulcerative colitis (UC) is aimed to treat active disease and to maintain remission. For patients in whom conventional treatment is no longer effective, biological or small molecule therapy may be an option. The aim was to assess the cost-effectiveness of induction and maintenance treatment up to 1 year of UC with infliximab (IFX), adalimumab (ADA), golimumab, vedolizumab (VDZ) and tofacitinib (TFB) compared with standard of care (SoC) in Poland.

Methods:

A hybrid decision tree/Markov model was used to estimate the expected costs and effects of four biologics, TFB and placebo in patients with the diagnosis of moderate to severe UC who had an inadequate response, lost response, or were intolerant to a conventional therapy. Prior exposure to anti-TNF was considered. At the beginning of the maintenance phase, the decision to continue biological therapy was determined by the achievement of response at the end of induction. Efficacy data were obtained from a network meta-analysis using placebo as the common comparator. Costs were presented in 2018 Polish zloty (PLN) and outcomes included quality-adjusted life-years (QALYs). The analysis was performed from the Polish public payer’s perspective and lifetime horizon was set.

Results:

In anti-TNF naïve, IFX and VDZ were characterized by the most favourable incremental cost-effectiveness ratios (ICURs) compared with SoC, PLN211,250.78 and PLN361,694.61/QALY (€49,589.38 and €84,904.84/QALY), respectively. In anti-TNF-exposed population the most effective treatment was TFB. Both ADA and VDZ were more effective than SoC; however, ICUR values were much above the cost-effectiveness threshold. The incorporation of biosimilars reversed the ranking of treatments in relation to the growing ICUR.

Conclusion:

Although ICUR values for all biological therapies exceeded the acceptability threshold in Poland, for anti-TNF-naïve UC patients IFX and for anti-TNF-exposed UC patients VDZ are currently the most cost-effective alternatives.
Ursolic Acid Alleviates Mucus Secretion and Tissue Remodeling in Rat Model of Allergic Rhinitis After PM2.5 Exposure
Authors: Sun Na , Deng Congrui , Zhao Qianbiao , Han Zhijin , Guo Zhiqiang , Wang Hong , Dong Weiyang , Duan Yusen , Zhuang Guoshun , Zhang Ruxin
Published: August 2020

Background

According to recent epidemiologic studies, exposure to fine particulate matter (particulate matter 2.5 ≤ µm [PM2.5]) in the air increases the incidence and severity of allergic rhinitis (AR). Ursolic acid (UA) has activities in immune regulation and anti-inflammatory. However, the role of UA intervention on PM2.5-exposed AR remains unknown. In this study, we investigated the effects of UA on tissue remodeling and mucus hypersecretion in a rat model of AR after PM2.5 exposure.

Methods

AR was induced in rats with ovalbumin (OVA) and they were exposed to ambient PM2.5(200 µg/m3) via a PM2.5 inhalation exposure system for 30 days(ARE group). Ursolic acid intervention was administrated in the AR model after PM2.5 exposure (UA group). Hyperplasia of goblet cells was detected by periodic acid-Schiff (PAS) staining and collagen deposition in the nasal mucosa was detected by Masson trichrome (MT) staining.MUC5AC expression was measured by immunohistochemistry.

Results

UA group showed reduced goblet cell hyperplasia and collagen deposition in the nasal mucosa which exacerbated after PM2.5 exposure, as reflected by PAS and MT staining when compared with the ARE group. Immunohistochemical results showed that the expression of MUC5AC in the UA group was lower than that in the ARE group.

Conclusion

Analysis of our data indicated that UA could attenuate nasal remodeling and mucus hypersecretion in aggravation of AR after PM2.5 exposure, which may be the pathophysiologic mechanisms for the prevention of AR exacerbated by exposure to PM2.5.
Newer magnetic resonance imaging techniques in neurocysticercosis
Authors: Batta Akash , Mahesh Karthik Vinay , Prabhat Nandita , Shree Ritu , Goyal Manoj K , Ahuja Chirag K , Rebello Alex , Tandyala Naresh , Goyal Abeer , Choudhary Aditya , Goyal Gunjan , Modi Manish , Singh Paramjeet
Published: August 2020

Introduction

The definitive diagnosis of neurocysticercosis continues to be challenging. We evaluate the role of newer magnetic resonance imaging techniques including constructive interference in steady state, susceptibility-weighted imaging, arterial spin labelling and magnetic resonance spectroscopy in the diagnosis of neurocysticercosis.

