bluuebunny/crossref_metadata_2025 huggingface dataset:
Expert recommendations for the management of diabetic macular edema with intravitreal dexamethasone implant: A Turkish Delphi study
Authors: Batıoğlu Figen , Yanık Özge , Saatçi Ali Osman , Eldem Bora , Akkın Cezmi , Afrashi Filiz , Özdemir Hakan , Menteş Jale , Güngör Kıvanç , Karabaş Levent , Karaçorlu Murat , Demircan Nihal , Koçak Nilüfer , Kır Nur , Ünlü Nurten , Avcı Remzi , Arvas Sema , Dündar Sema Oruç , Kadayıfçılar Sibel , Kaynak Süleyman , Özdek Şengül , Ovalı Tunç
Published: August 2022

Purpose

To provide consensus on the clinical use of intravitreal dexamethasone (DEX) implant for the treatment of diabetic macular edema (DME) in Turkey.

Methods

A panel of 22 retina experts prepared 77 statements of recommendation, and 80 retinal specialists practicing in Turkey were chosen to vote either in support or against each one. A Delphi-based method was used through which the ophthalmologists were able to view all of the results anonymously after two rounds and modify their subsequent answers. The survey was conducted via a mini website, and statements without consensus were resent to the specialists with the latest vote results a week later.

Results

A total of 72 ophthalmologists answered the first and second round questions. After the first stage, consensus was achieved on 55 of the statements, leaving 22 without agreement. After the second stage, consensus was reached on 11 of the remaining statements. Strong consensus was achieved on statements regarding the etiopathogenesis of DME and the first-line indications and safety of the DEX implant procedure. The panel recommended the use of DEX implant for patients with an arterial thromboembolic event in the last three months and also agreed that pro re nata DEX implant treatment not only provides better outcomes for DME patients but also reduces the treatment burden for those who could not receive an adequate number of anti-vascular endothelial growth factor (VEGF) injections.

Conclusion

This study provides clinical consensus and recommendations about the use of DEX implant in the clinical practice of DME management in Turkey.
Different Strategies for Counting the Depth of Coverage in Copy Number Variation Calling Tools
Authors: Kuśmirek Wiktor
Published: August 2022

There are many copy number variation (CNV) detection tools based on the depth of coverage. A characteristic feature of all tools based on the depth of coverage is the first stage of data processing—counting the depth of coverage in the investigated sequencing regions. However, each tool implements this stage in a slightly different way. Herein, we used data from the 1000 Genomes Project to present the impact of another depth of coverage counting strategies on the results of the CNVs detection process. In the study, we used 7 CNV calling tools: CODEX, CANOES, exomeCopy, ExomeDepth, CLAMMS, CNVkit, and CNVind; from each of these applications, we separated the process of counting the depth of coverage into independent modules. Then, we counted the depth of coverage by mentioned modules, and finally, the obtained depth of coverage tables were used as the input data set to other CNV calling tools. The performed experiments showed that the best methods of counting the depth of coverage are the algorithms implemented in the CLAMMS and CNVkit applications. Both ways allow obtaining much better sets of detected CNVs compared to counting the depth of coverage implemented in other tools. What is more, some CNV detection tools are reasonably resistant to changing the input depth of coverage table. In this study, we proved that the exomeCopy application gives an approximately similar set of the resulting rare CNVs, regardless of the method of counting the depth of coverage table.
Bioinformatic Tools for the Identification of MicroRNAs Regulating the Transcription Factors in Patients with β-Thalassemia
Authors: Kalaigar Sumayakausar S , Rajashekar Rajalaksmi Birur , Nataraj Suma M , Vishwanath Prashant , Prashant Akila
Published: August 2022

β-thalassemia is a significant health issue worldwide, with approximately 7% of the world’s population having defective hemoglobin genes. MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression at the post-transcriptional level by targeting multiple gene transcripts. The levels of fetal hemoglobin (HbF) can be increased by regulating the expression of the γ-globin gene using the suppressive effects of miRNAs on several transcription factors such as MYB, BCL11A, GATA1, and KLF. An early step in discovering miRNA:mRNA target interactions is the computational prediction of miRNA targets that can be later validated with wet-lab investigations. This review highlights some commonly employed computational tools such as miRBase, Target scan, DIANA-microT-CDS, miRwalk, miRDB, and micro-TarBase that can be used to predict miRNA targets. Upon comparing the miRNA target prediction tools, 4 main aspects of the miRNA:mRNA target interaction are shown to include a few common features on which most target prediction is based: conservation sites, seed match, free energy, and site accessibility. Understanding these prediction tools’ usage will help users select the appropriate tool and interpret the results accurately. This review will, therefore, be helpful to peers to quickly choose a list of the best miRNAs associated with HbF induction. Researchers will obtain significant results using these bioinformatics tools to establish a new important concept in managing β-thalassemia and delivering therapeutic strategies for improving their quality of life.
Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung Carcinoma
Authors: Yan Lin , Rust Bret M , Sundaram Sneha , Picklo Matthew J , Bukowski Michael R
Published: August 2022

