bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid identification of mosquito species and age by mass spectrometric analysis
Authors: Wagner Iris , Grigoraki Linda , Enevoldson Peter , Clarkson Michael , Jones Sam , Hurst Jane L. , Beynon Robert J. , Ranson Hilary
Published: January 2023

Background

A rapid, accurate method to identify and to age-grade mosquito populations would be a major advance in predicting the risk of pathogen transmission and evaluating the public health impact of vector control interventions. Whilst other spectrometric or transcriptomic methods show promise, current approaches rely on challenging morphological techniques or simple binary classifications that cannot identify the subset of the population old enough to be infectious. In this study, the ability of rapid evaporative ionisation mass spectrometry (REIMS) to identify the species and age of mosquitoes reared in the laboratory and derived from the wild was investigated.

Results

The accuracy of REIMS in identifying morphologically identical species of the Anopheles gambiae complex exceeded 97% using principal component/linear discriminant analysis (PC-LDA) and 84% based on random forest analysis. Age separation into 3 different age categories (1 day, 5–6 days, 14–15 days) was achieved with 99% (PC-LDA) and 91% (random forest) accuracy. When tested on wild mosquitoes from the UK, REIMS data could determine the species and age of the specimens with accuracies of 91 and 90% respectively.

Conclusions

The accuracy of REIMS to resolve the species and age of Anopheles mosquitoes is comparable to that achieved by infrared spectroscopy approaches. The processing time and ease of use represent significant advantages over current, dissection-based methods. Importantly, the accuracy was maintained when using wild mosquitoes reared under differing environmental conditions, and when mosquitoes were stored frozen or desiccated. This high throughput approach thus has potential to conduct rapid, real-time monitoring of vector populations, providing entomological evidence of the impact of alternative interventions.
Prediction of protein solubility based on sequence physicochemical patterns and distributed representation information with DeepSoluE
Authors: Wang Chao , Zou Quan
Published: January 2023

Background

Protein solubility is a precondition for efficient heterologous protein expression at the basis of most industrial applications and for functional interpretation in basic research. However, recurrent formation of inclusion bodies is still an inevitable roadblock in protein science and industry, where only nearly a quarter of proteins can be successfully expressed in soluble form. Despite numerous solubility prediction models having been developed over time, their performance remains unsatisfactory in the context of the current strong increase in available protein sequences. Hence, it is imperative to develop novel and highly accurate predictors that enable the prioritization of highly soluble proteins to reduce the cost of actual experimental work.

Results

In this study, we developed a novel tool, DeepSoluE, which predicts protein solubility using a long-short-term memory (LSTM) network with hybrid features composed of physicochemical patterns and distributed representation of amino acids. Comparison results showed that the proposed model achieved more accurate and balanced performance than existing tools. Furthermore, we explored specific features that have a dominant impact on the model performance as well as their interaction effects.

Conclusions

DeepSoluE is suitable for the prediction of protein solubility in E. coli; it serves as a bioinformatics tool for prescreening of potentially soluble targets to reduce the cost of wet-experimental studies. The publicly available webserver is freely accessible at http://lab.malab.cn/~wangchao/softs/DeepSoluE/.
Short-term air pollution exposure associated with death from kidney diseases: a nationwide time-stratified case-crossover study in China from 2015 to 2019
Authors: Cai Miao , Wei Jing , Zhang Shiyu , Liu Wei , Wang Lijun , Qian Zhengmin , Lin Hualiang , Liu Echu , McMillin Stephen Edward , Cao Yu , Yin Peng
Published: January 2023

Background

Long-term exposure to air pollution has been associated with the onset and progression of kidney diseases, but the association between short-term exposure to air pollution and mortality of kidney diseases has not yet been reported.

Methods

A nationally representative sample of 101,919 deaths from kidney diseases was collected from the Chinese Center for Disease Control and Prevention from 2015 to 2019. A time-stratified case-crossover study was applied to determine the associations. Satellite-based estimates of air pollution were assigned to each case and control day using a bilinear interpolation approach and geo-coded residential addresses. Conditional logistic regression models were constructed to estimate the associations adjusting for nonlinear splines of temperature and relative humidity.

Results

Each 10 µg/m3 increment in lag 0–1 mean concentrations of air pollutants was associated with a percent increase in death from kidney disease: 1.33% (95% confidence interval [CI]: 0.57% to 2.1%) for PM1, 0.49% (95% CI: 0.10% to 0.88%) for PM2.5, 0.32% (95% CI: 0.08% to 0.57%) for PM10, 1.26% (95% CI: 0.29% to 2.24%) for NO2, and 2.9% (95% CI: 1.68% to 4.15%) for SO2. 