Aims and objectives

To study the utility of newer magnetic resonance imaging sequences in the diagnosis of neurocysticercosis.

Patients and methods

Eighty-five consecutive patients with neurocysticercosis attending a tertiary care hospital and teaching centre in northern India were included in the study. The diagnosis of neurocysticercosis was made by the Del Brutto criteria. All patients received treatment according to standard guidelines and were followed at 3-month intervals. The following magnetic resonance sequences were performed at baseline: T1 and T2-weighted axial sequences; T2 fluid-attenuated inversion recovery axial sequences; diffusion-weighted imaging; susceptibility-weighted imaging; pre and post-contrast T1-weighted imaging; heavily T2-weighted thin sections (constructive interference in steady state); arterial spin labelling ( n = 19); and magnetic resonance spectroscopy ( n = 24).

Results

The mean (±SD) age was 29.4 ± 12.9 years and 76.5% were men. Seizures were the commonest symptom (89.4%) followed by headache (24.3%), encephalitis (9.4%) and raised intracranial pressure (9.4%). Scolex could be visualised in 43.7%, 55.5% and 61.2% of neurocysticercosis patients using conventional, susceptibility-weighted angiography and constructive interference in steady state imaging sequences, respectively. Susceptibility-weighted angiography and constructive interference in steady state images resulted in significantly higher ( P < 0.01) visualisation of scolex compared to conventional sequences.

Conclusion

Newer magnetic resonance imaging modalities have a lot of promise for improving the radiological diagnosis of neurocysticercosis.
‘Safeguarding Islam’ in modern times: Politics, piety and Hefazat-e-Islami ‘ulama in Bangladesh
Authors: Raqib Muhammad Abdur
Published: August 2020

Within Muslim communities, the ‘ulama are considered the most crucial corporate social agency that drives the ideological and spiritual energy to the members of the society who find religious teachings necessary for their individual and social, if not always political, lives. However, when the ‘ulama of Bangladesh gathered under the umbrella platform of Hefazat-e-Islam (HI) in 2010, agitated by the numerous upheavals of the government’s policies (which they argued were contrary to the teachings of the Qur’ān and Sunna), scholars and members of the civil society often dubbed them as regressive, reactionary, and insensitive to modern changes. While anthropologists have challenged this dichotomy, this article aims to understand the HI ‘ulama’s views on modern changes and how the ‘ulama safeguard the traditional integrity in legal, educational, and gender aspects within the domain of the Bangladeshi state mechanism. Based on anthropological notions of tradition and piety, this article argues that the ‘ulama’s position on education, woman, and legal questions is neither monolithic nor static; rather there is always discussion, debate, and dynamism within the ‘ulama itself.
Acquisition Planning for Regional Indigenous Heritage Languages in Indonesia
Authors: Suwarno Bambang
Published: August 2020

Regional indigenous heritage languages (RIHLs) are in decline in Indonesia, and this problem needs attention from language policy and planning. This study explores a subset of the Indonesian language policy, namely, its acquisition planning. Content analysis and doctrinal method were employed. The sample included national legislations and some regional legislations. The results are as follows. As subjects taught in schools, Indonesian is “compulsory” at all levels; RIHLs are “optional” at primary and secondary levels and “absent” at the tertiary level; English is “compulsory” at the secondary level and “optional” at the tertiary level. As the media of instruction, Indonesian is “compulsory” at all levels; RIHLs are “optional” in very limited cases; English is “optional” at the tertiary level. As languages for mass media, Indonesian is “compulsory”; English is “optional” for specific aims or audience; RIHLs are “optional” for local communities. There are possible “incoherences” among various legislations, that is, the Constitution, some national laws and regulations, and some regional bylaws. To implement constitutional mandate, the acquisition planning may need revision. In the revision, RIHLs may need to be included as mandatory subjects, while some RIHLs may need to be used as the media of instruction and in mass media. Further studies for the revision are recommended.
Management of Sacred Heritage Places in Tanzania: A Case of Kuumbi Limestone Cave, Zanzibar Island
Authors: Chami Maximilian F. , Chami Felix A.
Published: August 2020

