bluuebunny/crossref_metadata_2025 huggingface dataset:
RN-Autoencoder: Reduced Noise Autoencoder for classifying imbalanced cancer genomic data
Authors: Arafa Ahmed , El-Fishawy Nawal , Badawy Mohammed , Radad Marwa
Published: January 2023

Background

In the current genomic era, gene expression datasets have become one of the main tools utilized in cancer classification. Both curse of dimensionality and class imbalance problems are inherent characteristics of these datasets. These characteristics have a negative impact on the performance of most classifiers when used to classify cancer using genomic datasets.

Results

This paper introduces Reduced Noise-Autoencoder (RN-Autoencoder) for pre-processing imbalanced genomic datasets for precise cancer classification. Firstly, RN-Autoencoder solves the curse of dimensionality problem by utilizing the autoencoder for feature reduction and hence generating new extracted data with lower dimensionality. In the next stage, RN-Autoencoder introduces the extracted data to the well-known Reduced Noise-Synthesis Minority Over Sampling Technique (RN- SMOTE) that efficiently solve the problem of class imbalance in the extracted data. RN-Autoencoder has been evaluated using different classifiers and various imbalanced datasets with different imbalance ratios. The results proved that the performance of the classifiers has been improved with RN-Autoencoder and outperformed the performance with original data and extracted data with percentages based on the classifier, dataset and evaluation metric. Also, the performance of RN-Autoencoder has been compared to the performance of the current state of the art and resulted in an increase up to 18.017, 19.183, 18.58 and 8.87% in terms of test accuracy using colon, leukemia, Diffuse Large B-Cell Lymphoma (DLBCL) and Wisconsin Diagnostic Breast Cancer (WDBC) datasets respectively.

Conclusion

RN-Autoencoder is a model for cancer classification using imbalanced gene expression datasets. It utilizes the autoencoder to reduce the high dimensionality of the gene expression datasets and then handles the class imbalance using RN-SMOTE. RN-Autoencoder has been evaluated using many different classifiers and many different imbalanced datasets. The performance of many classifiers has improved and some have succeeded in classifying cancer with 100% performance in terms of all used metrics. In addition, RN-Autoencoder outperformed many recent works using the same datasets.
Presenilins regulate synaptic plasticity in the perforant pathways of the hippocampus
Authors: Lee Sang Hun , Bolshakov Vadim Y. , Shen Jie
Published: January 2023

Mutations in the Presenilin genes (PSEN1 and PSEN2) are the major cause of familial Alzheimer’s disease (AD), highlighting the importance of Presenilin (PS) in AD pathogenesis. Previous studies of PS function in the hippocampus demonstrated that loss of PS results in the impairment of short- and long-term synaptic plasticity and neurotransmitter release at hippocampal Schaffer collateral (SC) and mossy fiber (MF) synapses. Cortical input to the hippocampus through the lateral perforant pathway (LPP) and the medial perforant pathway (MPP) is critical for normal cognitive functions and is particularly vulnerable during aging and early stages of AD. Whether PS regulates synaptic function in the perforant pathways, however, remained unknown. In the current study, we investigate PS function in the LPP and MPP by performing whole-cell and field-potential electrophysiological recordings using acute hippocampal slices from postnatal forebrain-restricted excitatory neuron-specific PS conditional double knockout (cDKO) mice. We found that paired-pulse ratio (PPR) is reduced in the LPP and MPP of PS cDKO mice. Moreover, synaptic frequency facilitation or depression in the LPP or MPP, respectively, is impaired in PS cDKO mice. Notably, depletion of intracellular Ca2+ stores by inhibition of sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) minics and occludes the effects of PS inactivation, as evidenced by decreases of the evoked excitatory postsynaptic currents (EPSCs) amplitude in the LPP and MPP of control neurons but no effect on the EPSC amplitude in PS cDKO neurons, suggesting that impaired intracellular calcium homeostasis in the absence of PS may contribute to the observed deficits in synaptic transmission. While spontaneous synaptic events, such as both the frequency and the amplitude of spontaneous or miniature EPSCs, are similar between PS cDKO and control neurons, long-term potentiation (LTP) is impaired in the LPP and MPP of PS cDKO mice, accompanied with reduction of evoked NMDA receptor-mediated responses. These findings show the importance of PS in the regulation of synaptic plasticity and intracellular calcium homeostasis in the hippocampal perforant pathways.
Patient-derived cell-based pharmacogenomic assessment to unveil underlying resistance mechanisms and novel therapeutics for advanced lung cancer
Authors: Yu Namhee , Hwang Mihwa , Lee Youngjoo , Song Bo Ram , Kang Eun Hye , Sim Hanna , Ahn Beung-Chul , Hwang Kum Hui , Kim Jihyun , Hong Sehwa , Kim Sunshin , Park Charny , Han Ji-Youn
Published: January 2023

Background

A pharmacogenomic platform using patient-derived cells (PDCs) was established to identify the underlying resistance mechanisms and tailored treatment for patients with advanced or refractory lung cancer.

Methods

Drug sensitivity screening and multi-omics datasets were acquired from lung cancer PDCs (n = 102). Integrative analysis was performed to explore drug candidates according to genetic variants, gene expression, and clinical profiles.