Conclusions

Our study suggests that short-term exposure to ambient PM1, PM2.5, PM10, NO2, and SO2 might be important environmental risk factors for death due to kidney diseases in China.
RAGE inhibition alleviates lipopolysaccharides-induced lung injury via directly suppressing autophagic apoptosis of type II alveolar epithelial cells
Authors: Xiong Xi , Dou Jiaying , Shi Jingyi , Ren Yuqian , Wang Chunxia , Zhang Yucai , Cui Yun
Published: January 2023

Background

Advanced glycation end product receptor (RAGE) acts as a receptor of pro-inflammatory ligands and is highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention recently. However, the roles of autophagy and RAGE in the pathogenesis of acute lung injury remain unclear. Therefore, this study aimed to explore whether RAGE activation signals take part in the dysfunction of alveolar epithelial barrier through autophagic death.

Methods

Acute lung injury animal models were established using C57BL/6 and Ager gene knockout (Ager−/− mice) mice in this study. A549 cells and primary type II alveolar epithelial (ATII) cells were treated with siRNA to reduce Ager gene expression. Autophagy was inhibited by 3-methyladenine (3-MA). Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8 (CCK-8) assay. The serum and bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and soluble RAGE (sRAGE) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The involvement of RAGE signals, autophagy and apoptosis was assessed using western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test.

Results

The expression of RAGE was promoted by lipopolysaccharide (LPS), which was associated with activation of autophagy both in mice lung tissues and A549 cells as well as primary ATII cells. sRAGE in BALF was positively correlated with IL-6 and IL-8 levels. Compared with the wild-type mice, inflammation and apoptosis in lung tissues were alleviated in Ager−/− mice. Persistently activated autophagy contributed to cell apoptosis, whereas the inhibition of autophagy by 3-MA protected lungs from damage. In addition, Ager knockdown inhibited LPS-induced autophagy activation and attenuated lung injury. In vitro, knockdown of RAGE significantly suppressed the activation of LPS-induced autophagy and apoptosis of A549 and primary ATII cells. Furthermore, RAGE activated the downstream STAT3 signaling pathway.

Conclusion

RAGE plays an essential role in the pathogenesis of ATII cells injury. Our results suggested that RAGE inhibition alleviated LPS-induced lung injury by directly suppressing autophagic apoptosis of alveolar epithelial cells.
The worsening effect of anemia on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T CMR feature tracking study
Authors: Qian Wen-Lei , Xu Rong , Shi Rui , Li Yuan , Guo Ying-Kun , Fang Han , jiang Li , Yang Zhi-Gang
Published: January 2023

Objective

To explore the additive effects of anemia on left ventricular (LV) global strains in patients with type 2 diabetes mellitus (T2DM) with or without anemia via cardiac magnetic resonance (CMR) feature tracking technology.

Materials and methods

236 T2DM patients with or without anemia and 67 controls who underwent CMR examination were retrospectively enrolled. LV function parameters, LV global radial peak strain (GRPS), longitudinal peak strain (GLPS), and circumferential peak strain (GCPS) were used to analyze the function and global strain of the heart. One-way analysis of variance and the chi-square test were used for intergroup analysis. Multivariable linear regression analysis was performed for the two T2DM groups to explore factors associated with LV global strains.

Results

The T2DM group with anemia was oldest and had a lowest hemoglobin (Hb) concentration, lowest estimated glomerular filtration rate, highest LV end-systolic volume index, highest end-diastolic volume index and highest LV mass index than the control group and T2DM without anemia group (all P ≤ 0.001). Besides, The LV global peak strains in all three directions worsened successively from the control group to the T2DM without anemia group to the T2DM with anemia group (all p < 0.001). Among all clinical indices, the decrease in Hb was independently associated with the worsening in GRPS (β = 0.237, p = 0.001), GCPS (β = 0.326, p < 0.001), and GLPS (β = 0.265, p < 0.001).

Conclusion

Anemia has additive deleterious effects on LV function and LV global strains in patients with T2DM. Regular detection and early intervention of anemia might be beneficial for T2DM patients.
Successful percutaneous coronary intervention with extracorporeal membrane oxygenation in a patient with acute inferior wall myocardial infarction complicated by electrical storm, cardiogenic shock, and cardiac arrest: a case report
Authors: Yan Bixia , Zhang Guoqi , Huang Chaolong , Liu Zhengjiang
Published: January 2023

Background

High-risk patients with coronary heart disease who develop acute myocardial infarction (AMI) have severe coronary lesions. If severe complications occur, such as malignant ventricular arrhythmia, cardiogenic shock, and cardiac arrest, implementation of emergency percutaneous coronary intervention (PCI) may be hindered, leading to a higher perioperative mortality rate. Extracorporeal membrane oxygenation (ECMO) can pave the way for rapid myocardial reperfusion therapy. When cardiac arrest occurs, hemodynamic support with ECMO can facilitate revascularization with PCI, which can increase the time available for further salvage and treatment and reduce intraoperative risk during PCI.

