bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a recombinase-aided amplification assay for rapid detection of human norovirus GII.4
Authors: Qin Zhiwei , Xue Liang , Cai Weicheng , Gao Junshan , Jiang Yueting , Yang Jiale , Liang Yanhui , Wang Linping , Zhang Jumei , Hu Yongdan , Wu Qingping
Published: March 2021

Background

Human noroviruses are one of the main causes of foodborne illnesses and represent a serious public health concern. Rapid and sensitive assays for human norovirus detection are undoubtedly necessary for clinical diagnosis, especially in regions without more sophisticated equipment.

Method

The rapid reverse transcription recombinase-aided amplification (RT-RAA) is a fast, robust and isothermal nucleic acid detection method based on enzyme reaction. This method can complete the sample detection at 39 °C in 30 min. In this study, we successfully established a rapid reverse transcription recombinase-aided amplification (RT-RAA) assay for the detection of human norovirus GII.4 and applied this assay to clinical samples, as well as comparison with commercial reverse transcription real-time fluorescence quantitative PCR (RT-qPCR).

Results

At 95% probability, the detection sensitivity of RT-RAA was 3.425 log10 genomic copies (LGC)/reaction. Moreover, no cross-reaction was observed with other norovirus genogroups and other common foodborne viruses. Stool samples were examined by RT-RAA and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Compared of RT-qPCR, kappa values for human norovirus detection with RT-RAA were 0.894 (p < 0.001), indicating that both assays were in agreement.

Conclusion

This RT-RAA assay provides a rapid, specific, and sensitive assay for human norovirus detection and is suitable for clinical testing.
A new machine learning approach for predicting likelihood of recurrence following ablation for atrial fibrillation from CT
Authors: Atta-Fosu Thomas , LaBarbera Michael , Ghose Soumya , Schoenhagen Paul , Saliba Walid , Tchou Patrick J. , Lindsay Bruce D. , Desai Milind Y. , Kwon Deborah , Chung Mina K. , Madabhushi Anant
Published: March 2021

Objective

To investigate left atrial shape differences on CT scans of atrial fibrillation (AF) patients with (AF+) versus without (AF−) post-ablation recurrence and whether these shape differences predict AF recurrence.

Methods

This retrospective study included 68 AF patients who had pre-catheter ablation cardiac CT scans with contrast. AF recurrence was defined at 1 year, excluding a 3-month post-ablation blanking period. After creating atlases of atrial models from segmented AF+ and AF− CT images, an atlas-based implicit shape differentiation method was used to identify surface of interest (SOI). After registering the SOI to each patient model, statistics of the deformation on the SOI were used to create shape descriptors. The performance in predicting AF recurrence using shape features at and outside the SOI and eight clinical factors (age, sex, left atrial volume, left ventricular ejection fraction, body mass index, sinus rhythm, and AF type [persistent vs paroxysmal], catheter-ablation type [Cryoablation vs Irrigated RF]) were compared using 100 runs of fivefold cross validation.

Results

Differences in atrial shape were found surrounding the pulmonary vein ostia and the base of the left atrial appendage. In the prediction of AF recurrence, the area under the receiver-operating characteristics curve (AUC) was 0.67 for shape features from the SOI, 0.58 for shape features outside the SOI, 0.71 for the clinical parameters, and 0.78 combining shape and clinical features.

Conclusion

Differences in left atrial shape were identified between AF recurrent and non-recurrent patients using pre-procedure CT scans. New radiomic features corresponding to the differences in shape were found to predict post-ablation AF recurrence.
Early prediction of putamen imaging features in HIV-associated neurocognitive impairment syndrome
Authors: Qi Yu , Xu Man , Wang Wei , Wang Yuan-Yuan , Liu Jiao-Jiao , Ren Hai-Xia , Liu Ming-Ming , Li Rui-Li , Li Hong-Jun
Published: March 2021

Background

To explore the correlation between the volume of putamen and brain cognitive impairment in patients with HIV and to predict the feasibility of early-stage HIV brain cognitive impairment through radiomics.

Method

Retrospective selection of 90 patients with HIV infection, including 36 asymptomatic neurocognitive impairment (ANI) patients and 54 pre-clinical ANI patients in Beijing YouAn Hospital. All patients received comprehensive neuropsychological assessment and MRI scanning. 3D Slicer software was used to acquire volume of interest (VOI) and radiomics features. Clinical variables and volume of putamen were compared between patients with ANI and pre-clinical ANI. The Kruskal Wallis test was used to analysis multiple comparisons between groups. The relationship between cognitive scores and VOI was compared using linear regression. For radiomics, principal component analysis (PCA) was used to reduce model overfitting and calculations and then a support vector machine (SVM) was used to build a binary classification model. For model performance evaluation, we used an accuracy, sensitivity, specificity and receiver operating characteristic curve (ROC).

Result

There were no significant differences in clinical variables between ANI group and pre-clinical-ANI group (P>0.05). The volume of bilateral putamen was significantly different between AHI group and pre-clinical group (P<0.05), but there was only a trend in the left putamen between ANI-treatment group and pre-clinical treatment group(P = 0.063). Reduced cognitive scores in Verbal Fluency, Attention/Working Memory, Executive Functioning, memory and Speed of Information Processing were negatively correlated with the increased VOI (P<0.05), but the correlation was relatively low. In diagnosing the ANI from pre-clinical ANI, the mean area under the ROC curves (AUC) were 0.85 ± 0.22, the mean sensitivity and specificity were 63.12 ± 5.51 and 94.25% ± 3.08%.

