bluuebunny/crossref_metadata_2025 huggingface dataset:
QTL Detection for Rice Grain Length and Fine Mapping of a Novel Locus qGL6.1
Authors: Zhao Mingzhu , Wang Yuanzheng , He Na , Pang Xiu , Wang Lili , Ma Zuobin , Tang Zhiqiang , Gao Hong , Zhang Liying , Fu Liang , Wang Changhua , Liu Jingang , Zheng Wenjing
Published: November 2022

Background

Grain length (GL) that is directly associated with appearance quality is a key target of selection in rice breeding. Although abundant quantitative trait locus (QTL) associated with GL have been identified, it was still relatively weak to identify QTL for GL from japonica genetic background, as the shortage of japonica germplasms with long grains. We performed QTLs analysis for GL using a recombinant inbred lines (RILs) population derived from the cross between japonica variety GY8 (short grains) and LX1 (long grains) in four environments.

Results

A total of 197 RILs were genotyped with 285 polymorphic SNP markers. Three QTLs qGL5.3, qGL6.1 and qGL11 were detected to control GL by individual environmental analyses and multi-environment joint analysis. Of these, a major-effect and stable QTL qGL6.1 was identified to be a novel QTL, and its LX1 allele had a positive effect on GL. For fine-mapping qGL6.1, a BC1F2 population consisting of 2,487 individuals was developed from a backcross between GY8 and R176, one line with long grain. Eight key informative recombinants were identified by nine kompetitive allele specific PCR (KASP) markers. By analyzing key recombinants, the qGL6.1 locus was narrowed down to a 40.41 kb genomic interval on chromosome 6. One candidate gene LOC_Os06g43304.1 encoding cytochrome P450 (CYP71D55) was finally selected based on the difference in the transcriptional expression and variations in its upstream and downstream region.

Conclusions

Three QTLs qGL5.3, qGL6.1 and qGL11 were identified to control grain length in rice. One novel QTL qGL6.1 was fine mapped within 40.41 kb region, and LOC_Os06g43304.1 encoding cytochrome P450 (CYP71D55) may be its candidate gene. We propose that the further cloning of the qGL6.1 will facilitate improving appearance quality in japonica varieties.
Optimal construction of a functional interaction network from pooled library CRISPR fitness screens
Authors: Gheorghe Veronica , Hart Traver
Published: November 2022

Background

Functional interaction networks, where edges connect genes likely to operate in the same biological process or pathway, can be inferred from CRISPR knockout screens in cancer cell lines. Genes with similar knockout fitness profiles across a sufficiently diverse set of cell line screens are likely to be co-functional, and these “coessentiality” networks are increasingly powerful predictors of gene function and biological modularity. While several such networks have been published, most use different algorithms for each step of the network construction process.

Results

In this study, we identify an optimal measure of functional interaction and test all combinations of options at each step—essentiality scoring, sample variance and covariance normalization, and similarity measurement—to identify best practices for generating a functional interaction network from CRISPR knockout data. We show that Bayes Factor and Ceres scores give the best results, that Ceres outperforms the newer Chronos scoring scheme, and that covariance normalization is a critical step in network construction. We further show that Pearson correlation, mathematically identical to ordinary least squares after covariance normalization, can be extended by using partial correlation to detect and amplify signals from “moonlighting” proteins which show context-dependent interaction with different partners.

Conclusions

We describe a systematic survey of methods for generating coessentiality networks from the Cancer Dependency Map data and provide a partial correlation-based approach for exploring context-dependent interactions.
Transcriptomic response to ISAV infection in the gills, head kidney and spleen of resistant and susceptible Atlantic salmon
Authors: Gervais Ophélie , Papadopoulou Athina , Gratacap Remi , Hillestad Borghild , Tinch Alan E. , Martin Samuel A. M. , Houston Ross D. , Robledo Diego
Published: November 2022

Background

Infectious Salmon Anaemia virus (ISAV) is an orthomyxovirus responsible for large losses in Atlantic salmon (Salmo salar) aquaculture. Current available treatments and vaccines are not fully effective, and therefore selective breeding to produce ISAV-resistant strains of Atlantic salmon is a high priority for the industry. Genomic selection and potentially genome editing can be applied to enhance the disease resistance of aquaculture stocks, and both approaches can benefit from increased knowledge on the genomic mechanisms of resistance to ISAV. To improve our understanding of the mechanisms underlying resistance to ISAV in Atlantic salmon we performed a transcriptomic study in ISAV-infected salmon with contrasting levels of resistance to this virus.

Results

Three different tissues (gills, head kidney and spleen) were collected on 12 resistant and 12 susceptible fish at three timepoints (pre-challenge, 7 and 14 days post challenge) and RNA sequenced. The transcriptomes of infected and non-infected fish and of resistant and susceptible fish were compared at each timepoint. The results show that the responses to ISAV are organ-specific; an important response to the infection was observed in the head kidney, with up-regulation of immune processes such as interferon and NLR pathways, while in gills and spleen the response was more moderate. In addition to immune related genes, our results suggest that other processes such as ubiquitination and ribosomal processing are important during early infection with ISAV. Moreover, the comparison between resistant and susceptible fish has also highlighted some interesting genes related to ubiquitination, intracellular transport and the inflammasome.