Both clinical and laboratory studies have shown that monocyte chemotactic protein-1 (MCP-1) is involved in cancer spread. To understand the role of MCP-1 in metabolism in the presence of metastasis, we conducted an untargeted metabolomic analysis of primary metabolism on plasma collected from a study showing that MCP-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma (LLC) to the lungs in mice fed a high-fat diet (HFD). In a 2 × 2 design, wild-type (WT) or Mcp-1 knockout ( Mcp-1-/-) mice maintained on the AIN93G standard diet or HFD were subcutaneously injected with LLC cells to induce lung metastasis. We identified 87 metabolites for metabolomic analysis from this study. Amino acid metabolism was altered considerably in the presence of LLC metastases with the aminoacyl-tRNA biosynthesis pathways as the leading pathway altered. The HFD modified lipid and energy metabolism, evidenced by lower contents of arachidonic acid, cholesterol, and long-chain saturated fatty acids and higher contents of glucose and pyruvic acid in mice fed the HFD. These findings were supported by network analysis showing alterations in fatty acid synthesis and glycolysis/gluconeogenesis pathways between the 2 diets. Furthermore, elevations of the citrate cycle intermediates (citric acid, fumaric acid, isocitric acid, and succinic acid) and glyceric acid in Mcp-1-/- mice, regardless of diet, suggest the involvement of MCP-1 in mitochondrial energy metabolism during LLC metastasis. The present study demonstrates that MCP-1 deficiency and the HFD altered plasma metabolome in mice bearing LLC metastases. These findings can be useful in understanding the impact of obesity on prevention and treatment of cancer metastasis.
Recruitment interviews for intermediate labour markets: Identity construction under ambiguous expectations
Authors: Tiitinen Sanni , Lempiälä Tea
Published: August 2022

Intermediate labour markets (ILMs) provide fixed-term work opportunities and coaching for people in disadvantaged positions in labour markets. We study 46 sequences from six audio-recorded recruitment interviews for an ILM job targetted at people who have been unemployed for a prolonged period. Using an ethnomethodological approach to identity, membership categorisation analysis and conversation analysis, we study how interviewers and candidates construct and negotiate who is fit for the ILM job. We present interactional moves through which the participants jointly construct the ‘fit for the ILM job’ category and treat the candidate’s membership in it as a positive matter. Further, we demonstrate how the candidates are put in an interactionally difficult position in the interview as there are contradictory and ambiguous expectations about the ideal candidate. We discuss the results in relation to the interactional and institutional logics of a recruitment interview and suggest that enhancing the transparency might reinforce ethics of recruitment in ILMs.
A theoretical model of amplitude-dependent dynamical stiffness for cord-rubber air springs
Authors: Wu Mingyu , Chen Zhigang , Liu Dongqing , Wang Jing , Yin Hang , Dou Kaifang , Li Dongyang , Zhang Yang , Zhang Chong , Wei Yintao
Published: August 2022

Based on the principle of minimum complementary energy, a theoretical model considering the additional dynamic stiffness caused by the structural deformation of the cord-rubber diaphragm is proposed. The capability of modeling the dynamic stiffness change of the rolling lobe air spring provides guidance for material selection and the design of the diaphragm structure. The directly measured geometric parameters in the proposed model have physical meanings, while the relevant material parameters can be identified by combining the mechanics of composite materials and the Payne effect theory of rubber diaphragm structures. Three air springs with different designs and structures were selected for the indicator test and compared with the theoretical value. The comparison results show that the relative error was less than 3%, which verifies the universality and accuracy of the proposed dynamic stiffness theory of the rubber diaphragm. The results demonstrate that the amplitude-dependent additional stiffness generated by the rubber diaphragm is significant, and the lobe bending moment has the most considerable stiffness contribution to the rolling lobe air spring at low amplitudes. In the end, the changing trend of the entire dynamic stiffness with different design factors is given. The rubber diaphragm stiffness theory of rolling lobe air springs proposed in this paper provides powerful assistance for material selection and shape design for car air springs.
Neighborhood graph embedding interpretable fault diagnosis network based on local and non-local information balanced under imbalanced samples
Authors: Sun Zejin , Wang Youren , Sun Guodong , Gao Jiahao , PAN Zheng
Published: August 2022

Currently, the monitoring of the health status of mechanical systems is becoming more and more critical, and the actual monitoring data is massive and high-dimensional, and these data are characterized mainly by imbalance. To solve the problem of low fault recognition rate caused by data imbalance, this article proposed a novel local and non-local information balanced neighborhood graph embedding interpretable deep autoencoder (LGBNGEDAE) method for rotating machinery fault diagnosis. Specifically, the local and non-local neighborhood information graph is embedded into the original objective function of the deep autoencoder to smooth the manifold structure of the data in LGBNEDSAE, which endows the deep learning model with better data learning capability and robustness of feature extraction as well as more reasonable network interpretability, making it more suitable for feature learning and classification of unbalanced data. Further, the method’s excellent fault diagnosis capability and generalization performance are verified on two opposed experimental cases of gearboxes. Compared with other deep learning architectures and shallow learning models, the method performs better in the face of unbalanced datasets.
Does exercise during a ketogenic diet effectively alter appetite sensation, appetite-regulating hormones, and body composition?
Authors: Valinejad Amin , Khodaei Kazem
Published: August 2022