Conclusion

The volumes of putamen in patients with ANI may be larger than patients with pre-clinical ANI, the change of the volume of the putamen may have a certain process; there is a relationship between putamen and cognitive impairment, but the exact mechanism is unclear. Radiomics may be a useful tool for predicting early stage HAND in patients with HIV.
Association with CYP2C19 polymorphisms and Clopidogrel in treatment of elderly stroke patients
Authors: Li Changqing , Jia Weihua , Li Jian , Li Fangfei , Ma Jing , Zhou Lichun
Published: March 2021

Background

Clopidogrel is an antiplatelet drug used in the treatment of ischemic stroke. Safety and efficacy of clopidogrel has been confirmed in CAPRIE, PRoFESS trials. However, these studies focused on patients aged less than 75 years. CYP2C19 polymorphisms resulted in individual differences in clopidogrel response. Our objective was to determine whether elderly stroke patients aged over 75 years would benefit from CYP2C19-genotype-guided strategy for the secondary prevention of stroke.

Methods

A retrospective analysis of patients aged 75 years or older with non-cardiogenic stroke who received 75 mg clopidogrel was performed. CYP2C19 genotype-guided group included noncarriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles (LoFA) and compared against the non-genotype-guided group which may carriers CYP2C19 LoFA or not. The primary endpoints were composite of stroke and myocardial infarction at 24 months’ follow-up.

Results

Two hundred one patients were included: 99 in the genotype-guided group and 102 in the non-genotype-guided group. Kaplan-Meier(KM)analysis showed that CYP2C19 gene polymorphism was associated with the rate of the primary endpoints (P = 0.0031). The primary endpoints occurred in 13 patients (13.1%) in the genotype-guided group and in 30 patients (29.4%) in the non-genotype-guided group (hazard ratio(HR), 0.39; 95% confidence interval(CI), 0.20 to 0.75; p = 0.004). Cox regression analysis showed that CYP2C19 genotype-guided strategy was a protective factor for the primary endpoints (HR, 0.39; 95% CI:0.20 to 0.74, P = 0.004).

Conclusion

The CYP2C19 genotype-guided strategy could reduce the occurrence of composite of stroke and myocardial infarction compared to a non-genotype-guided strategy for non-cardiogenic stroke patients aged 75 years or older who received clopidogrel.
Single nucleotide polymorphisms in the ANGPTL4 gene and the SNP-SNP interactions on the risk of atherosclerotic Ischaemic stroke
Authors: Shen Chaoxiong , Fan Daofeng , Fu Huajun , Zheng Chong , Chen Yinjuan , Hu Zhizhou
Published: March 2021

Objectives

The purpose of this study was to investigate the impact of single nucleotide polymorphisms (SNPs) in the ANGPTL4 gene and the SNP–SNP interactions on atherosclerotic ischemic stroke (IS) risk.

Patients and methods

A case-control study was conducted. A total of 360 patients with atherosclerotic IS and 342 controls between December 2018 and December 2019 from Longyan First Hospital affiliated to Fujian Medical University were included. A logistic regression model was used to examine the association between SNPs and atherosclerotic IS risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the SNP-SNP interaction.

Results

Logistic regression analysis showed that atherosclerotic IS risk was significantly lower in carriers with the rs11672433-T allele than those with the CC genotype (CT+ TT vs. CC); adjusted OR, 0.005; 95% CI, 0.02–0.11. We found a significant 2-locus model (P = 0.0010) involving rs11672433 and rs4076317; the cross-validation consistency of this model was 10 of 10, and the testing accuracy was 57.96%. Participants with the CT or TT of rs11672433 and CC of rs4076317 genotype have the lowest atherosclerotic IS risk, compared to subjects with CC of rs11672433 and the CC of rs4076317 genotype, OR (95%CI) was 0.06(0.02–0.22), after covariates adjustment for gender, age, smoking and alcohol status, hypertension, Diabetes mellitus, TG, TC, HDL-C, LDL-C, Uric acid.

Conclusions

We found that rs11672433 was associated with decreased atherosclerotic IS risk; we also found that gene–gene interaction between rs11672433 and rs4076317 was associated with decreased atherosclerotic IS risk.
Multi-omics analysis of genomics, epigenomics and transcriptomics for molecular subtypes and core genes for lung adenocarcinoma
Authors: Zhao Yue , Gao Yakun , Xu Xiaodong , Zhou Jiwu , Wang He
Published: March 2021

Background

Lung adenocarcinoma (LUAD) is the most frequently diagnosed histological subtype of lung cancer. Our purpose was to explore molecular subtypes and core genes for LUAD using multi-omics analysis.

Methods

Methylation, transcriptome, copy number variation (CNV), mutations and clinical feature information concerning LUAD were retrieved from The Cancer Genome Atlas Database (TCGA). Molecular subtypes were conducted via the “iClusterPlus” package in R, followed by Kaplan-Meier survival analysis. Correlation between iCluster subtypes and immune cells was analyzed. Core genes were screened out by integration of methylation, CNV and gene expression, which were externally validated by independent datasets.