Case presentation

Herein, we report a case of a 61-year-old man with AMI who suffered electrical storm of sustained malignant ventricular fibrillation, cardiogenic shock, and cardiac arrest and was successfully treated with PCI with ECMO support. During PCI, repeated aspiration and removal of the right coronary artery thrombus were performed, and blood flow was restored after right coronary artery balloon dilation. One episode of defibrillation was delivered to restore sinus rhythm. Then, stents were implanted in the distal and proximal right coronary artery lesions to achieve revascularization. After PCI with ECMO support, irreversible malignant arrhythmia returned to sinus rhythm through coronary perfusion, which prevented death following unsuccessful cardiopulmonary resuscitation. After applying active treatments, including anti-shock, mechanical ventilation, anti-inflammation, and organ support, the patient was discharged after his condition and vital signs stabilized. The patient was followed up once a week after hospital discharge, and his cardiopulmonary function recovered well.

Conclusions

With ECMO support, PCI should be performed immediately in patients with inferior wall AMI complicated by electrical storm of sustained ventricular fibrillation, cardiogenic shock, and cardiac arrest to facilitate stent placement, achieve complete revascularization, restore coronary perfusion, and avoid death
Tracking unlabeled cancer cells imaged with low resolution in wide migration chambers via U-NET class-1 probability (pseudofluorescence)
Authors: Antonello Paola , Morone Diego , Pirani Edisa , Uguccioni Mariagrazia , Thelen Marcus , Krause Rolf , Pizzagalli Diego Ulisse
Published: January 2023

Cell migration is a pivotal biological process, whose dysregulation is found in many diseases including inflammation and cancer. Advances in microscopy technologies allow now to study cell migration in vitro, within engineered microenvironments that resemble in vivo conditions. However, to capture an entire 3D migration chamber for extended periods of time and with high temporal resolution, images are generally acquired with low resolution, which poses a challenge for data analysis. Indeed, cell detection and tracking are hampered due to the large pixel size (i.e., cell diameter down to 2 pixels), the possible low signal-to-noise ratio, and distortions in the cell shape due to changes in the z-axis position. Although fluorescent staining can be used to facilitate cell detection, it may alter cell behavior and it may suffer from fluorescence loss over time (photobleaching).

Here we describe a protocol that employs an established deep learning method (U-NET), to specifically convert transmitted light (TL) signal from unlabeled cells imaged with low resolution to a fluorescent-like signal (class 1 probability). We demonstrate its application to study cancer cell migration, obtaining a significant improvement in tracking accuracy, while not suffering from photobleaching. This is reflected in the possibility of tracking cells for three-fold longer periods of time. To facilitate the application of the protocol we provide WID-U, an open-source plugin for FIJI and Imaris imaging software, the training dataset used in this paper, and the code to train the network for custom experimental settings.
Retraction Note: Genistein inhibits stemness of SKOV3 cells induced by macrophages co-cultured with ovarian cancer stem-like cells through IL-8/STAT3 axis
Authors: Ning Yingxia , Feng Weifeng , Cao Xiaocheng , Ren Kaiqun , Quan Meifang , Chen A. , Xu Chang , Qiu Yebei , Cao Jianguo , Li Xiang , Luo Xin
Published: January 2023

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-018-1010-1.
Correction: Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility
Authors: Shirouzu Shinichiro , Sugita Naohiro , Choijookhuu Narantsog , Yamaguma Yu , Takeguchi Kanako , Ishizuka Takumi , Tanaka Mio , Fidya  , Kai Kengo , Chosa Etsuo , Yamashita Yoshihiro , Koshimoto Chihiro , Hishikawa Yoshitaka
Published: January 2023

An amendment to this paper has been published and can be accessed via the original article.
Determining external randomised pilot trial feasibility in preparation for a definitive trial: a web-based survey of corresponding authors of external pilot trial publications
Authors: Mellor Katie , Dutton Susan J. , Hopewell Sally
Published: January 2023

Background

External randomised pilot trials aim to determine whether a future definitive randomised controlled trial (RCT) should be conducted, and if so, how. However, not every pilot trial that suggests that a definitive trial will be feasible will progress to a definitive study. In this study, we surveyed corresponding authors of external randomised pilot trial publications to assess pilot trial outcomes in terms of feasibility and progression.

Methods

Web-based surveys were sent to corresponding authors of external randomised pilot trial publications, open for four weeks between January and February 2022. Four surveys were produced depending on whether the corresponding author had published a trial protocol or results publication, and whether progression criteria were reported. Surveys asked whether a future RCT was considered feasible, whether progression criteria were met (if applicable), what other factors informed the assessment of pilot trial feasibility, and whether the pilot trial has progressed to further research. Data was analysed using descriptive statistics and conventional content analysis.