Results

PDCs had genomic characteristics resembled with those of solid lung cancer tissues. PDC molecular subtyping classified patients into four groups: (1) inflammatory, (2) epithelial-to-mesenchymal transition (EMT)-like, (3) stemness, and (4) epithelial growth factor receptor (EGFR)-dominant. EGFR mutations of the EMT-like subtype were associated with a reduced response to EGFR-tyrosine kinase inhibitor therapy. Moreover, although RB1/TP53 mutations were significantly enriched in small-cell lung cancer (SCLC) PDCs, they were also present in non-SCLC PDCs. In contrast to its effect in the cell lines, alpelisib (a PI3K-AKT inhibitor) significantly inhibited both RB1/TP53 expression and SCLC cell growth in our PDC model. Furthermore, cell cycle inhibitors could effectively target SCLC cells. Finally, the upregulation of transforming growth factor-β expression and the YAP/TAZ pathway was observed in osimertinib-resistant PDCs, predisposing them to the EMT-like subtype. Our platform selected XAV939 (a WNT-TNKS-β-catenin inhibitor) for the treatment of osimertinib-resistant PDCs. Using an in vitro model, we further demonstrated that acquisition of osimertinib resistance enhances invasive characteristics and EMT, upregulates the YAP/TAZ-AXL axis, and increases the sensitivity of cancer cells to XAV939.

Conclusions

Our PDC models recapitulated the molecular characteristics of lung cancer, and pharmacogenomics analysis provided plausible therapeutic candidates.
Integrated multi-dimensional analysis highlights DHCR7 mutations involving in cholesterol biosynthesis and contributing therapy of gastric cancer
Authors: Chen Yuqi , Yan Wenying , Yang Kexi , Qian Yiting , Chen Yanjun , Wang Ruoqin , Zhu Jinghan , He Yuxin , Wu Hongya , Zhang Guangbo , Shi Tongguo , Chen Weichang
Published: January 2023

Background

Genetic background plays an important role in the occurrence and development of gastric cancer (GC). With the application of genome-wide association study (GWAS), an increasing number of tumor susceptibility genes in gastric cancer have been discovered. While little of them can be further applicated in clinical diagnosis and treatment due to the lack of in-depth analysis.

Methods

A GWAS of peripheral blood leukocytes from GC patients was performed to identify and obtain genetic background data. In combination with a clinical investigation, key SNP mutations and mutated genes were screened. Via in vitro and in vivo experiments, the function of the mutated gene was verified in GC. Via a combination of molecular function studies and amino acid network analysis, co-mutations were discovered and further identified as potential therapeutic targets.

Results

At the genetic level, the G allele of rs104886038 in DHCR7 was a protective factor identified by the GWAS. Clinical investigation showed that patients with the rs104886038 A/G genotype, age ≥ 60, smoking ≥ 10 cigarettes/day, heavy drinking and H. pylori infection were independent risk factors for GC, with odds ratios of 12.33 (95% CI, 2.10 ~ 72.54), 20.42 (95% CI, 2.46 ~ 169.83), and 11.39 (95% CI, 1.82 ~ 71.21), respectively. Then molecular function studies indicated that DHCR7 regulated cell proliferation, migration, and invasion as well as apoptosis resistance via cellular cholesterol biosynthesis pathway. Further amino acid network analysis based on the predicted structure of DHCR7 and experimental verification indicated that rs104886035 and rs104886038 co-mutation reduced the stability of DHCR7 and induced its degradation. DHCR7 mutation suppressed the malignant behaviour of GC cells and induced apoptosis via inhibition on cell cholesterol biosynthesis.

Conclusion

In this work, we provided a comprehensive multi-dimensional analysis strategy which can be applied to in-depth exploration of GWAS data. DHCR7 and its mutation sites identified by this strategy are potential theratic targets of GC via inhibition of cholesterol biosynthesis.
The association of serum vitamin D level and neonatal respiratory distress syndrome
Authors: Liu Weili , Xu Pingping
Published: January 2023

Background

Neonatal respiratory distress syndrome (NRDS) is a critical disease in premature infants. Vitamin D plays an important role in promoting the development of fetal lung structure and the formation of pulmonary surfactants. This study aimed to investigate the correlation between the serum 25(OH)D3level in the cord blood of premature infants and the prognosis of NRDS.

Methods

This retrospective study recruited 82 preterm infants (gestational age 28-36 weeks) diagnosed with NRDS as the NRDS group, and 82 non-NRDS preterm infants as the control group, respectively. The diagnostic efficiency of 25(OH)D3on NRDS was revealed by receiver operating characteristics curve (ROC) analysis. Enzyme linked immunosorbent assay (ELISA) was performed to evaluate the 25(OH)D3level in the serum of the cord blood in preterm neonates. The NRDS risk indicators were identified by the multivariate logistic regression analysis.

Results

Cord blood 25(OH)D3levels were significantly lower in NRDS preterm infants than control group infants. 25(OH)D3levels in cord blood can be used to predict NRDS in preterm infants. In addition, 25(OH)D3levels in cord blood were positively correlated with Apgar score (1 min/5 min) and negatively correlated with oxygen support/CPAP duration in preterm infants with NRDS. 25(OH)D3in cord blood <57.69 nmol/L (24 ng/ml), gestational age <31 weeks, birth weight <1.86 kg, Apgar score (1 min) <7 and Apgar score (5 min) < 8 were independent risk factors for NRDS.