Results

Two iCluster subtypes were conducted for LUAD. Patients in imprinting centre 1 (iC1) subtype had a poorer prognosis than those in iC2 subtype. Furthermore, iC2 subtype had a higher level of B cell infiltration than iC1 subtype. Two core genes including CNTN4 and RFTN1 were screened out, both of which had higher expression levels in iC2 subtype than iC1 subtype. There were distinct differences in CNV and methylation of them between two subtypes. After validation, low expression of CNTN4 and RFTN1 predicted poorer clinical outcomes for LUAD patients.

Conclusion

Our findings comprehensively analyzed genomics, epigenomics, and transcriptomics of LUAD, offering novel underlying molecular mechanisms for LUAD. Two multi-omics-based core genes (CNTN4 and RFTN1) could become potential therapeutic targets for LUAD.
Baseline liver steatosis has no impact on liver metastases and overall survival in rectal cancer patients
Authors: Besutti Giulia , Damato Angela , Venturelli Francesco , Bonelli Candida , Vicentini Massimo , Monelli Filippo , Mancuso Pamela , Ligabue Guido , Pattacini Pierpaolo , Pinto Carmine , Giorgi Rossi Paolo
Published: March 2021

Background

The liver is one of the most frequent sites of metastases in rectal cancer. This study aimed to evaluate how the development of synchronous or metachronous liver metastasis and overall survival are impacted by baseline liver steatosis and chemotherapy-induced liver damage in rectal cancer patients.

Methods

Patients diagnosed with stage II to IV rectal cancer between 2010 and 2016 in our province with suitable baseline CT scan were included. Data on cancer diagnosis, staging, therapy, outcomes and liver function were collected. CT scans were retrospectively reviewed to assess baseline steatosis (liver density < 48 HU and/or liver-to-spleen ratio < 1.1). Among patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was defined as steatosis appearance, ≥ 10% liver volume increase, or significant increase in liver function tests.

Results

We included 283 stage II to IV rectal cancer patients with suitable CT scan (41% females; mean age 68 ± 14 years). Steatosis was present at baseline in 90 (31.8%) patients, synchronous liver metastasis in 42 (15%) patients and metachronous liver metastasis in 26 (11%); 152 (54%) deaths were registered. The prevalence of synchronous liver metastasis was higher in patients with steatosis (19% vs 13%), while the incidence of metachronous liver metastasis was similar. After correcting for age, sex, stage, and year of diagnosis, steatosis was not associated with metachronous liver metastasis nor with overall survival. In a small analysis of 63 patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was associated with higher incidence of metachronous liver metastasis and worse survival, results which need to be confirmed by larger studies.

Conclusions

Our data suggest that rectal cancer patients with steatosis had a similar occurrence of metastases during follow-up, even if the burden of liver metastases at diagnosis was slightly higher, compatible with chance.
Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer
Authors: Chen Jingyi , Song Yuxuan , Li Mei , Zhang Yu , Lin Tingru , Sun Jie , Wang Di , Liu Yulan , Guo Jingzhu , Yu Weidong
Published: March 2021

Background

Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis.

Methods

RNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm.

Results

A prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types.

Conclusions

MIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma.
Neonatal eye screening for 203 healthy term new-borns using a wide-field digital retinal imaging system
Authors: Teow Kheng Leong Kenneth , Abu Kassim Siti Nur Amira , Sidhu Jasvinjeet Kaur , Zohari Zayani , Sivalingam Thivakar , Ramasamy Sunder , Mohd Khialdin Safinaz , Mohd Nordin Noraihan , Rahmat Jamalia
Published: March 2021

Background

The current practice for new-born eye examination by an Ophthalmologist in Malaysian hospitals is limited to only preterm new-borns, syndromic or ill infants. Healthy term new-borns are usually discharged without a thorough eye examination. This study is aimed at determining the proportion and types of ocular abnormalities detected in purportedly healthy term new-borns.

Method

This cross-sectional study is comprised of 203 participants, all purportedly healthy term new-born infants from the Obstetrics and Gynaecology ward at Hospital Kuala Lumpur over a 6 months period. The examination list includes external eye examination, red reflex test, and fundus imaging using a wide-field digital retinal imaging system (Phoenix Clinical ICON Paediatric Retinal Camera) by a trained Investigator. The pathologies detected were documented. The results were compared and correlated with similar studies published in the literature previously.

Results

Total ocular abnormalities were detected in 34% of the infants. The most common finding was retinal haemorrhage in 29.6% of the infants, of which 53.3% occurred bilaterally. Spontaneous vaginal delivery (SVD) remained the greatest risk factor which has nearly 3.5 times higher risk of new-borns developing retinal haemorrhage compared to Lower Segment Caesarean Section (LSCS). There was a 6% increased likelihood of developing retinal haemorrhage for every 1-min increment in the duration of 2nd stage of labour.