The use and management of sacred sites that are still in use provide challenges to site managers since visitors fail to abide by rules established for the sacred area. In this study, it was revealed that there are ritual practices, strict taboos and customary laws put in place to control access to cave areas which are regarded as sacred to the locals. The habit of visitors not adhering to the established regulations when visiting caves and their areas have created a disconnection between people and their traditional religions and actually caused some of them to join mainstream religions such as Islam. The article proposes measures to be adopted by the antiquities authority, and other heritage managers in Zanzibar and Tanzania, in general, to provide the best practice for cave visitors and enable the communities to continue using the caves as a crucial part of their religious life without any molestations.
How I perform hematopoietic stem cell transplantation on patients with a history of invasive fungal disease
Authors: Puerta-Alcalde Pedro , Champlin Richard E. , Kontoyiannis Dimitrios P.
Published: August 2020

Hematopoietic transplantation is the preferred treatment for many patients with hematologic malignancies. Some patients may develop invasive fungal diseases (IFDs) during initial chemotherapy, which need to be considered when assessing patients for transplantation and treatment posttransplantation. Given the associated high risk of relapse and mortality in the post–hematopoietic stem cell transplantation (HSCT) period, IFDs, especially invasive mold diseases, were historically considered a contraindication for HSCT. Over the last 3 decades, advances in antifungal drugs and early diagnosis have improved IFD outcomes, and HSCT in patients with a recent IFD has become increasingly common. However, an organized approach for performing transplantation in patients with a prior IFD is scarce, and decisions are highly individualized. Patient-, malignancy-, transplantation procedure–, antifungal treatment–, and fungus-specific issues affect the risk of IFD relapse. Effective surveillance to detect IFD relapse post-HSCT and careful drug selection for antifungal prophylaxis are of paramount importance. Antifungal drugs have their own toxicities and interact with immunosuppressive drugs such as calcineurin inhibitors. Immune adjunct cytokine or cellular therapy and surgery can be considered in selected cases. In this review, we critically evaluate these factors and provide guidance for the complex decision making involved in the peri-HSCT management of these patients.
Unlocking a signal of introgression from codons in Lachancea kluyveri using a mutation-selection model
Authors: Landerer Cedric , O’Meara Brian C. , Zaretzki Russell , Gilchrist Michael A.
Published: August 2020

Background

For decades, codon usage has been used as a measure of adaptation for translational efficiency and translation accuracy of a gene’s coding sequence. These patterns of codon usage reflect both the selective and mutational environment in which the coding sequences evolved. Over this same period, gene transfer between lineages has become widely recognized as an important biological phenomenon. Nevertheless, most studies of codon usage implicitly assume that all genes within a genome evolved under the same selective and mutational environment, an assumption violated when introgression occurs. In order to better understand the effects of introgression on codon usage patterns and vice versa, we examine the patterns of codon usage in Lachancea kluyveri, a yeast which has experienced a large introgression. We quantify the effects of mutation bias and selection for translation efficiency on the codon usage pattern of the endogenous and introgressed exogenous genes using a Bayesian mixture model, ROC SEMPPR, which is built on mechanistic assumptions about protein synthesis and grounded in population genetics.

Results

We find substantial differences in codon usage between the endogenous and exogenous genes, and show that these differences can be largely attributed to differences in mutation bias favoring A/T ending codons in the endogenous genes while favoring C/G ending codons in the exogenous genes. Recognizing the two different signatures of mutation bias and selection improves our ability to predict protein synthesis rate by 42% and allowed us to accurately assess the decaying signal of endogenous codon mutation and preferences. In addition, using our estimates of mutation bias and selection, we identify Eremothecium gossypii as the closest relative to the exogenous genes, providing an alternative hypothesis about the origin of the exogenous genes, estimate that the introgression occurred ∼6×108 generation ago, and estimate its historic and current selection against mismatched codon usage.

