bluuebunny/crossref_metadata_2025 huggingface dataset:
The tyrosine capsid mutations on retrograde adeno-associated virus accelerates gene transduction efficiency
Authors: Nakahama Ryota , Saito Aika , Nobe Sensho , Togashi Kazuya , Suzuki Ikuo K. , Uematsu Akira , Emoto Kazuo
Published: August 2022

Adeno-associated virus (AAV) vector is a critical tool for gene delivery through its durable transgene expression and safety profile. Among many serotypes, AAV2-retro is typically utilized for dissecting neural circuits with its retrograde functionality. However, this vector requires a relatively long-term incubation period (over 2 weeks) to obtain enough gene expression levels presumably due to low efficiency in gene transduction. Here, we aimed to enhance transgene expression efficiency of AAV2-retro vectors by substituting multiple tyrosine residues with phenylalanines (YF mutations) in the virus capsid, which is previously reported to improve the transduction efficiency of AAV2-infected cells by evading host cell responses. We found that AAV2-retro with YF mutations (AAV2-retroYF)-mediated transgene expression was significantly enhanced in the primary culture of murine cortical neurons at 1 week after application, comparable to that of the conventional AAV2-retro at 2 week after application. Moreover, transgene expressions in the retrogradely labeled neurons mediated by AAV2-retroYF were significantly increased both in the cortico-cortical circuits and in the subcortical circuits in vivo, while the retrograde functionality of AAV2-retroYF was equally effective as that of AAV2-retro. Our data indicate that YF mutations boost AAV2-retro-mediated retrograde gene transduction in vivo and suggest that the AAV2-retroYF should be useful for efficient targeting of the projection-defined neurons, which is suited to applications for dissecting neural circuits during development as well as future clinical applications.
Clinical validation of a multiplex droplet digital PCR for diagnosing suspected bloodstream infections in ICU practice: a promising diagnostic tool
Authors: Wu Jing , Tang Bin , Qiu Yuzhen , Tan Ruoming , Liu Jialin , Xia Jiang , Zhang Jing , Huang Jingjing , Qu Jieming , Sun Jingyong , Wang Xiaoli , Qu Hongping
Published: August 2022

Background

Droplet digital PCR (ddPCR) has emerged as a promising tool of pathogen detection in bloodstream infections (BSIs) in critical care medicine. However, different ddPCR platforms have variable sensitivity and specificity for diverse microorganisms at various infection sites. There is still a lack of prospective clinical studies aimed at validating and interpreting the discrepant ddPCR results for diagnosing BSI in intensive care unit (ICU) practice.

Methods

A prospective diagnostic study of multiplex ddPCR panels was conducted in a general ICU from May 21, 2021, to December 22, 2021. Paired blood cultures (BCs) and ddPCRs (2.5 h) were obtained synchronously to detect the 12 most common BSI pathogens and three antimicrobial resistance (AMR) genes. Firstly, ddPCR performance was compared to definite BSI. Secondly, clinical validation of ddPCR was compared to composite clinical diagnosis. Sensitivity, specificity, and positive and negative predictive values were calculated. Thirdly, the positive rate of AMR genes and related analysis was presented.

Results

A total of 438 episodes of suspected BSIs occurring in 150 critical patients were enrolled. BC and ddPCR were positive for targeted bacteria in 40 (9.1%) and 180 (41.1%) cases, respectively. There were 280 concordant and 158 discordant. In comparison with BCs, the sensitivity of ddPCR ranged from 58.8 to 86.7% with an aggregate of 72.5% in different species, with corresponding specificity ranging from 73.5 to 92.2% with an aggregate of 63.1%. Furthermore, the rate of ddPCR+/BC− results was 33.6% (147/438) with 87.1% (128 of 147) cases was associated with probable (n = 108) or possible (n = 20) BSIs. When clinically diagnosed BSI was used as true positive, the final sensitivity and specificity of ddPCR increased to 84.9% and 92.5%, respectively. In addition, 40 blaKPC, 3blaNDM, and 38 mecA genes were detected, among which 90.5% were definitely positive for blaKPC. Further, 65.8% specimens were predicted to be mecA-positive in Staphylococcus sp. according to all microbiological analysis.

Conclusions

The multiplexed ddPCR is a flexible and universal platform, which can be used as an add-on complementary to conventional BC. When combined with clinical infection evidence, ddPCR shows potential advantages for rapidly diagnosing suspected BSIs and AMR genes in ICU practice.
Combined analysis of whole-exome sequencing and RNA sequencing in type 2 diabetes mellitus patients with thirst and fatigue
Authors: Lv Bohan , Yang Xiuyan , An Tian , Wu Yanxiang , He Zhongchen , Li Bowu , Wang Yijiao , Tan Fang , Wang Tingye , Zhu Jiajian , Hu Yuanyuan , Liu Xiaokun , Jiang Guangjian
Published: August 2022

Background

The principal objective of this study was to gain a better understanding of the mechanisms of type 2 diabetes mellitus (T2DM) patients with fatigue (D-T2DM) through exome and transcriptome sequencing.

Methods

After whole-exome sequencing on peripheral blood of 6 D-T2DM patients, the consensus mutations were screen out and analyzed by a series of bioinformatics analyses. Then, we combined whole-exome sequencing and transcriptome sequencing results to find the important genes that changed at both the DNA and RNA levels.