Conclusion

Universal eye screening for all new-borns using a wide-field digital imaging system is realistically possible, safe, and useful in detecting posterior segment disorders. The most common abnormality detected is retinal haemorrhage.
Correction to: Efficacy of Mentalization-based group therapy for adolescents: the results of a pilot randomised controlled trial
Authors: Griffiths Helen , Duffy Fiona , Duffy Louise , Brown Sarah , Hockaday Harriet , Eliasson Emma , Graham Jessica , Smith Julie , Thomson Alice , Schwannauer Matthias
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Research on aging during the Venezuelan humanitarian crisis: the experience of the Maracaibo aging study
Authors: Maestre Gladys E. , Pirela Rosa V. , Paz Carmen L. , Melgarejo Jesus D. , Mena Luis J. , Chavez Carlos A. , Leendertz Reinier , Petitto Michele , Silva Eglé , Calmón Gustavo E. , Al-Aswad Lama , Lee Joseph H. , Terwilliger Joseph D.
Published: March 2021

Background

Venezuela is in the throes of a complex humanitarian crisis that is one of the worst in decades to impact any country outside of wartime. This case analysis describes the challenges faced by the ongoing Maracaibo Aging Study (MAS) during the deteriorating conditions in Venezuela. When the MAS began in 1997, it focused on memory-related disorders. Since then, strategic planning and proactive community participation allowed us to anticipate and address logistical, funding, and ethical challenges, and facilitated the enrollment and retention of more than 2500 subjects over 55 years of age. All participants, who are residents of the city of Maracaibo, Venezuela, underwent various assessments on several occasions. Here, we discuss how our approach to implementing a longitudinal, population-based study of age-related conditions has allowed our research program to continue throughout this period of political, economic, and social upheaval.

Discussion

As the social context in Venezuela became more complicated, new challenges emerged, and strategies to sustain the study and participation were refined. We identified five main mechanisms through which the evolving humanitarian crisis has affected implementation of the MAS: 1) community dynamics; 2) morale of researchers, staff, and participants; 3) financial feasibility; 4) components of the research process; and 5) impact on the health of staff, participants, and their families. Strategies to compensate for the impact on these components were implemented, based on inputs from community members and staff. Improved communication, greater involvement of stakeholders, broadening the scope of the project, and strengthening international collaboration have been the most useful strategies. Particular demands emerged, related to the increased mortality and comorbidities of participants and staff, and deterioration of basic services and safety.

Conclusion

Although the MAS has faced numerous obstacles, it has been possible to continue a longitudinal research project throughout the humanitarian crisis, because our research team has engaged the community deeply and developed a sense of mutual commitment, and also because our project has provided funding to help keep researchers employed, somewhat attenuating the brain drain.
Brief videoconferencing psychological intervention for reducing COVID-19 related distress: study protocol for a randomized controlled trial
Authors: Keyan Dharani , Dawson Katie , Azevado Suzanna , Yadav Srishti , Tran Jenny , Bryant Richard A.
Published: March 2021

Background

Globally COVID-19 has had a profound impact on the psychological wellbeing of millions of people, and there is an urgent imperative to address elevated levels of distress during the COVID-19 pandemic. The World Health Organization (WHO) has developed Problem Management Plus (PM+), a low intensity psychological intervention for adults experiencing psychological distress. This paper outlines the study protocol for a trial that tests the effectiveness of an adapted version of PM+ to reduce distress associated with COVID-19.

Methods

A single-blind, parallel, randomized controlled trial will be carried out for distressed people across Australia. via video conferencing on a small group basis. Following informed consent, adults that screen positive for levels of psychological distress (General Health Questionnaire-12 (GHQ-12 score ≥ 3) and have access to videoconferencing platform will be randomised to an adapted version of gPM+ (n = 120) or enhanced treatment as usual (ETAU) (n = 120). The primary outcome will be reduction in psychological distress including anxiety and depression at 2-months post treatment. Secondary outcomes include worry, sleep problems, anhedonia, social support, and stress in relation to COVID-19.

Discussion

The trial aims assess whether an adapted version of videoconferencing PM+ that is specifically designed to target COVI-19 related distress will result in reduced distress relative to enhanced usual care.

Trial registration

This trial was prospectively registered on the ANZCTR on 14/4/20 (ACTRN12620000468921).
Hypoglossal nerve palsy after gasless trans-axillary endoscopic thyroidectomy: a case report
Authors: Liu Qiao-Fei , Zhao Zhe-Wei , Cui Ming , Yang Sen , Liao Quan
Published: March 2021

Background

Gasless trans-axillary endoscopic thyroidectomy (GTAET) has satisfactory cosmetic effects for the patients who have benign goiter and small thyroid carcinoma, however the complications of this surgical procedure have not been fully documented. Ipsilateral hypoglossal nerve palsy (IHNP) associated with GTAET has never been reported before.

Case presentation

A 33-year old male patient presented with a 4 × 5 mm solid thyroid nodule in the right lobe. Papillary thyroid carcinoma was confirmed by the fine needle aspiration. He had strong cosmetic demand, therefore GTAET for right lobectomy and central cervical lymphadenectomy was performed in a supine position with cervical extension. Six hours after the operation, he developed tongue deviation to the right side, speech and swallowing difficulties, indicating IHNP. Head and cervical MRI showed no abnormality. The intravenous steroid was used for three days, and oral vitamin B1 and mecobalamin was prescribed for 1 month. Nine days after surgery, he was discharged. Three months after the operation, all the symptoms were completely resolved.