Conclusion

25(OH)D3level is an independent risk factor for NRDS in preterm infants.
Protocol for a parallel group, two-arm, superiority cluster randomised trial to evaluate a community-level complementary-food safety and hygiene and nutrition intervention in Mali: the MaaCiwara study (version 1.3; 10 November 2022)
Authors: Asamane Evans A. , Quinn Laura , Watson Samuel I. , Lilford Richard J. , Hemming Karla , Sidibe Cheick , Rego Ryan T. , Bensassi Sami , Diarra Youssouf , Diop Samba , Gautam Om Prasad , Islam Mohammad Sirajul , Jackson Louise , Jolly Kate , Kayentao Kassoum , Koita Ousmane , Manjang Buba , Tebbs Susan , Gale Nicola , Griffiths Paula , Cairncross Sandy , Toure Ousmane , Manaseki-Holland Semira
Published: January 2023

Background

Diarrhoeal disease remains a significant cause of morbidity and mortality among the under-fives in many low- and middle-income countries. Changes to food safety practices and feeding methods around the weaning period, alongside improved nutrition, may significantly reduce the risk of disease and improve development for infants. We describe a protocol for a cluster randomised trial to evaluate the effectiveness of a multi-faceted community-based educational intervention that aims to improve food safety and hygiene behaviours and enhance child nutrition.

Methods

We describe a mixed-methods, parallel group, two-arm, superiority cluster randomised controlled trial with baseline measures. One hundred twenty clusters comprising small urban and rural communities will be recruited in equal numbers and randomly allocated in a 1:1 ratio to either treatment or control arms. The community intervention will be focussed around an ideal mother concept involving all community members during campaign days with dramatic arts and pledging, and follow-up home visits. Participants will be mother–child dyads (27 per cluster period) with children aged 6 to 36 months. Data collection will comprise a day of observation and interviews with each participating mother–child pair and will take place at baseline and 4 and 15 months post-intervention. The primary analysis will estimate the effectiveness of the intervention on changes to complementary-food safety and preparation behaviours, food and water contamination, and diarrhoea. Secondary outcomes include maternal autonomy, enteric infection, nutrition, child anthropometry, and development scores. A additional structural equation analysis will be conducted to examine the causal relationships between the different outcomes. Qualitative and health economic analyses including process evaluation will be done.

Conclusions

The trial will provide evidence on the effectiveness of community-based behavioural change interventions designed to reduce the burden of diarrhoeal disease in the under-fives and how effectiveness varies across different contexts.

Trial registration

ISRCTN14390796. Registration date December 13, 2021
Assessing the effectiveness and cost-effectiveness of a solution-focused resource-orientated approach (DIALOG+) to improving the quality of life for people with psychosis in India and Pakistan—a cluster RCT
Authors: Bird Victoria Jane , Sajun Sana Zehra , Peppl Renata , Evans-Lacko Sara , Priebe Stefan , Singh Swaran , Venkatraman Lakshmi , Ramachandran Padmavati , Pasha Aneeta , Malik Ashar , Qureshi Onaiza
Published: January 2023

Background

Severe mental illness (SMI) presents a major challenge worldwide, affecting approximately 5–8% of the world’s population. It causes significant distress to affected people, families and wider communities, generating high costs through loss of productivity and ongoing healthcare use. Over 75% of patients with psychosis receive inadequate care and experience a negative financial impact and reduced quality of life (QoL). It is therefore a priority to reduce the treatment gap by providing low-cost, effective interventions for people with psychosis.

Our research project, PIECEs, is designed to explore, adapt and test a low-cost, approach (DIALOG+) that makes use of existing resources to improve community-based care for patients with psychosis. The research will be conducted in two urban sites: Karachi, Pakistan and Chennai, India. DIALOG+ is a novel, technology-assisted and resource-oriented intervention, based on QoL research, concepts of patient-centred communication, IT developments and solution-focused therapy. However, the approach has not been rigorously tested within India and Pakistan. Our randomised controlled trial (RCT) aims to test the effectiveness and cost-effectiveness of DIALOG+ in improving the QoL and clinical outcomes for individuals with long-term psychosis being treated in the community in India and Pakistan.

Methods

To assess the acceptability, feasibility, and cost effectiveness of DIALOG+, we will conduct a cluster RCT with 210 patients and 14 clinicians in each country. The intervention will be used during a routine interaction between a clinician and a patient. It consists of a patient-centred assessment (the DIALOG scale) whereby the clinician invites the patient to rate their satisfaction with different life domains and treatment aspects, which forms the active control group. The intervention group will follow this up with a four-step solution-focused approach to identify the patient’s resources and develop solutions to deal with the patient's concerns (DIALOG+).

Discussion

If shown to be effective DIALOG+ has the potential to improve community-based care and the QoL for millions of people within India and Pakistan who experience psychosis.

Trial registration

The trial was registered prospectively on the ISRCTN Registry: ISRCTN13022816 on 9 February 2022.
Mapping the methodological diversity of published drug discontinuation studies—a scoping review of study topics, objectives, and designs
Authors: Grede Nina , Kuss Katrin , Staudt Ina , Donner-Banzhoff Norbert , Viniol Annika
Published: January 2023

Background

Trials evaluating drug discontinuation (drug discontinuation trials, DDTs) show a broad methodological spectrum. There are several specific methodological aspects in drug discontinuation trials (e.g., determination of research question; configuration of intervention; definition of outcomes). To verify this specifies, we did a scoping review about the study designs of drug discontinuation trials.