Conclusions

Atlantic salmon infection by ISAV revealed an organ-specific response, implying differential function during the infection. An immune response was observed in the head kidney in these early timepoints, while gills and spleen showed modest responses in comparison. Comparison between resistance and susceptible samples have highlighted genes of interest for further studies, for instance those related to ubiquitination or the inflammasome.
Integrative physiological and transcriptome analyses provide insights into the Cadmium (Cd) tolerance of a Cd accumulator: Erigeron canadensis
Authors: Gan Chenchen , Liu Zhaochao , Pang Biao , Zuo Dan , Hou Yunyan , Zhou Lizhou , Yu Jie , Chen Li , Wang Hongcheng , Gu Lei , Du Xuye , Zhu Bin , Yi Yin
Published: November 2022

Cadmium (Cd) is a highly toxic pollutant in soil and water that severely hampers the growth and reproduction of plants. Phytoremediation has been presented as a cost-effective and eco-friendly method for addressing heavy metal pollution. However, phytoremediation is restricted by the limited number of accumulators and the unknown mechanisms underlying heavy metal tolerance. In this study, we demonstrated that Erigeron canadensis (Asteraceae), with its strong adaptability, is tolerant to intense Cd stress (2 mmol/L CdCl2 solution). Moreover, E. canadensis exhibited a strong ability to accumulate Cd2+ when treated with CdCl2 solution. The activity of some antioxidant enzymes, as well as the malondialdehyde (MDA) level, was significantly increased when E. canadensis was treated with different CdCl2 solutions (0.5, 1, 2 mmol/L CdCl2). We found high levels of superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities under 1 mmol/L CdCl2 treatment. Comparative transcriptomic analysis identified 5,284 differentially expressed genes (DEGs) in the roots and 3,815 DEGs in the shoots after E. canadensis plants were exposed to 0.5 mM Cd. Functional annotation of key DEGs indicated that signal transduction, hormone response, and reactive oxygen species (ROS) metabolism responded significantly to Cd. In particular, the DEGs involved in auxin (IAA) and ethylene (ETH) signal transduction were overrepresented in shoots, indicating that these genes are mainly involved in regulating plant growth and thus likely responsible for the Cd tolerance. Overall, these results not only determined that E. canadensis can be used as a potential accumulator of Cd but also provided some clues regarding the mechanisms underlying heavy metal tolerance.
Tyroviruses are a new group of temperate phages that infect Bacillus species in soil environments worldwide
Authors: Batinovic Steven , Stanton Cassandra R. , Rice Daniel T. F. , Rowe Brittany , Beer Michael , Petrovski Steve
Published: November 2022

Background

Bacteriophages are widely considered to be highly abundant and genetically diverse, with their role in the evolution and virulence of many pathogens becoming increasingly clear. Less attention has been paid on phages preying on Bacillus, despite the potential for some of its members, such as Bacillus anthracis, to cause serious human disease.

Results

We have isolated five phages infecting the causative agent of anthrax, Bacillus anthracis. Using modern phylogenetic approaches we place these five new Bacillus phages, as well as 21 similar phage genomes retrieved from publicly available databases and metagenomic datasets into the Tyrovirus group, a newly proposed group named so due to the conservation of three distinct tyrosine recombinases. Genomic analysis of these large phages (~ 160–170 kb) reveals their DNA packaging mechanism and genomic features contributing to virion morphogenesis, host cell lysis and phage DNA replication processes. Analysis of the three tyrosine recombinases suggest Tyroviruses undergo a prophage lifecycle that may involve both host integration and plasmid stages. Further we show that Tyroviruses rely on divergent invasion mechanisms, with a subset requiring host S-layer for infection.

Conclusions

Ultimately, we expand upon our understanding on the classification, phylogeny, and genomic organisation of a new and substantial phage group that prey on critically relevant Bacillus species. In an era characterised by a rapidly evolving landscape of phage genomics the deposition of future Tyroviruses will allow the further unravelling of the global spread and evolutionary history of these Bacillus phages.
Symptom recognition and treatment-seeking behaviors in women experiencing acute coronary syndrome for the first time: a qualitative study
Authors: Asghari Elnaz , Gholizadeh Leila , Kazami Leila , Taban Sadeghi Mohammadreza , Separham Ahmad , Khezerloy-aghdam Naser
Published: November 2022

Background

Women are more likely to delay medical help-seeking for ACS symptoms. Understanding patients’ experience of the symptoms and their response is essential in improving help-seeking behaviors and timely diagnosis and treatment for ACS. This study aimed to explore women’s experience of ACS, their response to the symptoms, and treatment-seeking decisions.

Methods

This qualitative descriptive study was conducted in a tertiary referral specialized heart hospital affiliated with Tabriz University of Medical Sciences, Iran. Participants included 39 women who had experienced ACS for the first time.

Results

Four main themes emerged from the analysis of interview transcripts: (1) the onset of symptoms, (2) the types of symptoms, (3) response to symptoms and (4) arriving at the hospital. These themes and associated sub-themes explained women’s experience of ACS symptoms, their response to the symptoms, and decision to seek medical help.