Exercise and diet are two essential interventions in weight control. The purpose of this study was to compare the effectiveness of two exercise training types during a ketogenic diet (KD) on appetite sensation, appetite-regulating hormones, and body composition in overweight or obese man. Thirty-six men, overweight or with obesity, voluntarily participated in this study. The participants were randomly assigned into three groups, including KD ( n = 12), aerobic training during KD (AT-KD) ( n = 12), and resistance training during KD (RT-KD) ( n = 12) groups. The participants followed a low-carbohydrate diet for 6 weeks. Exercise training programs consisted of three sessions per week over 6 weeks. Appetite sensation was analyzed using a visual analogue scale (VAS) in fasting and postprandial states. The Enzyme-Linked Immunosorbent Assay (ELISA) method analyzed appetite-regulating hormones, including spexin, leptin, and acylated ghrelin, in a fasting state. Body composition was measured using bioelectrical impedance analysis (BIA). Furthermore, the ketosis state was monitored by measuring urinary ketones weekly. The results indicated that in both AT-KD and RT-KD groups, spexin and acylated ghrelin increased while leptin decreased without any between-group differences. Hunger and prospective food consumption (PFC) declined while satiety and fullness increased in all groups. The AT-KD group experienced a significant decrease in hunger and PFC, while fullness increased compared with the KD group. Fat mass, weight, and body mass index (BMI) decreased in all groups. Lean body mass increased in the RT-KD group (+2.66 kg) compared with both AT-KD and KD groups (−1.71 and −1.33 kg, respectively). This study demonstrated that AT-KD and RT-KD effectively altered appetite-regulating hormones and suppressed appetite sensation. In addition, both interventions had a favorable effect on weight loss and body fat reduction, with a more pronounced effect of RT-KD on maintaining lean body mass in overweight or obese men.
Awareness regarding generic and ethical medicines, and Jan Aushadhi Kendra: A survey-based study
Authors: Sareen Ashutosh , Singh Gurvinder , Wadhwa Sheetu , Khurana Navneet , Kumar Rajesh
Published: August 2022

Background

Increased healthcare charges remain a prime subject worldwide, especially in underdeveloped and developing countries like India, where economic conditions are on the lower side. To control this, the Government of India (GoI) launched Jan Aushadhi scheme in April 2008 for providing low-cost generic medicines, however, the scheme has not been able to reach an extent. Moreover, the patients rely on branded prescribed medicines due to a lack of awareness. India is the world’s largest maker of generic medicines since its pharmaceutical sector fulfils over 50% of the global demand, still, Indians are spending their 10–20% of total income as health expenses.

Aim and Objective

This cross-sectional study was designed to have insight into the awareness of generic and ethical medicines among youth studying in different institutes. The main objective was to collect the responses from the students studying in various undergraduate and post-graduate professional programs. We aimed to collect 300 responses from students enrolled in various institutes located in Doaba region of Punjab.

Materials and Methods

A self-made questionnaire comprising basic questions based on generic and ethical medicines and Jan Aushadhi Kendra was randomly distributed amongst respondents through Google form.

Conclusion

According to the study’s findings, respondents had average understanding of the Jan Aushadhi Kendra. The study’s findings revealed a modest relationship between knowledge and attitude towards the Jan Aushadhi initiative. Despite the fact that the Jan Aushadhi plan was started many years ago, it has yet to gain limelight in the country.
N-trans-feruloyltyramine Protects Human Neuroblastoma SK-N-SH Cell Line Against H2O2-Induced Cytotoxicity
Authors: Soi-ampornkul Rungtip , Myint Ei Ei Phyo , Thangnipon Wipawan , Tantarungsee Nutnicha , Mitrpant Chalermchai , Tuchinda Patoomratana , Nobsathian Saksit , Vatanashevanopakorn Chinnavuth
Published: August 2022

Excessive accumulation of reactive oxygen species (ROS) has been regarded as a major contributor of pathogenesis in neurodegenerative diseases. N- trans-feruloyltyramine (NTF), an alkaloid isolated from several plants, has demonstrated an ability to be a potent antioxidant. In this study, the antioxidative and anti-apoptotic properties of NTF extracted from the stems of Polyalthia suberosa were investigated in the human neuroblastoma cell line SK-N-SH. NTF at concentrations ranging from 10 µM to 500 µM were not toxic to cells and reduced intracellular ROS levels significantly. Furthermore, pre-treatment of NTF significantly decreased H2O2-induced ROS generation and attenuated H2O2-mediated cytotoxicity. An increase in the expression of Bax and activated caspase-3 and reduction of Bcl-2 mediated by H2O2 was reversed by pre-treating the cells with 100 µM NTF. Likewise, NTF suppressed the increase of caspase-3 activity induced by H2O2. In conclusion, the findings reveal that NTF improves H2O2-induced intracellular ROS generation and decreases apoptosis. These protective effects of NTF could be useful for oxidative stress-related neurodegenerative conditions.
Government Digital Repression and Political Engagement: A Cross-National Multilevel Analysis Examining the Roles of Online Surveillance and Censorship
Authors: Chan Michael , Yi Jingjing , Kuznetsov Dmitry
Published: August 2022

