bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Accrual Accounting in the Public Sector: Evidence from Indonesia
Authors: Prabowo Tri , Martin-Sardesai Ann , Guthrie AM James
Published: March 2022

This article is inspired by complexities in the adoption and implementation of accrual accounting (AA), which has been explored in the public sector accounting literature, and seeks to examine its implementation in the Indonesian public sector. Using case-based research, the article is underpinned by Gramsci’s theory of hegemony to construe the process of the implementation of AA. The article adopts a qualitative research method including interviews with senior regulators of public sector reforms in Indonesia and an extensive review of documents, literature and reports to construct a historical analysis. The data reveal that international donor organizations such as the International Monetary Fund (IMF) and the World Bank influenced the implementation of AA in Indonesia. In line with Gramsci’s theory of hegemony, the international organizations directed the senior Indonesian regulators to perceive that AA was indispensable. Therefore, AA was implemented because of hegemonic influences and attempts to seek legitimacy. The empirical evidence provided identifies that major public sector reforms are complex. This is even more evident in new emerging market countries like Indonesia, where the intentions underpinning reforms may be challenging to realize and are driven by factors outside the control of those tasked with its adoption and implementation. The article is novel in identifying and interpreting the influence of the IMF, the World Bank, and other international organizations on the implementation of AA in Indonesia through the lens of Gramsci’s theory of hegemony.
Exosomes in multiple myeloma: from bench to bedside
Authors: Menu Eline , Vanderkerken Karin
Published: March 2022

Multiple myeloma (MM) remains an incurable plasma cell malignancy that develops in the bone marrow (BM). This BM is partially responsible for protecting the MM cells against current standard-of-care therapies and for accommodating MM-related symptoms such as bone resorption and immune suppression. Increasing evidence has implicated extracellular vesicles (EV), including exosomes in the different processes within the BM. Exosomes are <150-nm-sized vesicles secreted by different cell types including MM cells. These vesicles contain protein and RNA cargo that they deliver to the recipient cell. In this way, they have been implicated in MM-related processes including osteolysis, angiogenesis, immune suppression, and drug resistance. Targeting exosome secretion could therefore potentially block these different processes. In this review, we will summarize the current findings of exosome-related processes in the BM and describe not only the current treatment strategies to counter them but also how exosomes can be harnessed to deliver toxic payloads. Finally, an overview of the different clinical studies that investigate EV cargo as potential MM biomarkers in liquid biopsies will be discussed.
HLA-DQ heterodimers in hematopoietic cell transplantation
Authors: Petersdorf Effie W. , Bengtsson Mats , Horowitz Mary , McKallor Caroline , Spellman Stephen R. , Spierings Eric , Gooley Ted A. , Stevenson Phil ,   on behalf of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation
Published: March 2022

HLA-DQ heterodimers increase the susceptibility to autoimmune diseases, but their role in hematopoietic cell transplantation is unknown. We tested the hypothesis that outcome after HLA-matched and HLA-DQ–mismatched hematopoietic cell transplantation is influenced by HLA-DQ heterodimers. Heterodimers were defined in 5164 HLA-matched and 520 HLA-DQ–mismatched patients and their transplant donors according to well-established crystallographic criteria. Group 1 (G1) heterodimers are any DQA1*02/03/04/05/06α paired with any DQB1*02/03/04β. Group 2 (G2) heterodimers are DQA1*01α paired with any DQB1*05/06β. Multivariable models identified significantly higher relapse risk in G1G2 and G2G2 compared with G1G1 HLA-matched patients with malignant disease; risk increased with an increasing number of G2 molecules. In HLA-DQ–mismatched transplantation for malignant diseases, matching or mismatching for G2 increased relapse risk. G2 lowered disease-free survival after both HLA-matched and HLA-DQ–mismatched transplantation. A paradigm based on HLA-DQ heterodimers provides a functional definition of the hematopoietic cell transplantation barrier and a means to lower risks for future patients.
GRK2 regulates group 2 innate lymphoid cell mobilization in sepsis
Authors: Lai Dengming , Chen Weiwei , Zhang Kai , Scott Melanie J. , Li Yuehua , Billiar Timothy R. , Wilson Mark A. , Fan Jie
Published: March 2022

Background

Sepsis induces group 2 innate lymphoid cell (ILC2) expansion in the lung. However, the origin of these lung-recruited ILC2 and the mechanism of ILC2 expansion are unclear. This study aims to determine the origin of lung-recruited ILC2 and its underlying mechanism in sepsis.

Methods

Sepsis was induced by cecal ligation and puncture (CLP) model in wild-type, IL-33-deficient and ST2-deficient mice. The frequency, cell number and C-X-C chemokine receptor 4 (CXCR4) expression of ILC2 in bone marrow (BM), blood and lung were measured by flow cytometry. In the in vitro studies, purified ILC2 progenitor (ILC2p) were challenged with IL-33 or G protein-coupled receptor kinase 2 (GRK2) inhibitor, the CXCR4 expression and GRK2 activity were detected by confocal microscopy or flow cytometry.

Results

We show that IL-33 acts through its receptor, ST2, on BM ILC2p to induce GRK2 expression and subsequent downregulation of cell surface expression of CXCR4, which results in decreasing retention of ILC2p in the BM and promoting expansion of ILC2 in the lung. Importantly, we demonstrate that reduced IL-33 level in aging mice contributes to impaired ILC2 mobilization from BM and accumulation in the lung following sepsis.