Methods

A systematic literature search in Medline (PubMed), The Cochrane Library, EMBASE, CINAHL, Web of Science, and PsycINFO was performed. In a two-step selection process, we identified DDTs, which evaluate the discontinuation of one or more long-term medication as the investigated intervention, by two independent reviewers. Besides bibliographic data, we extracted several parameters to describe the used study design of the included DDTs: motivation for DDT, initially treatment aim of the discontinued medication, study design, methods of discontinuation, follow-up times, number of study participants, and outcome parameter.

Results

Out of 12,132 records, we included 581 DDTs. The most common motivation for doing a DDT were expected side effects (48.8%), the motivation of proving the efficacy of medication (21.6%), or doubts on the expected benefit of the used medication (13.8%). The majority of the discontinued medication was initially prescribed to improve the prognosis of a chronic disease (60.4%) or to relieve symptoms (31%). The study designs of the trials showed a broad methodological spectrum. The minority of the drug discontinuation trials were randomized controlled trials (34%).

Conclusion

The results of this scoping review illustrates the need for an evidence-based methodological standard for planning and conducting drug discontinuation trials.
Whole-transcriptome profiling across different developmental stages of Aedes albopictus (Diptera: Culicidae) provides insights into chitin-related non-coding RNA and competing endogenous RNA networks
Authors: Liu Wenjuan , An Sha , Cheng Peng , Zhang Kexin , Gong Maoqing , Zhang Zhong , Zhang Ruiling
Published: January 2023

Background

The Asian tiger mosquito,Aedes albopictus, is one of the most invasive species and a vector of numerous arboviruses. The deleterious effects of long-term and inappropriate use of chemical pesticides have stimulated the exploration of new, environmentally friendly control strategies. Non-coding RNAs (ncRNAs) have been proven to participate in almost all biological processes of insects.

Methods

In this study, circular RNAs (circRNAs) and microRNAs (miRNAs) covering five developmental stages [egg, early larvae, late larvae, pupae, adult (female and male)] ofA. albopictuswere obtained using whole-transcriptome sequencing technology. Combined with long non-coding RNAs (lncRNAs) from previous research, circRNA/lncRNA‒miRNA‒mitochondrial RNA (mRNA) networks were constructed.

Results

A total of 1434 circRNAs and 208 miRNAs were identified. More differentially expressed circRNAs (DE circRNAs) and miRNAs (DE miRNAs) were found in the egg versus early larvae comparison group. Functional enrichment analysis demonstrated that most of the circRNA/lncRNA‒miRNA‒mRNA networks were involved in chitin metabolism. Hub genes of each circRNA/lncRNA‒miRNA‒mRNA network were screened out, which can be used as novel targets to disturb the molting process ofA. albopictus.

Conclusions

Regulatory relationships obtained from competing endogenous RNA (ceRNA) networks provide more information to manipulate the metamorphosis process and are helpful for developing effective and sustainable methods to control mosquitoes.

Graphical Abstract
Localization of secreted ferritin (FER2) in the embryos of the tick Haemaphysalis longicornis
Authors: Hernandez Emmanuel Pacia , Shimazaki Kei , Niihara Hiroko , Umemiya-Shirafuji Rika , Fujisaki Kozo , Tanaka Tetsuya
Published: January 2023

Despite the absence of a blood meal, embryogenesis involves many processes that require nutrients and other essential elements, including iron. Due to the lack of an external source of these nutrients, these requirements are acquired maternally. Because of the toxic nature of iron, they are transferred through iron transport molecules such as secreted ferritin (FER2). Here we tried to follow the trail of the FER2 through indirect immunofluorescence, and we observed an apparent shift of FER2 from the germ layer at the early part of development to the appendages during the late stage of embryogenesis. FER2 is also found in the middle part of the legs of the embryo. The apparent movement not only sheds light on iron processing events during embryogenesis but also indirectly guides organogenesis in the tick.

Graphical Abstract
Genome-wide liver transcriptomic profiling of a malaria mouse model reveals disturbed immune and metabolic responses
Authors: Hu Xueyan , Zhao Jie , Zhao Junhui , Yang Ence , Jia Mozhi
Published: January 2023

Background

The liver is responsible for a range of functions in vertebrates, such as metabolism and immunity. In malaria, the liver plays a crucial role in the interaction between the parasite and host. Although malarial hepatitis is a common clinical complication of severe malaria, other malaria-related liver changes have been overlooked during the blood stage of the parasite life-cycle, in contrast to the many studies that have focused on parasite invasion of and replication in the liver during the hepatic stage of the parasite.

Methods

A rodent model of malaria was established using Plasmodium yoelii strain 17XL, a lethal strain of rodent malaria, for liver transcriptomic profiling.

Results

Differentially expressed messenger RNAs were associated with innate and adaptive immune responses, while differentially expressed long noncoding RNAs were enriched in the regulation of metabolism-related pathways, such as lipid metabolism. The coexpression network showed that host genes were related to cellular transport and tissue remodeling. Hub gene analysis of P. yoelii indicated that ubiquitination genes that were coexpressed with the host were evolutionarily conserved.

Conclusions

Our analysis yielded evidence of activated immune responses, aberrant metabolic processes and tissue remodeling changes in the livers of mice with malaria during the blood stage of the parasite, which provided a systematic outline of liver responses during Plasmodium infection.