Results

98 of 276 corresponding authors completed the survey (average response rate of 36% across all surveys). Of these, 89 respondents indicated that their trial had completed. Ninety per cent of respondents who were corresponding authors of completed pilot trials stated that their pilot trial was either feasible (42/89, 47%) or feasible with changes to the trial design (38/89, 43%), yet only 66% (59/89) reported the intention to conduct a future definitive trial. Availability of funding for a future definitive trial and changing priorities of the Chief Investigator were the most common barriers to progression identified. Qualitative research findings was the most frequent factor considered both by corresponding authors who reported and who did not report progression criteria when determining trial feasibility.

Conclusions

Just under one quarter (21/89, 24%) of respondents who considered their external randomised pilot trial to be feasible, or feasible with changes, did not intend to conduct a definitive trial highlighting research inefficiency and waste.

Trial registration

Open Science Framework osf.io/d28hr [20 December 2021]
Preoperative pain hypersensitivity is associated with axial pain after posterior cervical spinal surgeries in degenerative cervical myelopathy patients: a preliminary resting-state fMRI study
Authors: Su Qian , Li Jie , Chu Xu , Zhao Rui
Published: January 2023

Objective

To test whether preoperative pain sensitivity is associated with the postoperative axial pain (PAP) in degenerative cervical myelopathy (DCM) and to explore its underlying brain mechanism.

Methods

Clinical data and resting-state fMRI data of 62 DCM patients along with 60 age/gender matched healthy participants were collected and analysed. Voxel-wise amplitude of low frequency fluctuation (ALFF) was computed and compared between DCM patients and healthy controls. Correlation analyses were performed to reveal the association between the clinical metrics and brain alterations. Clinical data and ALFF were also compared between DCM patients with PAP and without PAP.

Results

(1) Relative to healthy participants, DCM patients exhibited significantly lower preoperative pain threshold which is associated with the PAP intensity; (2) Relative to patients without PAP, PAP patients exhibited increased ALFF in mid-cingulate cortex (MCC) and lower preoperative pain threshold; (3) Further, multivariate pattern analysis revealed that MCC ALFF provide additional value for PAP vs. non-PAP classification.

Conclusion

In conclusion, our findings suggest that preoperative pain hypersensitivity may be associated with postoperative axial pain in degenerative cervical myelopathy patients. This finding may inspire new therapeutic ideas for patients with preoperative axial pain.
Hypoimmunogenic human pluripotent stem cells are valid cell sources for cell therapeutics with normal self-renewal and multilineage differentiation capacity
Authors: Chen Yifan , Zhou Yanjie , Zhou Zhongshu , Fang Yujiang , Ma Lin , Zhang Xiaoqing , Xiong Jie , Liu Ling
Published: January 2023

Hypoimmunogenic human pluripotent stem cells (hPSCs) are expected to serve as an unlimited cell source for generating universally compatible “off-the-shelf” cell grafts. However, whether the engineered hypoimmunogenic hPSCs still preserve their advantages of unlimited self-renewal and multilineage differentiation to yield functional tissue cells remains unclear. Here, we systematically studied the self-renewal and differentiation potency of three types of hypoimmunogenic hPSCs, established through the biallelic lesion of B2M gene to remove all surface expression of classical and nonclassical HLA class I molecules (B2Mnull), biallelic homologous recombination of nonclassical HLA-G1 to the B2M loci to knockout B2M while expressing membrane-bound β2m-HLA-G1 fusion proteins (B2MmHLAG), and ectopic expression of soluble and secreted β2m-HLA-G5 fusion proteins in B2MmHLAG hPSCs (B2Mm/sHLAG) in the most widely used WA09 human embryonic stem cells. Our results showed that hypoimmunogenic hPSCs with variable expression patterns of HLA molecules and immune compromising spectrums retained their normal self-renewal capacity and three-germ-layer differentiation potency. More importantly, as exemplified by neurons, cardiomyocytes and hepatocytes, hypoimmunogenic hPSC-derived tissue cells were fully functional as of their morphology, electrophysiological properties, macromolecule transportation and metabolic regulation. Our findings thus indicate that engineered hypoimmunogenic hPSCs hold great promise of serving as an unlimited universal cell source for cell therapeutics.
Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke
Authors: Yabuno Satoru , Yasuhara Takao , Nagase Takayuki , Kawauchi Satoshi , Sugahara Chiaki , Okazaki Yosuke , Hosomoto Kakeru , Sasada Susumu , Sasaki Tatsuya , Tajiri Naoki , Borlongan Cesar V. , Date Isao
Published: January 2023

Background

Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke.

Methods

Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 105 cells/5 μl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups.

Results

SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05).