Results

The results showed that a total of 265,393 mutation sites were found in D-T2DM patients compared with normal individuals, 235 of which were consensus mutations shared with D-T2DM patients. These genes significantly enriched in HIF-1 signaling pathway and sphingolipid signaling pathway. At the RNA level, a total of 375 genes were identified to be differentially expressed. After the DNA-RNA joint analysis, eight genes were screened that changed at both DNA and RNA levels. Among these genes, FUS and LMNA were related to carbohydrate metabolism, energy metabolism, and mitochondrial function. Subsequently, we predicted the herbs, including Qin Pi and Hei Zhi Ma, that might play a therapeutic role in D-T2DM through the SymMap database.

Conclusion

These findings have significant implications for understanding the mechanisms of D-T2DM and provide potential targets for D-T2DM diagnosis and treatment.
Integrated multi-omics analyses reveal that BCAM is associated with epigenetic modification and tumor microenvironment subtypes of clear cell renal cell carcinoma
Authors: Zhao Junjie , Liang Jiayu , Yang Yang , Sun Guangxi , Zhang Xingming , Zhao Jinge , Hu Xu , Chen Junru , Zhu Sha , Ni Yuchao , Zhang Yaowen , Dai Jindong , Wang Zhipeng , Wang Zilin , Zeng Yuhao , Yao Jin , Chen Ni , Shen Pengfei , Liu Zhenhua , Zeng Hao
Published: August 2022

Background

Clear cell renal cell carcinoma (ccRCC) is the most common and highly heterogeneous subtype of renal cell carcinoma. Dysregulated basal cell adhesion molecule (BCAM) gene is associated with poor prognosis in various cancers. However, the dysregulated functions and related multi-omics features of BCAM in ccRCC stay unclear.

Results

BCAM expression was aberrantly downregulated in ccRCC and correlated with adverse pathological parameters and poor prognosis. Low mRNA expression of BCAM was remarkably associated with its CpG methylation levels and BAP1 mutation status. Patients with lower-expressed BCAM concomitant with BAP1 mutation had a worse prognosis. Using RNA-seq data from The cancer genome atlas, we found that compared to the BCAM-high expression subgroup, ccRCC patients in the BCAM-low expression subgroup had significantly higher levels of immune infiltration, higher immune checkpoint expression levels and lower TIDE (tumor immune dysfunction and exclusion) score, indicating potential better response to immunotherapy. Data from the Clinical Proteomic Tumor Analysis Consortium further validated the association between low BCAM expression and CD8 + inflamed phenotype at protein level. Meanwhile, our results suggested that the angiogenesis-related pathways were enriched in the BCAM-high expression subgroup. More importantly, according to the data from the GDSC database, we revealed that the BCAM-high expression subgroup should be more sensitive to anti-angiogenetic therapies, including sorafenib, pazopanib and axitinib.

Conclusions

These results suggest that BCAM could serve as a biomarker distinguishing different tumor microenvironment phenotypes, predicting prognosis and helping therapeutic decision-making for patients with ccRCC.
Imaging features of COVID-19-associated secondary sclerosing cholangitis on magnetic resonance cholangiopancreatography: a retrospective analysis
Authors: Ghafoor Soleen , Germann Manon , Jüngst Christoph , Müllhaupt Beat , Reiner Cäcilia S. , Stocker Daniel
Published: August 2022

Background

Despite emerging reports of secondary sclerosing cholangitis (SSC) in critically ill COVID-19 patients little is known about its imaging findings. It presents as delayed progressive cholestatic liver injury with risk of progression to cirrhosis. Diagnosis cannot be made based on clinical presentation and laboratory markers alone. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) can aid in the diagnosis. The aim of this study was to describe MRI/MRCP imaging features of COVID-19-associated SSC.

Results

Seventeen patients (mean age 60.5 years, 15 male) who underwent MRI/MRCP were included. All had been admitted to intensive care unit (ICU) (median duration of ICU stay 10 weeks, range, 2–28 weeks) and developed acute respiratory distress syndrome requiring mechanical ventilation. On imaging, all patients had intrahepatic bile duct strictures and 10 (58.8%) had associated upstream dilatation. Intrahepatic bile duct beading was seen in 14 cases (82.3%). Only one patient (5.9%) had extrahepatic bile duct stricturing. Patchy arterial phase hyperenhancement and high signal on T2- and diffusion-weighted images were seen in 7 cases (53.8%) and 9 cases (52.9%), respectively. Biliary casts were seen in 2 cases (11.8%). Periportal lymphadenopathy and vascular complications were not seen.