Graphical Abstract
Vimentin affects inflammation and neutrophil recruitment in airway epithelium during Streptococcus suis serotype 2 infection
Authors: Meng Yu , Lin Shaojie , Niu Kai , Ma Zhe , Lin Huixing , Fan Hongjie
Published: January 2023

Streptococcus suis serotype 2 (SS2) frequently colonizes the swine upper respiratory tract and can cause Streptococcal disease in swine with clinical manifestations of pneumonia, meningitis, and septicemia. Previously, we have shown that vimentin, a kind of intermediate filament protein, is involved in the penetration of SS2 through the tracheal epithelial barrier. The initiation of invasive disease is closely related to SS2-induced excessive local inflammation; however, the role of vimentin in airway epithelial inflammation remains unclear. Here, we show that vimentin deficient mice exhibit attenuated lung injury, diminished production of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and the IL-8 homolog, keratinocyte-derived chemokine (KC), and substantially reduced neutrophils in the lungs following intranasal infection with SS2. We also found that swine tracheal epithelial cells (STEC) without vimentin show decreased transcription of IL-6, TNF-α, and IL-8. SS2 infection caused reassembly of vimentin in STEC, and pharmacological disruption of vimentin filaments prevented the transcription of those proinflammatory cytokines. Furthermore, deficiency of vimentin failed to increase the transcription of nucleotide oligomerization domain protein 2 (NOD2), which is known to interact with vimentin, and the phosphorylation of NF-κB protein p65. This study provides insights into how vimentin promotes excessive airway inflammation, thereby exacerbating airway injury and SS2-induced systemic infection.
Effector protein Hcp2a of avian pathogenic Escherichia coli interacts with the endoplasmatic reticulum associated RPL23 protein of chicken DF-1 fibroblasts
Authors: Chen Zhe , Qi Zhao , Li Ziqi , Song Zichao , Wang Xiaoru , Shao Ying , Tu Jian , Song Xiangjun
Published: January 2023

The type VI secretion system (T6SS) is a secretion apparatus widely found in pathogenic Gram-negative bacteria and is important for competition among various bacteria and host cell pathogenesis. Hcp is a core component of functional T6SS and transports toxic effectors into target cells by assembling to form tube-like structures. Studies have shown that Hcp simultaneously acts as an effector to influence cellular physiological activities; however, the mechanism of its activity in host cells remains unclear. To investigate the target of effector protein Hcp2a in a chicken fibroblast cell line, we first detected the subcellular localization of Hcp2a in DF-1 cells by indirect immunofluorescence assay. The results showed that Hcp2a protein was localized in the endoplasmic reticulum of DF-1 cells. We also used a streptavidin–biotin affinity pull-down assay combined with LC–MS/MS to screen DF-1 cell lysates for proteins that interact with Hcp2a and analyze the cellular functional pathways affected by them. The results showed that Hcp2a interacted with 52 DF-1 cellular proteins that are involved in multiple intracellular pathways. To further explore the mechanism of Hcp2a protein targeting the endoplasmic reticulum of DF-1 cells, we screened three endoplasmic reticulum-associated proteins (RSL1D1, RPS3A, and RPL23) from 52 prey proteins of Hcp2a for protein–protein molecular docking analysis. The docking analysis showed that the effector protein Hcp2a and the RPL23 protein had good complementarity. Overall, we propose that Hcp2a has strong binding activity to the RPL23 protein in DF-1 cells and this may help Hcp2a anchor to the endoplasmic reticulum in DF-1 cells.
Triple-adaptive subgradient extragradient with extrapolation procedure for bilevel split variational inequality
Authors: Ceng Lu-Chuan , Ghosh Debdas , Shehu Yekini , Yao Jen-Chih
Published: January 2023

This paper introduces a triple-adaptive subgradient extragradient process with extrapolation to solve abilevel split pseudomonotone variational inequality problem(BSPVIP) with the common fixed point problem constraint of finitely many nonexpansive mappings. The problem under consideration is in real Hilbert spaces, where the BSPVIP involves a fixed point problem of demimetric mapping. The proposed rule exploits the strong monotonicity of one operator at the upper level and the pseudomonotonicity of another mapping at the lower level. The strong convergence result for the proposed algorithm is established under some suitable assumptions. In addition, a numerical example is given to demonstrate the viability of the proposed rule. Our results improve and extend some recent developments to a great extent.
Reexamining feedback in the context of different rhetorical patterns of writing
Authors: AL Harrasi Kothar Talib Sulaiman
Published: January 2023

Drawing upon research on the ways texts work as communication across different disciplines, this study investigated teacher and student feedback practices on three different patterns of writing: comparison-contrast essays, opinion essays, and cause-and-effect essays. The data were collected through three qualitative techniques: interviews, class observations, and an analysis of course documents and student-marked writing. The results showed that the participants did not always adhere to rhetorical features of different writing patterns when giving and responding to feedback. Rather, practices of feedback were majorly shaped by their beliefs about academic writing, assessment, and cognitive issues with rhetorical patterns. The results suggest a need for raising student and teacher awareness of the values of different patterns of writing for subject-domain studies; building a constructive alignment between writing course objectives, course assessment, and feedback practices; and involving students in the academic acculturation process.
Nomogram based on spectral CT quantitative parameters and typical radiological features for distinguishing benign from malignant thyroid micro-nodules
Authors: Song Zuhua , Li Qian , Zhang Dan , Li Xiaojiao , Yu Jiayi , Liu Qian , Li Zongwen , Huang Jie , Zhang Xiaodi , Tang Zhuoyue
Published: January 2023

Purpose

To analyse the predictive effect of a nomogram combining dual-layer spectral computed tomography (DSCT) quantitative parameters with typical radiological features in distinguishing benign micro-nodule from thyroid microcarcinoma (TMC).