Conclusion

This study identifies a novel pathway in regulating ILC2p mobilization and expansion during sepsis and indicates BM as the main source of ILC2 in the lung following sepsis.
Sero-survey on long-term care facility residents reveals increased risk of sub-optimal antibody response to BNT162b2: implications for breakthrough prevention
Authors: Caimi Barbara , Franzetti Marco , Velleca Rossella , Lai Alessia , Gatti Antonella , Rossi Pier Luigi , D’Orso Marco , Pregliasco Fabrizio , Balotta Claudia , Calicchio Giuseppe
Published: March 2022

Background

The impact of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on residents of long-term care facilities (LTCFs) has been dramatic on global scale as older age and comorbidities pose an increased risk of severe disease and death.

Methods

Aim of this study was to evaluate SARS-CoV-2 Spike-specific IgG (S-IgG) antibody titers in 478 residents and 649 health care workers of a large Italian long-term care facility two months after complete vaccination with BNT162b2. Associations among resident-related factors and predictors of humoral response were investigated.

Results

By stratifying levels of humoral responses, we found that 62.1%, 21.6%, 12.1% and 4.2% of residents had high (>1,000 BAU/ml), medium (101-1,000), low (1-100) and null (<1 BAU/mL) S-IgG titers, respectively. Residents with documented previous COVID-19 and those with SARS-CoV-2 nucleocapsid-specific IgG (N-IgG) positive serology showed higher level of serological response, while significant associations were observed for cancer with suboptimal response (p = 0.005) and the administration of corticosteroid for suboptimal response (p = 0.028) and a null one (p = 0.039). According to multivariate logistic regression, predictors of an increased risk of null response were advanced age (Odd ratio, OR: 2.630; Confidence interval, CI: 1.13-6.14; p = 0.025), corticosteroid therapy (OR: 4.964; CI: 1.06-23.52; p = 0.042) and diabetes mellitus (OR:3.415; CI:1.08-10.8; p = 0.037). In contrast, previous diagnosis of COVID-19 was strongly associated with a reduced risk of null response to vaccination (OR:0.126; CI:0.02-0.23; p < 0.001).

Conclusions

SARS-CoV-2 specific antibodies in elderly individuals should be consider when deciding the need of a third dose of vaccine for prevention of reinfections in LTCFs despite the maintenance of barrier measures.
An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy
Authors: Yang Mingli , Davis Thomas B. , Pflieger Lance , Nebozhyn Michael V. , Loboda Andrey , Wang Heiman , Schell Michael J. , Thota Ramya , Pledger W. Jack , Yeatman Timothy J.
Published: March 2022

Background

Over half of colorectal cancers (CRCs) are hard-wired to RAS/RAF/MEK/ERK pathway oncogenic signaling. However, the promise of targeted therapeutic inhibitors, has been tempered by disappointing clinical activity, likely due to complex resistance mechanisms that are not well understood. This study aims to investigate MEK inhibitor-associated resistance signaling and identify subpopulation(s) of CRC patients who may be sensitive to biomarker-driven drug combination(s).

Methods

We classified 2250 primary and metastatic human CRC tumors by consensus molecular subtypes (CMS). For each tumor, we generated multiple gene expression signature scores measuring MEK pathway activation, MEKi “bypass” resistance, SRC activation, dasatinib sensitivity, EMT, PC1, Hu-Lgr5-ISC, Hu-EphB2-ISC, Hu-Late TA, Hu-Proliferation, and WNT activity. We carried out correlation, survival and other bioinformatic analyses. Validation analyses were performed in two independent publicly available CRC tumor datasets (n = 585 and n = 677) and a CRC cell line dataset (n = 154).

Results

Here we report a central role of SRC in mediating “bypass”-resistance to MEK inhibition (MEKi), primarily in cancer stem cells (CSCs). Our integrated and comprehensive gene expression signature analyses in 2250 CRC tumors reveal that MEKi-resistance is strikingly-correlated with SRC activation (Spearman P < 10–320), which is similarly associated with EMT (epithelial to mesenchymal transition), regional metastasis and disease recurrence with poor prognosis. Deeper analysis shows that both MEKi-resistance and SRC activation are preferentially associated with a mesenchymal CSC phenotype. This association is validated in additional independent CRC tumor and cell lines datasets. The CMS classification analysis demonstrates the strikingly-distinct associations of CMS1-4 subtypes with the MEKi-resistance and SRC activation. Importantly, MEKi + SRCi sensitivities are predicted to occur predominantly in the KRAS mutant, mesenchymal CSC-like CMS4 CRCs.

Conclusions

Large human tumor gene expression datasets representing CRC heterogeneity can provide deep biological insights heretofore not possible with cell line models, suggesting novel repurposed drug combinations. We identified SRC as a common targetable node–-an Achilles’ heel–-in MEKi-targeted therapy-associated resistance in mesenchymal stem-like CRCs, which may help development of a biomarker-driven drug combination (MEKi + SRCi) to treat problematic subpopulations of CRC.
The impact of nursing staff education on diabetes inpatient glucose management: a pilot cluster randomised controlled trial
Authors: Piya Milan K. , Fletcher Therese , Myint Kyaw P. , Zarora Reetu , Yu Dahai , Simmons David
Published: March 2022

Background

An increasing number of patients in hospital have diabetes, with most of them cared for by non-specialist staff. The effect of diabetes education for staff on patient outcomes, as well as the most effective method of staff education is unclear. Therefore, the aim of this study was to compare diabetes outcomes in medical wards where nursing staff were offered one face-to-face (F2F) session followed by access to online education (online), F2F education only, or standard care (control).