Conclusion

On MRI/MRCP, COVID-19-associated SSC presents with multiple intrahepatic bile duct strictures with or without upstream dilatation and intrahepatic bile duct beading. Surrounding hepatic parenchymal changes including alterations in enhancement and T2 signal are common. The extrahepatic biliary tree was typically spared and periportal lymphadenopathy was missing in all patients.
Investigation of geomechanical properties of tephra relevant to roof loading for application in vulnerability analyses
Authors: Osman Sara , Thomas Mark , Crummy Julia , Carver Stephen
Published: August 2022

Tephra fall can lead to significant additional loading on roofs. Understanding the relevant geomechanical properties of tephra is critical when assessing the vulnerability of buildings to tephra fall and designing buildings to withstand tephra loads. Through analysis of published data and new experimental results on dry tephra (both natural samples from Ascension Island, South Atlantic and synthetic tephra made from crushed aggregates), we discuss the geomechanical properties of tephra relevant to roof loading, which include bulk density, grain size distribution and internal angle of friction. Compiled published data for deposits from 64 global eruptions reveal no clear trend in deposit densities based on magma composition or eruption size. The global data show a wide range of values within single eruptions and between eruptions of similar compositions. Published grain size distributions near to source (≤ 10 km) vary widely but again there are no clear trends relating to magma composition. We used laboratory tests to investigate the internal angle of friction, which influences deposit sliding behaviour. For dry tephra, at the low normal stresses likely to be experienced in roof loads (≤ 35 kPa), we found similar values across all our tests (35.8° - 36.5°) suggesting that any internal sliding will be consistent across a variety of deposits. By considering different magma compositions, densities and grain size distributions, we have provided an envelope of values for deposit parameters relevant to roof loading, in which future eruptions are likely to sit. Finally, we created synthetic tephra (fine- and coarse-grained pumice and scoria) by crushing volcanic aggregates and compared it to samples from Ascension and published data. Our results reveal that synthetic tephra successfully replicated the properties relevant to loading, potentially reducing the need to collect and transport natural samples.
The efficacy of imagery in the rehabilitation of people with Parkinson’s disease: protocol for a systematic review and meta-analysis
Authors: Singer Tabitha , Fahey Paul , Liu Karen P. Y.
Published: August 2022

Background

Parkinson’s disease (PD) is a neurodegenerative disorder of the nervous system that affects movement. Individuals with PD commonly experience difficulty initiating movements, slowness of movements, decreased balance, and decreased standing ability. It has been shown that these motor symptoms adversely affect the independence of individuals with PD. Imagery is the cognitive process whereby a motor action is internally reproduced and repeated without overt physical movement. Recent studies support the use of imagery in improving rehabilitation outcomes in the PD population. However, these data have inconsistencies and have not yet been synthesised. The study will review the evidence on the use of imagery in individuals with PD and to determine its efficacy in improving rehabilitation outcomes.

Methods

Randomised controlled clinical trials comparing the effects of imagery and control on activities, body structure and function, and participation outcomes for people with PD will be included. A detailed computer-aided search of the literature will be performed from inception to June 2021 in the following databases: MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library, Web of Science, and Scopus. Two independent reviewers will screen articles for relevance and methodological validity. The Physiotherapy Evidence Database (PEDro) scale will be utilised to evaluate the risk of bias of selected studies. Data from included studies will be extracted by two independent reviewers through a customised, pre-set data extraction sheet. Studies using imagery with comparable outcome measures will be pooled for meta-analysis using the random effect model with 95% CI. If individual studies are heterogeneous, a descriptive review will analyse variance in interventions and outcomes. A narrative data analysis will be considered where there is insufficient data to perform a meta-analysis.

Discussion

Several studies investigating imagery in the PD population have drawn dissimilar conclusions regarding its effectiveness in rehabilitation outcomes and clinical applicability. Therefore, this systematic review will gather and critically appraise all relevant data, to generate a conclusion and recommendations to guide both clinical practice and future research on using imagery in the rehabilitation of people with PD.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Systematic review registration

PROSPERO registration number CRD42021230556.
The role and mechanism of TXNDC5 in diseases
Authors: Wang Xueling , Li Haoran , Chang Xiaotian
Published: August 2022

Thioredoxin domain-containing protein 5 (TXNDC5) is a member of the protein disulfide isomerase (PDI) family. It can promote the formation and rearrangement of disulfide bonds, ensuring proper protein folding. TXNDC5 has three Trx-like domains, which can act independently to introduce disulfide bonds rapidly and disorderly. TXNDC5 is abnormally expressed in various diseases, such as cancer, rheumatoid arthritis (RA), etc. It can protect cells from oxidative stress, promote cell proliferation, inhibit apoptosis and promote the progression of disease. Aberrant expression of TXNDC5 in different diseases suggests its role in disease diagnosis. In addition, targeting TXNDC5 in the treatment of diseases has shown promising application prospects. This article reviews the structure and function of TXNDC5 as well as its role and mechanism in cancer, RA and other diseases.
The association of nonalcoholic fatty liver disease with bone mineral density in type 2 diabetes
Authors: Du Juan , Ma Yan , Lang Hongmei , Huang Changquan , Zhang Xingping
Published: August 2022

Objective

We examined the association between nonalcoholic fatty liver disease and lumbar spine bone mineral density in individuals with and without type 2 diabetes.

Methods

The lumbar BMD of 1088 subjects was measured using dual-energy X-ray absorptiometry (DXA). Liver fat content was quantified via B-mode ultrasound. Multivariable linear regression was used to study the association between NAFLD and lumbar BMD in participants with and without T2DM.