Much research has shown that online news engenders greater political participation, but less attention has been paid to how the relationship can be suppressed by government online surveillance and censorship, especially as Internet freedoms continue to decline in many parts of the world. Drawing from 2017–20 World Value Survey and Varieties of Democracy project data, we conducted multilevel analyses across forty-four countries from seven continents that have different political and media systems. Results showed that online news and online surveillance were positively related to political engagement while online censorship was negatively related. Cross-level interactions also showed some support for the informational theory of repression, whereby the relationships among online news, surveillance, and engagement were conditioned at different levels of online censorship. The results suggest that while country-level online surveillance and censorship is highly correlated, varying levels can engender or suppress political engagement in different ways, which have implications for future studies on the dynamics of government digital repression and citizen participation in politics from a global comparative perspective.
Timing of symptomatic intracranial hemorrhage after endovascular stroke treatment
Authors: van der Steen Wouter , van der Ende Nadinda AM , van Kranendonk Katinka R , Chalos Vicky , Brouwer Josje , van Oostenbrugge Robert J , van Zwam Wim H , van Doormaal Pieter J , van Es Adriaan CGM , Majoie Charles BLM , van der Lugt Aad , Dippel Diederik WJ , Roozenbeek Bob
Published: August 2022

Introduction:

Little is known about the timing of occurrence of symptomatic intracranial hemorrhage (sICH) after endovascular therapy (EVT) for acute ischemic stroke. A better understanding could optimize in-hospital surveillance time points and duration. The aim of this study was to delineate the probability of sICH over time and to identify factors associated with its timing.

Patients and methods:

We retrospectively analyzed data from the Dutch MR CLEAN trial and MR CLEAN Registry. We included adult patients who underwent EVT for an anterior circulation large vessel occlusion within 6.5 h of stroke onset. In patients with sICH (defined as ICH causing an increase of ⩾4 points on the National Institutes of Health Stroke Scale [NIHSS]), univariable and multivariable linear regression analysis was used to identify factors associated with the timing of sICH. This was defined as the time between end of EVT and the time of first CT-scan on which ICH was seen as a proxy.

Results:

SICH occurred in 205 (6%) of 3391 included patients. Median time from end of EVT procedure to sICH detection on NCCT was 9.0 [IQR 2.9–22.5] hours, with a rapidly decreasing incidence after 24 h. None of the analyzed factors, including baseline NIHSS, intravenous alteplase treatment, and poor reperfusion at the end of the procedure were associated with the timing of sICH.

Conclusion:

SICHs primarily occur in the first hours after EVT, and less frequently beyond 24 h. Guidelines that recommend to perform frequent neurological assessments for at least 24 h after intravenous alteplase treatment can be applied to ischemic stroke patients treated with EVT.
‘It's in the air here’: Atmosphere(s) of incarceration
Authors: Turner Jennifer , Moran Dominique , Jewkes Yvonne
Published: August 2022

Contrary to descriptions of a desensitising situation – with restrictions on movement, monotonous regimes and sparse surroundings – much research highlights imprisonment as sensorially and emotionally powerful. Following work within the ‘turn to affect’ that focuses on non-verbal, non-conscious and, often, non-human embodied experiences, scholars have attended to how such elements cohere into ‘atmospheres’. Whilst the language of atmosphere is synonymous with the prison – a space that is widely anecdotally considered to conjure a particular ‘feeling’ – discussion of the mechanisms for and experiences of atmospheric production and consumption in this space has, thus far, evaded scholarly attention. Atmosphere is a word often used in prison literature, but it is rarely analytically unpacked. Accordingly, drawing on qualitative research data from individuals designing, and working and living in prisons, we focus on how various components – including aesthetics, olfaction, temperature, and the performances that arise from them – comprise sensory atmospheric affects in prison. In doing so, we find atmosphere(s) emerge – not simply from the materiality of the prison itself, but from cultural constructions of carceral and non-carceral landscapes and in conjunction with personal practice and preference. Accordingly, the prison is tied to particular constructions about what a prison should feel like and how people should (re)act to/in such spaces. In some cases, prison designers attempt to engineer particular atmospheres that cohere with wider political motivations around penal philosophies. However, despite the common reflection that prisons generate some kind of atmosphere, respondents are unable to offer a concrete description of what this may be, and much of our data highlights a definite precarity and changeability to atmospheric affect, which is likely to raise ambiguity around attempts to design carceral atmospheres.
Minimal residual disease–driven treatment intensification with sequential addition of ibrutinib to venetoclax in R/R CLL
Authors: Scarfò Lydia , Heltai Silvia , Albi Elisa , Scarano Eloise , Schiattone Luana , Farina Lucia , Moia Riccardo , Deodato Marina , Ferrario Andrea , Motta Marina , Reda Gianluigi , Sancetta Rosaria , Coscia Marta , Rivela Paolo , Laurenti Luca , Varettoni Marzia , Perotta Eleonora , Capasso Antonella , Ranghetti Pamela , Colia Maria , Ghia Paolo
Published: August 2022