Conclusions

To the best of the authors’ knowledge, this is the first case of IHNP after GTAET, which will be valuable to add our knowledge to diagnose and treat rare complications of GTAET.
Diagnosis and treatment of obturator hernia: retrospective analysis of 86 clinical cases at a single institution
Authors: Li Zhengzheng , Gu Chaoyang , Wei Mingtian , Yuan Xing , Wang Ziqiang
Published: March 2021

Background

To explore the clinical characteristics, diagnosis and treatment of obturator hernia.

Methods

Eighty-six patients who were diagnosed as obturator hernia by abdominal CT in the Department of Gastrointestinal Surgery of our hospital between 2009 and 2019 were enrolled in this study. Patient characteristics, surgical method, postoperative complications and mortalities were retrospectively reviewed.

Results

Thirty days mortality rate of 5.5% and 46.1% were observed in surgery group and non-surgery group, respectively. Surgery was performed as an emergency procedure in 59 cases and elective procedure in 14 cases depending on different hernia contents, intestinal necrosis and signs of peritonitis. In the emergency surgery group, segmental intestinal resection with anastomosis was performed in 24 patients (24/59, 40.7%). There were 4 deaths (4/59, 6.8%) in this group, all of which occurred in patients undergoing SI resections. In contrast, no bowel resection, postoperative complications, or death occurred in the elective surgery group. 3-year recurrence rates of 5.1% (3/59) and 7.1% (1/14) were observed in the emergency surgery and the elective surgery group, respectively.

Conclusions

CT examination plays an important role in improving the diagnostic rate of obturator hernia. Timely surgical treatment is the key to improve the efficacy of obturator hernia and prevent the deterioration of the condition. In addition, intestinal resection and postoperative complications may be the important factors leading to postoperative death.
Metastatic intrapulmonary hemorrhagic foci secondary to cardiac angiosarcoma: a case report
Authors: Zheng Yu , Che Guowei , Wang Yun
Published: March 2021

Background

Cardiac angiosarcoma is a very rare malignant neoplasm, typically showing terrible prognosis. Therefore, early diagnosis is essential for efficacious intervention. Here we report a cardiac angiosarcoma with unique imaging findings because of pulmonary metastases.

Case presentation

A 55-year-old man presented to our Respiratory Department because of mild morning hemoptysis for five weeks with occasional palpitations, having undergone futile antibiotic therapy for two weeks at his local hospital before admission. Symptoms of hemoptysis were alleviated with venous hemostatic drugs. 18F-FDG PET/CT was performed, showing a right atrial mass with multiple parenchymal nodules in lungs surrounded by ground-glass opacity, and indicated an intracardiac malignant tumor associated with pulmonary metastases, consistent with cardiothoracic CT and ultrasound. No evidence of infection or neoplasm was found using a fiberoptic bronchoscope. After multidisciplinary consultation and discussion, provisional diagnosis was established such that metastatic intrapulmonary hemorrhagic foci were secondary to intracardiac malignancy. A percutaneous biopsy from the left lung was carried out and but showed mild chronic inflammation of the lung. Therefore, urgent wedge resections for biopsy were performed from the right lung and the histopathology revealed angiosarcoma. The patient died of cardiorespiratory failure before anticancer therapy.

Conclusions

Variety of clinical manifestations of cardiac angiosarcoma frequently makes its diagnosis difficult, the imaging features and epidemiology of cardiac malignancy are very significant to clinical diagnosis.
Maxillary and mandibular dental arch forms in a Jordanian population with normal occlusion
Authors: Aljayousi M. , Al-Khateeb S. , Badran S. , Alhaija E. S. Abu
Published: March 2021

Background

Ethnic background has been claimed to affect arch form. The purpose of this study was to describe and elucidate the maxillary and mandibular arch forms in Jordanian population and to develop a classification method for these forms which could be employed to construct orthodontic archwires accordingly.

Methods

The sample was comprised of study casts of five hundred and twenty subjects (231 males and 289 females with a mean age of 15.4 ± 1.02 years). All subjects had permanent dentition with normal occlusion. A mathematical method associated with a polynomial function of 6th degree was employed to assess the dental arch forms. The resultant arch forms were classified into 5 groups for both the maxilla and mandible utilizing a computer software with special code designed for this study. Each group was subdivided into 3 subgroup sizes namely: small, medium, and large.

Results

Catenary arch form was found in 47% and 41.2% (p ˂ 0.01) of maxilla and mandible arch forms, respectively. Form 2 (which is halfway between ellipse and U-shaped arch form) was found in 27.7% and 26.7%. Medium size arch form was found in 55.4% of the maxillary and 65.6% of the mandibular arch forms.

Conclusion

Catenary arch form was the most prevalent arch form, followed by wide elliptical form. The other forms, which included tudor arch, tapered equilateral and quadrangular forms were less frequent. Regarding size, the medium size was the most prevalent among the studied samples.
Validity and reliability of the English and translated Chinese versions of the Integrated Palliative care Outcome Scale (IPOS) in Singapore
Authors: Long Victoria Jane En , Cheung Yin Bun , Qu Debra , Lim Katherine , Lee Guozhang , Yee Alethea C. P. , Guo Ping , Harding Richard , Yang Grace Meijuan
Published: March 2021

Context

Measurement of patient-centred outcomes enables clinicians to focus on patient and family priorities and enables quality of palliative care to be assessed.