Methods

We conducted a pilot cluster randomised controlled trial involving 16-weeks baseline/rollout followed by a 28-week post-intervention period across three medical wards (clusters) in a Sydney Teaching Hospital. The online ward provided an online competency-based diabetes education program and 1-h F2F teaching from a diabetes nurse educator (DNE), the F2F ward provided four separate 1-h teaching sessions by a DNE, with no additional sessions in the control ward. The primary outcome was length of stay (LOS); secondary outcomes included good diabetes days (GDD), hypoglycaemia and medication errors. Poisson and binary logistic regression were used to compare clusters.

Results

Staff attendance/completion of ≥ 2 topics was greater with online than F2F education [39/48 (81%) vs 10/33 (30%);p < 0.001]. Among the 827/881 patients, there was no difference in LOS change between online [Median(IQR) 5(2–8) to 4(2–7) days], F2F [7(4–14) to 5(3–13) days] or control wards [5(3–9) to 5(3–7) days]. GDD improved only in the online ward 4.7(2.7–7.0) to 6.0(2.3–7.0) days;p = 0.038. Total patients with hypoglycaemia and appropriately treated hypoglycaemia increased in the online ward.

Conclusions

The inclusion of online education increased diabetes training uptake among nursing staff. GDD and appropriate hypoglycaemia management increased in the online education wards.

Trial registration

Prospectively registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) on 24/05/2017:ACTRN12617000762358.
The level of knowledge about palliative care in Iranian patients with cancer
Authors: Atena Dadgari , Imane Bagheri , Maryam Rassouli , Naiire Salmani , Fatemeh Tahani
Published: March 2022

Background

Patient awareness plays an important role in integrating palliative care into the patient care process. Lack of awareness can create a negative attitude towards palliative care and affect patients' decisions during the treatment process. The present study was conducted to determine the level of knowledge about palliative care in Iranian patients with cancer.

Methods

The descriptive study was conducted with a convenience sample of 103 cancer patients admitted to an oncology center in Yazd, Iran, A three-part questionnaire including demographic information, sources of palliative care information and the Palliative Care Knowledge Scale (PaCKS) was used to collect data. All statistical analyses were performed using software SPSS 21.

Results

The mean age of patients was 36.2 ± 13.5 years. Of the total, 38.8% of patients received information about palliative care through the media and 36.9% from the treatment team. On a scale of 0 to 13, the mean PaCKS score was 6.7 ± 3.7. A ‘good’ level of knowledge was reported by 29.1% of participants; however 84.5% stated that they should leave other doctors at the time of receiving palliative care, 71.8% considered palliative care for patients in the last six months of life, 84.5% considered palliative care for patients with cancer, and 70.9% stated that palliative care encourages people to discontinue treatments aimed at treating their disease.

Conclusion

Our study found most cancer patients have a moderate to weak level of knowledge and considerable misinformation about palliative care, which highlights the importance of providing palliative care education. The development of training programs in this area could play an effective role in improving patients' knowledge of palliative care.
Icariin regulates stem cell migration for endogenous repair of intervertebral disc degeneration by increasing the expression of chemotactic cytokines
Authors: Zhang Zhaofei , Qin Fengwei , Feng Yonghui , Zhang Sineng , Xie Chunliang , Huang He , Sang Chaohui , Hu Shaoyu , Jiao Feng , Jiang Jie , Qin Yi
Published: March 2022

Background

Icariin (ICA) can promote the migration and bone formation of bone marrow mesenchymal stem cells. This study explored a potential role of ICA in recruiting stem cell niches (SCNs) within the intervertebral disc region (ISN)-derived stem cells (ISN-SCs) to treat intervertebral disc degeneration (IVDD).

Materials and methods

EdU staining, transwell, and wound healing tests were used to analyze the function of ICA on ISN-SCs proliferation and migration ability. Simultaneously, the IVDD rat model was constructed by the acupuncture and divided into Sham, Sham + ICA, IVDD, and IVDD + ICA groups. H&E and PAS staining were performed to detect the pathological changes of IVDD tissues. Immunofluorescence was performed to discover relevant marker expression on the surface of stem cells in the IVDD tissues. Western blot and qPCR were executed to find the protein and mRNA expression of related cytokines in the IVDD tissues.

Results

ISN-SCs treated with 1 μM ICA obtained the better ability of proliferation and migration. H&E staining showed that the annulus fibrosus in the IVDD group was obviously hyperplasia with cavities and fissures; the nucleus pulposus was reduced. PAS staining showed that the content of polysaccharides was significantly reduced in the nucleus pulposus of IVDD group. However, the ICA treatment alleviated the pathological trends of the IVDD tissues. Simultaneously, ICA treatment increased significantly the expression of stem cells and IGF-1, TGF-β, SDF-1, CCL-5, Collagen I, Collagen II, Aggrecan, and SOX9 in IVDD tissues.