Conclusions

Our work illustrates how mechanistic, population genetic models like ROC SEMPPR can separate the effects of mutation and selection on codon usage and provide quantitative estimates from sequence data.
Integrative analysis of circRNAs, miRNAs, and mRNAs profiles to reveal ceRNAs networks in chicken intramuscular and abdominal adipogenesis
Authors: Zhang Meng , Han Yu , Zhai Yanhui , Ma Xiangfei , An Xinglan , Zhang Sheng , Li Ziyi
Published: August 2020

Background

Tissue-specific fat deposition is regulated by a series of complex regulatory mechanisms. Reports indicate that epigenetic regulators, such as circular RNAs (circRNAs), are crucial in diseases progression, animal development, metabolism, and adipogenesis. In this study, to assess the functional roles of circRNAs in adipogenesis and tissue-specific fat deposition, we comprehensively analyzed the Ribo-Zero RNA-Seq and miRNAs data during chicken intramuscular and abdominal adipogenic differentiation.

Results

circRNAs and miRNAs profiles during chicken adipogenic differentiation were found in adipocytes derived from various adipose tissues. It was also discovered that high levels of downregulated miRNAs potentially promote adipogenesis by activating their target genes which are associated with fatty acid metabolism and adipogenic differentiation. Through analysis of the correlation between the expression levels of circRNAs and adipogenic genes, as well as the dynamic expression patterns of circRNAs during adipogenic differentiation, several candidate circRNAs were identified. Moreover, competing endogenous RNA (ceRNAs) networks were constructed during chicken intramuscular and abdominal adipogenesis by combining miRNAs with mRNAs data. Several candidate circRNAs potentially influence adipogenesis by regulating miRNAs via PPAR and fatty acid metabolism-related pathways were identified, such as circLCLAT1, circFNDC3AL, circCLEC19A and circARMH1.

Conclusion

In conclusion, our findings reveal that circRNAs and the circRNA-miRNAs-mRNAs-ceRNAs network may play important roles in chicken adipocytes differentiation and tissue-specific fat deposition.
Combined transcriptome and proteome profiling of the pancreatic β-cell response to palmitate unveils key pathways of β-cell lipotoxicity
Authors: Lytrivi Maria , Ghaddar Kassem , Lopes Miguel , Rosengren Victoria , Piron Anthony , Yi Xiaoyan , Johansson Henrik , Lehtiö Janne , Igoillo-Esteve Mariana , Cunha Daniel A. , Marselli Lorella , Marchetti Piero , Ortsäter Henrik , Eizirik Decio L. , Cnop Miriam
Published: August 2020

Background

Prolonged exposure to elevated free fatty acids induces β-cell failure (lipotoxicity) and contributes to the pathogenesis of type 2 diabetes. In vitro exposure of β-cells to the saturated free fatty acid palmitate is a valuable model of lipotoxicity, reproducing features of β-cell failure observed in type 2 diabetes. In order to map the β-cell response to lipotoxicity, we combined RNA-sequencing of palmitate-treated human islets with iTRAQ proteomics of insulin-secreting INS-1E cells following a time course exposure to palmitate.

Results

Crossing transcriptome and proteome of palmitate-treated β-cells revealed 85 upregulated and 122 downregulated genes at both transcript and protein level. Pathway analysis identified lipid metabolism, oxidative stress, amino-acid metabolism and cell cycle pathways among the most enriched palmitate-modified pathways. Palmitate induced gene expression changes compatible with increased free fatty acid mitochondrial import and β-oxidation, decreased lipogenesis and modified cholesterol transport. Palmitate modified genes regulating endoplasmic reticulum (ER) function, ER-to-Golgi transport and ER stress pathways. Furthermore, palmitate modulated cAMP/protein kinase A (PKA) signaling, inhibiting expression of PKA anchoring proteins and downregulating the GLP-1 receptor. SLC7 family amino-acid transporters were upregulated in response to palmitate but this induction did not contribute to β-cell demise. To unravel critical mediators of lipotoxicity upstream of the palmitate-modified genes, we identified overrepresented transcription factor binding sites and performed network inference analysis. These identified LXR, PPARα, FOXO1 and BACH1 as key transcription factors orchestrating the metabolic and oxidative stress responses to palmitate.