Objectives

This study aimed to evaluate the validity and reliability of the English and translated Chinese versions of the Integrated Palliative care Outcome Scale (IPOS) among advanced cancer patients in Singapore.

Methods

IPOS was forward and backward translated from English into Chinese. Structural validity was assessed by confirmatory factor analysis; known-group validity by comparing inpatients and community patients; construct validity by correlating IPOS with Edmonton Symptom Assessment System-revised (ESAS-r) and Functional Assessment of Cancer Therapy–General (FACT-G); internal consistency by Cronbach’s alpha; inter-rater reliability between patient and staff responses; test-retest reliability of patient responses between two timepoints.

Results

One hundred eleven English-responding and 109 Chinese-responding patients participated. The three-factor structure (Physical Symptoms, Emotional Symptoms and Communication and Practical Issues) was confirmed with Comparative Fit Index and Tucker-Lewis-Index > 0.9 and Root Mean Square Error of Approximation < 0.08. Inpatients scored higher than outpatients as hypothesised. Construct validity (Pearson’s correlation coefficient, r ≥ |0.608|) was shown between the related subscales of IPOS and FACT-G and ESAS-r. Internal consistency was confirmed for total and subscale scores (Cronbach’s alpha≥0.84), except for the Communication and Practical Issues subscale (Cronbach’s alpha = 0.29–0.65). Inter-rater reliability (Intra-class correlation coefficient [ICC] ≤ 0.43) between patient and staff responses was insufficient. Test-retest reliability was confirmed with Intra-class correlation coefficient ICC = 0.80 (English) and 0.88 (Chinese) for IPOS Total.

Conclusion

IPOS in English and Chinese showed good validity, good internal consistency, and good test-retest reliability, except for the Communication and Practical Issues subscale. There was poor inter-rater reliability between patients and staff.
Transformer-based deep neural network language models for Alzheimer’s disease risk assessment from targeted speech
Authors: Roshanzamir Alireza , Aghajan Hamid , Soleymani Baghshah Mahdieh
Published: March 2021

Background

We developed transformer-based deep learning models based on natural language processing for early risk assessment of Alzheimer’s disease from the picture description test.

Methods

The lack of large datasets poses the most important limitation for using complex models that do not require feature engineering. Transformer-based pre-trained deep language models have recently made a large leap in NLP research and application. These models are pre-trained on available large datasets to understand natural language texts appropriately, and are shown to subsequently perform well on classification tasks with small training sets. The overall classification model is a simple classifier on top of the pre-trained deep language model.

Results

The models are evaluated on picture description test transcripts of the Pitt corpus, which contains data of 170 AD patients with 257 interviews and 99 healthy controls with 243 interviews. The large bidirectional encoder representations from transformers (BERTLarge) embedding with logistic regression classifier achieves classification accuracy of 88.08%, which improves the state-of-the-art by 2.48%.

Conclusions

Using pre-trained language models can improve AD prediction. This not only solves the problem of lack of sufficiently large datasets, but also reduces the need for expert-defined features.
When time matters: a qualitative study on hospital staff’s strategies for meeting the target times in cancer patient pathways
Authors: Melby Line , Håland Erna
Published: March 2021

Background

Cancer patient pathways (CPPs) were introduced in Norway in 2015. CPPs are time-bound standardised care pathways that describe the organisation of and responsibilities for diagnostics and treatment, as well as communication with the patient and next of kin. The aim is to ensure that cancer patients experience a well-organised, coherent and predictable pathway without any delays in assessment and diagnostics caused by non-medical reasons. Preventing delays in diagnostics by meeting specific target times is central to the successful implementation of CPPs. The aim of this paper is to describe how hospital staff cope with the increased focus on meeting CPP target times and the measures and strategies implemented by hospitals and their staff.

Methods

Data for this paper were collected in a larger study on implementation and experiences with CPPs among hospital staff, general practitioners, and patients in Norway (2017–2020). The study had a qualitative cross-sectional design, and data were collected through interviews. This article is based on semi-structured interviews with hospital staff (N = 60) in five hospitals.

Results

Hospital staff are highly aware of the target times, and try to comply with them, in the interest of both the patients and the hospitals. The implementation of CPPs was not accompanied by the allocation of additional resources; therefore, hospitals could not simply increase capacity to meet the target times. Instead, they had to develop other strategies. Four categories of strategies were identified: (i) introducing new roles and more staff, (ii) reorganising the workflow, (iii) gaming the system and (iv) outsourcing services.

Conclusions

Hospital staff are torn between meeting the target times and a lack of resources and capacity. This is not unusual in the current healthcare context, where staff face organisational reforms and increasing demands on a regular basis. It is important to recognise frontline workers’ efforts towards realising new organisational changes. Therefore, carefully weighing the benefits against the costs and undertaking the necessary planning are important in the design and implementation of future care and treatment pathways for patients.
Molecular detection and genetic diversity of Rickettsia spp. in pet dogs and their infesting ticks in Harbin, northeastern China
Authors: Shao Jian-Wei , Yao Xin-Yan , Song Xu-Dong , Li Wen-Jun , Huang Hui-Lan , Huang Shu-Jian , Zhang Xue-Lian
Published: March 2021

Background

Pet dogs are important companion animals that share the environment within households, and play an important role in local community life. In addition, pet dogs also are reservoirs of zoonotic agents, including Rickettsia spp., thus increasing the risk of rickettsial infections in humans. It’s meaningful to investigate the epidemiology of rickettsial agents in pet dogs, and make contribute to the surveillance of rickettsioses in human in China.