Conclusions

This study identified and discussed factors contributing to the prehospital delay in women and their decision-making to seek medical care for ACS symptoms. The results are consistent with previous research indicating that ACS symptoms in women are somewhat different from men, and women tend to underestimate their symptoms and attribute them to non-cardiac causes. Women should be supported to develop awareness and understanding of ACS symptoms and appreciate the importance of early treatment-seeking in the disease outcomes.
Meta-DiSc 2.0: a web application for meta-analysis of diagnostic test accuracy data
Authors: Plana Maria N. , Arevalo-Rodriguez Ingrid , Fernández-García Silvia , Soto Javier , Fabregate Martin , Pérez Teresa , Roqué Marta , Zamora Javier
Published: November 2022

Background

Diagnostic evidence of the accuracy of a test for identifying a target condition of interest can be estimated using systematic approaches following standardized methodologies. Statistical methods for the meta-analysis of diagnostic test accuracy (DTA) studies are relatively complex, presenting a challenge for reviewers without extensive statistical expertise. In 2006, we developed Meta-DiSc, a free user-friendly software to perform test accuracy meta-analysis. This statistical program is now widely used for performing DTA meta-analyses. We aimed to build a new version of the Meta-DiSc software to include statistical methods based on hierarchical models and an enhanced web-based interface to improve user experience.

Results

In this article, we present the updated version, Meta-DiSc 2.0, a web-based application developed using the R Shiny package. This new version implements recommended state-of-the-art statistical models to overcome the limitations of the statistical approaches included in the previous version. Meta-DiSc 2.0 performs statistical analyses of DTA reviews using a bivariate random effects model. The application offers a thorough analysis of heterogeneity, calculating logit variance estimates of sensitivity and specificity, the bivariate I-squared, the area of the 95% prediction ellipse, and the median odds ratios for sensitivity and specificity, and facilitating subgroup and meta-regression analyses. Furthermore, univariate random effects models can be applied to meta-analyses with few studies or with non-convergent bivariate models.

The application interface has an intuitive design set out in four main menus: file upload; graphical description (forest and ROC plane plots); meta-analysis (pooling of sensitivity and specificity, estimation of likelihood ratios and diagnostic odds ratio, sROC curve); and summary of findings (impact of test through downstream consequences in a hypothetical population with a given prevalence).

All computational algorithms have been validated in several real datasets by comparing results obtained with STATA/SAS and MetaDTA packages.

Conclusion

We have developed and validated an updated version of the Meta-DiSc software that is more accessible and statistically sound. The web application is freely available at www.metadisc.es.
Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study
Authors: Hirashita Yuka , Fukuda Masahide , Kodama Masaaki , Tsukamoto Yoshiyuki , Okimoto Tadayoshi , Mizukami Kazuhiro , Kawahara Yoshinari , Wada Yasuhiro , Ozaka Sotaro , Togo Kazumi , Kinoshita Keisuke , Fuchino Takafumi , Fukuda Kensuke , Okamoto Kazuhisa , Ogawa Ryo , Matsunari Osamu , Honda Koichi , Murakami Kazunari
Published: November 2022

Background

Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status, efficacy of eradication therapy, and GC risk in H. pylori-eradicated mucosa, and to reveal the potential downstream molecules of eEF1A dimethylation.

Methods

Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9 mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2.

Results

The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with the negative mucosa (surface, p = 0.0031; basal, p = 0.0036, respectively). The eEF1A dimethyl-levels in the surface area were significantly reduced by eradication therapy (p = 0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio = 3.6611, 95% confidence interval = 1.0350–12.949, p = 0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors, Oct4 and Nanog, by immunohistochemistry and in vitro genome editing experiments.

Conclusions

The results indicated that H. pylori infection induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori eradicated-gastric mucosa.
The association of fecal calprotectin and respiratory exacerbation in cystic fibrosis patients
Authors: Imanzadeh Farid , Kerami Fatemeh , Hassanzad Maryam , Hosseini Amirhossein , Hajipour Mahmoud , Khanbabaee Ghamartaj , Dara Naghi , Khatami Katayoun , Farahbakhsh Nazanin , Sayyari Aliakbar
Published: November 2022

Background

CF patients experience several episodes of pulmonary exacerbations and reduction in their lung function progressively. Lung function is not the only diagnostic index by physicians to decide if CF patients require antibiotic therapy following pulmonary exacerbations. Non-invasive fecal indicators are increasingly being used to assess intestinal inflammation. Calprotectin is the most extensively utilized fecal biomarker in recent CF researches.

Methods

In this longitudinal study, 30 CF patients (1–18 years) without current infectious gastroenteritis were recruited from Mofid Children's Hospital and Masih Daneshvari Hospital, Tehran, Iran. Then, fecal calprotectin levels were evaluated before treatment, two weeks after systemic antibiotic administration, as well as recurrence of pulmonary exacerbation after first post-hospital discharge.

Results

The initial fecal calprotectin level in CF patients receiving antibiotics was 651.13 ± 671.04, significantly decreasing two weeks after antibiotic therapy and following recurrence (171.81 ± 224.40, 607.93 ± 549.89, respectively; P < 0.01). Following systemic antibiotic treatment, the patient's respiratory and GI symptoms improved (P < 0.01).