Conclusions

This is the first study to combine transcriptomic and sensitive time course proteomic profiling of palmitate-exposed β-cells. Our results provide comprehensive insight into gene and protein expression changes, corroborating and expanding beyond previous findings. The identification of critical drivers and pathways of the β-cell lipotoxic response points to novel therapeutic targets for type 2 diabetes.
A new mechanism for a familiar mutation – bovine DGAT1 K232A modulates gene expression through multi-junction exon splice enhancement
Authors: Fink Tania , Lopdell Thomas J. , Tiplady Kathryn , Handley Renee , Johnson Thomas J. J. , Spelman Richard J. , Davis Stephen R. , Snell Russell G. , Littlejohn Mathew D.
Published: August 2020

Background

The DGAT1 gene encodes an enzyme responsible for catalysing the terminal reaction in mammary triglyceride synthesis, and underpins a well-known pleiotropic quantitative trait locus (QTL) with a large influence on milk composition phenotypes. Since first described over 15 years ago, a protein-coding variant K232A has been assumed as the causative variant underlying these effects, following in-vitro studies that demonstrated differing levels of triglyceride synthesis between the two protein isoforms.

Results

We used a large RNAseq dataset to re-examine the underlying mechanisms of this large milk production QTL, and hereby report novel expression-based functions of the chr14 g.1802265AA > GC variant that encodes the DGAT1 K232A substitution. Using expression QTL (eQTL) mapping, we demonstrate a highly-significant mammary eQTL for DGAT1, where the K232A mutation appears as one of the top associated variants for this effect. By conducting in vitro expression and splicing experiments in bovine mammary cell culture, we further show modulation of splicing efficiency by this mutation, likely through disruption of an exon splice enhancer as a consequence of the allele encoding the 232A variant.

Conclusions

The relative contributions of the enzymatic and transcription-based mechanisms now attributed to K232A remain unclear; however, these results suggest that transcriptional impacts contribute to the diversity of lactation effects observed at the DGAT1 locus.
Comparative transcriptome analysis provides insight into regulation pathways and temporal and spatial expression characteristics of grapevine (Vitis vinifera) dormant buds in different nodes
Authors: Shangguan Lingfei , Chen Mengxia , Fang Xiang , Xie Zhenqiang , Gong Peijie , Huang Yuxiang , Wang Zicheng , Fang Jinggui
Published: August 2020

Background

Bud dormancy is a strategic mechanism plants developed as an adaptation to unfavorable environments. The grapevine (Vitis vinifera) is one of the most ancient fruit vine species and vines are planted all over the world due to their great economic benefits. To better understand the molecular mechanisms underlying bud dormancy between adjacent months, the transcriptomes of ‘Rosario Bianco’ grape buds of 6 months and three nodes were analyzed using RNA-sequencing technology and pair-wise comparison. From November to April of the following year, pairwise comparisons were conducted between adjacent months.

Results

A total of 11,647 differentially expressed genes (DEGs) were obtained from five comparisons. According to the results of cluster analysis of the DEG profiles and the climatic status of the sampling period, the 6 months were divided into three key processes (November to January, January to March, and March to April). Pair-wise comparisons of DEG profiles of adjacent months and three main dormancy processes showed that the whole grapevine bud dormancy period was mainly regulated by the antioxidant system, secondary metabolism, cell cycle and division, cell wall metabolism, and carbohydrates metabolism. Additionally, several DEGs, such asVvGA2OX6andVvSS3, showed temporally and spatially differential expression patterns, which normalized to a similar trend during or before April.