Results

The lumbar BMD in the T2DM group and the non-diabetes group was higher in the NAFLD group than in the non-NAFLD group (P < 0.001). Multivariate regression analysis in the T2DM group showed that after adjusting for confounders, the positive association between lumbar spine BMD and NAFLD remained (P = 0.027). In the non-diabetes group, after adjusting for confounders, the association between NAFLD and lumbar spine BMD disappeared.

Conclusions

The relationship between nonalcoholic fatty liver disease and lumbar bone mineral density may differ in individuals with and without diabetes. The effect of nonalcoholic fatty liver disease on bone mineral density needs to be evaluated in different clinical contexts.
Social network addiction symptoms and body dissatisfaction in young women: exploring the mediating role of awareness of appearance pressure and internalization of the thin ideal
Authors: Delgado-Rodríguez Rafael , Linares Rocío , Moreno-Padilla María
Published: August 2022

Background

Previous studies testing for a direct relationship between social networking sites (SNS) addiction and body dissatisfaction (BD) have yielded inconsistent results. Here, we aimed to identify underlying processes that could mediate this relationship. Specifically, we studied the relationship between SNS addiction symptoms and BD through the awareness of appearance pressures and the internalization of beauty ideals, both individually and serially: SNS addiction → Awareness → BD; SNS addiction → Internalization → BD; SNS addiction → Awareness → Internalization → BD.

Method

A total of 368 female undergraduates with SNS accounts completed scales to assess SNS addiction symptoms (Social Network Addiction Questionnaire), BD (Body Shape Questionnaire), awareness, and internalization (Sociocultural Attitudes Towards Appearance Questionnaire-4; awareness and internalization scales). A theoretical serial mediation model was constructed to examine the proposed relationships. Body mass index was included as a covariate to control the influence of this important variable.

Results

The results indicated that both awareness and internalization independently mediated the relationship between SNS addiction symptoms and BD. Also, there was a significant serial mediation effect; women with more SNS addiction symptoms tended to be more aware of appearance pressure, which was associated with the internalization of beauty ideals. In turn, this internalization was positively related to BD symptoms.

Conclusions

These findings shed light on the indirect relationship between SNS addiction and BD, demonstrating independent and accumulative mediating effects of awareness and internalization.
Psychometric properties of the Farsi version of the gaming disorder scale for adolescents (GADIS-A)
Authors: Mazaherizadeh Ali , Taherifar Zahra , Farahani Hojjatollah
Published: August 2022

Background

Gaming disorder was added to the 11th version of the international classification of disease by the world health organization in early 2019. Adolescents are the most vulnerable group in this area. Thus, a screening tool for this age range is essential. This study aims to examine the psychometric properties of the gaming disorder scale for adolescents (GADIS-A) in an Iranian male sample.

Methods

260 male students-7th to 12th grade-from Isfahan city in the academic year 2020–2021 were selected using convenience sampling. The participants responded to the Farsi version of the GADIS-A and problematic online game questionnaire (POGQ). Thirty participants answered the scale again to assess the validity of the retest. Pearson’s correlation analysis, Cronbach’s alpha, and confirmatory factor analysis were used. The data were analyzed by SPSS version 24 and R software packages psych and lavaan.

Results

Confirmatory factor analysis revealed that the two-factor model, which included cognitive-behavioral symptoms and negative consequences, had good fitness indices. The GADIS-A convergent validity is confirmed by the scale’s significant correlation with the POGQ. Cronbach’s alpha coefficient was used to determine the scale’s validity, which was 0.85 for the full scale and 0.70 and 0.75 for two factors. The validity of the retest after two weeks also showed a correlation of 0.88.

Conclusion

The Farsi version of the gaming disorder scale for adolescents has a two-factor structure and is valid for use in Iran.
Nutrient-limited subarctic caves harbour more diverse and complex bacterial communities than their surface soil
Authors: Reboleira Ana Sofia , Bodawatta Kasun H. , Ravn Nynne M. R. , Lauritzen Stein-Erik , Skoglund Rannveig Øvrevik , Poulsen Michael , Michelsen Anders , Jønsson Knud Andreas
Published: August 2022

Background

Subarctic regions are particularly vulnerable to climate change, yet little is known about nutrient availability and biodiversity of their cave ecosystems. Such knowledge is crucial for predicting the vulnerability of these ecosystems to consequences of climate change. Thus, to improve our understanding of life in these habitats, we characterized environmental variables, as well as bacterial and invertebrate communities of six subarctic caves in Northern Norway.

Results

Only a minuscule diversity of surface-adapted invertebrates were found in these caves. However, the bacterial communities in caves were compositionally different, more diverse and more complex than the nutrient-richer surface soil. Cave soil microbiomes were less variable between caves than between surface communities in the same area, suggesting that the stable cave environments with tougher conditions drive the uniform microbial communities. We also observed only a small proportion of cave bacterial genera originating from the surface, indicating unique cave-adapted microbial communities. Increased diversity within caves may stem from higher niche specialization and levels of interdependencies for nutrient cycling among bacterial taxa in these oligotrophic environments.