Conclusions

This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF.
In-depth health surveillance and clinical nutrition in farmed Atlantic salmon: a strategic attempt to detect and mitigate an HSMI outbreak
Authors: Rennemo Johan , Myrvold Steinar , Berge Kjetil , Kileng Øyvind , Pedersen Børge , Aksberg Dan Sindre , Lisik Piotr , Crappe Delphine , McGurk Charles , Rimstad Espen , Wessel Øystein , Koppang Erling Olaf , Bjørgen Håvard
Published: January 2023

Fish health personnel have limited tools in combatting viral diseases such as heart and skeletal muscle inflammation (HSMI) in open net-pen farmed Atlantic salmon. In this study, we aimed to predict HSMI by intensified health monitoring and apply clinical nutrition to mitigate the condition. We followed a commercial cohort (G1) of Atlantic salmon that was PRV-1 naïve when transferred to a sea cage at a location where HSMI outbreaks commonly occur. The fish in the other cages (G2-G6) at the location had a different origin than G1 and were PRV-1 positive prior to sea transfer. By continuous analysis of production data and sequentially (approximately every fourth week) performing autopsy, RT-qPCR (for PRV-1 and selected immune genes), blood and histological analysis of 10 fish from G1 and G2, we identified the time of PRV-1 infection in G1 and predicted the onset of HSMI prior to any clinical signs of disease. Identical sequences across partial genomes of PRV-1 isolates from G1 and G2 suggest the likely transfer from infected cages to G1. The isolates were grouped into a genogroup known to be of high virulence. A commercial health diet was applied during the HSMI outbreak, and the fish had low mortality and an unaffected appetite. In conclusion, we show that fish health and welfare can benefit from in-depth health monitoring. We also discuss the potential health value of clinical nutrition as a mean to mitigate HSMI.
Stability of thermoelastic Timoshenko beam with suspenders and time-varying feedback
Authors: Mukiawa Soh Edwin , Enyi Cyril Dennis , Messaoudi Salim A.
Published: January 2023

This paper considers a one-dimensional thermoelastic Timoshenko beam system with suspenders, general weak internal damping with time varying coefficient, and time-varying delay terms. Under suitable conditions on the nonlinear terms, we prove a general stability result for the beam model, where exponential and polynomial decay are special cases. We also gave some examples to illustrate our theoretical finding.
Obesity difference on association blood malondialdehyde level and diastolic hypertension in the elderly population: a cross-sectional analysis
Authors: Huang Ying , Chen Hong , Liu Qifan , Hu Jinzhu , Hu Dongxi , Huang Zixi , Xu Zhenyan , Wan Rong
Published: January 2023

Aims

Although increased production of malondialdehyde (MDA), an end product of lipid oxidation caused by reactive oxygen species (ROS), has been found be elevated in hypertensive population, whether MDA contributed to a changed risk of hypertension is uncertain. We aimed to investigate whether elevated blood levels of MDA contribute to increased risk of hypertension and obesity has a modified effect on the association in an older Chinese population.

Methods

Data were obtained from 2011 to 2012 of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national cohort of older adults in China. Associations between blood MDA level and systolic and diastolic blood pressure (BP) and risk of hypertension were performed by multivariable linear regression and logistic regression analysis.

Results

The results of smooth curve revealed a gradual upward trend on association of blood MDA level with diastolic BP (P < 0.001), but not with systolic BP (P > 0.05). Logistic regression analysis suggested that elevated blood MDA levels were associated with increased risk of diastolic hypertension (OR = 1.079, 95% CI 1.039–1.122, P < 0.001) rather than systolic hypertension (OR = 0.978, 95% CI 0.943–1.015, P = 0.247) after adjustments of related confounding factors were made. Furthermore, we found the significant modification effect of obesity on the association between MDA level and risk of diastolic hypertension evaluated by body mass index (BMI, interaction P = 0.015) and by waist circumference (interaction P = 0.016).

Conclusion

Our results firstly identified that increased blood MDA levels were associated with elevated risk of diastolic hypertension, rather than systolic hypertension in the non-obese old population.
Diagnosis, pathophysiology and preventive strategies for cardiac surgery-associated acute kidney injury: a narrative review
Authors: Yu Ying , Li Chenning , Zhu Shuainan , Jin Lin , Hu Yan , Ling Xiaomin , Miao Changhong , Guo Kefang
Published: January 2023

Acute kidney injury (AKI) is a common and serious complication of cardiac surgery and is associated with increased mortality and morbidity, accompanied by a substantial economic burden. The pathogenesis of cardiac surgery-associated acute kidney injury (CSA-AKI) is multifactorial and complex, with a variety of pathophysiological theories. In addition to the existing diagnostic criteria, the exploration and validation of biomarkers is the focus of research in the field of CSA-AKI diagnosis. Prevention remains the key to the management of CSA-AKI, and common strategies include maintenance of renal perfusion, individualized blood pressure targets, balanced fluid management, goal-directed oxygen delivery, and avoidance of nephrotoxins. This article reviews the pathogenesis, definition and diagnosis, and pharmacological and nonpharmacological prevention strategies of AKI in cardiac surgical patients.
Sitravatinib as a potent FLT3 inhibitor can overcome gilteritinib resistance in acute myeloid leukemia
Authors: Zhang Yvyin , Wang Peihong , Wang Yang , Shen Yang
Published: January 2023

Background

Gilteritinib is the only drug approved as monotherapy for acute myeloid leukemia (AML) patients harboring FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation throughout the world. However, drug resistance inevitably develops in clinical. Sitravatinib is a multi-kinase inhibitor under evaluation in clinical trials of various solid tumors. In this study, we explored the antitumor activity of sitravatinib against FLT3-ITD and clinically-relevant drug resistance in FLT3 mutant AML.