Conclusions

ICA treatment promoted the migration of stem cell in IVDD by increasing the expression of chemotactic cytokines, including IGF-1, TGF-β, SDF-1, and CCL-5.
Developing a curriculum to improve cardiology fellows’ training in pregnancy and cardiovascular disease
Authors: Maxner Benjamin , Hansra Barinder , Sibai Diana , Moinul Sheikh , Panella Leslie , Jeha Jeannine , Fiore Catherine , Dumont Tina , Lauring Julianne , Aurigemma Gerard , Harrington Colleen M. , Kovell Lara C.
Published: March 2022

Background

Exposure to pregnant women with cardiovascular disease (CVD) during cardiology fellowship training is limited and without a standard curriculum in the United States. The authors sought to evaluate a dedicated curriculum to teach management of CVD in pregnancy to improve general cardiology fellowship training.

Methods

The authors developed a dedicated CVD in pregnancy curriculum for the general cardiology fellows at a large academic medical center in the fall of 2019. Fellows’ knowledge was assessed via a board-style examination and exposure and attitudes related to the care of pregnant women with CVD were evaluated with a needs assessment questionnaire before and after the curriculum.

Results

Of the 17 fellows who participated in the curriculum, 12 completed the needs assessment pre-curriculum and 9 post-curriculum. The mean (SD) number of pregnant women with CVD cared for by each fellow in the inpatient and outpatient settings were 0.75 (1.29) and 0.56 (0.73), respectively. After the curriculum, all fellows reported awareness of available resources to treat pregnant women with CVD, while a majority disagreed that they receive regular exposure to pregnant patients with CVD in their training. The authors observed significant increases in fellows’ confidence in their knowledge of normal cardiovascular physiology of pregnancy, physical exam skills, and ability to care for pregnant women with valvular disease and arrhythmias from pre to post-curriculum. A total of 15 fellows completed the board-style exam pre-curriculum and 15 post-curriculum. Fellows’ performance on the board-style examination improved slightly from before to after the curriculum (64.0 to 75.3% correct, p = 0.02).

Conclusions

A dedicated curriculum improved cardiology fellows’ knowledge to recognize and treat CVD in pregnancy and improved confidence in caring for this unique patient population.
Correction to: Economic evaluation of advanced practice physiotherapy models of care: a systematic review with meta-analyses
Authors: Lafrance Simon , Demont Anthony , Thavorn Kednapa , Fernandes Julio , Santaguida Carlo , Desmeules François
Published: March 2022

An amendment to this paper has been published and can be accessed via the original article.
Tumors carrying BRAF-mutations over-express NAMPT that is genetically amplified and possesses oncogenic properties
Authors: Audrito Valentina , Moiso Enrico , Ugolini Filippo , Messana Vincenzo Gianluca , Brandimarte Lorenzo , Manfredonia Ilaria , Bianchi Simonetta , De Logu Francesco , Nassini Romina , Szumera-Ciećkiewicz Anna , Taverna Daniela , Massi Daniela , Deaglio Silvia
Published: March 2022

Background

Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis, is up-regulated in several cancers, including metastatic melanoma (MM). The BRAF oncogene is mutated in different cancer types, among which MM and thyroid carcinoma (THCA) are prominent. Drugs targeting mutant BRAF are effective, especially in MM patients, even though resistance rapidly develops. Previous data have linked NAMPT over-expression to the acquisition of BRAF resistance, paving the way for therapeutic strategies targeting the two pathways.

Methods

Exploiting the TCGA database and a collection of MM and THCA tissue microarrays we studied the association between BRAF mutations and NAMPT expression. BRAF wild-type (wt) cell lines were genetically engineered to over-express the BRAF V600E construct to demonstrate a direct relationship between over-activation of the BRAF pathway and NAMPT expression. Responses of different cell line models to NAMPT (i)nhibitors were studied using dose–response proliferation assays. Analysis of NAMPT copy number variation was performed in the TCGA dataset. Lastly, growth and colony forming assays were used to study the tumorigenic functions of NAMPT itself.

Results

The first finding of this work is that tumor samples carrying BRAF-mutations over-express NAMPT, as demonstrated by analyzing the TCGA dataset, and MM and THC tissue microarrays. Importantly, BRAF wt MM and THCA cell lines modified to over-express the BRAF V600E construct up-regulated NAMPT, confirming a transcriptional regulation of NAMPT following BRAF oncogenic signaling activation. Treatment of BRAF-mutated cell lines with two different NAMPTi was followed by significant reduction of tumor growth, indicating NAMPT addiction in these cells. Lastly, we found that several tumors over-expressing the enzyme, display NAMPT gene amplification. Over-expression of NAMPT in BRAF wt MM cell line and in fibroblasts resulted in increased growth capacity, arguing in favor of oncogenic properties of NAMPT.

Conclusions

Overall, the association between BRAF mutations and NAMPT expression identifies a subset of tumors more sensitive to NAMPT inhibition opening the way for novel combination therapies including NAMPTi with BRAFi/MEKi, to postpone and/or overcome drug resistance. Lastly, the over-expression of NAMPT in several tumors could be a key and broad event in tumorigenesis, substantiated by the finding of NAMPT gene amplification.
Seasonal movements in caribou ecotypes of Western Canada
Authors: Theoret Jessica , Cavedon Maria , Hegel Troy , Hervieux Dave , Schwantje Helen , Steenweg Robin , Watters Megan , Musiani Marco
Published: March 2022

Background

Several migratory ungulates, including caribou, are dramatically declining. Caribou of the Barren-ground ecotype, which forms its own subspecies, are known to be mainly migratory. By contrast, within the Woodland subspecies, animals of the Boreal ecotype are known to be mainly sedentary, while those within the Northern and Central Mountain ecotypes to be partially migratory, with only some individuals migrating. Promotion of conservation actions (e.g., habitat protection) that are specific to both residents and migrants, as well as to the areas they frequent seasonally (which may be separate for migrants), requires distinguishing migration from other movement behaviours, which might be a challenge.