Conclusions

Taken together this suggest that environmental changes, e.g., faster melting of snow as a result of global warming that could alter nutrient influx, can have a detrimental impact on interactions and dependencies of these complex communities. This comparative exploration of cave and surface microbiomes also lays the foundation to further investigate the long-term environmental variables that shape the biodiversity of these vulnerable ecosystems.
Acute effect of Melon Manis Terengganu peel powder on glycemic response, perceived satiety, and food intake: a randomized, placebo-controlled crossover trial in adults at risk of type 2 diabetes
Authors: Ong Ying Qian , Harith Sakinah , Shahril Mohd Razif , Shahidan Norshazila , Hapidin Hermizi
Published: August 2022

Background

Melon Manis Terengganu (MMT) peel has a high dietary fiber content, but there is no data examining its health benefits in adults at risk of type 2 diabetes. The objective of the study was to evaluate whether consumption of MMT peel powder improves glycemic response, satiety, and food intake in adults at risk of type 2 diabetes.

Methods

An open-label, randomized, placebo-controlled, crossover design trial was conducted among adults (n = 30, ages 18–59 y) at risk of type 2 diabetes. They consumed Formulation 3 (formulated MMT peel powder) [A] and control (glucose) [B] with study breakfast based on randomly assigned treatment sequences (AB, BA) established by Research Randomizer (www.randomizer.org). Capillary blood glucose and perceived satiety were determined at baseline (0 min), 30, 60, 90 and 120 min, followed by a post-intervention food intake measurement.

Results

The repeated measures analysis of variance (ANOVA) revealed significant time (F = 84.37,p <  0.001, ηp2 = 0.744), condition (F = 22.89,p <  0.001, ηp2 = 0.441), and time*condition effects (F = 24.40,p <  0.001, ηp2 = 0.457) in blood glucose levels. Respondents (n = 30) who consumed Formulation 3 also had a significantly lower blood glucose 2-hour incremental area under the curve (iAUC) of 134.65 ± 44.51 mmol/L*min and maximum concentration (CMax) of 7.20 (7.10, 8.20) mmol/L with relative reduction of 26.8 and 13.3% respectively, when compared with control (p <  0.001). Besides, significantly greater perceived satiety, lower energy and fat intake as well as higher dietary fiber intake were also observed in the intervention group compared with the placebo group (p <  0.05). There were no marked side effects associated with the ingestion of the test products.

Conclusions

Short-term consumption of formulated MMT peel powder may improve glycemic response, increase perceived satiety and reduce food intake in adults at risk of type 2 diabetes with the potential to be utilized as a functional beverage. Medium-to long-term clinical trial is warranted to determine whether taking this formulated MMT peel powder on a daily basis has an influence on health outcomes.

Trial registration

ClinicalTrials.govIdentifier: NCT05298111. Registered 28/03/2022.
Engaging with patients in research on knowledge translation/implementation science methods: a self study
Authors: MacLeod Martha L. P. , Leese Jenny , Garraway Leana , Oelke Nelly D. , Munro Sarah , Bailey Sacha , Hoens Alison M. , Loo Sunny , Valdovinos Ana , Wick Ursula , Zimmer Peter , Li Linda C.
Published: August 2022

Background

In 2017, the British Columbia (Canada) SUPPORT (SUpport for People and Patient-Oriented Research) Unit created six methods clusters to advance methodologies in patient and public oriented research (POR). The knowledge translation (KT)/implementation science methods cluster identified that although there was guidance about how to involve patients and public members in POR research generally, little was known about how best to involve patients and public members on teams specifically exploring POR KT/implementation science methodologies. The purpose of this self-study was to explore what it means to engage patients and the public in studies of POR methods through the reflections of members of five KT/implementation science teams.

Methods

Informed by a collaborative action research approach, this quality improvement self-study focused on reflection within four KT/implementation science research teams in 2020–2021. The self-study included two rounds of individual interviews with 18 members across four teams. Qualitative data were analyzed using a thematic analysis approach followed by a structured discussion of preliminary findings with the research teams. Subsequently, through two small group discussion sessions, the patients/public members from the teams refined the findings.

Results

Undertaking research on POR KT/implementation science methodologies typically requires teams to work with the uncertainty of exploratory and processual research approaches, make good matches between patients/public members and the team, work intentionally yet flexibly, and be attuned to the external context and its influences on the team. POR methodological research teams need to consider that patients/public members bring their life experiences and world views to the research project. They become researchers in their own right. Individual and team reflection allows teams to become aware of team needs, acknowledge team members’ vulnerabilities, gain greater sensitivity, and enhance communication.

Conclusions

The iterative self-study process provided research team members with opportunities for reflection and new understanding. Working with patients/public team members as co-researchers opens up new ways of understanding important aspects of research methodologies, which may influence future KT/implementation science research approaches.
A resilient adjustment method to weigh pseudorange observation in precise point positioning
Authors: Zhang Qieqie , Zhao Long , Zhou Jianhua
Published: August 2022