Conclusion

Considering these results, the molecular mechanisms underlying bud dormancy in the grapevine can be hypothesized, which lays the foundation for further research.
Reverse takotsubo cardiomyopathy in fulminant COVID-19 associated with cytokine release syndrome and resolution following therapeutic plasma exchange: a case-report
Authors: Faqihi Fahad , Alharthy Abdulrahman , Alshaya Rayan , Papanikolaou John , Kutsogiannis Demetrios J. , Brindley Peter G. , Karakitsos Dimitrios
Published: August 2020

Background

Fulminant (life-threatening) COVID-19 can be associated with acute respiratory failure (ARF), multi-system organ failure and cytokine release syndrome (CRS). We present a rare case of fulminant COVID-19 associated with reverse-takotsubo-cardiomyopathy (RTCC) that improved with therapeutic plasma exchange (TPE).

Case presentation

A 40 year old previous healthy male presented in the emergency room with 4 days of dry cough, chest pain, myalgias and fatigue. He progressed to ARF requiring high-flow-nasal-cannula (flow: 60 L/minute, fraction of inspired oxygen: 40%). Real-Time-Polymerase-Chain-Reaction (RT-PCR) assay confirmed COVID-19 and chest X-ray showed interstitial infiltrates. Biochemistry suggested CRS: increased C-reactive protein, lactate dehydrogenase, ferritin and interleukin-6. Renal function was normal but lactate levels were elevated. Electrocardiogram demonstrated non-specific changes and troponin-I levels were slightly elevated. Echocardiography revealed left ventricular (LV) basal and midventricular akinesia with apex sparing (LV ejection fraction: 30%) and depressed cardiac output (2.8 L/min) consistent with a rare variant of stress-related cardiomyopathy: RTCC. His ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen was < 120. He was admitted to the intensive care unit (ICU) for mechanical ventilation and vasopressors, plus antivirals (lopinavir/ritonavir), and prophylactic anticoagulation. Infusion of milrinone failed to improve his cardiogenic shock (day-1). Thus, rescue TPE was performed using the Spectra Optia™ Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA) without protective antibodies. Over 5 days he received daily TPE (each lasting 4 hours). His lactate levels, oxygenation, and LV function normalized and he was weaned off vasopressors. His inflammation markers improved, and he was extubated on day-7. RT-PCR was negative on day-17. He was discharged to home isolation in good condition.

Conclusion

Stress-cardiomyopathy may complicate the course of fulminant COVID-19 with associated CRS. If inotropic therapy fails, TPE without protective antibodies may help rescue the critically ill patient.
Anti-modified citrullinated vimentin antibody: a novel biomarker associated with cardiac systolic dysfunction in patients with rheumatoid arthritis
Authors: Norouzi Somayye , Javinani Ali , Aminorroaya Arya , Masoumi Maryam
Published: August 2020

Background

Studies have demonstrated that seropositive patients with rheumatoid arthritis (RA) are susceptible to cardiovascular diseases (CVDs). In this study, we aimed to determine the association of autoantibodies with the echocardiographic parameters of systolic and diastolic dysfunction in such patients.

Methods

In this cross-sectional study, we evaluated patients with RA who were referred to our clinic from October 2017 to August 2018. After the exclusion of patients with concomitant CVD, all patients underwent transthoracic echocardiography and measurement of plasma autoantibodies. Moreover, possible confounders—including medications, CVD risk factors, Framingham risk score, disease activity score-28, duration of disease, simple disease activity index, and functional status—were assessed.

Results

We studied 135 patients with RA (mean age = 52.3 years; 111 (82.2%) females). We had missing data rates of up to 8.9% for some characteristics. E velocity was inversely correlated with rheumatoid factor (P = 0.009). Furthermore, the plasma levels of anti-citrullinated protein and anti-modified citrullinated vimentin (anti-MCV) antibodies were negatively correlated with left ventricular ejection fraction (LVEF) (P = 0.019 and P<0.001, respectively). After an adjustment for possible confounders, the linear regression model demonstrated that the anti-MCV level and the patient’s age are significant predictors of LVEF. The receiver operating characteristic curve showed that anti-MCV antibody titer≥547.5 (IU/mL) signifies reduced LVEF (<50%) with a sensitivity of 85.7% and specificity of 93% (C-statistic = 0.843).