Undetectable measurable residual disease (uMRD) is achievable in patients with chronic lymphocytic leukemia (CLL) with the BCL2-inhibitor venetoclax alone or combined with the Bruton’s tyrosine kinase inhibitor ibrutinib. This phase 2, multicenter, MRD-driven study was designed to discontinue treatment upon reaching uMRD4 (<10−4) in patients with relapsed/refractory CLL receiving venetoclax monotherapy or after the addition of ibrutinib. Primary end point of the study was proportion of uMRD4 with venetoclax ± ibrutinib. Secondary end points were overall response rate, partial response, complete response, progression-free survival, duration of response, overall survival, and safety of venetoclax ± ibrutinib. Patients with uMRD4 at Cycle 12 Day 1 discontinued venetoclax. MRD+ patients added ibrutinib and continued both drugs up to Cycle 24 Day 28/uMRD4/progression/toxicity. After Cycle 24 Day 28, MRD+ patients continued ibrutinib. Thirty-eight patients (29% with TP53 aberrations; 79% with unmutated IGHV) started venetoclax. Overall response rate with venetoclax was 36 (95%) of 38 patients (20 complete; 16 partial response). Seventeen patients (45%) with uMRD4 at Cycle 12 Day 1 discontinued venetoclax. Nineteen (55%) MRD+ subjects added ibrutinib. After a median of 7 months (range, 3-10 months) of combined treatment, 16 (84%) of 19 achieved uMRD4, thus stopping both drugs. Two MRD+ patients at Cycle 24 Day 28 continued ibrutinib until progression/toxicity. After a median follow-up of 36.5 months, median progression-free survival was not reached; 10 patients progressed (4 restarted venetoclax, 3 without treatment need, 2 developed Richter transformation, and 1 dropped out). Seven (22%) of 32 patients remain uMRD4 after 3 years of follow-up. Neutropenia was the most frequent grade 3 to 4 adverse event; no grade 5 events occurred on study. This sequential MRD-guided approach led to uMRD4 in 33 (87%) of 38 patients, with venetoclax monotherapy or combined with ibrutinib, delivering treatment combination only in a fraction, and ultimately identifying the few patients benefiting from continuous therapy. This trial was registered at www.clinicaltrials.gov as # NCT04754035.
MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy
Authors: Matuszyk Janusz
Published: August 2022

Background

The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs).

Aim

To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein.

Main body

Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA.

Conclusion

The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.
Discovery of cold-resistance genes in Vitis amurensis using bud-based quantitative trait locus mapping and RNA-seq
Authors: Ma Xiaolele , Zhao Fangyuan , Su Kai , Lin Hong , Guo Yinshan
Published: August 2022

Background

In cold regions, low temperature is the main limiting factor affecting grape production. As an important breeding resource,V. amurensisRupr. has played a crucial role in the discovery of genes which confer cold resistance in grapes. Thus far, many cold-resistance genes have been reported based on the study ofV. amurensis. In order to identify more candidate genes related to cold resistance inV. amurensis, QTL mapping and RNA-seq was conducted based on the hybrid population and different cold-resistance cultivars in this study.

Results

In this study, highly cold-resistant grape cultivar ‘Shuangyou’ (SY) which belongs toV. amurensis,and cold-sensitive cultivar ‘Red Globe’ (RG) which belongs toVitis viniferaL.were used to identify cold resistance genes. Cold-resistance quantitative trait locus (QTL) mapping was performed based on genetic population construction through interspecific crossing of ‘Shuangyou’ and ‘Red Globe’. Additionally, transcriptome analysis was conducted for the dormant buds of these two cultivars at different periods. Based on transcriptome analysis and QTL mapping, many new structural genes and transcription factors which relate toV. amurensiscold resistance were discovered, including CORs (VaCOR413IM), GSTs (VaGST-APIC,VaGST-PARB,VaGSTF9andVaGSTF13), ARFs (VaIAA27andVaSAUR71), ERFs (VaAIL1), MYBs (VaMYBR2,VaMYBLLandVaMYB3R-1) and bHLHs (VaICE1andVabHLH30).