Methods

Growth inhibitory assays were performed in AML cell lines and BaF3 cells expressing various FLT3 mutants to evaluate the antitumor activity of sitravatinib in vitro. Immunoblotting was used to examine the activity of FLT3 and its downstream pathways. Molecular docking was performed to predict the binding sites of FLT3 to sitravatinib. The survival benefit of sitravatinib in vivo was assessed in MOLM13 xenograft mouse models and mouse models of transformed BaF3 cells harboring different FLT3 mutants. Primary patient samples and a patient-derived xenograft (PDX) model were also used to determine the efficacy of sitravatinib.

Results

Sitravatinib inhibited cell proliferation, induced cell cycle arrest and apoptosis in FLT3-ITD AML cell lines. In vivo studies showed that sitravatinib exhibited a better therapeutic effect than gilteritinib in MOLM13 xenograft model and BaF3-FLT3-ITD model. Unlike gilteritinib, the predicted binding sites of sitravatinib to FLT3 did not include F691 residue. Sitravatinib displayed a potent inhibitory effect on FLT3-ITD-F691L mutation which conferred resistance to gilteritinib and all other FLT3 inhibitors available, both in vitro and in vivo. Compared with gilteritinib, sitravatinib retained effective activity against FLT3 mutation in the presence of cytokines through the more potent and steady inhibition of p-ERK and p-AKT. Furthermore, patient blasts harboring FLT3-ITD were more sensitive to sitravatinib than to gilteritinib in vitro and in the PDX model.

Conclusions

Our study reveals the potential therapeutic role of sitravatinib in FLT3 mutant AML and provides an alternative inhibitor for the treatment of AML patients who are resistant to current FLT3 inhibitors.
Pharmacist perceptions of a “good death” and differences in perception between patients with cancer, oncologists, and oncology nurses: a questionnaire survey
Authors: Konishi Reiko , Isogai Junichi , Mukai Akira , Komori Koji , Majima Takashi , Ito Shinji , Kawada Kou
Published: January 2023

Background

For pharmacists expected to encounter the deaths of many of their patients in the near future, it is important to understand the perception of a “good death” for patients with cancer who are likely to be aware of the circumstances of their poor prognosis. In this study, we clarified pharmacists’ perceptions of a “good death” and considered the differences in perception among patients with cancer, oncologists, and oncology nurses.

Methods

From April to June 2022, an anonymous questionnaire survey was conducted on pharmacists working in hospitals and pharmacies and on members of the Japanese Society for Pharmaceutical Palliative Care and Sciences. The questionnaire consisted of 57 questions, called attributes, developed by Miyashita et al. to investigate the perception of “good death” in Japanese cancer medicine. The importance of those attributes was investigated using a 7-point Likert scale.

Results

Three thousand four hundred thirty-two pharmacists were made aware of this survey, and 207 participated in the survey. The responses of pharmacists to the 57 questions were very similar to those of the oncologists. Among them, “Fighting against disease until one’s last moment” and “Not making trouble for others” had very low importance, which was the most significantly different from the responses of patients with cancer. “Fighting against disease until one’s last moment” tended to be significantly underestimated by pharmacists engaged in patient guidance and interview compared to that by pharmacists not engaged in the duty (p = 0.02). Also, when we compared pharmacists with or without qualifications related to cancer and palliative care, there was no significant difference in the importance of “Fighting against disease until one’s last moment.” However, the importance of “Not making trouble for others” for qualified pharmacists was significantly underestimated (p = 0.04).

Conclusion

Since pharmacists understand the limits of chemotherapy, they may want to be close to the patient but may not strongly agree with the “Fighting against cancer” component that patients with cancer prefer. It may be necessary to reconsider better ways of approaching the wishes and satisfaction of patients with cancer under the care of medical professionals in the field of oncology.
The influence of in-groups and out-groups on the theory-of-mind processing: evidence from different ethnic college students
Authors: Zhu Tingyu , Zhang Lijin , Wang Ping , Xiang Meiqiu , Wu Xiujuan
Published: January 2023