Methods

We aimed at assessing seasonal movement behaviours, including migratory, resident, dispersing, and nomadic, for caribou belonging to the Barren-ground and Woodland subspecies and ecotypes. We examined seasonal displacement, both planar and altitudinal, and seasonal ranges overlap for 366 individuals that were GPS-collared in Northern and Western Canada. Lastly, we assessed the ability of caribou individuals to switch between migratory and non-migratory movement behaviours between years.

Results

We detected migratory behaviour within each of the studied subspecies and ecotypes. However, seasonal ranges overlap (an index of sedentary behaviour) varied, with proportions of clear migrants (0 overlap) of 40.94% for Barren-ground caribou and 23.34% for Woodland caribou, and of 32.95%, 54.87%, and 8.86% for its Northern Mountain, Central Mountain, and Boreal ecotype, respectively. Plastic switches of individuals were also detected between migratory, resident, dispersing, and nomadic seasonal movements performed across years.

Conclusions

Our unexpected findings of marked seasonal movement plasticity in caribou indicate that this phenomenon should be better studied to understand the resilience of this endangered species to habitat and climatic changes. Our results that a substantial proportion of individuals engaged in seasonal migration in all studied ecotypes indicate that caribou conservation plans should account for critical habitat in both summer and winter ranges. Accordingly, conservation strategies are being devised for the Woodland subspecies and its ecotypes, which were found to be at least partially migratory in this study. Our findings that migration is detectable with both planar and altitudinal analyses of seasonal displacement provide a tool to better define seasonal ranges, also in mountainous and hilly environments, and protect habitat there.
Debugging behaviors of early childhood teacher candidates with or without scaffolding
Authors: Kim ChanMin , Vasconcelos Lucas , Belland Brian R. , Umutlu Duygu , Gleasman Cory
Published: March 2022

It is critical to teach all learners to program and think through programming. But to do so requires that early childhood teacher candidates learn to teach computer science. This in turn requires novel pedagogy that can both help such teachers learn the needed skills, but also provide a model for their future teaching. In this study, we examined how early childhood teacher candidates learned to program and debug block-based code with and without scaffolding. We aimed to see how approaches to debugging vary between early childhood teacher candidates who were provided debugging scaffolds during block-based programming and those who were not. This qualitative case study focused on 13 undergraduates majoring in early childhood education. Data sources included video recording during debugging, semi-structured interviews, and (in the case of those who used scaffolding) scaffold responses. Research team members coded data independently and then came to consensus. With hypothesis-driven scaffolds, participants persisted longer. Use of scaffolds enabled the instructor to allow struggle without immediate help for participants. Collaborative reasoning was observed among the scaffolded participants whereas the participants without scaffolds often debugged alone. Regardless of scaffolds, participants often engaged in embodied debugging and also used trial and error. This study provides evidence that one can find success debugging even when engaging in trial and error. This implies that attempting to prevent trial and error may be counterproductive in some contexts. Rather, computer science educators may be advised to promote productive struggle.
Improved voltage tracking of autonomous microgrid technology using a combined resonant controller with lead-lag compensator adopting negative imaginary theorem
Authors: Haque Md. Yah-Ya Ul , Islam Md. Rashidul , Ahmed Tanvir , Sheikh Md. Rafiqul Islam
Published: March 2022

Growing application of distributed generation units at remote places has led to the evolution of microgrid (MG) technology. When an MG system functions independently, i.e., in autonomous mode, unpredictable loads and uncertainties emerge throughout the system. To obtain stable and flexible operation of an autonomous MG, a rigid control mechanism is needed. In this paper, a robust high-performance controller is introduced to improve the performance of voltage tracking of an MG system and to eliminate stability problems. A combination of a resonant controller and a lead-lag compensator in a positive position feedback path is designed, one which obeys the negative imaginary (NI) theorem, for both single-phase and three-phase autonomous MG systems. The controller has excellent tracking performance. This is investigated through considering various uncertainties with different load dynamics. The feasibility and effectiveness of the controller are also determined with a comparative analysis with some well-known controllers, such as linear quadratic regulator, model predictive and NI approached resonant controllers. This confirms the superiority of the designed controller.
Evaluation of Turkey’s contribution to SCI-E indexed publications on COVID-19
Authors: Yılmaz Fulya , Bas Koray
Published: March 2022

Background

In December of 2019, a new disease which is caused by SARS-CoV-2, as an epidemic disease out of Wuhan, China, began to circulate. On March 11, 2020, the Republic of Turkey Ministry of Health had announced the first case from Turkey. The aim of this study is to analyze the scientific publications in the field of COVID-19 included in Science Citation Index Expanded (SCIE) from Turkey and to establish a theoretical background for future studies in the health literature with obtained valuable information about the publications. We searched all papers published in the field of COVID-19 by using the terms of “COVID-19,” “2019-n-CoV,” “SARS-CoV-2,” “Coronavirus disease 19,” and “2019 novel coronavirus” as scientific nomenclatures of COVID-19 in the topic search section of the software.