The accurate weighting of pseudorange observations is important to improve the convergence time and positioning quality of Precise Point Positioning (PPP). Currently, the weight of a pseudorange observation is mainly determined with empirical stochastic models. However, in a complex environment, due to the inability to adapt for the dynamic changes of the user environment, the empirical stochastic models usually cannot reflect the real error level of pseudorange observations. To address this problem, a resilient adjustment method to weigh pseudorange observations is proposed, which constructs the real-time estimation and inflation model for the variance of pseudorange multipath error and measurement noise to replace the empirical stochastic model to determine the weights of pseudorange observations. A set of static and dynamic Global Positioning System (GPS) test data are used to verify the effectiveness of the proposed method. The test results indicate that the proposed real-time estimation model can provide a better representation of the pseudorange accuracy, and the positioning performance of PPP using the real-time estimation model is better than that with the empirical stochastic model. Compared with the optimal empirical stochastic model, the positioning accuracy of PPP with the real-time estimation model is improved by at least 20%, and the convergence time is reduced by at least 50%.
Teprotumumab and the Evolving Therapeutic Landscape in Thyroid Eye Disease
Authors: Kossler Andrea Lora , Douglas Raymond , Dosiou Chrysoula
Published: August 2022

Context

Thyroid eye disease (TED) is a sight-threatening and debilitating autoimmune condition, with limited therapies available, that often poses diagnostic and therapeutic challenges. In recent years, the treatment landscape has shifted to early intervention with targeted therapy.

Methods

A PubMed review of the literature was conducted for the period between 1979 and 2021. Search terms included thyroid eye disease, teprotumumab, targeted therapy, Graves disease, Graves ophthalmopathy, dysthyroid optic neuropathy, and related terms in different combinations. Novel biologic therapies for TED have emerged as alternatives to traditional steroid regimens in recent years. New insights into TED pathophysiology have uncovered the role of the insulin-like growth factor 1 receptor (IGF-1R) and led to the development of teprotumumab, an IGF-1R–inhibiting monoclonal antibody.

Results

Randomized clinical trials demonstrating the efficacy of teprotumumab for TED led to Food and Drug Administration approval. Teprotumumab is gradually replacing immunosuppressive agents as first-line therapy in the United States for active moderate-to-severe TED, while emerging reports also show its use in other stages of the disease. Recent data highlight risk factors for adverse events and screening protocols to maximize patient safety. Personalized therapeutic plans developed through effective partnership between endocrinologists and ophthalmologists aim to enhance the safety and outcomes of TED treatments and improve care for this complex disease.

Conclusion

TED management is shifting to an era of targeted therapy with multidisciplinary care. Teprotumumab has demonstrated superior efficacy to conventional treatments and has transformed our therapeutic and surgical algorithms. Clinical guidelines and additional studies are needed to further guide and refine therapy.
Future Projections in Thyroid Eye Disease
Authors: Barbesino Giuseppe , Salvi Mario , Freitag Suzanne K
Published: August 2022

Background and Aims

This review aims to summarize current and emerging therapies for treatment of thyroid eye disease (TED), in the light of novel understanding of pathogenetic mechanisms, leading to new treatment options and clinical trials.

Methods

We reviewed and analyzed peer-reviewed literature reporting recent translational studies and clinical trials in the treatment of TED. Searches were made at www.pubmed.gov with keywords “thyroid eye disease,” “Graves’ ophthalmopathy,” “thyroid orbitopathy,” and “Graves’ orbitopathy.”

Results

Surgery is reserved for rehabilitation in chronic TED or for emergent compressive optic neuropathy. Oral and intravenous glucocorticoid therapy has been used for decades with variable efficacy in acute TED, but results may be temporary and side effects significant. Nonsteroidal oral immunosuppressive agents offer modest benefit in TED. Several immunomodulatory monoclonal antibodies, including rituximab and tocilizumab, have shown efficacy for inactivating TED. Recently, teprotumumab, an insulin-like growth factor 1 receptor (IGF-1R) inhibitor, has demonstrated significant improvement in proptosis, clinical activity score, diplopia, and quality of life in patients with active TED, with good tolerability. Newly proposed TED therapies, currently in preclinical and clinical trial phases, include thyroid-stimulating hormone (TSH) receptor inhibitory drugs, RVT-1401, local anti-vascular endothelial growth factor therapy, IGF-1R drugs delivered subcutaneously and orally, and desensitization to the TSH receptor with modified TSH receptor peptides.

Conclusion

New, albeit incomplete, understanding of the molecular mechanisms of TED has led to new promising therapies and offered improved outcomes in TED patients. Their full role and their relationship to classical immune suppression should be clarified over the next few years.
Beyond sound: bimodal acoustic calls used in mate-choice and aggression by red-eyed treefrogs
Authors: Caldwell Michael S. , Britt Kayla A. , Mischke Lilianna C. , Collins Hannah I.
Published: August 2022

Airborne sound signals function as key mediators of mate-choice, aggression and other social interactions in a wide range of vertebrate and invertebrate animals. Calling animals produce more than sound, however. When displaying on or near a solid substrate, such as vegetation or soil, they also unavoidably excite substrate vibrations because of the physics of sound production and of acoustic propagation, and these vibrations can propagate to receivers. Despite their near ubiquity, these vibrational signal components have received very little research attention and in vertebrates it is unknown whether they are relevant to mate-choice, an important driver of evolutionary divergence. Here, we show that female red-eyed treefrogs are more than twice as likely to choose a male mating call when airborne sound is paired with its corresponding substrate vibrations. Furthermore, males of the same species are more aggressive towards and display a greater range of aggressive behaviors in response to bimodal (sound and vibration) versus unimodal (sound or vibration alone) calls. In aggressive contexts, at least, air- and substrate-borne signal components function non-redundantly. These results are a clear demonstration that vibrations produced by a calling animal can function together with airborne sound to markedly enhance the function of a signal. If this phenomenon proves widespread, this finding has the potential to substantially influence our understanding of the function and evolution of acoustic signals.
A systematic review assessing the effectiveness of COVID-19 mRNA vaccines in chronic kidney disease (CKD) individuals
Authors: Malik Soniya A. , Modarage Kavindiya , Goggolidou Paraskevi
Published: August 2022