Methods

Data from 342 instances with thyroid micro-nodules (≤1 cm) who underwent DSCT (benign group: n = 170; malignant group: n = 172) were reviewed. Typical radiological features including micro-calcification and enhanced blurring, and DSCT quantitative parameters including attenuation on virtual monoenergetic images (40 keV, 70 keV and 100 keV), the slope of the spectral HU curve (λHU), normalized iodine concentration (NIC), and normalized effective atomic number (NZeff) in the arterial phase (AP) and venous phase (VP), were measured and compared between the benign and malignant groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of significant quantitative DSCT parameters or the models combining DSCT parameters respectively and typical radiological features based on multivariate logistic regression (LR) analysis. A nomogram was developed using predictors with the highest diagnostic performance in the above model, as determined by multivariate LR analysis.

Results

The DSCT parameter APλHU showed the greatest diagnostic efficiency in identifying patients with TMC, with an area under the ROC curve (AUC) of 0.829, a sensitivity and specificity of 0.738 and 0.753, respectively. Then, APλHU was combined with the two radiological features to construct the DSCT-Radiological nomogram, which had an AUC of 0.858, a sensitivity of 0.791 and a specificity of 0.800. The calibration curve of the nomogram demonstrated that the prediction result was in good agreement with the actual observation. The decision curve revealed that the nomogram can result in a greater net benefit than the all/none-intervention strategy for all threshold probabilities.

Conclusion

As a valid and visual noninvasive prediction tool, the DSCT-Radiological nomogram incorporating DSCT quantitative parameters and radiological features shows favourable predictive efficiency for identifying benign and malignant thyroid micro-nodules.
Association of genetic polymorphism of NUDT15, TPMT and ITPA gene in the toxicity and efficacy of azathioprine-based regimen in Egyptian inflammatory bowel disease patients
Authors: Eltantawy Nashwa , El-Zayyadi Islam Abd El-Hamid , Elberry Ahmed A. , Salah Layla M. , Abdelrahim Mohamed E. A. , Kassem Amira B.
Published: January 2023

Background

Inflammatory Bowel disease (IBD) is a chronic progressive condition that prompts generous physical and mental morbidity. Choosing the best kind of management and medication dosage prevents new episodes of high disease activity during therapy because of adverse drug reactions (ADRs). This can lead to cessation or inefficacy of the treatment, or complete non-responsiveness to specific medications. Pharmacogenetics (PGx) is a well-established aspect in IBD. One of the exemplary instances of PGx is thiopurines, which are frequently utilized as IBD therapy. This study aimed to evaluate specific gene polymorphism involved in the toxicity and efficacy of Azathioprine (AZA) use in the management in Egyptian patients and to find the correlation between the polymorphism of Nudix Hydrolase15 (NUDT15) gene (rs116855232), The Thiopurine methyltransferase (TPMT) gene (rs1800460) and Inosine Triphosphatase (ITPA) gene (rs1127354) which are involved in the metabolism of the medications utilized in IBD management.

Methods

This prospective study was performed in 150 patients with IBD. All patients were treated with 2 mg/kg per day AZA (Imuran, GlaxoSmithKline®) for at least 3 months at therapeutic doses to induce remission. Subsequent treatment of AZA. The minimum follow-up period for those who did not experience ADR was one year. Among the studied patients, one hundred twenty-nine patients were treated with combination regimen of steroids (oral prednisone 1 mg/kg/day).

Also, treatment failure was considered among the patients who could not tolerate AZA side effects, or there was no improvement after dose modification.

Results

The most identifiable adverse effect among the studied population was anemia followed by leukopenia and myelosuppression. SNPs genotype TPMT (rs1800460) and ITPA gene (rs1127354) were significantly related to adverse effects among IBD patients receiving Azathioprine treatment. There was a lack of any variants in the NUDT15 genotype among the Egyptian population.

Conclusion

Further research is required in to clarify the relationship between NUDT15 PGx and AZA-ADRs. The effect of NUDT15 PGx on toxicity and ADRs as yet necessitates to be elucidated. Studies with a larger sample size and involving different ethnicities are also necessary.
The awareness and knowledge of dysphagia among health care practitioners in Egypt
Authors: Hady Aisha Fawzy Abdel , Farag Heba Mahmoud , Sheikhany Ayatallah Raouf
Published: January 2023

Background

There is a lack of research relating to awareness associated with dysphagia-specific knowledge of health care practitioners in Egypt. The study aimed at determining the level of awareness and knowledge of dysphagia among health care practitioners in Egypt to detect the pitfalls to be addressed through awareness-raising programs.

Methods

A questionnaire was distributed online to be filled in by health care practitioners apart from those with the highest knowledge about dysphagia as otolaryngologists, phoniatricians, and gastroenterologists. It consists of 4 sections including sociodemographic data, the participants’ level of awareness and knowledge about dysphagia through questions about dysphagia identification, symptoms and signs, and complications, data about the practice of dysphagia in their hospitals, and their level of awareness and knowledge of the role played by the phoniatricians in dysphagia management in addition to the availability of this specialty in their centers.