Results

Overall, 47,368 papers, indexed by SCI-E, were found related to COVID-19 between January 1, 2020, and December 13, 2020. Of these, 931 were from Turkey. In terms of specialities, the most contribution was from the Medicine General Internal followed by Dermatology. Most of the publications were article. English was the most preferred language in papers. Dermatological Theraphy published the most paper.

Conclusions

Applying this kind of analysis on an intermittent basis gives a general perspective for contribution of a countries to scientific publications and useful for the further studies.
Sucrose- and formaldehyde-modified native starches as possible pharmaceutical excipients in tableting
Authors: Okeke Ifeanyi Justin , Oli Angus Nnamdi , Ojiako Chioma Miracle , Ibezim Emmanuel Chinedum , Okoyeh Jude N.
Published: March 2022

Background

Starches have been shown to be important across various disciplines such as the pharmaceutical industries, food industries and also paper industries. Starch is basically a mixture of polymers consisting of α-d-glucose as the monomeric unit. The goal of this study is to modify the native starches which were obtained from Zea mays, Triticumestivum and Oriza sativa through cross-linking (using sucrose and formaldehyde at different concentrations) and also to assess the utilizability of the modified starches as potential excipients [binder] for tableting of paracetamol.

Results

Maize and rice starches cross-linked with 2.5% sucrose gave the least percentage moisture content. The batches cross-linked with 40% formaldehyde showed the highest moisture content. The densities (bulk and tapped) of maize wheat and rice starches showed a reduction with the increasing concentration of the cross-linking agent for sucrose, which is the reverse case for formaldehyde. The different concentrations of sucrose and formaldehyde cross-maize, wheat and rice starches had pH values between 4.50 and 5.52. The onset and end set of the glass transition temperatures were varied for all the starches modified with formaldehyde. The melting peak temperatures obtained indicated that the formaldehyde-modified rice starch had significantly lower melting temperature than those of wheat and maize starches.

Conclusions

This study reveals that various concentrations of sucrose and formaldehyde had some influence on the properties of the native starches and resulted in the production of new starch motifs with improved or new functionalities suitable for use as drug excipients in tableting.
Evaluation of the flexion gap with a distal femoral trial component in posterior-stabilized total knee arthroplasty
Authors: Kamei Goki , Ishibashi Shigeki , Yoshioka Koki , Sakurai Satoru , Inoue Hiroyuki , Mochizuki Yu , Ishikawa Masakazu , Adachi Nobuo
Published: March 2022

Purpose

A distal femoral trial component was manufactured, and flexion gap size and inclination were evaluated with or without the distal femoral trial component in total knee arthroplasty (TKA). This study aimed to evaluate the effect of the distal femoral trial component on flexion gap size and joint inclination in posterior-stabilized (PS)-TKA.

Materials and methods

A total of 84 patients with medial osteoarthritis who underwent mobile-bearing PS-TKA using modified gap techniques were included in this retrospective study. The flexion gap size and inclination before and after setting the distal femoral trial component were evaluated and compared with the final gap size and inclination.

Results

The joint gap size and inclination were significantly lower in those with than in those without the distal femoral trial component (P = 0.005, P < 0.001). The final gap size and inclination were similar to the gap size and inclination with the distal trial component (P = 0.468, P = 0.158).

Conclusions

The joint gap size and medial tension in PS-TKA were significantly reduced after setting the distal femoral trial component. The flexion gap measured using the distal femoral trial component was similar to that when the final trial component was set. To more accurately perform the gap technique TKA, the flexion gap should be measured using the distal femoral trial component.
An investigation of 6-Shogaol effects on MCF7 cell lines through a systems biology approach
Authors: Amjad Elham , Sokouti Babak , Asnaashari Solmaz
Published: March 2022

Introduction

In the literature, to investigate hormonal mechanisms of cell growth of patients with breast cancer (BC), as the second most common cause of death in the world, the researchers frequently used MCF-7 cell lines. And, identifying the functional mechanisms of therapeutics agents as new cancer inhibitors is still unclear.

Methods

We used the NCBI-GEO dataset (GSE36973) to study the effects of 6-Shogaol on MCF-7 cell lines commonly used for more than 45 years in several studies. The pre-processing and post-processing stages were carried out for the target samples to identify the most significant differentially expressed genes between two MCF-7 with and without treated by 6-Shogaol. Furthermore, various analyses, including biological process and molecular function from the DAVID website, the protein–protein interaction (PPI) network, gene-miRNA, gene-transcription factor, gene-drugs, and gene-diseases networks, statistically significant assoications with clinical features and survival rates were conducted.

Results

The initial outcomes revealed thirty significant DEGs. Among which the approach resulted in eleven upregulated and nineteen downregulated genes. Over-expression of TRADD and CREB3L1 and low-expression of KIF4A and PALMD were substantial in the TNF signaling pathway. Moreover, hsa-mir-16-5p and hsa-mir-124-3p were inhibitors of breast cancer growth.