Background: SARS-CoV-2 is a coronavirus that has rapidly spread across the world with a detrimental effect on the global population. Several reports have highlighted an increased mortality rate and a higher severity of COVID-19 infection in chronic kidney disease (CKD) individuals. Upon the development of various SARS-CoV-2 vaccines, mRNA vaccines including BNT162b2 and mRNA-1273 were deemed safe, with a high efficacy in preventing COVID-19 in the general population. This review investigates whether  SARS-CoV-2 mRNA vaccines are as effective in triggering an immune response in Dialysis Patients (DPs) and Kidney Transplant Recipients (KTRs) and if a third dose is required in this  population.

Methods: A systematic search employing the PRISMA criteria was conducted in several major databases, with the data being extracted from publications for the period January 2021 to May 2022 (PROSPERO: CRD42022338514, June 15, 2022).

Results: 80 studies were included in this analysis with a total cohort number of 15,059 participants. Overall, 85.29% (OR = 17.08, 95% CI = 15.84-18.42, I2 = 98%) and 41.06% (OR = 0.52, 95% CI = 0.48-0.5, I2 = 95%) of DPs and KTRs included in this review showed positive seroconversion after two doses of either mRNA vaccine, respectively. A total 76% (OR = 6.53, 95% CI = 5.63-7.5, I2 = 96%) of the cohort given a third dose of an mRNA vaccine demonstrated positive seroconversion, with 61.86% (OR = 2.31, 95% CI = 1.95-2.75 I2 = 95%) of the cohort that was assessed for a cellular response displaying a positive response.

Conclusions: This data emphasises a reduced incidence of a positive immune response in DPs and KTRs compared to healthy controls, albeit a better response in DPs than when compared to KTRs alone was observed. A third dose  appears to increase the occurrence of an immune response in the overall DP/KTR cohort.
Determinants of adherence to insulin and blood glucose monitoring among adolescents and young adults with type 1 diabetes in Qatar: a qualitative study
Authors: AlBurno Hanan , Schneider Francine , de Vries Hein , Al Mohannadi Dabia , Mercken Liesbeth
Published: August 2022

Background: Adherence to insulin and blood glucose monitoring (BGM) is insufficient in adolescents and young adults (AYAs) with type 1 diabetes (T1D) worldwide and in Qatar. Little is known about the factors related to being aware of non-adherence and the beliefs related to non-adherence in this group. This qualitative study investigated factors related to awareness of, and beliefs about non-adherence, as well as the existence of specific action plans to combat non-adherence using the I-Change model.

Methods: The target group was comprised of 20 Arab AYAs (17–24 years of age) with T1D living in Qatar. Participants were interviewed via semi-structured, face-to-face individual interviews, which were audio-recorded, transcribed verbatim, and analyzed using the Framework Method.

Results: Suboptimal adherence to insulin, and particularly to BGM, in AYAs with T1D was identified. Some AYAs reported to have little awareness about the consequences of their non-adherence and how this can adversely affect optimal diabetes management. Participants also associated various disadvantages to adherence (e.g., hypoglycemia, pain, among others) and reported low self-efficacy in being adherent (e.g., when outside home, in a bad mood, among others). Additionally, goal setting and action-planning often appeared to be lacking. Factors facilitating adherence were receiving support from family and healthcare providers, being motivated, and high self-efficacy. 

Conclusions: Interventions that increase awareness concerning the risks of non-adherence of AYAs with T1D are needed, that increase motivation to adhere by stressing the advantages, creating support and increasing self-efficacy, and that address action planning and goal parameters.
A study protocol to prepare an RBD protein for vaccine against COVID-19
Authors: Jahangir ZMG Sarwar , Marnik Arleta Helena
Published: August 2022

Background: SARS-CoV-2 pandemic is a global threat to humans and the world’s economy. Effective and safe vaccines against this virus are essential to control and eradicate the pandemic. The currently applied vaccines carry SARS-CoV-2 spike-protein mRNA/cDNA. These vaccines go through several cellular processes in the recipients for producing antigens. On the contrary, the SARS-CoV-2 RBD (receptor binding domain)-protein is an antigen. It will directly stimulate antibody production against SARS-CoV-2. Hence, we propose to produce SARS-CoV-2 RBD-protein as a fast acting, effective and safe vaccine. 