Conclusion

Our findings revealed that fecal calprotectin modifications are associated with CF pulmonary exacerbations and antibiotic treatment could reduce calprotectin levels. Therefore, the fecal calprotectin level could be considered as a diagnostic tool and an index to follow the response to treatment in CF pulmonary exacerbations.
Prognostic clinical indexes for prediction of acute gangrenous cholecystitis and acute purulent cholecystitis
Authors: Chen Jie , Gao Qi , Huang Xinyu , Wang Yingqi
Published: November 2022

Background

Preoperative prediction of severe cholecystitis (SC), including acute gangrenous cholecystitis (AGC) and acute purulent cholecystitis (APC), as opposed to acute exacerbation of chronic cholecystitis (ACC), is of great significance, as SC is associated with high mortality rate.

Methods

In this study, we retrospectively investigated medical records of 114 cholecystitis patients, treated in Shanghai No. 6 People’s Hospital from February 2009 to July 2020. Gallbladder wall thickness (GBWT), indexes of blood routine examination, including white blood cell (WBC), alkaline phosphatase (ALP), the percentage of neutrophil, alanine transaminase (ALT), aspartate aminotransferase (AST), fibrinogen (FIB), gamma-glutamyl transferase, prothrombin time and total bilirubin were evaluated. One-way analysis of variance (ANOVA) was used to evaluate significant differences between a certain kind of SC and ACC to select a prediction index for each kind of SC. Receiver operating characteristic (ROC) curve analysis was conducted to identify the prediction effectiveness of these indexes and their optimal cut-off values.

Results

Higher WBC and lower ALP were associated with AGC diagnosis (P < 0.05). Higher percentage of neutrophils was indicative of APC and AGC, while higher GBWT was significantly associated with APC diagnosis (P < 0.05) The optimal cut-off values for these indexes were established at 11.1*109/L (OR: 5.333, 95% CI 2.576–10.68,P < 0.0001, sensitivity: 72.73%, specificity: 66.67%), 79.75% (OR: 5.735, 95% CI 2.749–12.05,P < 0.0001, sensitivity: 77.92%, specificity: 61.9%) and 5.5 mm (OR: 22, 95% CI 4.757–83.42,P < 0.0001, sensitivity: 78.57%, specificity: 85.71%), respectively.

Conclusion

We established a predictive model for the differentiations of APC and AGC from ACC using clinical indexes, such as GBWT, the percentage of neutrophil and WBC, and determined cut-off values for these indexes based on ROC curves. Index values exceeding these cut-off values will allow to diagnose patients as APC and AGC, as opposed to a diagnosis of ACC.
A case-control study on the effects of incomplete, one, and more than one dexamethasone course on acute respiratory problems in preterm neonates born between 280 and 366 weeks of gestation
Authors: Chawanpaiboon Saifon , Pooliam Julaporn , Chuchotiros Monsak
Published: November 2022

Objective

To compare the effects of an incomplete course and more than 1 course of dexamethasone, relative to a control of a single complete course, on foetal respiratory problems and other adverse outcomes of preterm birth.

Methods

This was a retrospective chart review of 1800 women with preterm delivery. Data were collected on newborns whose mothers administered 1 full course of dexamethasone (916/1800; 50.9%), a partial course (716/1800; 39.8%) and more than 1 course (168/1800; 9.3%). Demographic data and adverse maternal and neonatal outcomes were recorded.

Results

Preterm singleton newborns whose mothers received several steroid hormone courses were significantly more likely to have adverse outcomes than newborns of mothers given 1 course. The negative outcomes were the need for positive pressure ventilation ([aOR] 1.831; 95% CI, (1.185,2.829);P = 0.019), ventilator support ([aOR] 1.843; 95% CI, (1.187,2.861);P = 0.011), and phototherapy ([aOR] 1.997; 95% CI, (1.378,2.895);P <  0.001), transient tachypnoea of the newborn ([aOR] 1.801; 95% CI, (1.261,2.571);P = 0.002), intraventricular haemorrhage ([aOR] 2.215; 95% CI, (1.159, 4.233);P = 0.027), sepsis ([aOR] 1.737; 95% CI, (1.086, 2.777);P = 0.007), and admission to neonatal intensive care ([aOR] 1.822; 95% CI, (1.275,2.604);P = 0.001). In the group of very preterm infants, newborns of mothers administered an incomplete course had developed respiratory distress syndrome (RDS) ([aOR] 3.177; 95% CI, (1.485, 6.795);P = 0.006) and used ventilatory support ([aOR] 3.565; 95% CI, (1.912, 6.650);P <  0.001) more than those of mothers receiving a single course.