Conclusions

Our findings showed a significant inverse correlation between anti-MCV antibody titer and LVEF. These results indicate that the application of anti-MCV is promising for the screening and early detection of cardiac systolic dysfunction. Future prospective studies will determine its role.
Time-to-reperfusion in patients with acute myocardial infarction and mortality in prehospital emergency care: meta-analysis
Authors: Fu Xing , Wilson Philip , Chung Wing Sun Faith
Published: August 2020

Background

People living in rural areas usually suffer comparatively disadvantaged emergency health care than those living in urban areas, reasons including long transit time due to geographic factors. As for many time critical diseases, it is necessary to obtain treatment as quickly as possible.

Methods

Screening of eligible studies were conducted based on inclusion an exclusion criteria. A comprehensive search was conducted by using following database: EMBASE, Medline, Cochrane library and Scopus. Quality assessment tool for observational cohort and cross-sectional study is used for assessing the risk of bias. The time group were defined based on the median or mean transit time among patients. In symptom onset-balloon time, we take 120 min transit time as the standard so patients in included studies are divided into two groups:less than 120 min (group A) and more than 120 min (group B). The collected data were used for quantitative analysis, they were inputted into Review Manager Software (v5.3) to produce summary results.

Results

Ten studies representing 71,099 patients were included in the meta-analysis. All studies were retrospective and prospective observational studies and RCTs in which patients experienced ST-elevation myocardial infarction (STEMI) and were treated with percutaneous coronary intervention (PCI). Random effects meta-analysis of the point estimate was 0.69 (CI 0.60, 0.79). Heterogeneity between study results was evaluated via examination of the forest plots and quantified by using I2 statistic. Heterogeneity in two stage time was moderate among studies (I2 = 29%, P = 0.23).

Conclusion

The meta-analysis for included studies report less mortality in less than 120 min symptom onset-balloon and door-balloon time than that in more than 120 min. It is necessary to optimize the prehospital system for rapid decision making and logical destination and mode of transport with prehospital notification of the cath lab so that the hospital is ready to optimize door to balloon time.
Rapid establishment of a COVID-19 perinatal biorepository: early lessons from the first 100 women enrolled
Authors: Shook Lydia L. , Shui Jessica E. , Boatin Adeline A. , Devane Samantha , Croul Natalie , Yonker Lael M. , Matute Juan D. , Lima Rosiane S. , Schwinn Muriel , Cvrk Dana , Gardner Laurel , Azevedo Robin , Stanton Suzanne , Bordt Evan A. , Yockey Laura J. , Fasano Alessio , Li Jonathan Z. , Yu Xu G. , Kaimal Anjali J. , Lerou Paul H. , Edlow Andrea G.
Published: August 2020

Background

Collection of biospecimens is a critical first step to understanding the impact of COVID-19 on pregnant women and newborns - vulnerable populations that are challenging to enroll and at risk of exclusion from research. We describe the establishment of a COVID-19 perinatal biorepository, the unique challenges imposed by the COVID-19 pandemic, and strategies used to overcome them.

Methods

A transdisciplinary approach was developed to maximize the enrollment of pregnant women and their newborns into a COVID-19 prospective cohort and tissue biorepository, established on March 19, 2020 at Massachusetts General Hospital (MGH). The first SARS-CoV-2 positive pregnant woman was enrolled on April 2, and enrollment was expanded to SARS-CoV-2 negative controls on April 20. A unified enrollment strategy with a single consent process for pregnant women and newborns was implemented on May 4. SARS-CoV-2 status was determined by viral detection on RT-PCR of a nasopharyngeal swab. Wide-ranging and pregnancy-specific samples were collected from maternal participants during pregnancy and postpartum. Newborn samples were collected during the initial hospitalization.

Results

Between April 2 and June 9, 100 women and 78 newborns were enrolled in the MGH COVID-19 biorepository. The rate of dyad enrollment and number of samples collected per woman significantly increased after changes to enrollment strategy (from 5 to over 8 dyads/week, P < 0.0001, and from 7 to 9 samples, P < 0.01). The number of samples collected per woman was higher in SARS-CoV-2 negative than positive women (9 vs 7 samples, P = 0.0007). The highest sample yield was for placenta (96%), umbilical cord blood (93%), urine (99%), and maternal blood (91%). The lowest-yield sample types were maternal stool (30%) and breastmilk (22%). Of the 61 delivered women who also enrolled their newborns, fewer women agreed to neonatal blood compared to cord blood (39 vs 58, P < 0.0001).