According to previous studies of theory of mind (ToM), social environment and cultural background affect individuals’ cognitive ability to understand other people’s minds. There are cross-group differences in ToM. The present study aimed to examine whether social environment and culture affect the ToM in Uygur and Han groups and whether the individual’s cognitive ToM and affective ToM show in-group advantages. Han and Uygur college students were recruited as participants. The “self/other differentiation task” was used to measure cognitive ToM (Study 1), and the “Yoni task” was used to measure both cognitive and affective ToM (Study 2). We found that Han participants processed the cognitive and affective states of others faster and more accurately than Uygur ones. Uygur and Han participants processed in-group members’ cognitive and affective states faster and more accurately. Furthermore, Uygur participants were more accurate in the cognitive ToM processing of in-group members, while Han participants were faster in the affective ToM processing of in-group members. The findings indicated that ethnic culture and group identify might influence ToM processing. Strengthening exchanges between ethnic groups may enable individuals to better process out-group members’ psychological states.
Assessment of 24-h moving average PM2.5 concentrations in Bangkok, Thailand against WHO guidelines
Authors: Sooktawee Sirapong , Kanchanasuta Suwimon , Bunplod Natthaya
Published: January 2023

Particulate matter less than 2.5 μm in diameter (PM2.5) pollution has gained more concern, as can be seen from the World Health Organization (WHO) revised air quality guideline (AQG) value. To compare with the 24-h AQG value, the 24-h mean (daily average) of hourly monitoring data has been widely used, but the nature of data in hourly variation has been lost. The 24-h moving average can be an alternative approach to preserving hourly data behavior, while various positions of the hour (leftmost, center, or rightmost hour) can be used to store the moving average. In this study, similarity testing by cross-correlation and Euclidean distance was performed to present a suitable 24-h moving average time series for hourly data, and then presented proportions of PM2.5 concentrations within each interim target and AQG ranges. The PM2.5 time series of the leftmost and rightmost 24-h moving average revealed lags of − 13 to − 10 h and 10 to 13 h for the observed hourly data, respectively. The lags of the center 24-h moving average time series were of − 2 to 1 h, which showed more similar events to the hourly PM2.5 fluctuation than the leftmost and rightmost time series. The center 24-h moving average concentrations measured in Bangkok were categorized into interim target and AQG ranges. The results revealed that the proportion of concentrations lower than AQG during nighttime and daytime was approximately 40 and 28%, respectively. However, the results given from the leftmost and rightmost time series showed time shifts and differences in diurnal variation caused by the position used to store the average value. To keep hourly PM2.5 variation that can be compared with the 24-h WHO guidelines, this should be performed with careful and precautionary consideration of misinterpretation over a time scale, especially for implementing countermeasures and policies.
Genetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative review
Authors: Borra Swathi Swaroopa , Jane Niva Rose , Palaniappan Dhivyaprasath , Subramanian Rupakrishnan , Patankar Mithila Amar , Krishnamoorthy Sadagoban Gopal , Parthasarathy Arun Kanniyappan
Published: January 2023

Background

Organic cation transporter 2 (OCT2) is a renal carrier transporter protein found in the basolateral membrane of proximal epithelial cells, which facilitates active secretion of Metformin. The genetic polymorphism of OCT2 influences the pharmacodynamic and pharmacokinetic effect of Metformin in type 2 diabetes mellitus (T2DM) patients. This is also mainly associated with frequencies of the associated risk allele in a particular population.

Objective

The purpose of the study is to determine the impact of OCT2 genetic polymorphism on Metformin pharmacodynamics (PD) and pharmacokinetics (PK).

Method of study

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for performing the research. Following databases were used to conduct the search: PubMed/MEDLINE, Google Scholar, and the Cochrane Library. Relevant studies were retrieved and literatures were appraised for methodology, demographic characteristics, relevant SNPs, genetic intervention trials, and outcomes.

Results

Based on the data collected, 13 OCT2 Single nucleotide polymorphisms (SNPs) were identified across various ethnic groups. There were significant differences between the frequency distribution of shared alleles and impact of thirteen SNPs on Metformin. Among the thirteen OCT2 variants studied, rs316019 variant produced the most diverse responses in population by showing positive and negative impact on PK & PD of Metformin.

Discussion and conclusion

Each population's OCT2 polymorphism had a distinct effect on Metformin responsiveness. The findings of this study could bring significant benefits to patients with OCT2 genetic polymorphism if individualised T2DM therapy is introduced. Patient-centered treatment would improve the Metformin efficacy leading to new research in personalised medicine.
Machining process parameters optimization using soft computing technique
Authors: El Hossainy Tarek M. , Zeyada Yasser , Abdelkawy Abdallah
Published: January 2023