Conclusions

This discovery of candidate cold-resistance genes will provide an important theoretical reference for grape cold-resistance mechanisms, research, and cold-resistant grape cultivar breeding in the future.
A novel, non-GMO surface display in Limosilactobacillus fermentum mediated by cell surface hydrolase without anchor motif
Authors: Vasquez Robie , Bagon Bernadette B. , Song Ji Hoon , Han Nam Soo , Kang Dae-Kyung
Published: August 2022

Recent studies have demonstrated the potential of surface display technology in therapeutic development and enzyme immobilization. Utilization of lactic acid bacteria in non-GMO surface display applications is advantageous due to its GRAS status. This study aimed to develop a novel, non-GMO cell wall anchoring system for lactic acid bacteria using a cell-surface hydrolase (CshA) from Lactiplantibacillus plantarum SK156 for potential industrial and biomedical applications. Analysis of the CshA revealed that it does not contain any known classical anchor domains. Although CshA lacks a classical anchor domain, it successfully displayed the reporter protein superfolder GFP on the surface of several lactic acid bacteria in host dependent manner. CshA-sfGFP fusion protein was displayed greatest on Limosilactobacillus fermentum SK152. Pretreatment with trichloroacetic acid further enhanced the binding of CshA to Lm. fermentum. The binding conditions of CshA on pretreated Lm. fermentum (NaCl, pH, time, and temperature) were also optimized, resulting in a maximum binding of up to 106 CshA molecules per pretreated Lm. fermentum cell. Finally, this study demonstrated that CshA-decorated pretreated Lm. fermentum cells tolerates gastrointestinal stress, such as low pH and presence of bile acid. To our knowledge, this study is the first to characterize and demonstrate the cell-surface display ability of CshA. The potential application of CshA in non-GMO antigen delivery system and enzyme immobilization remains to be tested.
Heparin-induced thrombocytopenia post-cardiovascular interventional therapy: a case report
Authors: Shen Lishui , Liu Xiaohua , Chen Lian , Gao Xiaofei , Xu Yizhou
Published: August 2022

Background

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction characterized by thrombocytopenia and thromboembolism. Herein, we present a case of HIT with subcutaneous hemorrhage after cardiovascular interventional therapy.

Case presentation

A 74-year-old man was admitted to the hospital for elective atrial fibrillation (AF) catheter ablation and left atrial appendage closure because of intermittent dizziness and palpitations. At presentation, the routine laboratory test results showed no abnormalities. He received subcutaneous enoxaparin for stroke prevention and unfractionated heparin for intraprocedural anticoagulation during coronary angiography and the AF procedure. On the second day after the AF procedure, the patient developed profound thrombocytopenia, moderate anemia, and mild subcutaneous hematoma. Blood tests and imaging examinations excluded acute hemolysis and other active bleeding. A 4Ts score of 5 and markedly positive platelet factor 4 IgG antibody established the diagnosis of HIT. Due to progressive subcutaneous hemorrhage in the thighs that could not be suppressed by pressure dressing, the patient received platelet transfusion and rivaroxaban for anticoagulation. The following days, the patient remained clinically stable from the hemorrhage, and his platelet count recovered. No thrombotic events occurred during hospitalization or follow-up.

Conclusion

This case emphasizes the significance of suspecting HIT in patients with unexplained rapid thrombocytopenia after frequent heparin exposure. Decision-making regarding alternative anticoagulation and platelet transfusion in HIT with hemorrhage must be based on unique patient characteristics.
Toxic leukoencephalopathy with axonal spheroids caused by chemotherapeutic drugs other than methotrexate
Authors: Lim Ka Young , Kim Seong-Ik , Kim Hyunhee , Kang Jeongwan , Park Jin Woo , Won Jae Kyung , Shin Dong-Yeop , Park Sung-Hye
Published: August 2022

Background

The objective of this report is to share the clinicopathological features of chemotherapy-induced toxic leukoencephalopathy, which is a rare and under-recognized disease, clinically characterized by rapidly progressive cognitive loss that often leads to sudden death.

Case presentation

A 64-year-old woman and a 63-year-old man, who had both suffered from a rapid deterioration of consciousness, were autopsied under the clinical impressions of either the central nervous system graft versus host disease (CNS-GVHD), infectious encephalitis, or autoimmune encephalitis. Both patients had been treated with multiple chemotherapy regimens, including adriamycin, cytarabine arabinoside, daunorubicin, fludarabine, azacitidine, and allogeneic peripheral blood stem cell transplantation to treat hematological malignancies (acute myelogenous leukemia and myelodysplastic syndrome). Neuropathological findings at autopsy revealed rarefaction and vacuolar changes of the white matter with axonal spheroids, reactive gliosis, and foamy macrophage infiltration, predominantly in the visual pathways of the occipital and temporal lobes. Damaged axons exhibited immunoreactivity to beta-amyloid, consistent with axonopathy. However, there was no lymphocyte infiltration that suggested CNS-GVHD or any type of encephalitis.

Conclusion

The neuropathology found in the presented cases had the characteristic features of toxic leukoencephalopathy (chemobrain). Our cases showed that toxic leukoencephalopathy can also be caused by chemotherapy drugs other than methotrexate.
The effect of virtual cognitive-behavioral sexual counseling on sexual function and sexual intimacy in pregnant women: a randomized controlled clinical trial
Authors: Fathalian Manizheh , Lotfi Razieh , Faramarzi Mahbobeh , Qorbani Mostafa
Published: August 2022

Background & aim

Pregnancy is associated with numerous physical and psychological changes and affects the sexual function of couples. Since the root of many marital problems lies in the quality of the relationship and sexual function, the present study investigates the effect of virtual cognitive-behavioral sexual counseling on pregnant women’s sexual function and intimacy.