Results

Forty-seven percent of the participants rated themselves as having moderate to high contract with dysphagia cases. Sixty-six percent of the participants did not receive training in dysphagia. Only 18.1% of the participants indicated the presence of a dysphagia clinic in their institute. Forty percent of the participants refer dysphagia cases to GIT followed by 37.8% of the participants refer to ENT then 18.6% of them refer to Phoniatrics. Forty-six percent of the participants do not know the investigations work-up for dysphagia.

Conclusion

Egyptian health care practitioners in the Greater Cairo area encountered in this study differ in their knowledge and awareness level about dysphagia according to their specialties and their degree of contact with dysphagia cases. Minimal awareness was found in specialties with low contact. Fair awareness was found in specialties with moderate to high contact with dysphagia cases. There was insufficient knowledge about non-overt symptoms and signs of dysphagia, the widely used investigations, and the role of phoniatricians in dealing with dysphagia cases. Neurology was the specialty with a relatively higher awareness.
Evaluation of myocardial performance by serial speckle tracking echocardiography in diagnosis and follow-up of a patient with eosinophilic myocarditis
Authors: Sharifkazemi Mohammadbagher , Rezaian Gholamreza , Lotfi Mehrzad
Published: January 2023

Background

Speckle tracking echocardiography (STE) has been used as an adjunct diagnostic modality in patients with eosinophilic myocarditis. Its serial dynamic nature, however, has never been reported before.

Case presentation

A 17-year-old boy presented in cardiogenic shock state. His full blood count revealed an absolute eosinophilic count of 11.18 × 103/μL. An emergency 2D echocardiogram (2DE) showed global left ventricular hypokinesia with LVEF = 9.0% by Simpson’s method and a large amount of pericardial effusion. STE showed a global longitudinal strain (GLS) of − 4.1%. Because of his poor clinical status and presence of marked hypereosinophilia and the possibility of eosinophilic myocarditis (EM), parenteral pulse therapy with methylprednisolone and inotropes was started with subsequent improvement within the next 48 h. Over the next few days, he had his first cardiovascular magnetic resonance imaging (CMR), which showed late gadolinium enhancement (LGE) in different cardiac regions. After two weeks of therapy, he left the hospital in a stable condition, with LVEF = 38.0%, and GLS = − 13.9%. He did well during his two months of outpatient follow-ups and was found to have an absolute eosinophil count of 0.0% on several occasions. Unfortunately, he was re-admitted because of treatment non-compliance with almost the same, albeit milder, symptoms. The WBC count was 18.1 × 103 per microliter, and the eosinophilic count was 5.04 × 103/μL (28%). Heart failure treatment and high-dose prednisolone were started. After 15 days of admission, he got better and was discharged. During both hospital admissions and several months of follow-up, he had multiple 2DEs, STE, and two CMR studies. None of his STEs were identical to the prior studies and were dynamic with frequent wax and wanes throughout the admissions and follow-ups. Thus a single admission-time STE study was not sufficient enough to properly predict the patient’s outcome. Follow-up STEs showed new sites of myocardial involvement despite the absence of eosinophilia.

Conclusion

The use of STE in this patient, proved to have an added value in the evaluation and stratification of the left ventricular function in patients with EM and can be used as a diagnostic adjunct to CMR for diagnosis of EM.
Mutational heterogeneity of imatinib resistance and efficacy of ripretinib vs sunitinib in patients with gastrointestinal stromal tumor: ctDNA analysis from INTRIGUE.
Authors: Bauer Sebastian , Jones Robin Lewis , George Suzanne , Gelderblom Hans , Schöffski Patrick , von Mehren Margaret , Zalcberg John Raymond , Kang Yoon-Koo , Abdul Razak Albiruni Ryan , Trent Jonathan C. , Attia Steven , Le Cesne Axel , Reichmann William , Sprott Kam , Achour Haroun , Sherman Matthew L. , Ruiz-Soto Rodrigo , Blay Jean-Yves , Heinrich Michael C.
Published: January 2023

397784

Background: Ripretinib, a switch-control tyrosine kinase inhibitor (TKI), is indicated for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with ≥3 TKIs, including imatinib. Sunitinib is approved for advanced GIST after imatinib failure. Circulating tumor DNA (ctDNA) analysis may provide insight into the efficacy of these agents in second-line advanced GIST. Here, we present exploratory baseline ctDNA results from INTRIGUE. Methods: INTRIGUE is an open-label, phase 3 study that enrolled adult pts with advanced GIST who progressed on or had intolerance to imatinib (NCT03673501). Randomization was 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 wks on/2 wks off). Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing (NGS)-based assay. Only KIT mutations are reported here. Results: Of 453 pts in the overall intent-to-treat (ITT) population, 362 (80%) samples were analyzed. ctDNA was detected in 280/362 (77%), with KIT mutations detected in 213/280 (76%). Common resistance mutations were in the KIT activation loop (AL; exons 17/18; 89/213, 42%) and ATP-binding pocket (ATP-BP; exons 13/14; 81/213, 38%). Efficacy in pts with detectable ctDNA in the KIT exon 11 and overall ITT populations was consistent with the primary analysis based on tumor data used for randomization. Pts with KIT exon 11 + 17/18 (−9/13/14) mutations had superior progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) with ripretinib vs sunitinib, whereas pts with exon 11 + 13/14 (−9/17/18) mutations had better PFS, ORR, and OS with sunitinib vs ripretinib (Table). Subgroup safety profiles were consistent with the primary analysis. Conclusions: While KIT ATP-BP mutations predicted clinical benefit from sunitinib vs ripretinib, pts harboring resistance mutations in the KIT AL derived meaningful clinical benefit from ripretinib but not sunitinib. This study demonstrates the value of ctDNA NGS-based sequencing of the complex landscape of KIT mutations to predict the clinical benefit of ripretinib or sunitinib as second-line therapy in pts with advanced GIST. Clinical trial information: NCT03673501 . [Table: see text]
Radioactive Iodine Therapy Decreases the Recurrence of Intermediate-Risk PTC With Low Thyroglobulin Levels
Authors: Tian Tian , Qi Zhibing , Huang Shuhui , Wang Hongxi , Huang Rui
Published: January 2023