Conclusions

Preterm singleton newborns whose mothers were given multiple courses of dexamethasone had an increased incidence of RDS and other adverse outcomes than those of mothers receiving a full course. However, very preterm newborns whose mothers were administered 1 full dexamethasone course had a significantly lower incidence of RDS than those whose mothers were given partial courses.
EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling
Authors: Meng Xianguo , Li Wei , Meng Ziqi , Li Yan
Published: November 2022

CircBRWD3 is a newly discovered circRNA, and its potential function has not been probed. Here, we aimed to molecularly dissect the role of circBRWD3 in the tumorigenesis and progression of breast cancer (BC). qRT-PCR analysis revealed that circBRWD3 expression was dramatically upregulated in BC tissues, a feature that was positively correlated with the poor prognosis of patients with BC. CircBRWD3 knockdown repressed cell proliferation and metastasis, while promoting cell apoptosis in vitro. Consistently, an in vivo circBRWD3 deficiency model exhibited suppressed tumor metastasis and oncogenesis. On the other hand, circBRWD3 overexpression promoted cancer cell activity and tumorigenesis. Further, mechanistic studies elucidated that circBRWD3 sponged both miR-142-3p and miR-142-5p to modulate RAC1 expression, which subsequently activated the RAC1/PAK1 signaling to facilitate the tumorigenesis and progression of BC. Moreover, we discovered that EIF4A3 facilitated circBRWD3 expression by targeting the upstream of BRWD3 pre-mRNA. In conclusion, our study reveals that circBRWD3 facilitates BC tumorigenesis by regulating the circBRWD3/miR-142-3p_miR-142-5p /RAC1/PAK1 axis. In addition, circBRWD3 expression is positively regulated by an RNA-binding protein, EIFA3. Our results provide valuable scientific data for early diagnosis and therapy for breast cancer patients.
Increased prevalence of human papillomavirus in fresh tissue from penile cancers compared to non-malignant penile samples: a case-control study
Authors: Kristiansen Sinja , Bjartling Carina , Torbrand Christian , Grelaud Diane , Lindström Martin , Svensson Åke , Forslund Ola
Published: November 2022

Background

HPV has been detected in approximately 50% of invasive penile cancers but with a large span between 24 and 89%, most likely due to different types of tumors and various methods for HPV analysis. Most studies of HPV in penile cancer have been performed using paraffin-embedded tissue, argued to be at risk for contaminated HPV analysis. Viral activity of HPV, by the use of HPV mRNA expression is well studied in cervical cancer, but seldom studied in penile cancer.

The aim was to determine prevalence of HPV types in fresh tissue of penile cancers compared to non-malignant age-matched penile controls. Additional aims were to analyze the viral expression and copy numbers of HPV16-positive tumors and 10 mm adjacent to the tumor.

Methods

Fresh tissue from penile cancer cases was biopsied inside the tumor and 10 mm outside the tumor. Controls were males circumcised for non-malignant reasons, biopsied at surgery.

PCR and Luminex assays were used for identification of HPV types. HPV16-positive samples were investigated for copy numbers and expression of HPV16-mRNA.

Results

Among tumors (n = 135) and age-matched controls (n = 105), HPV was detected in 38.5% (52/135) and 11.4% (12/105), respectively (p < 0.001), adjusted odds ratio 12.8 (95% confidence interval 4.9–33.6). High-risk HPV types were found in 35.6% (48/135) of tumors and 4.8% (5/105) of controls (p < 0.001). Among tumors and controls, HPV16 was present in 27.4% (37/135) and 1% (1/105), respectively (p < 0.001). Among HPV16-positive penile cancers, mean HPV16 viral copy/cell was 74.4 (range 0.00003–725.4) in the tumor and 1.6 (range 0.001–14.4) 10 mm adjacent from the tumor. HPV16-mRNA analysis of the tumors and 10 mm adjacent from the tumors demonstrated viral activity in 86.5% (32/37) and 21.7% (5/23), respectively.

Conclusions

The prevalence of HPV was significantly higher in penile cancer (38.5%) than among age-matched non-malignant penile samples (11.4%). HPV16 predominates (27.4%) in penile tumors. HPV16 expression was more common in penile cancer than in adjacent healthy tissue, strongly suggesting an etiological role for HPV16 in the development of penile cancer.
Short-course pembrolizumab and continuous afatinib therapy for recurrent or metastatic head and neck squamous cell carcinoma: a real-world data analysis
Authors: Kao Hsiang-Fong , Huang Huai-Cheng , Liao Bin-Chi , Hong Ruey-Long
Published: November 2022

Objectives

The optimal duration of anti-PD-1 for cancer therapy has not been tested, especially when using combination therapy. Epidermal growth factor receptor (EGFR) pathway blocker was the top compound that enhanced T-cell killing of tumor cells in a high-throughput immune-oncology screen, possibly by stimulate the antigen presentation machinery and other mechanisms. We explored the effect of combination of EGFR inhibition with a short course of anti-PD-1 therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

Method

We analyzed the effect of a short course of anti-PD-1 with continuous afatinib on the survival of a real-world cohort of R/M HNSCC patients. Patient characteristics, treatments, efficacies, and toxicities were reviewed and recorded for analysis.