Methods & Materials

This study is a randomized clinical trial, and 80 pregnant women aged 18 to 35 years and in 16–24 weeks of pregnancy were assigned to two intervention and control groups based on randomized blocks from June 2021 to July 2021. The control group received routine prenatal care, but the intervention group, in addition to routine prenatal care, underwent virtual counseling with a cognitive-behavioral approach during eight sessions of 90 minutes. Data were collected using the Female Sexual Function Index (FSFI) and sexual intimacy questionnaire. SPSS software was used for statistical analysis.

Results

The comparison of mean scores of sexual function and intimacy in the two groups before the intervention was not statistically significant with each other. However, after the intervention, the mean scores of sexual function and intimacy in the intervention group were significantly increased compared to the control group (p < 0.001). The effect size of the intervention was 0.52 for sexual function and 0.272 for sexual intimacy.

Conclusion

Virtual cognitive-behavioral counseling can be used as an effective treatment to promote sexual function and intimacy of women during pregnancy.

Trial registration

IRCT20161230031662N10. Registry date: 21/06/2021.
Characterization and comparison of human glioblastoma models
Authors: Schulz Julia A. , Rodgers Louis T. , Kryscio Richard J. , Hartz Anika M.S. , Bauer Björn
Published: August 2022

Glioblastoma (GBM) is one of the deadliest cancers. Treatment options are limited, and median patient survival is only several months. Translation of new therapies is hindered by a lack of GBM models that fully recapitulate disease heterogeneity. Here, we characterize two human GBM models (U87-luc2, U251-RedFLuc). In vitro, both cell lines express similar levels of luciferase and show comparable sensitivity to temozolomide and lapatinib exposure. In vivo, however, the two GBM models recapitulate different aspects of the disease. U87-luc2 cells quickly grow into large, well-demarcated tumors; U251-RedFLuc cells form small, highly invasive tumors. Using a new method to assess GBM invasiveness based on detecting tumor-specific anti-luciferase staining in brain slices, we found that U251-RedFLuc cells are more invasive than U87-luc2 cells. Lastly, we determined expression levels of ABC transporters in both models. Our findings indicate that U87-luc2 and U251-RedFLuc GBM models recapitulate different aspects of GBM heterogeneity that need to be considered in preclinical research.
Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor
Authors: Montagna Daniela R. , Duarte Alejandra , Chiarella Paula , Rearte Bárbara , Bustuoabad Oscar D. , Vermeulen Mónica , Ruggiero Raúl A.
Published: August 2022

Background

Although immune-checkpoint inhibitors (ICI) are overall promissory for cancer treatment, they entail, in some cases, an undesired side-effect called hyperprogressive-cancer disease (HPD) associated with acceleration of tumor growth and shortened survival.

Methods

To understand the mechanisms of HPD we assayed the ICI therapy on two murine tumors widely different regarding immunogenicity and, subsequently, on models of local recurrences and metastases of these tumors. To potentiate the immune response (IR), we combined ICI with meta-tyrosine—that counteracts immune-suppressive signals—and a selective inhibitor of p38 pathway that proved to counteract the phenomenon of tumor-immunostimulation.

Results

ICI were therapeutically effective against both tumor models (proportionally to their immunogenicity) but only when they faced incipient tumors. In contrast, ICI produced acceleration of large and residual tumors. The combined treatment strongly inhibited the growth of large tumors and it managed to cure 80% of mice with local recurrences and 60% of mice bearing residual metastases.

Conclusions

Tumor enhancement was paradoxically correlated to a weak increase of the antitumor IR suggesting that a weak IR – different from a strong tumor-inhibitory one—may produce stimulation of tumor growth, mimicking the HPD observed in some clinical settings.
The variation of antenatal corticosteroids administration for the singleton preterm birth in China, 2017 to 2018
Authors: Wang Qing , Jiang Siyuan , Hu Xuefeng , Chen Chao , Cao Yun , Lee Shoo Kim , Liu Jiang-Qin ,   On behalf of the Reduction of Infection in Neonatal Intensive Care Units using the Evidence-based Practice for Improving Quality (REIN-EPIQ) Study Group, Ji Yong , Han Shuping , Wang Sannan , Li Zhankui , Xia Shiwen , Yang Changyi , Yang Chuanzhong , Chen Ling , Yuan Jing , Liu Ling , Yi Bin , Lin Zhenlang , Wang Yang , He Ling , Li Mingxia , Pan Xinnian , Guo Yan , Liu Cuiqing , Zhou Qin , Li Xiaoying , Xiong Hong , Qi Yujie , Hei Mingyan
Published: August 2022

Background

The administration of antenatal corticosteroids (ACS) to women who are at risk of preterm birth has been proven to reduce not only the mortality, but also the major morbidities of the preterm infants. The rate of ACS and the risk factors associated with ACS use in Chinese population is unclear. This study aimed to investigate the rate of ACS use and the associated perinatal factors in the tertiary maternal centers of China.