Context

Whether radioactive iodine therapy (RAIT) is necessary for intermediate-risk papillary thyroid cancer (PTC) after total thyroidectomy is still lacking reliable evidence, especially for patients with low postoperative thyroglobulin (Tg) levels.

Objective

This study conducted a propensity score matching (PSM) analysis to investigate whether RAIT is effective in reducing the recurrence of intermediate-risk PTC with low Tg levels.

Methods

In total, 1487 patients with intermediate-risk PTC with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL after total thyroidectomy were enrolled retrospectively. The clinicopathological characteristics were compared between the non-RAIT and RAIT groups before and after PSM (1:4 matching). The impact of RAIT on biochemical recurrence and structural recurrence was evaluated.

Results

Overall, 1349 (90.7%) patients underwent RAIT, and 138 (9.3%) did not. After a median follow-up time of 51 months, 30 patients presented with recurrence, including 11 structural and 19 biochemical recurrences. After PSM, the non-RAIT group had a higher rate of structural recurrence (5/138 vs 5/552, P = .046) and biochemical recurrence (6/138 vs 4/552, P = .005) than the RAIT group. Multivariate analysis showed that not receiving RAIT was an independent risk factor for structural recurrence (hazard ratio [HR] 10.572, 95% CI 2.439-45.843, P = .002) and biochemical recurrence (HR 16.568, 95% CI 3.670-74.803, P < .001). Kaplan–Meier analysis showed that the non-RAIT group had more unfavorable recurrence-free survival (structural and biochemical, all P < .05).

Conclusion

RAIT could decrease the recurrence risk of intermediate-risk PTC in patients with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL. Further prospective randomized studies are needed to confirm these findings.
Dissident Practices
Authors: Calirman Claudia
Published: January 2023

In Dissident Practices, Claudia Calirman examines sixty years of visual art by prominent and emerging Brazilian women artists from the 1960s to the present, covering the period from the military dictatorship to the return to democracy in the mid-1980s, the social changes of the 2000s, the rise of the Right in the late-2010s, and the recent development of an overtly feminist art practice. Though they were lauded as key figures in Brazilian art, these artists still faced adversity and constraints because of their gender. Although many of them in the 1960s and 1970s disavowed the term feminism, Calirman gives a nuanced account of how they responded to authoritarianism, engaged with trauma in the aftermath of the military dictatorship, interrogated social gender norms, and fought against women’s objectification. By battling social inequalities, structures of power, and state violence, these artists create political agency in a society in which women remain targets of brutality and discrimination.
Deep Brain Stimulation of the Centromedian Nucleus of the Thalamus for Lennox-Gastaut Syndrome: A Systematic Review and Individual Patient Data Analysis
Authors: Shlobin Nathan A. , Hofmann Katherine , Cohen Nathan T. , Koubeissi Mohamad Z. , Gaillard William D. , Oluigbo Chima O.
Published: January 2023

BACKGROUND:

Lennox-Gastaut syndrome (LGS) is a severe childhood-onset pharmacoresistant epilepsy. Deep brain stimulation (DBS) of the centromedian nucleus of the thalamus (CMN) has been utilized.

OBJECTIVE:

To conduct a systematic review and individual patient data (IPD) analysis to characterize outcomes of DBS of CMN in LGS.

METHODS:

PubMed, Embase, and Scopus were searched per Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles were screened by title/abstract then full text. Included articles were reviewed for bibliographic, demographic, and outcome data. IPD were extracted from studies providing IPD for all patients.

RESULTS:

Of 72 resultant articles, 10 studies (114 patients) were included. Six of 7 studies reporting the outcome of ≥50% seizure reduction indicated that ≥50% of patients achieved this, with improved functional ability. Seizure freedom rate was generally <10%. Six studies with 47 patients provided IPD. The mean ages at epilepsy onset and CMN DBS were 3.9 ± 4.5 years and 17.4 ± 8.8 years, respectively. Nineteen of 41 (46.3%) patients had positive MRI findings. Seizure types included atypical absence in 39 (83.0%) patients, generalized tonic-clonic in 32 (68.1%), tonic in 22 (46.8%), and atonic in 20 (42.6%). Thirty-eight (80.9%) patients experienced ≥50% reduction in seizure frequency, and only 3 (6.4%) experienced seizure freedom. The mean seizure reduction was 62.9% ± 31.2% overall. Quality of life improved in 30/34 (88.2%) and was unchanged in the remainder (11.8%). The complication rate was 2/41 (4.9%). The mean length of follow-up was 19.8 ± 26.1 months (IQR: 4-18 months).

CONCLUSION:

Limited data indicate that DBS of the CMN may be effective and safe for people with LGS.