Results

From November 2016 to May 2018, 51 consecutive patients received pembrolizumab and afatinib. The cutoff date was June 30, 2022. The most common toxicities (all grades) were diarrhea (62.7%), skin rash (43.1%), mucositis (31.4%), and paronychia (23.5%). The objective response rate was 54.9% (95% confidence interval [CI] 40.3–68.9%). Median progression-free survival was 5.9 months (95% CI: 4.4–7.6 months), and the median overall survival was 10.5 months (95% CI: 6.8–16.5 months). The 12-month, 24-month, 36-month, and 48-month survival rate was 47.0%, 22.5%, 17.7%, and 12.6% respectively.

Conclusions

This retrospective study showed that short course pembrolizumab with afatinib therapy has acceptable efficacy in R/M HNSCC patients. The durable response and long-term survival rates were similar to prospective clinical trials. Short course anti-PD-1 therapy, especially in combination with EGFR blocker, is worth for further prospective study.
Blue light attenuates TGF-β2-induced epithelial-mesenchymal transition in human lens epithelial cells via autophagy impairment
Authors: Zhang Dongyan , Zhu Hong , Yu Xin , Wang Liyin , Wen Yingying , Zhang Liyue , Tong Jianping , Shen Ye
Published: November 2022

Background

Pathogenesis of posterior capsular opacification (PCO) was related to pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). It has been reported that blue light could have an effect on EMT. This study aims to elucidate the role and potential mechanism of autophagy in EMT after blue light exposure in LECs.

Methods

HLE-B3 cells were treated with TGF-β2 with different concentration and time to induce EMT as a model of PCO in vitro. Cells were exposed to blue light with or without TGF-β2. The expression levels of EMT-associated markers were analyzed by qRT-PCR, western blotting and cell migration ability was determined by transwell migration assay and wound healing assay. The expressions of autophagy-related proteins were analyzed by western blotting, immunofluorescence and transmission electron microscopy. Rapamycin and chloroquine were utilized in cells for autophagy activation and inhibition.

Results

TGF-β2 induced autophagy activation during EMT progression in HLE-B3 cells in a dose- and time-dependent manner. Blue light exposure inhibited TGF-β2-induced EMT characterized by inhibited expression of EMT related markers and reduced migration capacity. Meanwhile, blue light exposure impaired autophagy activated by TGF-β2. Furthermore, Autophagy activation with rapamycin rescued EMT attenuated by blue light. Autophagy inhibition with chloroquine reduced TGF-β2-induced EMT in HLE-B3 cells.

Conclusion

Blue light exposure had inhibited effects on TGF-β2-induced EMT in LECs through autophagy impairment, which provides a new insight on prevention and treatment of PCO.
Endoscopic aqueductal membrane fenestration was effective for intractable hydrocephalus after removal of a nongerminomatous germ cell tumor exhibiting growing teratoma syndrome: a case report
Authors: Kajiwara Sosho , Nakamura Hideo , Sakata Kiyohiko , Komaki Satoru , Negoto Tetsuya , Morioka Motohiro
Published: November 2022

Background

Primary central nervous system (CNS) germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. A mixed GCT including immature teratoma exhibiting growing teratoma syndrome is presented. The pathogenesis of growing teratoma syndrome remains unclear, and its treatment strategy has not been established. GCTs are often located within the ventricles, causing hydrocephalus, which sometimes improves after removal of the tumor due to restoration of cerebrospinal fluid (CSF) flow. On the other hand, even if the flow route of CSF from the third ventricle to arachnoid granulations on the brain surface quadrigeminal cistern is restored after removal of the tumor, hydrocephalus may not improve.

Case presentation

A case whose intractable hydrocephalus improved after penetrating the aqueductal membrane via endoscopy is described. An 11-year-old boy was treated for pineal intracranial growing teratoma syndrome (IGTS). The tumor grew rapidly in a short period, and hydrocephalus progressed despite endoscopic third ventriculostomy (ETV). Although the obstruction was removed by radiation, chemotherapy, and total tumor resection, the hydrocephalus did not improve. Endoscopic membrane perforation was performed because a membrane-like structure was seen at the entrance of the cerebral aqueduct on magnetic resonance imaging. The hydrocephalus improved immediately after the operation, and the patient’s consciousness disturbance also improved significantly.

Conclusion

The purpose of this report is to update the current knowledge and standards of management for patients with growing teratoma syndrome, as well as to drive future translational and clinical studies by recognizing the unmet needs concerning hydrocephalus.
Dialectical behavioral therapy-based group treatment versus treatment as usual for adults with attention-deficit hyperactivity disorder: a multicenter randomized controlled trial
Authors: Halmøy Anne , Ring Anna Edith , Gjestad Rolf , Møller Merete , Ubostad Bente , Lien Tage , Munkhaugen Ellen Kathrine , Fredriksen Mats
Published: November 2022

Background

Studies on structured skills training groups have indicated beneficial, although still inconclusive, effects on core symptoms of ADHD in adults. This trial examined effects of Dialectical Behavioral Therapy-based group treatment (DBT-bGT) on the broader and clinically relevant executive functioning and emotional regulation in adults with ADHD.