Conclusion

The fact that some of genes are associated with survival rates as well as various clinical features including disease stages, it can be deduced that the 6-Shogaol treatment on MCF7 cell lines at the genome level shows inhibition functionalities of the herbal medicine in breast cancer at early stages and pave the way in developing new therapeutic agents.
Radiological approach to non-compressive myelopathies
Authors: Swarup M. Sarthak , Chandola Stuti , Batra Radhika , Prakash Anjali , Garg Anju
Published: March 2022

Background

Myelopathy, a pathological condition related to the spinal cord can broadly be categorized into compressive and non-compressive aetiologies. Magnetic resonance imaging remains the modality of choice when suspecting non-compressive myelopathy as it helps to localize the affected segment and exclude compression as the cause of myelopathy. This review deals with the imaging approach for non-compressive myelopathies.

Main body

Demyelinating disorders are the most common cause of non-compressive myelopathy and often show confounding features. Other causes include inflammatory, ischemic, metabolic, and neoplastic disorders. Non-compressive myelopathy can broadly be classified into acute and non-acute onset which can further be categorized according to the distribution of the signal abnormalities, including length of cord involvement, specific tract involvement, enhancement pattern, and the region of the spinal cord that is affected.

Conclusions

Imaging plays a critical role in the evaluation of clinically suspected cases of myelopathy and MR imaging (with or without contrast) remains the preferred modality. Compressive causes must be excluded as a cause of myelopathy. Despite a multitude of causes, the most common imaging appearance is a nonspecific T2 hyperintense signal in the spinal cord, and thus, a pragmatic diagnostic approach along with appropriate clinical and biochemical correlation is essential for arriving at an accurate diagnosis.
A Case of Methimazole-Induced Acute Pancreatitis With an HLA Allele Causing Antithyroid Drug-Induced Agranulocytosis
Authors: Yoshimura Yusuke , Tatsushima Keita , Goshima Yukiko , Hoshino Yoshitomo , Nakashima Saki , Inaba Tatsuro , Ikeda Sara , Hattori Daisuke , Koyama Rikako , Imamura Tsunao , Takeshita Akira , Takeuchi Yasuhiro
Published: March 2022

Among the side effects of methimazole (MMI) for the treatment of Graves’ disease, MMI-induced acute pancreatitis (MIP) is a rare adverse reaction, with only 7 cases being reported to date. However, 2 large-scale population-based studies recently revealed that the risk of MIP was significantly higher, ranging from 0.02% to 0.56%. Although MIP is common in middle-aged and elderly Asian women, its pathogenesis remains largely unknown. We herein present a case of a 72-year-old Japanese woman with Graves’ disease who developed MIP 12 days after the initiation of MMI. The MMI was discontinued, the patient was switched to propylthiouracil (PTU) therapy, and pancreatitis gradually resolved. Serological human leukocyte antigen (HLA) typing identified HLA-DRB1*08:03:02. This HLA allele was previously detected in a patient with MIP and is one of the major risk factors for agranulocytosis induced by antithyroid drugs, including PTU as well as MMI. In cases of MIP, PTU is being considered as an alternative to MMI; however, its safety needs further investigation and patients require close monitoring after the switch to PTU. Further studies are warranted, particularly on the relationship between MIP and the presence of HLA alleles causing antithyroid drug-induced agranulocytosis.
Diagnostic accuracy of a commercially available deep-learning algorithm in supine chest radiographs following trauma
Authors: Gipson Jacob , Tang Victor , Seah Jarrel , Kavnoudias Helen , Zia Adil , Lee Robin , Mitra Biswadev , Clements Warren
Published: March 2022

Objectives:

Trauma chest radiographs may contain subtle and time-critical pathology. Artificial intelligence (AI) may aid in accurate reporting, timely identification and worklist prioritisation. However, few AI programs have been externally validated. This study aimed to evaluate the performance of a commercially available deep convolutional neural network – Annalise CXR V1.2 (Annalise.ai) – for detection of traumatic injuries on supine chest radiographs.

Methods:

Chest radiographs with a CT performed within 24 h in the setting of trauma were retrospectively identified at a level one adult trauma centre between January 2009 and June 2019. Annalise.ai assessment of the chest radiograph was compared to the radiologist report of the chest radiograph. Contemporaneous CT report was taken as the ground truth. Agreement with CT was measured using Cohen’s κ and sensitivity/specificity for both AI and radiologists were calculated.

Results:

There were 1404 cases identified with a median age of 52 (IQR 33–69) years, 949 males. AI demonstrated superior performance compared to radiologists in identifying pneumothorax (p = 0.007) and segmental collapse (p = 0.012) on chest radiograph. Radiologists performed better than AI for clavicle fracture (p = 0.002), humerus fracture (p < 0.0015) and scapula fracture (p = 0.014). No statistical difference was found for identification of rib fractures and pneumomediastinum.

Conclusion:

The evaluated AI performed comparably to radiologists in interpreting chest radiographs. Further evaluation of this AI program has the potential to enable it to be safely incorporated in clinical processes.