Methods: We propose to reconstruct a plasmid carrying three types of  DNA sequences: RBD cDNA, FP (fusion peptide) DNA and sfGFP(superfolder-green-fluorescent-protein), cDNA creating the RBD-FP-sfGFP DNA within an orf (open-reading-frame). Escherichia coli, C2566H, transformed with the reconstructed plasmid will express RBD-FP-sfGFP fusion protein producing green fluorescent cfu (colony forming unit). The RBD-protein will be separated from the sfGFP using an FP specific enterokinase, and eluted by HIC (hydrophobic-interaction-chromatography), detected with a BioVision-Elisa-Kit, and quantified by spectrophotometry at UV280nm and immune simulation will be carried out using C57BL mice. 

Results: The plasmid reconstruct will carry ampr (ampicillin-resistant) gene as a selective marker and a T7 promoter controlling the expression of RBD-FP-sfGFP fusion protein. The transformed Escherichia coli will efficiently express the RBD-FP-sfGFP fusion protein. The highly efficient sfGFP fused within the RBD-FP-sfGFP will produce green fluorescent cfu. The RBD-FP-sfGFP protein extract from the green cfu, digested by enterokinase and separated by the HIC will produce pure immunoreactive RBD protein. 

Conclusion: A positive BioVision-ELISA test detects <10 pg RBD protein/ml of the sample. A larger sample of the purified RBD protein can be used as a vaccine following a standard formulation and safety protocols. Once administered, the RBD protein will stimulate antibody production against the SARS-CoV-2 virus. The RBD protein has no potential to recombine with human genome.
An Alternating Method for Cardinality-Constrained Optimization: A Computational Study for the Best Subset Selection and Sparse Portfolio Problems
Authors: Moreira Costa Carina , Kreber Dennis , Schmidt Martin
Published: August 2022

Cardinality-constrained optimization problems are notoriously hard to solve in both theory and practice. However, as famous examples, such as the sparse portfolio optimization and best subset selection problems, show, this class is extremely important in real-world applications. In this paper, we apply a penalty alternating direction method to these problems. The key idea is to split the problem along its discrete-continuous structure to obtain two subproblems that are much easier to solve than the original problem. In addition, the coupling between these subproblems is achieved via a classic penalty framework. The method can be seen as a primal heuristic for which convergence results are readily available from the literature. In our extensive computational study, we first show that the method is competitive to a commercial mixed-integer program solver for the portfolio optimization problem. On these instances, we also test a variant of our approach that uses a perspective reformulation of the problem. Regarding the best subset selection problem, it turns out that our method significantly outperforms commercial solvers and it is at least competitive to state-of-the-art methods from the literature.

History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms–Discrete.

Funding: The first author thanks the Deutsche Forschungsgemeinschaft (DFG) for its support within “Algorithmic Optimization” [Grant RTG 2126]. The third author thanks the DFG for its support within project A05 and B08 in the “Sonderforschungsbereich/Transregio 154 Mathematical Modeling, Simulation and Optimization using the Example of Gas Networks.”

Supplemental Material: The supplementary material is available at https://doi.org/10.1287/ijoc.2022.1211 .
GANGGUAN PSIKOGENIK LATAH GARY ISKAK: KAJIAN PSIKOLINGUISTIK
Authors: Nuril Phasa Hidayah
Published: August 2022

This research is motivated by the stigma of talkativeness suffered by women, people with low education, and belonging to the lower economic class category. The research entitled "Psychogenic Disorder of Talkative Gary Iskak (Psycholinguistic Study)" aims to describe the talkative and the background of talkative sufferers towards artist Gary Iskak. The theory used in this research is the talkative theory of  Abdul Chaer and Soenjono Darjowidjodjo with a psycholinguistic approach. The data collection method used is the referential method with the note-taking technique. In contrast, the data analysis method is the referential method with the determining determinants or the PUP technique. The results found in this study are that there are four general reaction types: Ekolalia, Ekopraxia, Auto Ekolalia, and Automatic Obedience. Then the two types of talkative reactions that are not included in the four categories are a mixture of Ekolalia and Ekopraxia talkative and the impact of voice talk. In addition to the type of talkativeness, it was also found that the factors causing the talkativeness experienced by Gary Iskak when he was in several events found four causes of talkativeness. Among the four, the most frequent cause of talkativeness is being surprised by other people's movements.
PERANG DAN LIYAN: KAJIAN FEMINISME EKSISTENSIALIS DALAM NOVEL LAMPUKI KARYA ARAFAT NUR
Authors: Gunawan Dedek
Published: August 2022

This study aims to discuss the existence of women as the other in the novel Lampuki by Arafat Nur, which raises the theme of conflict in Aceh. This novel shows more of the daily life of the conflict-stricken community so that the situation and position of women can be seen more deeply, namely in the community itself. Furthermore, the analysis will focus on three female characters who represent the general situation of Acehnese women during the conflict. The theory used in this study is existentialist feminism, developed by Simone de Beauvoir. This study uses the qualitative descriptive method. The results showed that society's deeply rooted patriarchal culture is the biggest challenge preventing women from achieving freedom and actualizing themselves. Halimah and Siti viewed their status as wives. In other words, they are part of their husbands. However, the condition of women who do not have a husband is not better, such as Rukiya, who still needs men or is not independent. This lack of independence is due to the social construct that makes women always dependent on men. In Beauvoir's view, men place themselves as subjects and women as objects whose existence is to be subdued. Furthermore, the fate of marginalized women, and dependence on men, including being victims in the conflict, is the result of the objectification that occurs to them.