Conclusions

Establishing a COVID-19 perinatal biorepository required patient advocacy, transdisciplinary collaboration and creative solutions to unique challenges. This biorepository is unique in its comprehensive sample collection and the inclusion of a control population. It serves as an important resource for research into the impact of COVID-19 on pregnant women and newborns and provides lessons for future biorepository efforts.
Discriminative validity of the Core outcome set functional independence in a population of older adults
Authors: Dockx Yvonne J. C. , Molenaar Esther A. L. M. , Barten Di-Janne J. A. , Veenhof Cindy
Published: August 2020

Background

Clinicians are currently challenged to support older adults to maintain a certain level of Functional Independence (FI). FI is defined as “functioning physically safely and independent from another person, within one’s own context”. A Core Outcome Set was developed to measure FI. The purpose of this study was to assess discriminative validity of the Core Outcome Set FI (COSFI) in a population of Dutch older adults (≥ 65 years) with different levels of FI. Secondary objective was to assess to what extent the underlying domains ‘coping’, ‘empowerment’ and ‘health literacy’ contribute to the COSFI in addition to the domain ‘physical capacity’.

Methods

A population of 200 community-dwelling older adults and older adults living in residential care facilities were evaluated by the COSFI. The COSFI contains measurements on the four domains of FI: physical capacity, coping, empowerment and health literacy. In line with the COSMIN Study Design checklist for Patient-reported outcome measurement instruments, predefined hypotheses regarding prediction accuracy and differences between three subgroups of FI were tested. Testing included ordinal logistic regression analysis, with main outcome prediction accuracy of the COSFI on a proxy indicator for FI.

Results

Overall, the prediction accuracy of the COSFI was 68%. For older adults living at home and depending on help in (i)ADL, prediction accuracy was 58%. 60% of the preset hypotheses were confirmed. Only physical capacity measured with Short Physical Performance Battery was significantly associated with group membership. Adding health literacy with coping or empowerment to a model with physical capacity improved the model significantly (p < 0.01).

Conclusions

The current composition of the COSFI, did not yet meet the COSMIN criteria for discriminative validity. However, with some adjustments, the COSFI potentially becomes a valuable instrument for clinical practice. Context-related factors, like the presence of a spouse, also may be a determining factor in this population. It is recommended to include context-related factors in further research on determining FI in subgroups of older people.
Determinants of overburdening among informal carers: a systematic review
Authors: Lindt Nienke , van Berkel Jantien , Mulder Bob C.
Published: August 2020

Background

The world’s population is ageing, resulting in rising care demands and healthcare costs, which in turn lead to a shift from formal to informal care. However, not only is the number of potential informal carers fast decreasing, but also informal caregivers are experiencing a higher caregiver burden. This literature review aims to synthesize the literature on the common determinants of caregiver burden in Western countries, to help ensure future continuation of informal care in the home context, and to improve or sustain the quality of life of caregivers and patients alike.

Method

A systematic review of peer-reviewed articles included in PubMed, Scopus, and/or PsychInfo was conducted.

Results

Seventeen articles were included. The most important predictors were the duration of caregiving and the patient’s dependency level, in terms of both physical and mental dependency stemming from decreased cognitive capacity or behavioural problems. Some specific illnesses and role conflicts or captivity also increased caregiver burden, whereas social support lowered it. Being a female caregiver or having an adult–child relationship led to a higher burden.

Conclusions

The most important predictors of caregiver burden are the duration of caregiving and the patient’s dependency level. In addition, the patient’s behavioural problems and cognitive capacity determine dependency level, and thus care burden. Interventions to relieve burden need to be adapted to the illness trajectory of specific diseases and corresponding needs for social support for both the recipient and the caregiver. Changing role expectations, leading to men being more involved, could reduce the disproportionately high burden for women.