Results

In this study, a total of 496 pet dogs’ blood samples and 343 ticks infested in pet dogs were collected, and the presence and prevalence of Rickettsia were determined by amplifying the partial gltA and 17-kDa genes, with an overall positive rate of 8.1 % in blood samples and 14.0 % in tick samples. In addition, the rrs, gltA, groEL, and ompA genes of rickettsial were also recovered to determine the species of Rickettsia detected furtherly. Sequencing blast and phylogenetic analyses revealed the presence of three human pathogenic Rickettsia species (Rickettsia raoultii, Candidatus Rickettsia tarasevichiae and Rickettsia felis) in samples associated with pet dogs. Moreover, all the sequences of Rickettsia that we obtained presented close relationship with others available in GenBank, and Rickettsia raoultii was the most predominant Rickettsia species infected in pet dogs’ blood samples or in tick samples.

Conclusions

This study provides the molecular epidemiology data about the Rickettsia spp. infection associated with pet dogs in urban areas of Harbin city. Three rickettisae species pathogenic to humans were identified from pet dogs’ blood and the infested ticks in urban areas of Harbin city. Considering the intimate relationship between human and pets, these results indicate the potential transmission risk of human rickettisal infections from pet dogs through ectoparasites, and also highlighting that more attention should be paid to rickettsial infection in pet dogs and the infested ticks from the “One health” perspective.
Induction of macrophage pyroptosis-related factors by pathogenic E. coli high pathogenicity island (HPI) in Yunnan Saba pigs
Authors: Shan Chunlan , Miao Shushu , Liu Chaoying , Zhang Bo , Zhao Weiwei , Wang Hao , Yang Wei , Cha Jinlong , Zhao Ru , Xiao Peng , Gao Hong
Published: March 2021

Background

Pyroptosis plays a pivotal role in the pathogenesis of many inflammatory diseases. The molecular mechanism by which pyroptosis is induced in macrophages following infection with pathogenic E. coli high pathogenicity island (HPI) will be evaluated in our study.

Results

After infection with the HPI+/HPI− strains and LPS, decreased macrophage cell membrane permeability and integrity were demonstrated with propidium iodide (PI) staining and the lactate dehydrogenase (LDH) assay. HPI+/HPI−-infection was accompanied by upregulated expression levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD, with significantly higher levels detected in the HPI+ group compared to those in the HPI− group (P < 0.01 or P < 0.05). HPI+ strain is more pathogenic than HPI− strain.

Conclusion

Our findings indicate that pathogenic E. coli HPI infection of Saba pigs causes pyroptosis of macrophages characterized by upregulated expression of pyroptosis key factors in the NLRP3/ASC/caspase-1 signaling pathway, direct cell membrane pore formation, and secretion of the inflammatory factor IL-1β and IL-18 downstream of NLRP3 and caspase-1 activation to enhance the inflammatory response.
Genetically determined tobacco and alcohol use and risk of atrial fibrillation
Authors: Lu Yunlong , Guo Yan , Lin Hefeng , Wang Zhen , Zheng Liangrong
Published: March 2021

Background

The causality between the use of alcohol and cigarettes and atrial fibrillation (AF) remains controversial. We conducted a Mendelian randomization (MR) study to evaluate the association of genetic variants related to tobacco and alcohol use with AF.

Methods

Single nucleotide polymorphisms (SNPs) related to smoking initiation (N = 374), age at initiation of regular smoking (N = 10), cigarettes per day (N = 55), and smoking cessation (N = 24) were derived from a genome-wide association studies (GWAS) of tobacco use (N = 1.2 million individuals). SNPs related to heavy alcohol use (N = 6) were derived from a GWAS of UK biobank (N = 125,249 individuals). The genetically matching instrumented variables were obtained from the GWAS of AF (N = 588,190 individuals). The estimates between tobacco and alcohol use and AF were combined by inverse-variance weighted (IVW), simple median, weighted median, MR-robust adjusted profile score method, MR-PRESSO, and multivariable MR.

Results

A total of 65,446 AF patients and 522,744 referents were included. In the IVW analysis, the odds ratio per one-unit increase of smoking initiation was 1.11 (95% CI, 1.06–1.16;P = 3.35 × 10−6) for AF. Genetically predicted age at initiation of regular smoking, cigarettes per day and smoking cessation were not associated with AF. The IVW estimate showed that heavy alcohol consumption increased AF risk (OR, 1.11; 95% CI, 1.04–1.18;P = 0.001). The results were consistent in complementary analyses and multivariable MR.

Conclusion

Our MR study indicated that regular smoking was associated with increased risk of AF, no matter the age at initiation of regular smoking, or the number of cigarettes smoked per day. Genetically predicted heavy alcohol consumption increased the risk of AF.
Comparative metabolomics analysis of amphotericin B high-yield mechanism for metabolic engineering
Authors: Zhang Bo , Chen Yu , Jiang Sheng-Xian , Cai Xue , Huang Kai , Liu Zhi-Qiang , Zheng Yu-Guo
Published: March 2021

Background

The polyene macrocyclic compound amphotericin B (AmB) is an important antifungal antibiotic for the clinical treatment of invasive fungal infections. To rationally guide the improvement of AmB production in the main producing strain Streptomyces nodosus, comparative metabolomics analysis was performed to investigate the intracellular metabolic changes in wild-type S. nodosus ZJB20140315 with low-yield AmB production and mutant S. nodosus ZJB2016050 with high-yield AmB production, the latter of which reached industrial criteria on a pilot scale.