Advances in knowledge:

Clinically useful AI programs represent promising decision support tools.
Seroconversion rates among different designs of COVID-19 vaccines: a network meta-analysis of randomized controlled trials
Authors: Soegiarto Gatot , Fajar Jonny Karunia , Wulandari Laksmi , Anshory Muhammad , Ilmawan Muhammad , Asmiragani Anisa , Illiyana Himma , Adam Azaria , Lamadi Sutini , Sa'adah Umi , Yuantoko Tubagus , Nanda Esi , Rachmawati Farida , Rahmadani Nabila , Talilah Randy , Katipana Madyline , Susanto Sharon , Hindom Maria , Anjasari Ufi , Hidayah Nur , Fadilla Nanda , Lekatompessy Vanela , Phoenna Uzi , Tamara Fredo , Kartini Dessy Aprilia , Mahendra Aditya Indra , Permana Andi , Pasaribu Erwin Alexander , Dhama Kuldeep , Harapan Harapan
Published: March 2022

BACKGROUND: The COVID-19 vaccination program, which uses various types of vaccines, has been applied since the beginning of 2021. However, the efficacy in the context of seroconversion rate remains unclear.

OBJECTIVE: To assess the seroconversion rates among different COVID-19 vaccines using a network meta-analysis approach.

METHODS: A network meta-analysis of randomized controlled trials (RCTs) was conducted during the study period. Data of interest, such as seroconversion rate and the type of COVID-19 vaccine, were extracted from each study. The analysis was performed using single-arm analysis by calculating the cumulative seroconversion rate. A network meta-analysis was conducted using the Bayesian method.

RESULTS: A total of 31 RCTs were included in our analysis. Our pooled calculation revealed that the seroconversion rates of inactivated messenger ribonucleic acid (mRNA), protein subunit, and vector COVID-19 vaccines during the follow-up periods were 93.2%, 93.9%, 65.3%, and 54.7%, respectively, at ≤ 15 days; 96.0%, 94.8%, 91.2%, and 89.7%, respectively, between days 16–30; and 98.5%, 98.6%, 98.5%, and 96.2%, respectively, between days 31–60.The indirect comparison revealed that in the follow-up periods of ≤ 15 and 16–30 days, the inactivated and mRNA COVID-19 vaccines had superior seroconversion rates compared with those of the protein subunit and vector vaccines. In the follow-up period of 31–60 days, the highest seroconversion rates were found in the inactivated, mRNA, and protein subunit COVID-19 vaccines.

CONCLUSION: This study provides valuable information regarding the comparison of seroconversion rates of COVID-19 vaccines.
Defining the burden of febrile illness in rural South and Southeast Asia: an open letter to announce the launch of the Rural Febrile Illness project
Authors: Chandna Arjun , Chew Rusheng , Shwe Nwe Htun Nan , Peto Thomas J. , Zhang Meiwen , Liverani Marco , Brummaier Tobias , Phommasone Koukeo , Perrone Carlo , Pyae Phyo Aung , Sattabongkot Jetsumon , Roobsoong Wanlapa , Nguitragool Wang , Sen Aninda , Ibna Zaman Sazid , Sandar Zaw Aye , Batty Elizabeth , Waithira Naomi , Abdad Mohammad Yazid , Blacksell Stuart D. , Bodhidatta Ladaporn , Callery James J. , Fagnark Watcharintorn , Huangsuranun Witchayoot , Islam Shayla , Lertcharoenchoke Sanchai , Lohavittayavikant Salisa , Mukaka Mavuto , Moul Vanna , Kumer Neogi Amit , Nedsuwan Supalert , Pongvongsa Tiengkham , Ponsap Pimsiri , Richard-Greenblatt Melissa , Schilling William H.K. , Thaipadungpanit Janjira , Tripura Rupam , Dondorp Arjen M. , Mayxay Mayfong , White Nicholas J. , Nosten François , Smithuis Frank , Ashley Elizabeth A. , Maude Richard J. , Day Nicholas P.J. , Lubell Yoel
Published: March 2022

In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria.

This Open Letter announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will run in Bangladesh, Cambodia, Lao PDR, Thailand, and Myanmar. It will define the epidemiological baseline of febrile illness in nine remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited.

The RFI project aims to determine the incidence, causes and outcomes of febrile illness; understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses; and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future.
Causal Decision Making and Causal Effect Estimation Are Not the Same…and Why It Matters
Authors: Fernández-Loría Carlos , Provost Foster
Published: March 2022

Causal decision making (CDM) at scale has become a routine part of business, and increasingly, CDM is based on statistical models and machine learning algorithms. Businesses algorithmically target offers, incentives, and recommendations to affect consumer behavior. Recently, we have seen an acceleration of research related to CDM and causal effect estimation (CEE) using machine-learned models. This article highlights an important perspective: CDM is not the same as CEE, and counterintuitively, accurate CEE is not necessary for accurate CDM. Our experience is that this is not well understood by practitioners or most researchers. Technically, the estimand of interest is different, and this has important implications both for modeling and for the use of statistical models for CDM. We draw on recent research to highlight three implications. (1) We should carefully consider the objective function of the causal machine learning, and if possible, optimize for accurate “treatment assignment” rather than for accurate effect-size estimation. (2) Confounding affects CDM and CEE differently. The upshot here is that for supporting CDM it may be just as good or even better to learn with confounded data as with unconfounded data. (3) Causal statistical modeling may not be necessary at all to support CDM because a proxy target for statistical modeling might do as well or better. This third observation helps to explain at least one broad common CDM practice that seems “wrong” at first blush—the widespread use of noncausal models for targeting interventions. The last two implications are particularly important in practice, as acquiring (unconfounded) data on both “sides” of the counterfactual for modeling can be quite costly and often impracticable. These observations open substantial research ground. We hope to facilitate research in this area by pointing to related articles from multiple contributing fields, most of them written in the last five years.