Methods

Data for this retrospective observational study came from a clinical database of preterm infants established by REIN-EPIQ trial. All infants born at < 34 weeks of gestation and admitted to 18 tertiary maternal centers in China from 2017 to 2018 were enrolled. Any dose of dexamethasone was given prior to preterm delivery was recorded and the associated perinatal factors were analyzed.

Results

The rate of ACS exposure in this population was 71.2% (range 20.2 – 92%) and the ACS use in these 18 maternal centers varied from 20.2 to 92.0% in this period. ACS exposure was higher among women with preeclampsia, caesarean section delivery, antibiotic treatment and who delivered infants with lower gestational age and small for gestational age. ACS use was highest in the 28–31 weeks gestational age group, and lowest in the under 26 weeks of gestational age group (x2 = 65.478, P < 0.001). ACS exposure was associated with lower odds of bronchopulmonary dysplasia or death (OR, 0.778; 95% CI 0.661 to 0.916) and invasive respiration requirement (OR, 0.668; 95% CI 0.585 to 0.762) in this population.

Conclusion

The ACS exposure was variable among maternity hospitals and quality improvement of ACS administration is warranted.
Analysis of the uptake and associated factors for virtual crisis care during the pandemic at a 24-h mental health crisis centre in Manitoba, Canada
Authors: Vakil Tanvi , Svenne Danielle Carignan , Bolton James M. , Jiang Depeng , Svenne Sasha , Hensel Jennifer M.
Published: August 2022

Background

The coronavirus pandemic necessitated the rapid transition to virtual care. At a 24-h walk-in mental health Crisis Response Centre (CRC) in Winnipeg, Canada we adapted crisis mental health assessments to be offered virtually while the crisis centre also remained open to in person visits. Little is known about the sustainability of virtual visits in the presence of comparable in person care, and which visits are more likely to be done virtually, particularly in the crisis setting.

Methods

An analysis of visits to the CRC from the first local lockdown on March 19, 2020 through the third local wave with heightened public health restrictions in June 2021. Analysis of Variance was used to compare the proportion of visits occurring virtually (telephone or videoconference) during the first wave of heightened public health restrictions (lockdown 1) and subsequent lockdowns as well as the in-between periods. A binary logistic regression examined visit, sociodemographic and clinical factors associated with receipt of a virtual visit compared to an in person visit over the first year of the pandemic.

Results

Out of 5,357 visits, 993 (18.5%) occurred virtually. There was a significant difference in proportion of virtual visits across the pandemic time periods (F(4, 62) = 8.56, p < .001). The proportion of visits occurring virtually was highest during lockdown 1 (mean 32.6% by week), with no differences between the other time periods. Receipt of a virtual visit was significantly associated with daytime weekday visits, age, non-male gender, living further away from the CRC, no prior year contact with the CRC, and visits that did not feature suicidal behaviour, substance use, psychosis or cognitive impairment.

Conclusions

A large proportion of virtual care occurring at the outset of the pandemic reflects public anxiety and care avoidance paired with health system rapid transformation. The use of virtual visits reduced over subsequent pandemic periods but was sustained at a meaningful level. Specific visit, sociodemographic and clinical characteristics are more likely to be present in visits occurring virtually compared to those in person. These results can help to inform the future planning and delivery of virtual crisis care.
Symptoms of Anxiety and Depression within the UNiversity community: the cross-sectional UN-SAD study
Authors: Scarpis E. , Del Pin M. , Ruscio E. , Tullio A. , Brusaferro S. , Brunelli L.
Published: August 2022

The increasing complexity of academia, with its demanding working conditions and uncertain career opportunities, may affect the mental health of academics and potentially lead to mental health problems. The aim of this study is to determine the prevalence of depressive and anxiety symptoms in the academic population of the University of Udine and to compare symptoms in senior and younger academics and administrative staff.

A cross-sectional survey was conducted between June and December 2020, involving academic and administrative staff in all departments. The prevalence of depressive and anxiety symptoms was assessed using the PHQ-9 and GAD-7 tools. The relationship between mental health outcomes and job role was analyzed using nonparametric tests and ordinal logistic regression.

A total of 366 individuals participated: 109 junior academics, 146 senior and 111 administrative staff. The proportion of women was 55.7% and the mean age was 47.9 years. The prevalence of depressive and anxiety symptoms in the studied population was 25.7% (95% IC 21.5–30.4) and 22.7% (95% IC 18.7–27.2) respectively, with junior academics having the higher prevalence of both symptoms. Univariate models suggest a higher risk for anxiety symptoms OR 1.89 (1.13–3.17) for women.

The prevalence of depressive symptoms is higher in our academic community than in the general population, especially among junior academics. These findings may reflect the impact of uncertain career and challenging environment on the mental health of young academics. Universities should provide more support to young academics so that they can contribute effectively and healthily to the advancement of research.