Methods

In a multicenter randomized controlled trial, adult patients with ADHD were randomly assigned to receive either weekly DBT-bGT or treatment as usual (TAU) during 14 weeks. Subsequently, participants receiving TAU were offered DBT-bGT. All were reassessed six months after ended DBT-bGT. Primary outcomes were the Behavior Rating Inventory of Executive Function (BRIEF-A) and the Difficulties in Emotion Regulation Scale (DERS). Secondary outcomes included self-reported ADHD-symptoms, depressive and anxiety symptoms, and quality of life. We used independent samples t- tests to compare the mean difference of change from pre- to post-treatment between the two treatment groups, and univariate linear models adjusting for differences between sites.

Results

In total, 121 participants (68 females), mean age 37 years, from seven outpatient clinics were included, of whom 104 (86%) completed the 14-week trial. Entering the study, 63% used medication for ADHD. Compared to TAU (n = 54), patients initially completing DBT-bGT (n = 50) had a significantly larger mean reduction on the BRIEF-A (-12.8 versus -0.37, P = 0.005, effect size 0.64), and all secondary outcomes, except for symptoms of anxiety. All significant improvements persisted at 6 months follow-up. Change on DERS did not differ significantly between the groups after 14 weeks, but scores continued to decrease between end of group-treatment and follow-up.

Conclusions

This DBT-bGT was superior to TAU in reducing executive dysfunction, core symptoms of ADHD and in improving quality of life in adults with ADHD. Improvements sustained six months after ended treatment. The feasibility and results of this study provide evidence for this group treatment as a suitable non-pharmacological treatment option for adults with ADHD in ordinary clinical settings.

Trial registrations

The study was pre-registered in the ISRCTN registry (identification number ISRCTN30469893, date February 19th 2016) and at the ClinicalTrials.gov (ID: NCT02685254, date February 18th 2016).
Virtual reality exposure and response prevention in the treatment of obsessive-compulsive disorder in patients with contamination subtype in comparison with in vivo exposure therapy: a randomized clinical controlled trial
Authors: Javaherirenani Razieh , Mortazavi Seyede Salehe , Shalbafan Mohammadreza , Ashouri Ahmad , Farani Abbas Ramezani
Published: November 2022

Background

Obsessive-Compulsive Disorder (OCD) is characterized by disturbing and unwanted thoughts as well as repetitive and time-consuming behaviors that interfere with performance. Cognitive Behavior Therapy (CBT) has shown to have beneficial effects on reducing OCD symptoms as the first line of treatment. Moreover, Virtual Reality (VR) has been a more feasible and accessible intervention for OCD in recent years. Regarding the point, the objective of this study was to evaluate the effectiveness of virtual reality exposure and response prevention (VRERP) in the treatment of the OCD contamination subtype.

Methods

A total number of 36 adults with OCD-contamination subtype were registered and randomly assigned to the intervention and control groups. The intervention group received a 60-min CBT including a “contaminated” virtual environment while the control group received CBT as a standardized treatment. Out of these, 29 patients completed the treatment in 12 weekly sessions. The patients completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Obsessive Beliefs Questionnaire-44(OBQ-44), and World Health Organization Disability Assessment Scale-2 (WHODAS-2) at week 0, week 12 and after 3 months follow-up.

Results

Based on the results of the repeated measure analysis of variances, the total score of obsession and compulsion subscales of Y-BOCS significantly decreased as a primary outcome in the intervention group (F = 60.97, P < 0.001, partial eta squared = 0.82; F = 20.46, P < 0.001, partial eta squared = 0.61; F = 29.57, P < 0.001, partial eta squared = 0.69; respectively). The total score of BDI-II and BAI was reduced in both groups but there was no significant difference between them (BDI-II: F = 0.54, P = 0.47, partial eta squared = 0.02; BAI: F = 3.12, P = 0.06, partial eta squared = 0.19). However, there was a significant difference in the OBQ-44 (F = 16.78, P < 0.001, partial eta squared = 0.56) and the total WHODAS-2 score between the groups (F = 14.64, P < 0.001, partial eta squared = 0.53).

Conclusions

This study demonstrated the effectiveness of VRERP in the treatment of the OCD-contamination subtype. Therefore, VRERP can be used in CBT as an alternative exposure tool.

Trial registration

Iranian Registry of Clinical Trials, IRCT ID: IRCT20210214050353N1, Registered on 16/10/2021.
COVID-19 related anxiety and its associated factors: a cross-sectional study on older adults in Bangladesh
Authors: Mistry Sabuj Kanti , Ali ARM Mehrab , Yadav Uday Narayan , Das Sukanta , Akter Nahida , Huda Md. Nazmul , Hadisuyatmana Setho , Rahman Sajedur , Lim David , Rahman Mohammad Mahmudur
Published: November 2022

Background

The COVID-19 pandemic has resulted in serious mental health conditions, particularly among older adults. This research explored the prevalence of COVID-19-related anxiety and its associated factors among older adults residing in Bangladesh.

Methods

This cross-sectional study was conducted among 1,045 older Bangladeshi adults aged ≥ 60 years through telephone interviews in September 2021. A semi-structured interview schedule was used to collect data on participants’ characteristics and COVID-19-related anxiety. The anxiety level was measured using the Bengali version of the five-point Coronavirus Anxiety Scale (CAS). A linear regression model explored the factors associated with COVID-19-related anxiety.