Results

To investigate the relationship of intracellular metabolites, 7758 metabolites were identified in mutant S. nodosus and wildtype S. nodosus via LC–MS. Through analysis of metabolism, the level of 26 key metabolites that involved in carbon metabolism, fatty acids metabolism, amino acids metabolism, purine metabolism, folate biosynthesis and one carbon pool by folate were much higher in mutant S. nodosus. The enrichment of relevant metabolic pathways by gene overexpression strategy confirmed that one carbon pool by folate was the key metabolic pathway. Meanwhile, a recombinant strain with gene metH (methionine synthase) overexpressed showed 5.03 g/L AmB production within 120 h fermentation, which is 26.4% higher than that of the mutant strain.

Conclusions

These results demonstrated that comparative metabolomics analysis was an effective approach for the improvement of AmB production and could be applied for other industrially or clinically important compounds as well.
MicroRNA-1182 and let-7a exert synergistic inhibition on invasion, migration and autophagy of cholangiocarcinoma cells through down-regulation of NUAK1
Authors: Pan Xin , Wang Gang , Wang Baoming
Published: March 2021

Background

Cholangiocarcinoma (CCA) is the second most common primary liver malignancy worldwide. Several microRNAs (miRNAs) have been implicated as potential tumor suppressors in CCA. This study aims to explore the potential effects of miR-1182 and let-7a on CCA development.

Methods

Bioinformatics analysis was conducted to screen differentially expressed genes in CCA, Western blot analysis detected NUAK1 protein expression and RT-qPCR detected miR-1182, let-7a and NUAK1 expression in CCA tissues and cell lines. Dual luciferase reporter gene assay and RIP were applied to validate the relationship between miR-1182 and NUAK1 as well as between let-7a and NUAK1. Functional experiment was conducted to investigate the role of miR-1182, let-7a and NUAK1 in cell migration, proliferation and autophagy. Then, the CCA cells that received various treatments were implanted to mice to establish animal model, followed by tumor observation and HE staining to evaluate lung metastasis.

Results

CCA tissues and cells were observed to have a high expression of NUAK1 and poor expression of miR-1182 and let-7a. NUAK1 was indicated as a target gene of miR-1182 and let-7a. Importantly, upregulation of either miR-1182 or let-7a induced autophagy, and inhibited cell progression and in vivo tumor growth and lung metastasis; moreover, combined treatment of miR-1182 and let-7a overexpression presented with enhanced inhibitory effect on NUAK1 expression and CCA progression, but such synergistic effect could be reversed by overexpression of NUAK1.

Conclusion

Taken together, the findings suggest the presence of a synergistic antitumor effect of miR-1182 and let-7a on the development of CCA via the down-regulation of NUAK1, providing novel insight into the targeted therapy against CCA.
Effect on 30-day mortality and duration of hospitalization of empirical antibiotic therapy in CRGNB-infected pneumonia
Authors: Li Rongrong , Tang Hao , Xu Huaming , Cui Kunwei , Li Shujin , Shen Jilu
Published: March 2021

Background

The objective of this study was to investigate whether unreasonable empirical antibiotic treatment (UEAT) had an impact on 30-day mortality and duration of hospitalization in bacterial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB).

Methods

This was a retrospective cohort study involving CRGNB-infected pneumonia. All CRGNB-infected pneumonia patients received empirical and targeted antibiotic treatment (TAT), and they were divided into reasonable empirical antibiotic treatment (REAT) and UEAT according to whether the empirical antibiotic treatment (EAT) was reasonable. The data of the two groups were compared to analyze their influence on the 30-day mortality and hospitalization time in CRGNB-infected pneumonia patients. Moreover, we also considered other variables that might be relevant and conducted multivariable regression analysis of 30-day mortality and duration of hospitalization in CRGNB-infected pneumonia patients.

Results

The study collected 310 CRGNB-infected pneumonia patients, the most common bacterium isAcinetobacter baumannii(211/310 [68%]), the rest wereKlebsiella pneumoniae(46/310 [15%]),Pseudomonas aeruginosaand others (53/310 [17%]). Among them, 76/310 (24.5%) patients received REAT. In the analysis of risk factors, dementia, consciousness were risk factors of 30-day mortality, pulmonary disease, hemodynamic support at culture taken day and recent surgery were risk factors for longer hospital stay. The analysis of 30-day mortality showed that UEAT was not associated with 30-day mortality for the 30-day mortality of REAT and UEAT were 9 of 76 (11.84%) and 36 of 234 (15.38%) (P = 0.447), respectively. Meanwhile, there was difference between REAT and UEAT (P = 0.023) in the analysis of EAT on hospitalization time in CRGNB-infected pneumonia patients.

Conclusions

UEAT was not associated with 30-day mortality while was related to duration of hospitalization in CRGNB-infected pneumonia patients, in whichAcinetobacter baumanniiiaccouned for the majority.