This work introduces an approach for optimization machinability measures of power consumption, machining time, and the surface roughness (PMS). This approach is starting with market customer’s demands, passing by optimizing the machinability measures (PMS), and ending by the optimized cutting conditions. The fuzzy logic was used to define the weights of each of required machinability measurement using method through expert rules depending on factory requirements. Genetic algorithm was formulated for giving optimum output values based on the customer’s demands. A neural network was designed for controlling the input cutting conditions with the PMS output parameters. The proposed soft computing technique creates reasonable results compared to experimental results and gives rich investigations for optimizing the output parameters not only for increasing productivity and quality demands but also for saving power consumed. The variation of consumed power, machining time, and surface roughness was calculated based on different customer demand levels. When the machining time and power consumed importance increased, the proposed technique reduced them by about 20% and 10% for the testes case.
Impact of a mental health patient portal on patients’ views of compassion: a mixed-methods study
Authors: Shin Hwayeon Danielle , Durocher Keri , Lo Brian , Chen Sheng , Ma Clement , Wiljer David , Strudwick Gillian
Published: January 2023

Background

Compassion is central to achieving positive clinical outcomes, commonly studied as a concept that enhances therapeutic alliance between patients and clinicians. Within mental health care, compassion may be enhanced by a patient portal, a digital platform where information is exchanged between clinicians and patients. The portal is viewed as a compassion-oriented technology, as it may positively influence safety, disease management, and patient engagement. As portals have limited implementation in mental health care, it is imperative to research the impact of portal use on patient’s perspectives of compassion expressed by clinicians.

Methods

We conducted a convergent mixed methods study to assess and understand the impact of portal use on patients’ experience of compassion in mental health care settings. The quantitative strand encompassed a self-administered survey consisting of a validated compassion scale at the time of enrolment in the portal and after both three and 6 months of portal use. The qualitative strand consisted of semi-structured interviews with patients after the three-month mark of portal use. Data collection and analysis of both strands happened independently, then these two complementary findings were merged narratively.

Results

A total of 113 patient surveys and ten interviews were included in analysis. The univariate model with time as the only independent variable did not show significant differences in the total compassion scores across the three time points, F (2, 135) = 0.36p = 0.7. The model was then adjusted for sex, age, and diagnosis and did not show significant changes in the total compassion scores, F (2, 135) = 0.42p = 0.66. Interview findings identified both positive and negative influences of portal use in patients’ perception of compassion. Some participants described compassion as something personal, not associated with the portal use. However, some participants reported that portals facilitated treatment experiences, being reflective of compassionate care.

Conclusions

Patient portals in mental health care may allow for timely exchange of information and create a space outside appointments to strengthen relationships between clinicians and patients, improving compassionate delivery of care. Further research can help better understand how portals can contribute to digital compassion as technological advancements continue to be integrated into mental health care contexts.
Negative hyperselection of patients with RAS wild-type metastatic colorectal cancer for panitumumab: A biomarker study of the phase III PARADIGM trial.
Authors: Shitara Kohei , Muro Kei , Watanabe Jun , Yamazaki Kentaro , Ohori Hisatsugu , Shiozawa Manabu , Yasui Hirofumi , Oki Eiji , Sato Takeo , Naito Takeshi , Komatsu Yoshito , Kato Takeshi , Soeda Junpei , Yamamoto Kouji , Yamashita Riu , Akagi Kiwamu , Ochiai Atsushi , Uetake Hiroyuki , Tsuchihara Katsuya , Yoshino Takayuki
Published: January 2023

11

Background: The PARADIGM trial showed longer median overall survival (OS) with first-line mFOLFOX6 plus panitumumab (PAN) vs bevacizumab (BEV) in patients (pts) with RAS wild type (WT) and left-sided metastatic colorectal cancer (mCRC) (37.9 vs 34.3 months, respectively; hazard ratio [HR], 0.82; P=0.031) and similar OS in right-sided pts (HR 1.09; Yoshino T, et al. ASCO 2022 LBA1). We evaluated the usefulness of negative hyperselection by gene alterations in ctDNA related to primary resistance to anti-EGFR therapy. Methods: Baseline plasma ctDNA (>10 ng/mL and >10 nM DNA) from pts enrolled in the biomarker study (NCT02394834) was assessed using a custom panel (PlasmaSELECT-R 91, PGDx). Preplanned gene alterations for hyperselection included KRAS, NRAS, PTEN, and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET, or NTRK1 fusions. Results: Among 802 pts in the full analysis set, 733 (91%) had evaluable pretreatment samples for ctDNA analysis. Of these pts, 204 (28%) had at least 1 gene alteration, including KRAS/NRAS (8%), BRAF V600E (11%), PTEN (5%), EGFR (3%), HER2 (5%), MET (1%), and fusions (1%). In 529 (72%) hyperselected pts without any gene alterations, OS tended to be longer with PAN vs BEV regardless of primary sidedness; the OS HRs ranged from 0.76 to 0.82, and the median OS gains ranged from 6.6 to 8.0 months (Table). Meanwhile, OS was similar or inferior with PAN vs BEV irrespective of the primary sidedness in pts with any of these gene alterations (Table). Conclusions: Negative hyperselection using ctDNA rather than tumor sidedness may identify appropriate pts for first-line PAN over BEV. These results warrant further validation in additional cohorts. Clinical trial information: NCT02394834 . [Table: see text]