Results

Overall, the prevalence of COVID-19-related anxiety was 23.2%. The regression analysis revealed that the average COVID-19-related anxiety score was significantly higher among females (β: 0.43, 95% CI: 0.05 to 0.81), and among those who faced difficulty getting medicine (β: 0.57, 95% CI: 0.16 to 0.97), felt isolated (β: 0.60, 95% CI: 0.24 to 0.95), and felt requiring additional care during the pandemic (β: 0.53, 95% CI: 0.16 to 0.91). Alternatively, the average COVID-19-related anxiety score was significantly lower among those who were widowed (β: -0.46, 95% CI: -0.87 to -0.04) and living distant from the health centre (β: -0.48, 95% CI: -0.79 to -0.17).

Conclusion

The findings of the present study suggest providing immediate psychosocial support package to the older adults, particularly females and those who are vulnerable to receive health and social care support during the COVID-19 pandemic in Bangladesh.
Association between percentage of smokers and prevalence of smoking attributable morbidity in Indonesia: one decade after implementation of smoke-free area regulation
Authors: Martini Santi , Artanti Kurnia Dwi , Hargono Arief , Widati Sri , Ahsan Abdillah , Prabandari Yayi Suryo
Published: November 2022

Background

For more than ten years, Indonesia has health law, one of which states that local governments are mandated to establish Smoke Free Area (SFA). The results of 2018 National Basic Health Research shows tobacco consumption is still quite high and increasing compared to the results of 2007 and 2013 National Basic Health Research. The burden of disease in Indonesia is increasing every year. 

Methods

This study aims to describe SFA regulation and analyze the relationship between the percentage of smokers and the prevalence of smoking attributable morbidity. Data from the 2018 Basic Health Research in Indonesia with the number of units of analysis were 514 districts and cities level. The design of the study was cross-sectional study. The variables analyzed were the percentage of smokers, the prevalence of diabetes, hypertension, upper respiratory tract infections (URTI), pneumonia, lung tuberculosis, asthma, and mental emotional disorders. Geographical mapping of the distribution of District/City with Smoking-Free Areas was made using QGIS 3·16. 

Results

Around 72% of districts/cities in Indonesia already had local regulations of SFA after more than ten years implementation of the regulation of the health law. There was a significant relationship between the high percentage of smokers and the high prevalence of diabetes (p value: 0·000, PR: 1·342, 95%CI 1·135 to 1·587), hypertension (p value: 0·000, PR 1·631, 95%CI 1·252 to 2·124), and lung tuberculosis (p value: 0·008, PR 1·219, 95%CI 1·049 to 1·417) at the District/City level. However, there was no significant association between URTI, pneumonia, asthma, and mental emotional disorders.

Conclusion

The percentage of smokers in an area was associated with diabetes, hypertension, and lung tuberculosis. The implementation of Smoke Free Area should be evaluated.
Factors associated with COVID-19 booster vaccine willingness among migrants from the Eastern Mediterranean living in Australia: a cross-sectional study
Authors: Allen Keeley , Lambert Stephen B. , Yuen Aidan , Pourmarzi Davoud
Published: November 2022

Background

Migrants have been disproportionally affected by COVID-19 in Australia. Vaccination against COVID-19 is a key pillar of Australia's public health response, but little is known about the willingness to receive booster vaccinations among migrants. This study aimed to assess the factors associated with a willingness to receive a COVID-19 booster vaccine among migrants living in Australia born in the World Health Organization’s Eastern Mediterranean Region (EMRO).

Methods

A cross-sectional survey was conducted from September to November 2021 (n = 300). Participants were questioned on booster vaccine willingness, sociodemographic characteristics, COVID-19 vaccine information needs and sources, and perceptions of COVID-19 vaccines. Univariate and multivariate logistic regression were used to assess factors associated with booster willingness.

Results

Most respondents (87%) had received two doses of COVID-19 vaccine, of which 81% were willing to receive a booster dose. About half of the participants reported high or very high needs for receiving information about “COVID-19 vaccines’ safety monitoring in Australia”, “COVID-19 vaccines protection against illness”, “Safety of COVID-19 vaccines used in Australia”, and “The Australian COVID-19 vaccination program”. People who were willing to receive a boost dose had significantly higher self-estimated knowledge of COVID-19 vaccines, confidence in COVID-19 vaccines and trust in the Australian government’s vaccine recommendations, and perceived COVID-19 as a greater risk compared to those who were unsure/hesitant. Both groups reported similar perceptions of their personal risks from COVID-19 but diverged on their views of COVID-19 as a broader health problem. There were no statistically significant differences between the two groups in terms of channels used to find information about COVID-19 vaccines. Factors associated with willingness to receive a COVID-19 booster vaccine in the multivariate logistic regression were age (aOR 1.07 95% CI 1.02–1.12), and no exposure to concerning news about COVID-19 vaccines (aOR 3.71 95% CI 1.51–9.09).

Conclusion

Vaccine acceptance and reported booster willingness was high. The results suggest the news and information seen may impact willingness to receive booster doses, even among those who have already received doses of COVID-19 vaccine. Addressing vaccine concerns and transparent communication about uncertainty should be a priority in the current and in future pandemics.